The COVID-19 pandemic dramatically changed the nature of social interaction, creating negative impacts and challenges, but also opportunities for progressing how we communicate, as humans. Social distancing policies, lockdown measures, and mandatory quarantines accelerated technological communication. For example, Artificial Intelligence (AI) mediated communication grew at an unprecedented rate, willingly or otherwise. As part of pandemic control efforts, many activities, such as workplace meetings, education, and conferences, moved online, using social media platforms, the metaverse, and specialized programs accessed through mobile devices or laptops. As a result, digitally mediated channels became critical for information acquisition and communication across a wide spectrum of human activities in our personal and professional lives. As the scientific understanding of COVID-19 improved, pandemic restrictions loosened. However, it remains to be seen whether the pandemic communication paradigm, characterized by heavy technological mediation and reliance on non-human agents, will gradually decline, or whether the paradigm shift will become deeply entrenched with further acceleration of the dependency on technological mediation and non-human agents.Such unprecedented reliance on technological mediation and non-human agents for information and communication is akin to a social-psychological experiment on a global scale. Much remains unknown, however, since this communication paradigm shift began almost 3 years ago. There are two main problems that require attention. First, the psychological impact of and underlying mechanisms behind the extended and extensive reliance on technological mediation and non-human agents is not yet well understood, especially regarding the influence of AI technologies. Second, the extent to which the impact of this reliance is likely to persist and influence future communication is also not well understood, especially in different national and cultural contexts. Research involving new approaches to data collection, such as big data techniques, together with more traditional data techniques, can help in providing greater insights into these two problems.In this Research Topic, we sought to extend current understanding about how the COVID-19 pandemic has reshaped human communication, especially cognitive, psychological, and behavioral shifts in social interactions. We focused on research that explored new possibilities for interpersonal communication practices in the post-pandemic era. Eighteen manuscripts were selected for inclusion and draw intensive attention with more than 26,000 views.Information technologies, such as social media platforms, offer individuals various functionality to support the maintenance, development, and sustainability of individuals and organizations. For instance, when COVID-19 emerged, the provision of resources and social support became a major concern for many.The Importance of Project Description to Charitable Crowdfunding Success: The Mediating Role of Forwarding Times,” Lu et al. considered 205 COVID-19 charitable projects and 11,177,249 donors to assess the process by which nonprofit organizations raise funds through information descriptions about project descriptions. The results of the study indicated that understandability and a negative tone for descriptions help to improve the amounts raised. A question remains: might quarantines and economic disadvantages exacerbate social anxiety among impoverished individuals?In the article titled “Social Media as Online Shelter: Psychological Relief in COVID-19 Pandemic Diaries,” Feng et al. explored how individual narratives on social media affect people's psychological health during a state of emergency using data collected from 19 interviews with Chinese diary writers. The study found that a pandemic diary could promote self-relief, public communication, emotional drive, meaning connection, and identity construction in public spaces, thus helping shape a sense of unity and belonging and facilitating the psychological reconstruction of people who are vulnerable to potential mental health crises.In the article titled “Online Collaborative Documents as Media Logic: The Mediatization of Risk Response in the Post-pandemic Era,” Jiang et al. used a mixed-method design approach to examine treating online collaborative documents as a special approach to risk response in public health and natural disaster situations. The study found that the editability, accessibility, activability, and normality of technological affordances connected the functional features of a digital platform with users' potential actions.In the article titled “In this Research Topic, the authors also explored the drawbacks of information technology adoption. As the COVID-19 pandemic progressed, human reliance on information technology increased. For example, social media and the metaverse are now routinely being used for entertainment, learning, daily communication, and work.Personal network protects, social media harms: Evidence from two surveys during the COVID-19 pandemic,” Ren and Yan demonstrated the increasingly critical and multifaceted role of communication technologies in affecting mental health conditions, indicating the destructive outcomes of the overuse of social media.In the article titled “How do Internet moms raise children? The reshaping of Chinese urban women's parenting psychology by COVID-19 online practices,” Zhao and Ju, focusing on a special group of internet mothers, examined how they raised their children using the internet during the pandemic. The study found that social media created a new platform for information empowerment, mutual action, and ideation of motherhood for urban women formerly bound to family and parenting matters.In the article titled “Metaverse as a possible tool for reshaping schema modes in treating personality disorders,” Yin et al. showed the potential role of the metaverse and virtual worlds in reshaping schema modes for treating personality disorders by reconstructing a new object world for a patient with the prescription of a psychotherapist.In the article titled “Psychological distance and user engagement in online exhibitions: Visualization of moiré patterns based on electroencephalography signals,” Li J. et al. followed an Electroencephalography (EEG) signaling approach to highlight the possibility of EEG-visualization media devices in reducing the psychological distance and promotion of interpersonal communication between two participants experiencing an online exhibition.In the article titled “Social media also provides new opportunities for many as we enter a post-pandemic era, including the public, institutions, media, and governments.The application of network agenda setting model during the COVID-19 pandemic based on latent Dirichlet allocation topic modeling” and “Event history analysis of the duration of online public opinions regarding major health emergencies,” Liu K. et al.  and Liu X. et al. explored the public opinion landscape of the pandemic, as well as the dynamics of public opinion evolution.In the articles titled “Social media interactions between government and the public: A Chinese case study of government WeChat official accounts on information related to COVID-19” and “Government crisis communication innovation and its psychological intervention coupling: Based on an analysis of China's provincial COVID-19 outbreak updates,” Shao et al. and Zhou et al. drew on the perspective of government-public relationships to focus on issues pertaining to government-public interactions and government crisis communication in an attempt to provide practical implications for crisis communication systems and public administrations during a public health crisis.In the articles titled “Relationship Between Hardiness and Social Anxiety in Chinese Impoverished College Students During the COVID-19 Pandemic: Moderation by Perceived Social Support and Gender,” Cheng et al. studied 673 impoverished Chinese college students and found that perceived social support moderated the effect of hardiness on social anxiety.In the article titled “Self-Efficacy, Proxy Efficacy, Media Literacy, and Official Media Use in COVID-19 Pandemic in China: A Moderated Mediation Model,” Li Q. et al. explored the determinants of self-efficacy for fighting against the COVID-19 pandemic under social cognitive theory. The authors found that official media use was a negative moderator of the association between media literacy and proxy efficacy.In the article titled “Unpacking the effects of personality traits on algorithmic awareness: The mediating role of previous knowledge and moderating role of internet use,” Fang and Jin revealed that previous knowledge of algorithms and internet use are mediators and moderators between personality and algorithm awareness.In the article titled “The mediating role of personal values between COVID-19-related posttraumatic growth and life satisfaction among Chinese college students: A two-wave longitudinal study,” Xie et al. established that COVID-19-related posttraumatic growth is positively associated with life satisfaction, while self-transcendence and self-enhancement values partially mediate this association.In the article titled “Personal space increases during the COVID-19 pandemic in response to real and virtual humans,” Holt et al. suggested that personal space boundaries were expanded during the pandemic. The authors provided an index of recovery from the psychological effects of the crisis.In the article titled “Exploring factors that influence COVID-19 vaccination intention in China: Media use preference, knowledge level and risk perception,” Chen et al. examined the role of media use preference, knowledge level, and risk perception in predicting people's intentions to take a COVID-19 vaccine in the Chinese context.In the article titled “Influence of personality traits on online self-disclosure: Considering perceived value and degree of authenticity separately as mediator and moderator,” Lv et al. revealed the role of personality traits in online selfdisclosure, while separately assessing the perceived value and degree of authenticity as mediator and moderator.Finally, in the article titled “In summary, this Research Topic aimed to unite efforts to explore various aspects of communicative practices during and after a major crisis, although most of the studies were situated in the Chinese context. While we cannot say that this Research Topic provides a comprehensive knowledge map of post-pandemic communication practices, we hope that it will contribute to broadening the scope of conventional theoretical versions of information, media technology, and psychology.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


In the published article, there was an error. We mistakenly described the trend of changes in the levels of some metabolites after treatment of SpA patients.Results, “Dynamic alterations in the metabolic profile before and after treatment of spondyloarthritis,” Paragraphs 2 and 4. These sentences previously stated:A correction has been made to “Kapoor et al.  and BoguAnd“In addition, in the serum of JIA patients, MTX therapy increased the level of omega-3 unsaturated fatty acids (docosahexanoic acid and linoleic acid), which are anti-inflammatory mediators.”The corrected sentence appears below:“Kapoor et al.  and BoguAnd“In addition, in the serum of JIA patients, MTX therapy reduced the level of omega-3 unsaturated fatty acids (docosahexanoic acid and linoleic acid), which are anti-inflammatory mediators.”The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


Cells, several up-to-date reviews and original studies have provided new insights into the basic and translational aspects of AMPK signaling.5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme regulating numerous cellular processes involved in cell survival as well as health- and lifespan. AMPK has emerged not only as a key cellular energy sensor but also as an important integrator of signals that manages cellular energy balance. Due to this property and being ubiquitously expressed in all mammalian cell types, AMPK has attracted interest in virtually all areas of biomedical research. In this Special Issue of Visnjic et al.  considerIn the other review paper, Aslam and Ladilov  describeObesity has been categorized by the American Medical Association as a chronic progressive metabolic disorder and is a growing public health concern worldwide. In the paper by van der Vaart et al. , an impoFinally, an original study by Li et al.  providedIn a sophisticated study, Olivier et al.  investigNon-alcoholic fatty liver disease (NAFLD) is emerging as a leading cause of chronic liver illness affecting > 30% of the European population, and even higher rates can be seen in the US population ,12. The Both transcriptional and genetic alterations in AMPK pathways may impact tumor microenvironments in a tissue-dependent manner either positively or negatively . This asLastly, Bhutta et al.  reviewed


