The circular interactions between type 2 diabetes (TMD2) and major depressive disorder (MDD) are well documented but the understanding of their mechanisms has only recently gained more clarity. Latest research indicates, that the association between TMD2 and MDD is largely mediated by insulin resistance (IR).A metabolic subtype of MDD can be distinguished from other MDD subpopulations, that is characterized by predominantly atypical clinical presentation, IR and different responsiveness to antidepressant interventions. IR is a predictor of nonresponse to some antidepressants. The IR seems to be a state-marker of clinical or subclinical depression and the relationship between IR and MDD varies between sexes and ethnicities. Insulin has a direct impact on the monoaminergic systems known to underlie MDD symptoms: serotoninergic and dopaminergic, which are dysregulated in IR subjects. Several trials assessed the efficacy of insulin-sensitizing drugs in MDD with mixed results for metformin and more consistent evidence for pioglitazone and lifestyle intervention/physical activity.Recently published data suggest a significant role of IR in the clinical presentation, pathophysiology and treatment response in MDD. Further research of IR in MDD and integration of existing data into clinical practice are needed. Their work showed, that IR was elevated in atypical but not typical depression. Some researchers focused on specific symptoms and attempted to disentangle their links to metabolic markers. Chae et al.[▪▪] reported an analysis of German nationwide database which assessed data on the clinical presentation, metabolic syndrome components and inflammation variables in MDD patients. Regarding insulin levels, results showed significant associations between higher insulin and increased appetite, hypersomnia, insomnia and suicidal ideation. In sum their work unraveled several symptom-marker connections between: higher metabolic markers and increased appetite; lower metabolic markers and decreased appetite; lower metabolic markers and insomnia; higher insulin and increased appetite; higher insulin and lower albumin and insomnia. In line with the findings of the Netherlands Study of Depression and Anxiety [▪▪], their work reinforced the links between metabolic markers and atypical presentation of MDD and the observation, that those relationships are mainly noted for insomnia rather than hypersomnia. Similarly, in a cross-sectional analysis of primary care population Shell et al. reported that IR is only elevated during acute MDD episodes, while comparisons of patients with remitted MDD and general population indicated no significant differences. Another work comparing subjects with current MDD, remitted MDD and controls also concluded, that IR was significantly higher in acute MDD vs. controls [et al.[▪▪] noted that IR decreased in patients who experienced symptomatic improvement. They also noted that while baseline C-reactive protein (CRP) levels had a significant effect on the changes in depression severity it was fully mediated by IR. A study comparing IR in normal weight, nondiabetic adolescents included MDD and euthymic participants. It found associations between MDD and IR, which became insignificant after controlling for age, sex and BMI. However, the study sample was small (n = 196) and less than a fourth of subjects presented IR (defined as HOMA >2.5), therefore the study was potentially underpowered to detect IR related differences [The above-mentioned meta-analysis by Fernandes et al.▪▪ reportcontrols . Rashidis [et al.▪▪ noted mall n = 6 and lesferences .et al.[▪▪] published a cross-sectional study exploring the links between IR and depression status in obese individuals without diabetes, not medicated with antidiabetic drugs. They observed, that in female subjects IR (defined as 4th quartile vs. 1st–3rd quartiles HOMA that is >5.5) was significantly associated with mild, moderate or severe depression, with higher depression severity being related to higher risk of IR. To the contrary, no significant link between IR and depression was noted in male participants. Łapińska et al.[et al.[▪▪] performed a longitudinal assessment of links between baseline IR and depressive symptoms measured biennially for 8 years. The results indicated that high IR (4th vs. 1st quartile of studied population) was associated with progression of depressive symptoms. This relationship was significant in subgroups of men, overweight and elderly subjects but not in women, participants with normal BMI, those aged <65 years.He et al.▪▪ publiska et al. studied l.. On the other hand, Gruber et al.[▪▪] summarized data coming from animal and human trials exploring the impact of insulin and IR on dopaminergic transmission. Based on the animal studies they have concluded that (a) insulin differently modulates dopamine release, increasing it if applied in the striatum and inhibiting it if applied in the ventral tegmental area (VTA), (b) insulin deficiency and resistance limits the synthesis and reuptake of dopamine as well as the excitatory stimulation and firing frequency of dopaminergic neurons in VTA, (c) restricted insulin signaling/IR in the nucleus accumbens reduces dopamine release and reuptake, (d) IR is linked to increased food intake, motivation to work for food, dampens reward sensitivity, impairs learning and preference formation as well as promotes behavioral despair resulting in anhedonic/anxious phenotype. Moreover, they summed human studies noting that (i) peripheral IR is a surrogate measure of central IR, (ii) intranasal