Many researchers rely on animal studies to elucidate the mechanisms underlying diverse disease processes and to test the safety of emerging medical interventions. Animal research serves as a bridge between in vitro experiments and human trials in the preclinical stage. The majority of animal research employs almost genetically identical laboratory-bred mice or rats. Testing genetically similar individuals in a laboratory environment provides a level of control not available in clinical trials and is crucial for all phases of biomedical research. Numerous animal models have been developed to imitate pathophysiological abnormalities observed in humans. For an animal model of a human disease to be optimal, it must have similar pathophysiology, phenotypic, and histopathological traits; predictive biomarkers for disease progression or prognosis; therapeutic responsiveness; and levels of pharmacological safety or toxicity responses ,2. Thus,Various animal models have been critical in basic scientific and preclinical research on human neurological disorders, including traumatic or non-traumatic, neuroinflammatory, neuropsychological, and neurodegenerative diseases. The animal models are designed to mimic several facets of the disorders, including their genetic basis, neuropathological lesions, and clinical symptoms . These aHence, the Special Issue “Modeling Neurological Disorders in Experimental Animals: New Insights and Emerging Roles ” aimed tThe research articles in this Special Issue have mostly focused on the alterations of behavioral and histopathological characteristics and signal transduction, as well as the testing of potential therapeutic compounds in genetically manipulated and/or exogenous factor-induced animal models for neurological disorders. To begin, the articles by Ang et al., entitled “Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice”  and “SREThis Special Issue contains two additional research articles on animal models of schizophrenia. Chang et al. reported in their article “Interaction of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia”  that disAnother article in this Special Issue demonstrated a non-genetic and exogenous factor-induced animal model of neurological disorders. Although exposure to radiofrequency electromagnetic fields (RF-EMFs) has increased in the pediatric population, data on the consequences of the exposure to the central nervous system to RF-EMFs in them are scarce. The article by Kim et al. entitled “Exposure to RF-EMF Alters Postsynaptic Structure and Hinders Neurite Outgrowth in Developing Hippocampal Neurons of Early Postnatal Mice”  reveled This Special Issue featured a research article testing a prospective therapeutic drug in a genetically manipulated mouse model of neurological disorder. Ding et al., in their article “Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome” , uncoverAdditionally, in a research paper on the hormonal effect on maternal behavior, the article by Leko et al. entitled “Transcriptome Sequencing in the Preoptic Region of Rat Dams Reveals a Role of Androgen Receptor in the Control of Maternal Behavior”  revealedsgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA” by Douek et al. [sgsh (Deltaex5-6) zebrafish mutant could be a valuable resource for gaining a better understanding of MPS IIIA pathobiology and developing timely and effective therapeutic interventions.Apart from the rodent models mentioned above, this Special Issue included an article describing the development of a zebrafish model that mimicked a human disease. Mucopolysaccharidosis IIIA , a pediatric neurological lysosomal storage disease, is caused by a deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (sgsh), resulting in an impairment in heparan sulfate-glycosaminoglycan catabolism and its accumulation in tissues. The article “An Engineered k et al.  suggesteThe review articles presented in this Special Issue demonstrated the ingenuity of researchers in addressing the critical task of modeling human neurological disorders in animals in meaningful ways. The articles mainly reviewed various animal models for neurological disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), epilepsy, Parkinson disease (PD), peripheral nerve injury, and post-traumatic stress disorder (PTSD). These animal models will be useful to gain better understanding of the mechanisms leading to signs of neurological disorders, validating drug targets, and providing assurance that therapeutic approaches will ultimately benefit patients. ALS is a fatal, multigenic, multifactorial, and non-cell autonomous neurodegenerative disease characterized by upper and lower motor neuronal loss. Bonifacino et al.  reviewedAD is the most common cause of dementia, and its pathogenesis is complex, including Aβ deposits, tau aggregates, excitotoxicity, and neuroinflammation. Robert et al.  reviewedPD is the second most prevalent neurodegenerative disorder after AD. No cure for PD has been discovered, and treatment strategies are aimed at relieving symptoms through the restoration of dopaminergic functions. Liu and Cheung  reviewedNeurons are structurally distinct and have injury-prone dendrites and axons. Peripheral nerves that have been injured, but not central nerves, have the ability to recover and reinnervate their target organs. Numerous animal models have been used to elucidate the mechanisms of axon regeneration. Lee and Cho  reviewedKetamine has evolved into a versatile drug, which is used for a number of indications ranging from trauma analgesia to depression and PTSD therapy. Due to the inherent ethical problems associated with performing prospective clinical studies on traumatic events and stress-related diseases in humans, researchers frequently use preclinical rat models to investigate the effects of ketamine on fear memory and PTSD-like behaviors. A review by Choi et al.  summarizConsequently, this Special Issue provides an update on current knowledge of the importance of animal models in mechanistic and therapeutic research on neurological disorders. I hope that readers will gain an understanding of current research trends and insights on future research directions through this Special Issue. However, I recognize that this Special Issue is insufficient to address the diverse animal models for a variety of neurologic disorders and that the articles included in this issue cannot possibly cover all on this topic. Thus, to complement any latest research data or research trends, I have re-launched the Special Issue “Modeling Neurologic Disorders in Experimental Animals: New Insights and Emerging Roles 2.0 ” to soli


Pseudomonas aeruginosa via LasIR/RhlIR circuitry’ by Mayank D. Shah et al., RSC Adv., 2019, 9, 40228–40239.Correction for ‘Potassium 2-methoxy-4-vinylphenolate: a novel hit exhibiting quorum-sensing inhibition in  The authors would like to add affiliation d as the current affiliation for Prashant S. Kharkar. The corrected list of affiliations is as shown above.The authors regret that one of the affiliations (affiliation The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Countrywide multi-serotype outbreak of Salmonella Bovismorbificans ST142 and monophasic Salmonella Typhimurium ST34 associated with dried pork sausages in France, September 2020 to January 2021’ by Pardos de la Gandara et al., upon publication on 12 January 2023, the title was missing the year of 2020 after September. This was corrected on 13 January 2023 at the request of the authors.In the article ‘


Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive triglyceride (TG) accumulation in hepatocytes, have become a serious health problem worldwide . Due to Decades of studies have demonstrated that cytokines derived from metabolic organs, including liver, adipose tissues and skeletal muscles, play crucial role in the regulation of hepatic and systemic lipid homeostasis . These oGuo et al., identified dysregulated myokines in the development of NAFLD and NASH through comprehensive transcriptome profiling. Mao et al., identified adipokines and hepatokines associated with high-salt-diet in mice. Wang et al., analyzed the relationship between circulating Ism1 and diabetes and diabetes-associated NAFLD. Gao et al., provided a novel view on endoplasmic reticulum-related and secretome gene in NAFLD progression.Therefore, at this stage, we set up a Research Topic entitled “The Roles and Mechanisms of Hepatokines, Adipokines and Myokines in the Development of Non-Alcoholic Fatty Liver Disease (NAFLD)” in the Frontiers in Endocrinology. Through this Research Topic, we aimed to further establish the roles of hepatokines, adipokines and myokines in NAFLD and NASH. In this collection, Overall, these studies together identified some new cytokines associated with NAFLD pathogenesis, which further strengthened our understanding of metabolic liver disease. However, intensive work is still required, such as investigations into the roles and mechanisms of these cytokines through genetic models, translational studies in human subjects, and screening potential therapeutic target for treatment. We hope that more and more studies on this Research Topic would help us better understand the molecular mechanisms of NAFLD development and identify more therapeutic targets for its treatment.The author confirms being the sole contributor of this work and has approved it for publication.


Berrones-Reyes et al., RSC Adv., 2019, 9, 30778–30789.Correction for ‘Quantum chemical elucidation of the turn-on luminescence mechanism in two new Schiff bases as selective chemosensors of Zn The correct email address is The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


As a result of their rapid development, polymer composites are seeing wider use in transportation infrastructure in China and worldwide. Styrene–butadiene–styrene (SBS), epoxy resin (ER), polyethylene (PE), expanded polyethylene (EP), polyurethane (PU), crumb rubber and other polymer materials can be used to modify asphalt and improve the performance of asphalt mix. Meanwhile, the application of polymer admixtures such as PE fiber, polyvinyl alcohol (PVA) fiber, polypropylene (PP) fiber, etc., in bituminous, cementitious or soil materials also improves their strength and durability. Polymer materials are also widely used in pavement maintenance and treatment; they can quickly restore road function and extend the road’s service life.This Special Issue contains sixteen research papers and one systematic review. The low-temperature properties of SBS-modified asphalt are not satisfactory; thus, Chen et al. analyzed the main factors for improving the low-temperature performance of SBS-modified asphalt base on the orthogonal tests . To solvSome research studies are devoted directly to the polymer materials applied in bituminous, cementitious or soil materials. Ren et al. studied the fatigue life and the material design of polymer concrete including ER and PU . Ji et aThe Special Issue concludes with a review on fiber-reinforced geopolymers and highlights the difficult aspects of current research, in addition to assessing the literature records .


Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease’ by Min-Che Tung et al., RSC Adv., 2021, 11, 31062–31072, https://doi.org/10.1039/D1RA05311F.Correction for ‘Discovery of 8-prenylnaringenin from hop ( The authors regret that the name of one of the authors (Hsing-Mien Hsu) was shown incorrectly in the original article. The corrected author list is as shown above.The authors also regret an incorrect version of The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


The brain weighs approximately 2% of the body, but utilizes about 20% of the total energy and oxygen supply, thus energy supply is critically important for the brain. In addition, the brain has no energy reserve, except some glycogens in the astrocytes, and the neurons can only use ATP, which comes from glucose degradation in the essential structure mitochondria. Mitochondria impairment, such as electron transport chain damage, can induce decreased ATP levels, decreased antioxidant defense, which is prevalent in many neurodegenerative disorders. For example, ATP dysfunction has been suggested to be the major impaired in depression . NumerouIt is critically important to understand the central facets of physiology and pathophysiology of energy supply in the brain, however, the energy supply regulation in the brain is not clear, for example how emotion affects energy supply, and does it activated by monoamine neurotransmitters. Emotion plays an important role in the regulation of the energy supply for the brain. Emotion parallels with behavior all the time, from the initiation of a behavior, the process of behavior to the end of the behavior. Emotion is the tendency for behavior, is also the motivation of a behavior. Emotion is also important for appraisal of behavioral consequences, marking the behavior as reward or punishment . Emotionvia autonomous nervous system, but also affect the energy supply in the brain. For example, the monoamine transmitters stimulate Na+, K+-ATPase activity in astrocytes and facilitate their role in ion concentrations , and suggested the berberine might be used as encouraging antidepressants to modulate depressed emotion.In another paper titled “Current evidence and future directions of berberine intervention in depression”, via TRPV1”, the authors Meng et al. studied the effects of berberine on transient receptor potential vanilloid (TRPV1) in dorsal root ganglia inflammation via inhibiting NF-κB and activating the JNK/p38 MAPK pathways in early injury, which inhibited the overexpression of TRPV1. The study suggested that berberine can reverse neuropathic pain response via inhibiting TRPV1 expression.In the experimental study about berberine titled “Berberine Alleviate Cisplatin-induced Peripheral Neuropathy by Modulating Inflammation Signal Li et al. introduced another kind of natural product, echinacoside, which is a kind of phenylethanoid glycoside (PhG) in Cistanche tubulosa. In the paper “Therapeutic potential and molecular mechanisms of Echinacoside in neurodegenerative diseases”, they reviewed many recent studies about its mechanisms in neuroprotective efficacy in the prevention and treatment of neurodegenerative diseases, and proposed that the major effect of echinacoside is improving mitochondrial function and reducing anti-oxidative stress.In another review, the authors Tao et al. summarized recent in vitro and in vivo studies about Chinese herbs in treating dementia, and found that the extracts of these Chinese herbs work on reducing generation of reactive oxygen species and inhibiting inflammation and neurotoxicity.In the review paper titled “Progress in the mechanism of autophagy and traditional Chinese medicine herb involved in dementia”, Lyu et al. studied a kind of Chinese herb Yi-zhi-fang-dai formula, and its effects on pyroptosis and glymphatic dysfunctions. The study suggested that the Chinese herb Yi-zhi-fang-dai formula could inactivate pyroptosis via inhibiting caspase-1/11 activation and gasdermin D cleavage, and induce AQP-4 depolarization thus increase glymphatic function to reduce neuronal damage.In the experimental paper titled “Yi-zhi-fang-dai formula exerts neuroprotective effects against pyroptosis and blood-brain barrier-glymphatic dysfunctions to prevent amyloid-beta ccute accumulation after cerebral ischemia and reperfusion in rats”, the authors Yin et al. studied the antioxidant activity of natural product rhein, and also its effects in clearance of β-amyloid (Aβ) in Alzheimer’s disease. The study found that rhein could significantly reduce reactive oxygen species, and activate mitochondrial biogenesis by increased cytochrome C oxidase and superoxide dismutase activities.In the experimental paper titled “Rhein relieves oxidative stress in an Aβ1-42 oligomer-burdened neuron model by activating the SIRT1/PGC-1α-regulated mitochondrial biogenesis”, the authors Liu et al. introduced a study about a kind of Chinese herb named danzhi xiaoyao powder and its effects on the symptoms of generalized anxiety disorder. The results suggested that the power could improve the weight growth and improve appetite and reduce the anxious mood via notch signaling pathway in the hippocampus. The study suggested that danzhi xiaoyao powder is a good therapy method for mood disorders.In the experimental paper “Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder”, the authors He et al. introduced a kind of classic Chinese herb formula, qiangji decoction in the paper “Qiangji Decoction alleviates neurodegenerative changes and hippocampal neuron apoptosis induced by d-galactose via regulating AMPK/SIRT1/NF-κB signaling pathway”. The herbs have been widely used in the traditional Chinese medicine, but the mechanisms are not clear. This paper found the major effect of qiangji decoction is reducing inflammation via reducing TNF-α, IL-1β and IL-6 in the hippocampus via regulating AMPK/SIRT1/NF-κB signaling pathway in hippocampal neuron apoptosis.In the experimental study, Zheng et al. introduced a kind of Chinese herb ginkgo biloba extract and donepezil on Alzheimer’s disease. In the paper titled “Effects of ginkgo biloba extract and donepezil on functional recovery in Alzheimer’s disease: a multi-level characterized study based on clinical features and resting-state functional magnetic resonance imaging”, they used neuroimage study and found that the herbs could change the ALFF values in right gyrus rectus and decreased PerAF values in left fusiform gyrus. And the authors concluded that the imaging metrics in specific brain regions may serve as biomarkers for therapeutic efficacy of medicines.In the experimental study, Zheng et al. introduced a study on the mechanism of sytisine on temporal lobe epilepsy, in the paper titiled “Cytisine exerts an anti-epileptic effect via α7nAChRs in a rat model of temporal lobe epilepsy”. Cytisine is an agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and has shown neuroprotection in many neurological diseases. This study found that sytisine could increase hippocampal function via enhancing ACh levels and α7nAChR expression, and decrease glutamate level to reduce seizures. The authors Arrodi et al. introduced one paper titled “Modulatory effects of alpha- and gamma-tocopherol on the mitochondrial respiratory capacity and membrane potential in Alzheimer’s disease an in vitro model of Alzheimer’s disease”, which suggested that mitochondrial abnormalities are an early feature in the pathogenesis of AD. They found that alpha-tocopherol or gamma-tocopherol could modulate mitochondrial function by increasing the production of ATP and reducing mitochondrial reactive oxygen species via altering mitochondrial metabolic pathways such as oxidative phosphorylation.The authors in vitro: implication for a potential therapy of Alzheimer’s disease”, Cheng et al. investigated the role of mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease. In addition, they investigated the effects of tortoise plastron gelatin and dear antler gelatin in preventing neuronal mitochondria function. The found that these two natural products could increase cell viability by modulating intracellular ATP and calcium level, and also regulate mitochondrial membrane potential (MMP) and ultrastructure, and finally inducing anti-dementia effects.In the paper titled “Tortoise plastron and dear antler gelatin prevents against neuronal mitochondrial dysfunction In all, these studies demonstrate that astrocytic function and neuronal mitochondria function play important roles in many neurodegenerative disorders. In addition, this topic introduced many natural drugs in treating these diseases. We expected that this Research Topic will stimulate interest in the study of the mechanisms of modulating the energy supply.


Current studies in the domain of cognitive neuroscience are devised to ensure a high signal-to-noise ratio. Measures from numerous participants are averaged to allow for commonalities to emerge, washing out possible differences. Albeit generally a good thing, a “one-size-fits-all” approach has a drawback: it fails to take inter-individual variability into account, a limitation that is no longer tenable given the increasing attention to so-called precision medicine , to relatively innocuous, though possibly intrusive, routines (as in superstitions), to frankly pathological states (as in compulsions). The common thread is the reliance on the mechanisms supporting habit formation. Neurofunctional models of OCD describe an imbalance between the goal-directed and the habit system of action control, which would lead to over-reliance on the latter (Gillan and Robbins, disturbance in the way in which one's body weight or shape is experienced,” the other criteria being significantly low weight and intense and persistent fear of becoming fat. In AN body size is generally overestimated (Schneider et al., Perceiving our body in space is instrumental to all approach/avoidance interactions with the environment (Sirigu et al., Overestimation of bodily space is not exclusive to AN. Young and perfectly healthy individuals misjudge their body size, particularly along the width dimension (Casper et al., So far, we provided two among many possible examples (e.g., agoraphobia, Indovina et al., For example, detecting and learning associations, a relevant step in habit formation, varies considerably based on personality traits and cognitive style (Kaufman et al., In sum, susceptibility factors for pathology may be nested within cognitive variability and—though still poorly explored—should be considered alongside psychosocial and biological markers (Jacobi et al., variability into the newly developing models of disease.Recent neuropsychological approaches to psychiatry have underlined the multifactorial origin of mental illnesses, drawing attention to cognitive variables (Wood et al., The study of cognitive variability is notoriously laden by methodological and reliability issues (Hedge et al., and applying the visuospatial skills required to view oneself “from the outside” (deVignemont, and constitute a vulnerability trait for disease. Detecting this trait within the healthy population (whereby variability exists; Samuel et al., Consider the example of body-size delusions. Describing one's body implies reporting beliefs and/or attitudes related to it Thus, while not implying a causal link between one cognitive style and development of a psychiatric condition, investigating cognitive variability could prove fruitful in characterizing disease and informing on the most probable direction malfunctioning could take, should other factors co-occur.ED drafted the paper. All authors discussed the ideas presented in the paper. All authors reviewed and approved the submitted version.