insulin alters the activity and connectivity of dopaminergic circuitry and modulates reward behavior, (iii) the effects of intranasal insulin on reward processing differs with its dose, with low and high doses increasing the thresholds for reward the most, (iv) IR disrupts the reactivity to food cues, learning and motivation for reward (the last association is highly related to the state of satiety/hunger). While the relationship between high BMI and dysregulation of reward processing of food cues and intake is well established, a study exploring the effects of intranasal insulin on functional connectivity of the dopaminergic midbrain in humans reported, that the, these alterations are better predicted by IR rather than BMI [The alterations of serotonin, dopamine transmission are known to induce depressive symptoms. In an animal study, Martin the drug ▪▪. On ther et al.▪▪ summarthan BMI .et al.[et al.[▪▪,Surprisingly, IR seems to differently moderate treatment outcomes depending on its modality. In the earlier mentioned work by Brouwer et al., the trel.[et al.▪▪,26 obset al.▪▪,▪. Also, et al.▪▪,. On the et al.▪▪,.et al.[et al.[et al.[et al.[Moulton et al. performel.[et al. publishel.[et al.. Lucianol.[et al.▪ reportel.[et al.▪ assesseIn sum, latest research suggests that a metabolic subtype of MDD can be distinguished from other MDD populations by the presence of particular pathophysiological mechanisms, symptomatology and responsiveness to treatment. IR seems to play an important role in this metabolic MDD subtype and it is positively linked to atypical depressive symptomatology. Insulin has a direct effect on the serotoninergic and dopaminergic neurotransmission which becomes disrupted by IR. The relationship between IR and MDD seems restricted to current depressive states of either clinical of subclinical severity and it differs between sexes, ethnicities normal/overweight subjects. Moreover, IR limits the efficacy of antidepressant drugs but light therapy might be more effective for subjects with IR than insulin sensitive ones. Insulin-sensitizing treatments might be beneficial for MDD patients, with most robust data supporting the addition of pioglitazone or interventions promoting healthy lifestyle and physical activity. Studies exploring the role of IR in MDD need replication in larger groups/patients of different ethnicities/in various metabolic states  and so do trials verifying the potential efficacy of insulin-sensitizing treatments in MDD. Existing data already allow for a step towards personalizing therapeutic approaches and may inform clinical decisions as well as future research for more individualized and efficacious MDD treatment.None.None.There are no conflicts of interest.


Marek’s disease virus (MDV), an Alphaherpesvirus belonging to the genus Mardivirus, causes T cell lymphomas in chickens and remains one of the greatest threats to poultry production worldwide. While losses caused by Marek’s disease have been reduced through live-attenuated vaccines, field strains have increased in virulence over recent decades. MDV research has led to a profound understanding of virus-induced pathogenesis and tumor development ,2,3. OurA timely summary of the major methods of manipulating herpesvirus genomes was provided by Liao et al., with an emphasis on their applications in MDV research. The authors reviewed both the “traditional” methods, such as site-directed mutagenesis and the use of cosmids, and more recent methods, like bacterial artificial chromosomes (BACs) and CRISPR/Cas9-mediated genome editing . The samYou et al. reported the characterization of a new splice variant of viral interleukin 8 (vIL-8), a chemotactic cytokine, showing that this new vIL-8 isoform is dispensable for MDV replication and pathogenesis .Two papers addressed pressing questions in MDV research using CRISPR/Cas9 approaches: the switch between lytic and latent MDV infections and the use of gene technology to generate MDV-resistant chickens. Roy et al. used CRISPR activation (CRISPRa) of viral genes to investigate the lytic–latent switch. This switch seems to rely on the two MDV phosphoproteins pp24 and pp38 [In an attempt to improve MDV vaccines in the context of immunosuppression commonly caused by MDV and its widely used vaccines, Conrad et al. generated genetically modified vaccine candidates and assessed their vaccine-mediated protection and immunosuppressive effects .Ikaros cancer driver gene can contribute to MDV-induced tumorigenesis. Similar mutations also exist in some human cancers, suggesting that somatic mutations may explain the origin of MDV-induced lymphomas [Three contributions highlight the value of MDV infections in chickens as a model for human diseases. Erf et al. used a Mardivirus in vivo model to gain new insights into vitiligo, a chronic autoimmune disorder . A genomymphomas . Gennartymphomas .Finally, the methods paper on a cell culture system to study MDV integration by You and Vychodil et al. provided a method that allows the investigation of molecular mechanisms of MDV telomere integration, as well as the quantification of virus genome integration, without requiring laboratory animals .Although much progress has been made in MDV research and a growing body of knowledge about this DNA tumor virus exists, a number of challenges need to be overcome. Through this Special Issue, we hope to contribute to a better understanding of MDV as an important poultry pathogen, but also as a valuable animal model for herpesvirus research, virus–host interactions, and virus-induced tumorigenesis.