Xu et al.) respectively.Our interest in Non-coding RNA and Wnt/β-catenin Signaling Pathway in Human Cancer were initiated from our earlier studies: one was that the long non-coding RNA (LncRNA-NEF) antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/β-catenin signaling  and anotOut of the many manuscripts that we have received, seven were published in this research topic, including 2 reviews and 5 original research articles.Mu et al. summarized recent studies on the function and mechanisms of tumor resistance to cisplatin mediated by circular RNAs (circRNAs). The authors described various types of mechanisms in detail and the role of circRNAs in regulation of tumor proliferation, invasion, chemosensitivity, and other biological behaviors in the tumor microenvironment (TME). The authors emphasized that circRNA can be used as a promising target gene to reverse drug resistance and improve therapeutic efficacy.One review contributed by Li et al. summarized studies on the regulatory mechanisms of lncRNAs and their target gene signaling pathways in laryngeal squamous cell carcinoma, which is the second most frequent tumor of the respiratory system. This has significance in that by summarizing ncRNAs biological functions and important regulatory mechanisms in laryngeal squamous cell carcinoma the authors provide ideas for the improvement of diagnosis, prognostic evaluation, and development of pre-clinical targeted drugs.A second review contributed by Zhu et al. reported that the lncRNA LINC-PINT suppresses cell proliferation, invasion and Epithelial–Mesenchymal Transition (EMT) by blocking Wnt/β-catenin signaling in glioblastoma. They started with bioinformatics prediction of the role of LINC-PINT, followed by in vitro RT-PCR, clonal assays, and wound healing experiments to study the mechanism, and then they used in vivo tumor grating experiments to confirm the role of this lncRNA.The article contributed by Liu et al. and colleagues reported that microRNA (miRNA)-142-3p inhibits tumorigenesis of colorectal cancer (CRC) via suppressing the activation of Wnt signaling by directly targeting β-catenin. They used clinical samples and compared miRNA expression profiles between healthy donors and CRC patients. Colony formation and MTT assays were used to test cell proliferation. Luciferase assay, immunohistochemistry, and Western blotting were employed to explore the molecular mechanisms.Chen et al. reported that the lncRNA SNHG1 regulates the proliferation, apoptosis and autophagy of prostate cancer cells (PCa) via the Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. The PCa cells were transfected with a small interfering RNA plasmid (si-SNHG1) and si-SNHG1+multicellular protein EZH2 small interfering RNA plasmid (si-EZH2) to study the molecular mechanisms. Another article related to PCa was contributed by Jia et al. who reported that a traditional Chinese medicine Astragalus polysaccharides (APS) inhibits tumorigenesis and lipid metabolism through the miR-138-5p/SIRT1/SREBP1 pathway in prostate cancer. The approach used was microarray studies upon drug (APS) exposure, and they have successfully shown that ecoptic expression of SIRT1 inhibits the expression and nuclear translocation of SREBP1 via activating AMPK phosphorylation.The article contributed by Shao et al. studied the anti-tumor mechanisms of curcumin in hepatocellular carcinoma (HCC). The authors reported a novel role for curcumin in inducing cell cycle arrest and apoptosis by downregulating the lncRNA LincROR, in turn reducing β-catenin and inactivating Wnt signaling. They approached the study by choosing lncRNAs that were previously reported to be related to tumorigenesis, and LincROR was the most down-regulated in the curcumin-treated HCC cells by examination of their expression levels.Altogether, this research topic on non-coding RNA and Wnt/β-catenin Signaling Pathway in Human Cancer provided new ideas and mechanistic data on the role of several ncRNAs in cancers, shedding new light on the current state of the field and, more importantly, providing new avenues for future diagnostic and therapeutic avenues.


Chronic Inflammation and Neurodegeneration in Retinal Disease, Volume II” presents eight original research articles and one mini review from seven different countries with important contributions in the field of retinal inflammation. Most of the contributions are related to diabetic retinopathy (DR), the others cover age-related macular degeneration (AMD), retinitis pigmentosa, and the spontaneous polygenic model of inherited retinal dystrophy.Inflammation and neurodegeneration have a widely recognized role in the pathogenesis of the main retinal conditions. However, the exact mechanism through which inflammation causes alteration of the retinal structure—with consequent dysfunction of the retinal pigment epithelium, of neurons, and ultimately of photoreceptors—is not entirely known. This Research Topic “Stravalaci et al. focused on long pentraxin 3 (PTX3), an emerging new player in ocular homeostasis and a potential pharmacological target in neurodegenerative disorders of the retina. Physiologically present in the human eye and induced in inflammatory conditions, this protein is strategically positioned at the blood retinal barrier interface, where it acts as a “molecular trap” for complement and modulates inflammation both in homeostatic and pathological conditions such as AMD and DR. Gesualdo et al. presented an interesting study on fingolimod and DR, investigating the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 . This Research Topic is a typical example of repurposing since fingolimod is a drug approved to treat relapsing-remitting multiple sclerosis. The authors demonstrated, in an in vivo model of DR, that fingolimod has anti-angiogenic activity mediated not only through S1P1R, but also by melanocortin receptors. Another interesting pre-clinical study on DR was provided by Canovai et al. The authors showed the efficacy of a novel substance containing cyanidin-3-glucoside (C3G), verbascoside, and zinc to maintain the integrity of the blood retinal barrier and retinal function in streptozotocin-induced diabetic rats.The review by in vitro study by Schmalen et al. underlined the importance of Müller cell signaling in the inflamed retina, indicating an active role in chronic retinal inflammation. These authors demonstrated an intense signaling capacity of Müller cells, which reacted in a highly discriminating manner upon treatment with different cytokines, showing several characteristics of atypical antigen-presenting cells.Accumulating data provide evidence for a pivotal role of Müller cells in the pathogenesis of DR. In this regard the Parravano et al., where the authors carried out a randomized clinical trial on patients with diabetic macular edema (DME) treated with a special oral curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier and intravitreal injections of dexamethasone. They demonstrated a significant reduction in central retinal and inner retinal layer thickness with the combined therapy in patients affected by DME. This study also showed that the pharmacological combination therapy (curcumin and dexamethasone) was well-tolerated. On this regard, a good long-term safety profile of intravitreal dexamethasone has been demonstrated on real-world studies when used to manage DME -induced macular edema, steroid implant is a valid option for DME patients not responding to anti-VEGF therapy and non-DME patients with macular edema. The final contribution on the topic of DME focused on the anti-inflammatory effects of subthreshold micropulse yellow laser (SMYL). The authors, Bonfiglio et al., demonstrated that SMYL may reduce macular thickening and improve best-corrected visual acuity in eyes with persistent macular edema after pars plana vitrectomy and membrane peeling for tractional DME.An important clinical contribution on the Research Topic of DR has been provided by nage DME . Furthernage DME . AnotherHollingsworth et al.) have used systems genetics to identify possible models of spontaneous polygenic AMD by mining the BXD family of mice using single nucleotide polymorphism analyses of known genes associated with the human retinal disease. The goal of these scientists was to propose a pre-clinical mouse model (BXD32) to better understand the pathophysiology of progressive retinal dystrophies and discover efficacious treatments. Their study demonstrated that the BXD32 mouse strain exhibits a severe neurodegenerative phenotype accompanied by adverse effects on the retinal vasculature. Finally, Canto et al. showed that sulforaphane, a natural compound, modulates the inflammation and delays neurodegeneration in a retinitis pigmentosa (RP) mouse model. Specifically, they assessed the modulation of glial cells in the RP rd10 mouse model showing that sulforaphane treatment regulated the microglial activation state.A group of scientists from University of Tennessee (Overall, the contributions of the present Topic Research focused on inflammation and retinal degeneration, highlighting new insights in retinal diseases mechanisms and novel pharmacological approaches.


Inflammation is a well-known consequence of many traditional cancer treatments that can serve to enhance antitumor immunity and promote unwanted side effects. These side effects are often sustained long after cancer treatment has ended and may coincide with sustained chronic low-grade systemic inflammation that compromises the health of organs in the body and central nervous system (CNS). Assessment of circulating cytokines and their downstream products are considered to serve as potential biomarkers for systemic inflammation, identifying cancer survivors at risk of inflammation-associated disorders. In relation to the CNS, inflammatory markers are associated with cancer-related fatigue ; anxietyWe congratulate Bower et al.  for condThe longitudinal nature of the study  is a majBower et al.’s  findingsΚB) transcription pathway. Studies in patients with schizophrenia who, apart from psychosis, share several anxiety, depression, and cognitive symptoms with cancer patients, have identified a subgroup of patients that exhibit elevated brain and blood cell NF-ΚB–mediated cytokines. These low-grade cytokine elevations are explained by dysregulation of the NF-ΚB, including reduced expression of NF-ΚB pathway inhibitors (Although CRP and cytokine levels in Bower et al.’s  study arhibitors . Althoughibitors  compelliIn addition to providing a platform for new approaches and discoveries regarding the measurement of inflammatory biomarkers in cancer patients, Bower et al.’s  work claAnother direction for investigation is related to the evolving treatment landscape. For example, an increasing number of women are receiving T-DM-1. Given there are more prevalent and severe toxicities associated with T-DM1 compared with Trastuzumab , future As the RISE study focuses on fatigue and longitudinal design , we awaiNo funding was used for the writing of this editorial.Role of the funder: Not applicable.Disclosures: The authors have no disclosures to declare.Author contributions: AKW, RJC, JLV: writing—original draft, writing—review & editing.