Glioblastoma (GBM) is the most lethal and prevalent primary brain tumor in adults with a five-year survival rate of only around 5 percent, afflicting about 3.19 people in every 100,000 . It is wEpigenetics and epitranscriptomics—molecular changes of cellular DNA, chromatin, and RNA—can alter the levels of gene transcripts and subsequently change the amount of proteins produced, including those responsible for tumor suppression, progression, or maintenance . Until nIn the early 2000’s, Helen Blau et.al., introduced an evolving concept for adult stem cells suggesting that stem cells is rather a biological function instead of an entity . AccordiYu et al., combined analysis of transcriptome and DNA methylation profiles of TCGA to derive a 6-gene model-based risk score. This approach allowed the authors to predict survival and the role of personalized treatment plans for GBM. Wang et al., analyzed tumor associated fibroblasts infiltration by Estimating the Proportion of Immune and Cancer cells (EPIC) based on multiple glioma databases. They describe a novel transcript signature that predicts glioma prognosis. Shi et al., showed that individual glioblastoma cell lines displayed increased expression of the short splice variant of YKL-40 after low serum treatment. In addition, unlike the full-length (FL) version, which was localized to all cell compartments, the short isoform could not be secreted and was localized only to the cytoplasm. Functionally, FL YKL-40 promoted cell proliferation and migration, whereas SV YKL-40 suppressed them. The authors described pathways that regulate the expression of the SV YKL-40 and discuss the significance for development of new therapies. Majc et al., investigated the use of bioactive peptides from venoms as novel therapies targeting cancer specific pathways in glioblastoma. Finally, Basilico et al., revealed that changing the rigidity of the mechanical environment tuned the response of glioblastoma cell lines through change in morphological features, epithelial-mesenchymal markers , EGFR and ROS expressions in an interrelated manner. Their work highlights the importance of microenvironment stiffness in the regulation of glioblastoma invasive properties.This Research Topic includes 5 original research papers. NT wrote the initial draft of the editorial. H-WL edited and both agreed on the final version.


In the last decades, complex networks have been used extensively in neuroscience and other fields by employing networks to model interactions among system’s components . MoreoveA common research theme in the study of complex networks is that of the determination of the role and impact of network topology on the emerging properties due to interactions and dynamics. How structural properties in brain regions affect neural dynamics or how do they differ in healthy and diseased subjects? How different types of plasticity affect the dynamics of neural activity in a network?This Research Topic contributes to better understand the impact of dynamics at different spatiotemporal scales, structure and plasticity on brain synchronous activity. To this end, it hosts interdisciplinary analytical and computational works from different fields, such as from complex systems, biophysics, systems biology, and computational neuroscience.Liu et al., aims to better understand the effect of the amyloid β peptide (Aβ) which is hypothesized to be the major factor driving Alzheimer’s disease (AD) pathogenesis. To this end, the authors derived and investigated a concise mathematical model for Aβ-mediated multi-pathway astrocytic intracellular Ca2+ dynamics. They investigated several interventions, such as ion channel blockers or receptor antagonists and demonstrated that a “combination therapy” targeting multiple pathways simultaneously is more effective towards the treatment of AD.The first paper, by Cambell et al. investigated the fractal dynamics of blood oxygen level-dependent (BOLD) signals during naturalistic conditions. They implemented fractal analysis to quantify scaling behavior using the Hurst exponent (H) in data from the Human Connectome Project to compare H values across movie-watching and rest. Their results showed that movie-watching induces fractal signal dynamics and markedly different than dynamics observed during conventional tasks.van der Vlag et al. introduced a new computational tool called RateML that enables users to generate whole brain network models from a succinct declarative description, in which the mathematics of the model are described without specifying how their simulation should be implemented. With RateML, the end user describes the model’s mathematics once and generates and runs code for different languages/platforms, targeting both CPUs for fast single simulations and GPUs for parallel ensemble simulations .Lei et al. introduced a new type of burst-oscillation mode (BOM), i.e. an alternating transition between two distinct phases . BOM was derived by extensively investigating the response dynamics of a one-dimensional (1D) paced excitable system with unidirectional coupling. These findings may facilitate a deeper understanding of bursts in nature and will have a useful impact in related fields.Shi et al. proposed a deep attributed network representation learning with community awareness (DANRL-CA) framework and two variants, i.e., DANRL-CA-AM and DANRL-CA-CSM, which incorporate the community information and attribute semantics into node neighbours with different methods. They designed a neighbourhood enhancement autoencoder module to capture the 2-step relations between node pairs. They conducted comparisons for node classification and link prediction and found that DANRL-CA-CSM can more flexibly coordinate the role of node attributes and community information in the process of network representation learning, and shows superiority in the networks with sparse topological structure and node attributes.Madadi Asl et al. employed a computational model to show that inhibitory spike-timing-dependent plasticity (iSTDP) at pallido-subthalamic synapses can account for pathological strengthening of pallido-subthalamic synapses in Parkinson’s disease (PD) by further promoting correlated neuronal activity in the globus pallidus (GPe) - subthalamic nucleus (STN) network. Their results may shed light on how abnormal reshaping of GPe-STN connectivity by synaptic plasticity during parkinsonism is related to PD pathophysiology and contribute to the development of therapeutic brain stimulation techniques targeting plasticity-induced rewiring of network connectivity.Zheng et al. studied the emergence of spatiotemporal patterns in a general networked Hindmarsh-Rose (HR) model. Furthermore, they investigated stability properties, namely they obtained conditions leading to Turing instability in networks without delays and showed that there is a difference between the collected current and the outgoing current affecting the neuronal activity, which is relevant in the generation mechanism of short-term memory.Li et al. investigated the dynamics of networks of identical coupled oscillators in a setting where coherent oscillations coexist with incoherent ones, the so-called chimera state. They showed that stable and breathing chimera states in the original two coupled networks typically have very small basins of attraction. Then, they studied the emergence of chimera states by stimulating brain regions and quantified it using the order parameter and chimera index. These two indices were found to be weakly and negatively correlated.


Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by defective cardiac ryanodine receptor (RyR2) calcium release during times of adrenergic stimulation, resulting in bidirectional or polymorphic ventricular tachycardia. Flecainide is a class 1c anti-arrhythmic drug that has demonstrated therapeutic efficacy in treating CPVT. However, its mechanism of action remains disputed. One group proposes a direct effect of flecainide on RyR2-mediated calcium release, while another proposes an indirect effect via sodium channel blockade and modulation of intracellular calcium dynamics. In light of recent studies, this commentary aims to explore and discuss the evidence base for these potential mechanisms. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by adrenergically mediated polymorphic or bidirectional ventricular tachycardia, leading to syncope and sudden cardiac death. The most common genetic mutations resulting in CPVT are found within genes responsible for coding the cardiac ryanodine receptor (RyR2). These are usually inherited in an autosomal dominant manner and are termed CPVT1. A recessive form (CPVT2) is caused by gene mutations for cardiac calsequestrin. CPVT is linked to seven genes with autosomal dominant  or autosomal recessive  inheritance [This results in a transient inward current, perpetuating the onset of malignant arrhythmias via delayed afterdepolarizations (DAD) and triggered activity. The first-line drug therapy for CPVT is β-adrenergic receptor blockers. However, some patients are refractory and experience persistent tachyarrhythmias. The class 1c antiarrhythmic drug flecainide, a known inhibitor of the sodium current (INa), has demonstrated effectiveness in treating CPVT; however, the mechanism responsible for the therapeutic efficacy of flecainide in CPVT remains disputed.Gaining a comprehensive mechanistic understanding of the clinical efficacy of flecainide in CPVT is critical for cases of arrhythmias that may share similar clinical presentation but differ significantly in their underlying mechanisms. Furthermore, abnormalities in calcium handling, including defective RyR2 functioning, are implicated in several other diseases of significant global burden, including muscular dystrophy, malignant hyperthermia, and Alzheimer’s disease. Consequently, RyR2 is a major therapeutic target, and the development of new drugs targeting RyR2 carries significant clinical potential for treating CPVT and other diseases.et al. [Hilliard et al.  comparedet al. [In a recent study, Kryshtal et al.  investiget al. [Other studies proposed contrasting mechanisms explaining wave suppression. Liu et al.  examinedet al. [In adult rat cardiomyocytes, Sikkel et al.  conducteet al. [Bannister et al.  investiget al. [et al. [Several factors should be considered to account for the varying results of flecainide on SR Ca2+ release via RyR2, which suggest a direct effect in some studies  and no eet al.  demonstr [et al.  only appet al. [et al. [Yang et al.  used in  [et al. . As estaThe debate regarding the primary mechanism responsible for the therapeutic efficacy of flecainide in CPVT remains highly disputed and unresolved. Numerous studies propose INa-mediated modulation of intracellular calcium dynamics, while several others propose direct RyR2 inhibition as the primary mechanism. Moving forward, the mechanisms of flecainide in CPVT will increase our knowledge of Ca2+ dysregulation in cardiac myocytes and aid in the development of a more specialized therapeutic approach for CPVT.