Renal fibrosis is the progressive and complicated process manifested by histological aberrance and functional decline in the kidney. The pathogenesis involves multiple molecular pathways and cellular targets leading to myofibroblast activation and accumulation of extracellular matrix, which is in response to excessive epithelial injury and inflammation. Formation and exacerbation of fibrosis during the development of chronic kidney disease (CKD) is the common pathway to end-stage renal failure. However, few interventions are available that specifically target the pathogenesis of renal fibrosis. Emerging evidences prove that natural product therapy directly targets the pathogenesis of renal fibrosis, and exhibits beneficial effects in clinical. Further research (such as multi-omics studies and network pharmacology) is urgently needed to investigate the puzzle from the active compounds to underlying mechanisms and therapeutic targets of natural product against renal fibrosis.The Research Topic intends to highlight the latest advances from the active compounds to underlying mechanisms and therapeutic targets molecular mechanism of natural product against renal fibrosis. The issue includes 25 articles that is contributed by more than 200 authors in the fields of renal pharmacology. We have generated a collaborative discussion that facilitated the development of new mechanisms, new therapeutic targets, and candidate drugs from natural product against renal fibrosis.Zheng et al. illustrate that astragalus polysaccharide extract plays a beneficial role in reducing renal inflammation and fibrosis and in improving renal function by regulating the TGF-β/ILK pathway in hypertensive mice. Ren et al. confirm that natural flavonoid pectolinarigenin alleviates renal fibrosis to delay hyperuricemic nephropathy via suppressing TGFβ/SMAD3 and JAK2/STAT3 signaling pathways. By targeting non-TGF-β pathway, Yu et al. report the medical leech saliva extract, hirudin, protects the kidney from fibrotic injury by ameliorating renal autophagy impairment via PI3K/Akt pathway. Liu et al. demonstrate that quercetin alleviates podocytes apoptosis in vitro and in vivo by regulating the EGFR pathway, providing a novel approach to reveal the therapeutic mechanisms of quercetin against DN. Gong et al. identify proanthocyanidins (OPC) as active compounds of grape seeds. OPC exhibits beneficial protection against cadmium-induced DN in multidimensional aspects by the regulation of oxidative-antioxidative status, metal-binding ability, mediation of the levels of essential elements, and activation of the p38 MAPK and Keap1/Nrf2 signaling pathways.New mechanisms of renal fibrosis and the protective effects of natural product have been investigated and uncovered. Fibrosis-related signaling pathways are the common therapeutic targets, especially TGF-β pathway. Ma et al. prove that farrerol reverses oxidative stress, inflammation, and fibrosis in renal tubular epithelial cells by activating Nrf2 and subsequently increasing PINK/Parkin-mediated mitophagy and eliminating damaged mitochondria. Xiang et al. show that the restoration of PPARα activity delays diabetic nephropathy progression and attenuates lipid metabolism disorders by downregulating miR-21 expression to improve mitochondrial function. Li et al. report that maintaining the balance of mitochondrial dynamics exhibits renoprotection in kidney by inhibiting mitochondrial fission and promoting mitochondrial fusion via the downregulation of the primary mediator proteins of mitochondrial fission (Drp1 and Fis1) and the upregulation of fusion proteins (Opa1 and Mfn1). Zhang et al. carries out the serum metabonomics analysis of patients with diabetic kidney disease and shows the potential role of specific gut microbiota in the progression of renal fibrosis and diabetic kidney disease that involves the dysfunction of phenylalanine and tryptophan metabolisms. This study suggests the kidney-gut axis functions as a potential therapeutic target of renal fibrosis.Additionally, metabolic regulation and kidney-gut axis function as a promising therapeutic target against renal fibrosis. Shao et al. summarized five Chinese herbal medicines with sufficient clinical efficacy, high frequency of use, and well-studied mechanism, including Abelmoschus manihot and Huangkui capsule, Salvia miltiorrhiza and its components ; Rhizoma coptidis and its monomer berberine; Tripterygium wilfordii and its components ; Kudzu root Pueraria and its monomer Puerarin. The researches of these five Chinese herbal medicines set the study pattern for natural product against renal fibrosis, which are the promising candidate for widespread and standardized application.Since Chinese herbal medicine exhibits beneficial effects against renal fibrosis, the lack of randomized controlled trial and clear mechanism hinder natural product to pass modern assessments. Here, Dong et al. designed a multicenter, nonrandomized, single-arm clinical trial to explore the clinical effects of MFSD on idiopathic membranous nephropathy (MN), presenting an inspiring result that MFSD has significantly beneficial effects on idiopathic MN treatment, and has the same beneficial effects on patients with MN who are newly treated and who accepted with immunosuppressive therapy without remission. Further study from the same group by Gao et al. investigates the main active compounds of MFSD by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and more than 30 active compounds are identified. These active compounds alleviate podocyte injury by modulating autophagy-related protein and Wnt/β-catenin pathway, indicating autophagy and Wnt/β-catenin pathway as potential targets of MFSD for MN treatment. Zhang et al. demonstrate the anti-fibrotic and anti-inflammatory effects of Bupi Yishen Formula in vivo and in vitro by suppressing TLR4-mediated NF-κB signaling.The study of Luo et al. reveals the anti-oxidant and anti-inflammatory ability of Shenkang injection (SKI) in kidney, and identifies chrysophanol, emodin, and rhein as active compounds against renal fibrosis via simultaneously targeting IκB/NF-κB and Keap1/Nrf2 signaling pathways. Jia et al. report TLYS decoction improves mitochondrial dynamics to attenuates renal fibrosis and renal function decline by suppressing oxidative stress and mitophagy. The comparative network pharmacology analysis is the alternative approach to explore the mechanisms of natural products with limited experiments. Chan et al. performed comparative network pharmacology to figure out the mechanism of Liu-wei-di-huang-wan. Liu-wei-di-huang-wan may ameliorate fibrosis, angiogenesis, inflammation, disease susceptibility, and oxidative stress via modulating TNF signaling pathway, which could be validated through clinical trials.Beyond to five Chinese herbal medicines, studies from the present issue provide the clinical evidences of natural products against renal fibrosis and explore underlying mechanisms. Mahuang Fuzi and Shenzhuo Decoction (MFSD), a Chinese herbal formula, is a promising candidate for renal fibrosis and CKD treatment in clinial. In conclusion, the collection of 25 articles in the Research Topic contributes to better understanding of natural products against renal fibrosis from the active compounds to underlying mechanisms and therapeutic targets. These studies provide promising and potential candidates against renal fibrosis by modulating novel pathways in clinical trial and animal experiment. Accompanying with the evolution of high throughput screening method and model, novel candidates and therapeutic targets will emerge to facilitate the drug discovery, which hold great potential for treatment with renal fibrosis.


The implementation of sustainable food packaging solutions within future circular food supply chains is essential to protect customers and ensure food quality, safety, and optimal shelf-life. This will be improved by new innovative packaging materials and will contribute to reducing food waste. In this direction, it is important to employ lifecycle assessment (LCA) to define food supply chain impacts, taking into consideration food waste, global food industry environmental impacts, and shipping distances, with the aim of achieving consumer satisfaction. It is important to share data on (i) the consequences of specific food product–package interactions, (ii) the consideration of the utilization of novel packaging biomaterials, and (iii) overall consumer behavior and satisfaction as a critical focus. The aim of this Special Issue was to bring the most updated information in the new era of sustainability and food packaging.Dörnyei et al.  proposedThe work of Wang et al.  presenteThe study of Shin et al.  showed tPleva et al.  investigChen et al.  developeSalmonella enterica via different contact materials (polypropylene from reusable plastic crates (RPCs), corrugated cardboard, and medium-density fiberboard (MDF) from wooden boxes). The survival of the pathogenic microorganism was studied in cauliflowers and the contact materials during storage. The LCA approach was used to evaluate the environmental impact of produce-handling containers fabricated from the different food-contact materials tested. The results showed a higher risk of cross-contamination via polypropylene compared with cardboard and MDF. Another outcome of the study was the potential of Salmonella surviving both in cross-contaminated produce and in contact materials under supply chain conditions. Regarding environmental sustainability, RPCs showed a lower environmental impact than single-use containers (cardboard and wooden boxes).López-Gálvez et al.  assessedCruz et al.  presenteIn the article of Miller et al.  various The review from Krauter et al.  contextuBauer et al.’s  study aiIn another study, Bauer et al.  presenteJunior et al.  presente