Exercise and lifestyle modifications have established themselves as the pillars of primary care, proving to be potent weapons in the war against non-communicable diseases. With the World Health Organization (WHO) naming physical inactivity as a leading risk factor for global mortality , it is cThere is extensive research highlighting the wide-ranging benefits of physical activity, spanning from mitigating the risks of cardiovascular diseases, diabetes, and stroke, as well as mental health conditions  includinConsidering this, primary care professionals across the world are progressively incorporating exercise-based lifestyle modifications,  particulAddressing the evaluation of physical activity within the context of primary care practice presents a noteworthy challenge . The impIn addition, adherence rates continue to fall below satisfactory levels, underscoring the imperative need for the development of strategies aimed at bolstering acceptance and participation . CentralZhang et al.; Hu et al.; Liu Y. et al.; Cheng et al.; Mainous et al.; Lin et al.; Wattanapisit et al.; Liu Z. et al.; Feng et al.; Felemovicius et al.; Heyn et al.).Furthermore, illustrating instances of successful integration of exercise recommendations within real-world settings can serve as practical models for future endeavors . CollaboZhang et al. in their paper “Exercise for Neuropathic Pain: A Systematic Review and Expert Consensus” emphasize that a proper exercise program can serve as an effective alternative treatment or complementary therapy for most patients with neuropathic pain (NP). This consensus provides actionable recommendations for clinicians and policymakers alike in formulating exercise prescriptions to treat NP.Hu et al. evaluated all-cause mortality and cardiovascular mortality in the Guangzhou Heart Study (GZHS), an ongoing prospective population-based cohort study in South China. Specifically, they investigated the effect of the Healthy Lifestyle Index and lifestyle patterns on the risk of mortality in a large Chinese population. Their study results suggest that accumulative dimensions of a healthy lifestyle can lower the risk of death, and adherence to the healthy lifestyle pattern was associated with non-smoking and low-level alcohol consumption which reduces the risk of all-cause mortality. These findings highlight the need to consider multi-dimensional lifestyle approaches when developing health promotion strategies.A population-based study by Efficacy of electro-acupuncture in postpartum women with diastasis recti abdominis: A randomized controlled clinical trial” by Liu Y. et al. evaluated the long-term efficacy and safety of electro-acupuncture (EA) in treating diastasis rectus abdominis (DRA) during postpartum. The study results showed that AE treatment improved multiple health parameters and symptoms related to Diastasis Recti Abdominis (DRA), displaying lasting effects up to 26 weeks postpartum.The clinical trial “Cheng et al. investigated the effectiveness and response of a multidisciplinary Workplace health promotion (WHP). They used a retrospective cohort sample of healthcare workers participating in a multidisciplinary WHP program in five healthcare facilities. The 20-week intervention included exercise classes, nutrition consultation, and behavioral education followed by anthropometrics, body composition, and physical fitness (PF) measures. Their study results demonstrated that a multidisciplinary WHP could enhance anthropometric and physical fitness profiles among healthcare workers.Furthermore, Mainous et al. evaluated the relationship between depression-high depressive symptomatology and adherence to lifestyle interventions among patients with prediabetes. They analyzed the 2017-20 20 National Health and Nutrition Examination Survey (NHANES), a nationally representative population of U.S. adults. Their findings showed that depression-high depressive symptomatology decreases the likelihood of adherence to exercise-based lifestyle recommendations among patients with a confirmed diagnosis of prediabetes underscoring the interplay between mental health and lifestyle changes.Lin et al. conducted a randomized controlled trial with 66 full-term infants with eczema randomly assigned to an eczema control (EC) group and an eczema with MPIM (EM) group as compared to a healthy control (HC) group. The mothers in the EC group received the instruction of routine care, while the mothers in the EM group applied massage on the infants plus receiving the same instruction of the routine care. HC group received no specific intervention. Compared with the EC group, the EM group showed significantly lower scores on eczema outcomes supporting the reduction of infantile eczema, along with relieving maternal anxiety and depression.A randomized trial by Wattanapisit et al. highlights the importance of training, integrating, and applying knowledge and skills pertaining to PA promotion in clinical settings with the goal of covering several aspects of sport and exercise science. They remind us that PCPs are usually not specialists in these subject areas, and it is essential to supplement and provide knowledge for proper clinical practices. They include the collective perspective of experts in the field.An intriguing opinion paper by Liu Z. et al. conducted a systematic review and meta-analysis to evaluate the effects of a traditional Chinese Qigong therapy called Baduanjin which is characterized by symmetrical body posture and actions, breathing control, meditative state, and concentration. They reviewed randomized controlled trials evaluating Baduanjin therapy's effects on neck pain and functional movement in older individuals. Although the results of the synthesis methods support Baduanjin therapy as a safe and positive treatment for neck pain in older individuals, they called for caution as more studies are needed to validate and support its benefit.Feng et al. through a population-based study in Taiwan, investigated whether physical activity (PA) is associated with a reduced risk of hemorrhagic stroke (HS). Their study supports the beneficial effect of PA on reducing HS risk. However, high-PA did not appear to have a greater protective effect than low-PA in diabetes and hypertension outcomes. Thus, their conclusions support that even <90 min of PA per week might be beneficial in reducing HS risk. They also note that recommendations based on low PA levels are more likely achievable and sustainable across the general population. Additionally, personalized recommendations, based on pre-existing comorbidities, may help optimize the beneficial effects of PA on HS prevention.Felemovicius et al. evaluated a novel composite topical Lidocaine agent treatment for Pruritus ani, or rectal or anal itch, which is a common perianal disorder that affects approximately five percent of the population of the developed world. The SOOTHER Trial showed efficacy in providing rapid and effective relief of pruritus ani in an ambulatory population.The SOOTHER Trail by Heyn et al.) from the University of Colorado School of Medicine and Colorado Children's Hospital underscores the importance of lifelong monitoring of children with disabilities to identify and modify disease-induced risk factors through lifestyle interventions. Their study, “The association between isometric strength and cognitive function in adults with cerebral palsy,” supports using simple tests like hand grip strength to evaluate early signs of frailty and neurocognitive decline in adults with Cerebral Palsy.Finally, a study by a research team , it becomes evident that they underscore the pivotal significance of exercise and lifestyle modifications within primary care. Through their findings, they shed light on the multifaceted roles of these interventions across various health contexts. As we continue to navigate the intricacies involved in implementing efficacious exercise prescriptions and clinical physical activity recommendations in primary care settings, these studies serve as valuable resources that enrich our comprehension and improve our ability to promote healthier lifestyles effectively for diverse patients within the realm of primary care.In summary, when considering the results of the studies from this Research Topic collectively (PH: Writing—original draft, Writing—review and editing.


HormoneWang et. al.), but its regulatory network in many non-model fruits is not yet fully understood. Li et al. investigated the regulation of ethylene in mango fruit ripening, using ethylene and 1-methylcyclopropene (1-MCP), the action inhibitor of ethylene.They found that MiERF2 and MiERF8 may play critical roles in regulating mango fruit softening. Wang et al. reported that blueberry had an atypical climacteric ripening process, where a respiratory climacteric character was developmentally regulated by ethylene, but with non-autocatalytic ethylene production during fruit ripening. Except for ethylene, increasing evidence show that other hormones such as auxin, abscisic acid (ABA), brassinosteroids (BRs), gibberellins (GAs), melatonin (MT) and cytokinins (CKs) control fruit ripening . It is generally considered that ethylene is the key actor of climacteric fruit ripening and ABA is the core player of non-climacteric fruit . However, increasing evidences have shown that fruit ripening is regulated by a balance of multiple hormones rather than by a single one, and the crosstalk between ethylene and ABA signaling plays a leading role in regulating fruit ripening. In climacteric fruits, ABA usually accumulates before the initiation of climacteric period that can promote ethylene biosynthesis via upregulating ethylene biosynthesis related genes and accelerating ethylene-triggered ripening  plays a negative role in fruit ripening process (Liu et al. also found that CK suppressed the loss of total sugar and sucrose and the accumulation of acetic acid and ethanol in the fruit aril, reduced the malondialdehyde accumulation in the pericarp of the overripe litchi fruit. Cytokinin treatment repressed the litchi fruit ripening process and maintained fruit quality in the on-tree overripe fruit. However, more information is needed about the interaction of CKs with other hormones.GA works as a negative regulator of fruit ripening, which inhibits the ethylene biosynthesis and perception during fruit ripening of tomato . SA regu process . The app process . Liu et In conclusion, the exciting new findings presented in the present topic collection and other works provide a broad and in-depth understanding of hormone signal interactions in regulating fruit ripening. It is believed that increasing new knowledge will emerge in this exciting and evolving field.XZ and QZ wrote the manuscript, HZ edited and reviewed the manuscript. All authors contributed to the article and approved the submitted version.


Skeletal muscles are an indispensable actor for daily activities, playing an essential role in locomotion through both the control of posture and position and by joint stabilization. In addition, they are involved in body temperature maintenance and constitute nutrient reserves. Skeletal muscle represents approximately 40% of human body weight, but this percentage physiologically decreases when tissue undergoes atrophy. During aging, a decline in muscle strength and mass can be observed and muscle mass decreases by approximately 3–8% per decade after 30 years of age and this reduction appears significant after 60 years . Muscle With regard to sarcopenia, Shin et al. (2023)  discusseIn their paper, Jeun and Choung (2023)  describeAnother high-quality protein that contributes to the maintenance of skeletal muscle mass is egg white protein (EGG), an arginine-rich protein source with a lower amount of leucine. Koshinaka et al. (2023) demonstrated that EGG supplementation in rats had a higher efficiency in muscle gain compared to other common animal-based proteins .Continuing the discussion of dietary protein as an important strategy to manage and prevent sarcopenia, Lees et al. (2023) , in theiThis Special Issue also includes a paper evaluating rosemary leaf extract activity in primary skeletal muscle cells . RosemarAmong the original articles published in this Special Issue, Salucci et al. (2023)  describeFinally, this Special Issue contains two reviews that recognize nutritional interventions as an important strategy to manage and prevent skeletal muscle loss. In this regard, Massini and colleagues (2023)  discusseNutrients, titled “Nutrition and Regulation of Muscle Protein Synthesis”, highlights the strategic role of nutritional approaches, based on supplementation with vitamin (B6), herbal extract (GBE), phenolic compounds , and high-quality dietary proteins , in the prevention of muscle mass loss associated with diseases or aging.In conclusion, this Special Issue in The Guest Editor warmly thanks all of the authors for their contributions to this Special Issue.