At present, cancers are described in both biological and clinical settings with static models that characterize tumors by the phenotypic and genotypic features observed at a given time point. However, cancers are highly dynamic processes that evolve based on specific genomic and epigenomic changes. Such dissonance between the model used to describe tumors and their true nature reverberates all the way from basic biological research to clinical practice. For instance, it is well established that anti-cancer treatments impose selective pressures leading to the emergence of resistant clones . This evHistorically, the first barrier to the characterization of the evolutionary properties of cancer was the limited amount of available data to accurately reflect tumor heterogeneity, which was traditionally based on a single tissue biopsy . Severala priori expectation when we proposed this research topic was to be confronted by a barrage of works focusing mainly on the genetic aspects of cancer evolution. Looking retrospectively at the collection of accepted manuscripts, however, we were surprised to observe some specific yet unexpected topics recurrently emerging.The articles in this research topic address important aspects of cancer evolution, encompassing models associated with a diversity of tumor types including renal cell carcinoma, glioblastoma, breast, colorectal, lung, ovarian, pancreatic and prostate cancer. Our Duică et al.; Gao et al.; Qi et al.; Li et al.; Zheng et al.; Li et al.; Chen et al.; Zhao et al.). Duică et al. presented a review of the role of miRNAs in cancer-relevant processes, focusing on gynecological malignancies . Another study  evaluated exosomal miRNAs as a mechanism of resistance in small cell lung cancer with particular elevation of exosomal miR-92b-3p that was associated with the PTEN/AKT pathway based on preclinical models . Importantly, this study also included a clinical cohort of 50 patients to help validate the authors’ hypothesis that downregulation of this biomarker was associated with better clinical outcomes. Junchen Li et al., instead, focused on the anti-cancer mechanism of andrographolide in patients with luminal-like breast cancer through the inhibition of miR-21-5p . Similarly, Chen et al. investigated the role of circular RNA (circRNAs) in prostate cancer. The authors focused on the regulation, expression, and functional effects of circNOLC1 for in vitro and in vivo models, proposing circNOLC1 as a potential biomarker and target for prostate cancer treatment.Multiple articles within this collection focused on the role of non-coding RNA in cancer, including in particular microRNA (miRNA), circular RNA (circRNA) and long non-coding RNA (lncRNA) . Qi et al. evaluated lncRNAs as potential biomarkers to assess heterogeneity in metastasis for colon and rectal cancers. The analysis identified two biomarker lncRNAs, KCNQ1OT1 and SNHG1, associating with cancer initiation and metastatic potential. Interestingly, the authors proposed different mechanisms of actions of these two lncRNAs in colon and rectal cancers . Finally, Zheng et al. identified a panel of prognosis-associated lncRNAs that were significantly associated with survival in ovarian cancer across multiple independent cohorts, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The authors further selected and validated the expression of four lncRNAs in vitro on multiple ovarian cancer cell lines .Multiple studies focused on lncRNAs as well. Zheng et al. published a review on the communication between EMT and cancer stem cells (CSC). While this was once thought to be an unidirectional evolution, more recent studies suggest that this transition is bi-directional, stochastic, and mediated by the tumor microenvironment, ultimately showing how such “hybrid state” or “plasticity” is linked to poor prognosis and resistance. Cui et al. studied the role of ENC1 in accelerating EMT processes in colorectal cancer, whereas the study by Shou et al. reported an inverse relation between tissue inhibitor matrix metalloproteinases 1 (TIMP1) and prognosis in samples from patients with renal cell carcinoma. The study evaluated TIMP1 as a biomarker to enhance metastasis via the EMT signaling pathway. Another study explored EMT-related genes using TCGA and local samples for pancreatic ductal adenocarcinoma . This study identified a 8-gene signature that impoved prediction compared to clinical variables alone, particularly to assess adjuvant treatment response, such as to immune checkpoint inhibitor therapy. In the future, evaluating therapies that target cells in this “hybrid” EMT state may have specific applications to prevent seeding of metastatic sites.A second theme that was recurrent in our collection is the plasticity of the epithelial-mesenchymal transition (EMT). Within this collection, Lu et al. produced a review of Liquid–liquid Phase Separation (LLPS) and protein/nucleic acid condensates. LLPS are a new paradigm in the study of cellular activities recently coming under more intense research focus. Recent progress has been made to understand the roles of LLPS in cancer. Additionally, Dai et al. published a review on RNA modifications and their role in cancer with a deep discussion on the YTH protein family of m6A readers, summarizing the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and therapy applications.Finally, it is worth mentioning two reviews on protein condensates and RNA modifications. This collection of articles highlights promises and challenges of characterizing the dynamic aspects of cancer. They nicely expose the critical need for multi-omics biomarkers to track cancer evolution in both research and clinical settings. Interestingly, we observed an emerging interest towards previously less studied molecular players, such as non-coding RNAs, condensates, and RNA modifications, both in the context of cancer cells and tumor microenvironment. We anticipate that the use of integrated models based on multiple biomarkers  will be necessary to capture the complexity of cancer evolution, especially in today’s clinical settings dominated by a paradigm shift from monotherapy approaches towards combinations of chemotherapy, immune checkpoint inhibitors and targeted therapies.


Cassia occidentalis Linn. stem using liquid chromatography tandem mass spectrometry: application to its pharmacokinetic studies’ by Mohammed Riyazuddin et al., RSC Adv., 2020, 10, 4579–4588. DOI: 10.1039/C9RA07482ACorrection for ‘Simultaneous quantification of five biomarkers in ethanolic extract of  The authors regret that the one of the affiliations (affiliation d) was incorrectly shown in the original manuscript. The corrected list of affiliations is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Considered a simple and versatile technique, electrospinning has emerged as a technology for developing 3D materials for a wide range of applications. Electrospun fibers ranging from nanometers to micrometers in diameter have been applied in many research areas including chemistry, materials science, engineering, and chemical engineering, as well as medicine, pharmacology, and pharmaceutics. Based on a large variety of polymers , types of collectors, and nozzle configurations, a vast and complex number of electrospun materials can be obtained, allowing those electrospun fibers to be applied for catalysis , separatBased on In their review entitled “Tunable Spun Fiber Constructs in Biomedicine: Influence of Processing Parameters in the Fibers’ Architecture”, Felgueiras et al. described how processing parameters can affect the architecture of electrospun fibers . In addiSt. John et al., in their review entitled “Advances in Electrospun Nerve Guidance Conduits for Engineering Neural Regeneration”, reported the capability of the electrospun approach to fabricate fibers of various scales and which have a large surface area with a three-dimensional porous structure resembling the native extracellular matrix for regeneration of the nervous system . ConsideIn the third review published in this Special Issue—“Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing” by Costa et al.—the most recent advances in osteochondral tissue engineering are summarized . The autIn two different research articles, Tawfik et al. reported the uses of coaxial electrospun fibers for as fast dissolving matrixes. In the paper entitled “Fabrication and Characterization of Fast-Dissolving Films Containing Escitalopram/Quetiapine for the Treatment of Major Depressive Disorder” , authorsChen et al. demonstrated uses of aligned core-shell fiber for the delivery of docosahexaenoic acid and brain-derived neurotropic factor  . The cord,l)-lactide-co-glycolide (PLGA) nanofibers were loaded and spun on the metal stent. Electrospun fibers were characterized and the presence of drug on the material’s surface was suggested based on water contact angle. The drug release was evaluated, in which the telmisartan was released over 30 days. In vitro and in vivo results of hybrid stent/PLGA nanofibers loaded with telmisartan indicated that this material can controllably release disease-relevant therapeutics, enhance the migration of endothelial progenitor cells, providing complete endothelial coverage and recovery, and reducing intimal hyperplasia.The research article “Telmisartan Loaded Nanofibers Enhance Re-Endothelialization and Inhibit Neointimal Hyperplasia” by Lee, Kuo, Liu and co-authors demonstrated the electrospun nanofibers loaded with telmisartan for sustained and local delivery of drug to injured arterial vessels . Poly evaluated the antibacterial activity of the fibers loaded with curcumin against polyresistant bacteria, using hyaluronic acid sodium as a polymer basis . Based ol-lactide-co-poly-ε-caprolactone (PLA-PCL) electrospun tubular scaffold engineered with mesenchymal stem cells (MSCs), in order to promote and speed up the regeneration process, ensuring an adequate support to esophageal tissue reconstruction, avoiding the use of autologous conduits. They observed an interesting correlation between the asymmetrical shape of the scaffold and its p-MSCs cellularization process, which helped in keeping the scaffold’s mechanical properties suitable for esophageal application. The authors also observed that the advantage of their pro-posed scaffold with hybrid composition (polymer combined to p-MSCs). Preliminary results collected after in vivo implantation in a porcine model were promising; but further studies are required to statistically validate the data.In terms of biologic applications, Pisani et al., in their research entitled “Engineered Full Thickness Electrospun Scaffold for Esophageal Tissue Regeneration: From In Vitro to In Vivo Approach” , developSteinberg et al.,  , developKim, D., Kim, S., and co-authors detailed in their article entitled Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment  a biodegDean, Thomas, and co-authors detailed, in “Uni-Directionally Oriented Fibro-Porous PLLA/Fibrin Bio-Hybrid Scaffold: Mechano-Morphological and Cell Studies” , a biohyCurrently, numerous polymers, blends and hybrid systems have been electrospun in order to improve these materials in biomedical applications. In addition to the several approaches in order to obtain electrospun fibers with a vast range of morphologies, including coaxial and side-by-side nozzles, and different collectors, combining this strategy with others microfabrication techniques has increased the applicability of these materials for different biological systems and chemical sciences.


RSC Adv., 2018, 8, 18396–18399.Correction for ‘Synthesis and optical properties of lead-free cesium germanium halide perovskite quantum rods’ by Lin-Jer Chen,  The affiliation in the original article was incorrect. The correct affiliation is listed herein.RSC Advances article and their previous related paper published in Journal of Physical Chemical Letters, cited as ref. 21 in the original article.The author apologises that there are portions of text overlap between this In addition, there is an error in the ‘Characterization and measurements’ section of the ESI. The first sentence should be changed from “The as-prepared samples were characterized by X-ray powder diffraction (XRD), and transmission electron microscopy (TEM)” to “The as-prepared samples were characterized by X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM)”. There was no XRD data reported, therefore the ESI has been updated online to reflect this change.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