Klebsiella variicola strain during a laboratory evolution study, resembling genetic changes observed in clinical isolates.The appearance of colony morphotypes is a signature of genetic diversification in evolving bacterial populations. Colony structure highly depends on the cell–cell interactions and polymer production that are adjusted during evolution in an environment that allows the development of spatial structures. Nucci and colleagues describe the emergence of a rough and dry morphotype of a noncapsulated  Klebsiella variicola.Commentary on the paper by Nucci et al that explains the genetic basis and fitness effects of specific mutations leading to rdar-like colony morphotypes in noncapsulated IS elements drive rapid loss of K. pneumoniae capsule production in experimentally evolved population (Nucci et al. Bacillus thuringiensis, where an IS4-like element disrupts a gene encoding a guanylyltransferase, causing increased hydrophobicity and aggregation (Lin et al. B. thuringiensis fuzzy morphotypes, K. variicola rdar-like derivatives display diminished aggregation (Nucci et al. In their recent ria Fig. . While tK. variicola display increased growth rate and fitness advantage compared with the ancestor (Nucci et al. The rdar-like clones of K. variicola background was used, while colonies with distinct morphology were less apparent in capsulated strains that followed a different evolutionary path (Nucci et al. mrkH or nac alleles demonstrated that these mutations convey lower influence on cell–to–cell aggregation in the capsulated background and the fitness effects were only marginally larger in capsulated strains compared to noncapsulated strains. Historical contingency, where the existing mutations influence the subsequent adaptation path might explain the larger rdar-like morphotype frequency in noncapsulated K. variicola. This highlights the opportunity to discover novel evolutionary paths in strains lacking the most frequently mutated targets. Deleting the three most frequently mutated pathways in Pseudomonas fluorescens and subsequent experimental evolution in a static microcosm revealed 13 new mutational pathways that all result in wrinkly spreader colony morphotype (Lind et al. B. subtilis permits the evolution of clones with enhanced biofilm formation, explained by the production of novel, cysteine containing amyloid fibre variants (Dragoš et al. P. fluorescens example, the reconstituted B. subtilis strains with cysteine-encompassing amyloid fibres convey a disadvantage in the presence of the exopolysaccharide (Dragoš et al. The rdar-like morphotype was detected after plating by Nucci and colleagues  when a nK. pneumoniae genomes revealed comparable IS element insertion in the mrkH gene of numerous clinical isolates. Isolates with interrupted mrkH genes were mostly originated from human host samples, including urine and blood as the main source (Nucci et al. Klebsiella isolates, potentially explained by the negative frequency selection of these mutations. The detection of specific mutations or gene disruptions in natural populations further validate the relevance of experimental evolution studies in the laboratory settings as previously reported in Klebsiella (Nucci et al. Finally, the work by Nucci et al. highlights the relevance of laboratory evolution for real-life scenarios. Detailed analysis of The study of Nucci et al.  highligh


Ralstonia solanacearum is one of the most devastating agents affecting different plants in 45 families. Several management practices have been used effectively for the management of this bacterium in different plants, including the use of biological control agents . However, because of difficulties in handling, culturing, and maintaining biocontrol agents or the issues related to their practical efficacy in soil, the use of their antimicrobial compounds is considered a good alternative. Ye et al. investigated an antibacterial furoic acid compound, 5-(hydroxymethyl)-2-furoic acid, produced by the fungus Aspergillus niger. The soil application of this compound effectively controlled the R. solanacearum population in soil by direct killing effect as well as enhancing host resistance in tomato plants. Wang et al. reviewed other studies for the management of this bacterium, including biological, organic, breeding, genetic engineering, physical, cultural, chemical and nano-technological approaches.Soil-borne plant pathogens pose a significant threat to plants, and their management is comparatively more difficult than other plant pathogens because of their nature of the hidden enemy, long persistency in soil, vast genetic diversity and host range . HoweverDutta et al., in their review, focused on several aspects of the use of nanotechnology in the management of soil-borne plant pathogens highlighting the role of nanoparticles as protectants and inducers of plant defense against soil-borne plant pathogens. Uncovering the mechanism of host resistance and discoveries of host genes/proteins that regulate host resistance against soil-borne plant pathogens will help plant genetic engineers develop plants that can better fight against soil-borne plant pathogens. Tian et al. reported that small G-protein StRab5b positively regulates potato resistance against the soil-borne fungus Phytophthora infestans. Pazarlar