The skin is comprised of multiple types of cells that serve as a protective barrier. Mutations in the genes that are responsible for protecting the functional integrity of the skin are often found in many inherited skin diseases, more commonly known as the Mendelian human skin disorders. Advances in molecular techniques and sequencing technologies have enabled identification of novel pathogenic variants, which helps to provide insight into genotype–phenotype correlations and to define the genetic basis of these skin disorders. In this Research Topic, a total of ten articles are published, including those describing findings from case studies and original research, as well as a mini review of current genetic diagnosis strategies, novel gene variants, and genotype–phenotype correlations in human Mendelian skin disorders.Xu et al. report on the use of WES in identifying a de novo pathogenic variant c.2T>C (p.M1T) in KLHL24 in Chinese twin boys with epidermolysis bullosa simplex. Similarly, Wang et al. demonstrate the detection using WES of a missense mutation, c.1156G > A (p.Ala386Thr) in DKC1, which leads to a benign form of dyskeratosis congenita syndrome with the mucocutaneous triad. In another article appearing in the Research Topic, WES analysis also reveals a heterozygous missense mutation c.293G>A in GJB3, which is associated with erythrokeratodermia variabilis, ichthyosis, and non-syndromic hearing loss Gao et al.Recent developments in genome-wide association studies (GWAS) and next-generation sequencing (NGS) techniques have resulted in an integrative approach to the use of functional genomics and expression data in deciphering the causative genetic variants of inherited skin diseases. Because most of the mutations identified in human Mendelian skin disorders reside in protein-coding genes, whole exome sequencing (WES) has been widely used in the identification of such pathogenic variants, and in the genetic diagnosis of Mendelian skin conditions with atypical or unique phenotypes. Wang et al. the genetic profiling of epidermolysis bullosa cases Alharthi et al. and the discovery of a novel CREBBP variant for genetic diagnosis of Rubinstein–Taybi Syndrome Lee et al. Recent evidence from large-scale expression studies (using microarrays and RNA sequencing) has also revealed the roles played by non-coding RNA molecules, such as small non-coding RNAs or miRNAs, in the pathogenesis of several complex skin diseases  with a significant pathogenicity score. In addition, a novel homozygous missense mutation (p.L154R) in gene ABHD5 has been detected in a patient with Chanarin–Dorfman syndrome, a rare autosomal recessively inherited genetic disease Liang et al. Finally, Wu et al. also report in this Research Topic on a new case of congenital poikiloderma with a novel missense mutation in the FAM111B gene c.1883G>A (rs587777238).Molecular genetic studies based on family case reports and large-scale regional profiling analyses often provide significant insight into novel pathogenic variants, thereby helping to extend the spectrum of the genetic profile, improve diagnosis, and establish an improved understanding of human Mendelian skin disorders. In this Research Topic, Xu et al. provide an initial description of their discovery of a c.2T>C pathogenic variant in KLHL24, affecting twins in China, and its correlation with epidermolysis bullosa simplex. Their research has identified correlations between phenotypes and genotypes in epidermolysis bullosa, in which KLHL24 pathogenic variants are associated with the mild phenotype. In contrast, the study by Liang et al. on genotype–phenotype analysis in patients with reported Chanarin–Dorfman syndrome reveals no correlation. Meanwhile, as indicated in a review by How et al. there is no significant genotype–phenotype relation in incontinentia pigmenti, a rare type of X-linked dominant genetic disease characterized by ectodermal dysplastic disorder. However, the literature does suggest that variation in a combination of the types of mutations, functional domains affected, X-inactivation, and genomic background may lead to the variability observed in incontinentia pigmenti phenotypes How et al. The authors propose that a detailed understanding of the genotype–phenotype correlation in incontinentia pigmenti will support further investigations concerning prognosis and future reproductive options. Meanwhile, a recent large cohort study involving investigation of genotype–phenotype correlations in patients with autosomal recessive ichthyosis has provided new insights on and definitions of specific phenotypic clues for corresponding genetic mutations (Certain phenotypic features of inherited skin disorders may be associated with particular gene mutations, but paradigms for clinical genotype–phenotype correlation remain unclear in many instances due to the highly variable phenotypic expressivity of the relevant mutations; these paradigms require further refinement. In this Research Topic, utations . In addiutations .In summary, this Research Topic enhances our knowledge of recent exciting progress in the field of genodermatosis, including molecular diagnostics protocols, novel pathogenetic variants, and genotype–phenotype correlations. Together, these studies provide value in the form of greater diagnostic precision, a source of information for clinical assessments, and ways to improve clinical care and management.


Cardiovascular and metabolic bone diseases are demanding health problems with high morbidity and mortality ,2. AlthoIn this context, the Special Issue (SI) “Dietary Bioactives: Their Role in the Prevention and Treatment of Cardiovascular and Metabolic Bone Diseases” has published nine novel papers on this topic ,13,14,15The narrative review was published by Mandatori et al. (2021). The authors summarized the most relevant recent knowledge concerning the role of Vitamin K2, a bioactive compound with a key role in the “calcium paradox” phenomenon, which involves both vascular and bone tissue . The chaLycii radicis cortex in a paper published by Park et al. (2021). Using an animal model of ovariectomized-induced osteoporotic mice, the authors identified scopolin as the candidate bioactive compound extracted from Lycii radicis cortex capable of preventing and treating osteoporosis [Cucurbita moschata leaves, a pumpkin cultivar in Western countries, were published by Lambertini et al. [Subsequently, the specific mechanism of Vitamin K2 in bone health was also addressed in an in vitro study . Specifioporosis . Finallyi et al. .Allium sativum extract in an ex vivo study on mouse heart samples exposed to E. coli lipopolysaccharide inflammatory stimulus [i) the capability of Sasa quelpaertensis to ameliorate metabolic dysfunction conditions including dyslipidemia, insulin resistance, and hepatic lipid accumulation, induce in rats by a high-fructose-diet [ii) the protective effects of Vitis labrusca on cardiovascular dysfunction due to hypertensive conditions—employed the model of Spontaneously Hypertensive Rats [Regarding cardiovascular health, in this Special Issue, one in vitro, one ex vivo and two pre-clinical animal studies were published. Baldassare et al. (2021) reported the anti-inflammatory and anti-oxidative role of myo-inositol using a model of cultured human endothelial cells isolated from the umbilical cord vein of women affected by gestational diabetes . Indeed,stimulus . Additioose-diet  and (ii)ive Rats .Finally, in this SI, Esposito et al. (2021) published a cross-sectional analysis performed on a sub-cohort of 4592 subjects from the Moli-sani Study (2005–2010) which suggested that intake polyphenols, which contribute to slowing down the biological aging process, may exert protective effects on the long-term risk of cardiovascular and metabolic bone disease development .In conclusion, this SI allowed us to publish a number of encouraging scientific studies based on in vitro, ex vivo and in vivo approaches confirming the increasing interest of researchers in the discovery of new potential bioactive compounds for human health. However, future research must better understand the mechanisms of action of natural molecules and nutritional supplements for the management of cardiovascular and metabolic bone diseases.


The article of Yamashita et al. illustrates the ability of in situ crystal growth to bypass kinetic barriers between phases, demonstrating the importance of this approach in phase discovery (Oswald et al., 2008Although chemically simple, the salt hydrates are very sensitive to external conditions, with complex energy landscapes containing multiple viable phases. However, transformations between solid phases are frequently kinetically hindered, and KCl·H


The innate immune system is the first line of defense against bacterial and viral infections and sterile inflammation through the recognition of pathogen-associated molecular patterns (PAMPs) as well as danger-associated molecular patterns (DAMPs) by pathogen-recognition receptors (PRRs), and produces proinflammatory and antiviral cytokines and chemokines . Cells is devoted to many aspects of innate immunity and gives an overview of different DAMPs, immune cells, special mechanisms, and therapeutic options for treating diseases related to chronic inflammation or infections.This Special Issue of One of the well-known DAMPs is the high-mobility group box 1 protein (HMGB1), which is either passively released by dying cells or actively secreted by immune and other cells and was described as implicated in both stimulating and inhibiting innate immunity. Andersson et al. reported that the pro- and anti-inflammatory activities of HMGB1 depend on post-translational modification of its disulfide bonds by binding to different extracellular cell surface receptors either directly or as a cofactor of PAMPs . Another DAMP, extracellular ribosomal RNA, which is released under pathological conditions from damaged tissue, acts synergistically with Toll-like receptor 2 ligands, inducing the release of cytokines in a nuclear factor kappa B-dependent manner in vitro as well as in vivo. Grote et al. suggest that extracellular RNA might sensitize Toll-like receptor 2 to enhance the immune response under pathological conditions and therefore might serve as a new target for the treatment of bacterial or viral infections .Arnholdt et al. demonstrate that cells related to innate immunity and influencing immunoregulatory and inflammatory processes, such as gamma delta T cells, play an important role in angiogenesis and tissue generation. By using a femoral artery ligation model in mice, depletion of this subset of T cells was demonstrated to impair angiogenesis, increase the number of leukocytes and inflammatory M1-like macrophages, and promote the formation of neutrophil extracellular traps (NETs) . The topic of autoinflammation is also covered in this Special Issue. The review of P. Georgel provides some examples of autoimmune/autoinflammatory diseases caused by the deregulated expression of type I interferons and interleukin-1β. The role of interleukin-1 and type I interferons and their crosstalk in autoinflammatory diseases such as rheumatic diseases are analyzed to reveal novel therapeutic opportunities .Gullet et al. discuss the key components of programmed cell death pathways and highlight the plasticity of pyroptosis, apoptosis, and necroptosis as well as significant crosstalk among these pathways. The concept of PANoptosis, an inflammatory cell death pathway that integrates components of different cell death pathways and is implicated in driving innate immune responses and inflammation, is explained . A review by Papendorf et al. provides a comprehensive overview of molecular pathogenesis disorders caused by proteostasis perturbations, and current knowledge of the various mechanisms by which impaired proteostasis promotes autoinflammation is summarized .2+-binding protein [To investigate the crosstalk between coagulation and innate immunity, the effect of thrombin on macrophage polarization is investigated by Ukan et al. Results demonstrate that thrombin induces an anti-inflammatory phenotype in macrophages, which shows similarities to as well as differences from the classical M2 polarization states regarding the expression of secreted modular Ca protein .D. Suzuki third-instar larvae is described by Carrau et al. as a valuable tool for investigating hemocyte-derived effector mechanisms against pathogens, particularly for the formation of extracellular traps [To investigate insect innate immunity, the in vitro cultivation of primary hemocytes from ar traps . Drugs such as ganciclovir and its pro-drug valganciclovir are often used to treat viremic patients transfected with, e.g., human cytomegalovirus (HCMV). Results from Landázuri now suggest that binding and signaling through endothelin receptor B (ETBR) is crucial for viral replication and that selected ETBR blockers inhibit HCMV infections .Lin et al. report that albumin attenuates chronic liver diseases (CLDs) via alleviating inflammation of Kupffer cells caused by bacterial products, which might provide a compelling rationale for albumin therapy in patients with CLDs .


Wang et al. develop a new iron cathode electro-Fenton process coupled with a pH-regulation divided electrolysis cell for p-nitrophenol degradation. In the electrochemical Fenton system, an iron plate was used as the cathode to inhibit the release of iron ions and promote the reduction of Fe3+ to Fe2+. Therefore, excellent electrocatalytic degradation performance towards organic pollutants was achieved. Wang and Wang synthesized a NiO modified BiVO4 nanocomposite by a hydrothermal and calcination method. The as-prepared nanocomposite showed enhanced photoelectrochemical performance due to the unique NiO lamellar structure that provided a large number of active sites.Numerous metals and metal oxides have been employed as electro- or photo-catalysts for energy conversion and pollutant degradation. Wang et al. used a sol-gel self-combustion method to prepare carboxylate-rich carbon-modified Fe3O4 magnetic catalysts for heterogeneous Fenton degradation of organic pollutants. The prepared Fe3O4-based catalysts displayed improved heterogeneous Fenton degradation performance due to the enhanced pollutant adsorption. Zhu et al. synthesized a CdS/microcrystalline cellulose nanocomposite photocatalyst using an ultrasonic-assisted method. The prepared nanocomposite photocatalyst displayed enhanced pollutant degradation performance under visible light due to the heterojunction formation that efficiently separates the photogenerated electrons and holes of the photocatalyst. Wang et al. prepared a Co3O4/Ti cathode by electrodeposition for electrocatalytic reduction of nitrate, in which the NO3− was reduced to N2 and NH4+ by the catalysis of Co3O4/Ti, and then NH4+ was selectively oxidized into N2 assisted by chloride ions and using IrO2-RuO2/Ti as the anode. Qiu et al. prepared Pt-modified TiO2 nanotubes as catalysts for photocatalytic degradation of Rhodamine B (RhB) under UV light. It was reported that the superoxide radical anions (O2−∙), photogenerated hole (h+) and hydroxyl radical (OH∙) were the main active species contributing for RhB degradation.Bai et al. reported the Fischer–Tropsch synthesis performance of Co-based catalysts supported on graphitized ordered mesoporous carbon. The high catalytic performance resulted from the highly crystallized graphitic structure of the mesoporous carbon and the uniform dispersion of CoO on the support. Dai et al. used ion-exchange, in situ modification and complexation-excessive impregnation modification methods to modify SAPO-11 molecular sieves with Ni. The Ni-modified SAPO-11 molecular sieves were supported by NiWS catalysts for hydroisomerization of n-Hexadecane. The complexation-excessive impregnation modification method led to the best hydroisomerization performance. Huang et al. studied the effect of Ga2O3 on the hydrodesulfurization performance of 4,6-dimethyldibenzothiophene catalyzed by the stepwise impregnation method. Ga2O3 promoted Ni and Mo species to disperse uniformly and doping of more Ni atoms into the MoS2 crystals, increasing the average stacking number and the length of MoS2. As a result, enhanced hydrodesulfurization performance was achieved due to the formation of more NiMoS active phases in the system.In addition, metal and metal oxide based or modified materials have also been used for other catalytic applications. Zhang et al. prepared a series of nanostructured Fe-Cu binary oxides for arsenic removal. The crystallinity and structure of the Fe-Cu binary oxides had a significant impact on the arsenic adsorption performance. The oxides with lower crystallinity showed higher surface hydroxyl density and better adsorption performance. Li et al. reviewed the preparation, classification and applications of templated materials, particularly adsorbents in wastewater treatment. The templating method can endow materials with high specific area and unique porous structures, thereby enhancing the material sorption performance towards aqueous pollutants. Wei et al. reviewed the composite adsorbents for fluoride removal, including the adsorbent types , preparation and sorption performance. The adsorption mechanisms for fluoride removal involving electrostatic attraction, ion exchange, complexation, and hydrogen bonding were also discussed.Adsorption is a simple but effective way for environmental decontamination . VariousYu et al. prepared new biochar from excess sludge, followed by acetic acid modification. The modified sludge-derived biochar displayed improved porosity and enriched–COOH functional groups, thereby enhancing its adsorption performance to uranium. However, the catalytic performance of the sorbent was not discussed. Zeng et al. fabricated porous glass-ceramics based on coal fly ash without using pore forming agents by direct overfiring, in which borax was used to destroy the structure of quartz and amorphous vitreous body in coal fly ash and thus reduce the sintering temperature by the B-O bond. Chen et al. fabricated a non-sintered ceramsite from pyrite tailings for phosphorus removal. Both Plackett-Burman Design (PBD) and Box-Behnken Design (BBD) based response surface methodology were used to optimize the fabrication parameters.Recently, with the promotion of the circular economy, waste based materials have attracted growing interest for various applications, such as fertilizers , carbon Wang et al. reviewed the significant roles of surfactants in oriented immobilization of cellulase on nanocarriers as well as a surfactant reversed micelle system.Cellulase plays a key role in the production of fuel ethanol by enzymatic hydrolysis of lignocellulose, and immobilization of cellulase on the nanocarriers is an effective way to improve the hydrolysis efficiency. In summary, this Research Topic discussed various inorganic materials as catalysts or adsorbents with unique nanostructures and functionalities for energy conversion and environmental decontamination. In the future, inorganic materials will continue to play a vital role in addressing global energy and environmental challenges, such as climate change, energy shortages and environmental pollution. Engineering new high performance heterogeneous catalysts and understanding the limiting factors and their mechanisms in the catalytic reaction are two key research directions that should be paid more attention to.


The rapidly growing industry of crop biostimulants leverages the application of plant growth promoting rhizobacteria (PGPR) to promote plant growth and health. However, introducing nonnative rhizobacteria may impact other aspects of ecosystem functioning and have legacy effects; these potential consequences are largely unexplored. Nontarget consequences of PGPR may include changes in resident microbiomes, nutrient cycling, pollinator services, functioning of other herbivores, disease suppression, and organic matter persistence. Importantly, we lack knowledge of whether these ecosystem effects may manifest in adjacent ecosystems. The introduced PGPR can leave a functional legacy whether they persist in the community or not. Legacy effects include shifts in resident microbiomes and their temporal dynamics, horizontal transfer of genes from the PGPR to resident taxa, and changes in resident functional groups and interaction networks. Ecosystem functions may be affected by legacies PGPR leave following niche construction, such as when PGPR alter soil pH that in turn alters biogeochemical cycling rates. Here, we highlight new research directions to elucidate how introduced PGPR impact resident microbiomes and ecosystem functions and their capacity for legacy effects. Like other introduced species, plant growth promoting rhizobacteria (PGPR) have unpredictable ecosystem consequences and legacy effects; these outcomes are a current knowledge gap. Commercially available crop biostimulants sometimes contain PGPR that directly or indirectly increase plant productivity or crop yield, stimulate nutrient uptake, improve nutrient cycling efficiency, reduce pathogen loads, and increase plant tolerance to abiotic stress . Interest in this research topic has expanded in recent years. Before 2015, fewer than 10 articles per year were published on this topic; the count jumped to 50+ per year since 2019. Despite increased interest in PGPR, only 12 of the 313 articles included the search term ‘ecosystem’ and one article included ‘legacy’. Here, we highlight potential effects of PGPR species introductions that may extend beyond the host plant to ecosystem functions that may persist longer than the PGPR populations , Box 1How do PGPR affect macronutrient and micronutrient cycling beyond host–plant acquisition? PGPR may have traits to solubilize and mobilize macronutrients and micronutrients. Some research into nitrogen and potassium root acquisition and soil leaching currently exists. More research is needed into micronutrients important to plant productivity and organic matter persistence, such as iron and manganese.How do PGPR affect organic matter persistence? PGPR may shift relative abundance or activity of key players in the resident microbiome. These changes in microbe–microbe interactions could cascade to changes in soil properties mediated by microbes such as pH, erodibility, porosity, and water holding capacity of soil. Experimental applications of PGPR under field conditions that quantify soil parameters are needed.What are the multi‐trophic consequences of introduced PGPR? PGPR are known to release volatile organic compounds (VOCs) that can deter herbivores. Some VOCs attract pollinators, but whether PGRP VOCs attract pollinators is unexplored. Indirect multitrophic interactions, mediated by changes in plant phenology like budbreak or flowering, may be spurred by PGPR and this remains a current knowledge gap. Additionally, PGPR may indirectly affect resident microbial abundances through antagonisms with bacterivores or fungivores.Do PGPR spread to other plant hosts in the ecosystem? Host specificity is low among biostimulant microbes due to their application across various crops. Thus, escape from crops to adjacent ecosystems has a high potential, although persistence may be negligible. Mitigating effects caused by the escape of biostimulant microbes is an area of active research  contains Bacillus velezensis GB03. Application is intended to reduce pathogens such as those causing blight , root rot (Pythium), and wilt (Fusarium). The hypothesized mechanism is that B. velezensis induces a systemic immune response across a wide range of plant hosts. Another potential mechanism is that the PGPR increases anti‐fungal indigenous taxa (Xiong et al., Another ecosystem consequence that affects crop yield is plant disease suppression. Many PGPR in biostimulants are added to crops for the purposes of reducing pathogen loads (Pieterse et al., et al., et al., et al., Microbial interactions affect organic matter persistence. Biostimulant PGPR may have indirect effects on ecosystem functions such as the accumulation and decomposition of organic matter through their interactions with the resident microbiome (Hellequin et al., et al., et al., et al., et al., Introduction of new microbes could lead to genetic changes in the inoculant or community, yet the genetic impact of PGPR introductions remains largely unexplored. Any location with a high microbial density, such as the rhizosphere, can support rapid and pervasive horizontal gene transfer (Kent et al., et al., et al., et al., Legacy effects on resident microbial community structure can arise as PGPR establish and persist following introduction. Establishment and persistence can occur through at least two mechanisms: augmentation and displacement (Kurkjian et al., et al., Plant growth promoting rhizobacteria that persist following introduction can leave a legacy by altering their microenvironment to promote their own fitness, through a process known as ‘niche construction’ (Callahan et al., et al., et al., et al., et al., et al., et al., Plant growth promoting rhizobacteria introductions that do not persist in the community may still leave legacy effects (Mallon et al., Introducing PGPR may have unintended effects that cascade throughout the resident microbiome, adjacent plant communities, and the whole ecosystem Box . We urgeJAMM wrote the initial draft of this manuscript and conceived original ideas. JAMM, PEA, JKM, WM and MAC contributed to idea refinement, writing, and revising the manuscript.