et al. found that Bacillus cereus EC9 protects tomatoes against Fusarium wilt through JA/ET-activated immunity. In another study by Ling et al., it was shown that WRKY genes confer resistance to Cucumis metuliferus against root-knot nematodes (RKN). The RKN-resistant variety of C. metuliferus (cm3) was found to specifically recruit beneficial bacterial communities in soil upon infestation with RKN, as reported by Song et al. Similarly, Sikandar et al. reviewed overall management strategies, including several recent efforts to improve host resistance against Meloidogyne enterolobii.Nanotechnology emerged as one of the most rapidly advancing sciences of the twenty-first century, and plant scientists revealed the effective application of nanotechnology for the management of plant pathogens. Dutta et al. unveil the molecular mechanism by which Trichoderma fungus, one of the most used and studied biocontrol fungus, induce host resistance against pathogens including the role of exogenous elicitors in the induction of host resistance. Zhou et al. proved that exogenous application of elicitor isotianil could significantly alleviate the symptoms of Fusarium wilt on the banana. They further confirmed that isotianil application might contribute to disease control by inducing host plant defense against Fusarium infection. Investigation into how the pathogens achieve virulence at the molecular level is also essential for understanding the action mechanism of the pathogen. Xu et al. revealed the role of cAMP phosphodiesterase in the formation of sclerotia and achieving virulence in Sclerotinia sclerotiorum, an important phytopathogenic fungus that causes stem rot and white mold disease.Enhancing host resistance is also a prominent action mechanism of many biocontrol agents. In their review, Most investigations conducted for the management of soil-borne pathogens are based on greenhouse or controlled laboratory conditions. Although the outcomes of these studies provide useful insights into the action mechanism and control efficacy, field investigations are vital for assessing the practical applications of these strategies. Field assessments consider the complex interplay between plants, pathogens and soil, and environmental factors that can affect disease management and development. This more accurately illustrates how these strategies perform in real agricultural scenarios. Moreover, field assessment can give an actual clue of management strategy on economic feasibility.RK: Writing – original draft, Writing – review & editing, Conceptualization.


The 38th issue of Financial Innovation (FIN), Volume 9, No. 2 (2023) presents 23 papers contributed by authors and co-authors from nineteen countries and areas: Canada, Chile, China, France, Germany, Italy, Netherlands, New Zealand, Oman, Portugal, Romania, Russia, Spain, South Africa, Taiwan, Türkiye, UK, USA and Vietnam. These papers can mainly be categorized into three sub themes. • Financial risk management and analysisGómez-Águila et al. (2022) introduce a new procedure to improve the estimation of the Hurst exponent in financial time series and prove that pure price series are not necessarily self-similar. Yeh and Liu (2023) use visualization techniques to help explore the Growth Value Model (GVM) intuitively. De Blasis (2023) addresses the calibration issues of the weighted-indexed semi-Markov chain (WISMC) model applied to high-frequency financial data. Ivanyuk (2023) presents an optimization approach—residual-based bootstrap averaging (RBBA) and shows why and how it works. Monteiro et al. (2023) examine the linear interdependencies between international industries, with a focus on the relationships between the US and other six countries, focusing mainly on international stock indexes or firm-level returns. Mo et al. (2023) present an adaptive measurement model of spatiotemporal correlation coefficients based on the clustering theory and conduct an empirical analysis based on the model. Loughran and McDonald (2023) find a slight positive correlation between industry performance and the use of pandemic-related words, as opposed to the expected negative correlation. Gupta and Pierdzioch (2023) prove that aggregate and state-level economic conditions can predict the subsequent realized volatility of oil price returns.• Behavior financeCheng et al. (2023) find that rumor propagation outperforms management shocks and other variables in predicting abnormal trading behavior. Wang and Lee (2023) chose three life insurance stock futures in India and one in Taiwan as samples and examine that insurance futures are a safe haven for COVID-19 pandemic risks. Duréndez et al. (2023) find that Management control systems (MCS) and managers’ risk attitudes fully mediate the relationship between financial literacy (FL) and innovation. Alp et al. (2023).examine the presence of investor overconfidence by employing an artificial intelligence technique and a nonlinear approach to impulse responses to analyze the impact of different return regimes on the overconfidence attitude. Madeira (2023) demonstrates how households’ characteristics affect their choice of lenders, consumer debt amounts and default behavior. Cruz et al. (2023) propose an approach to the profile of microcredit holders from the Hispanic minority in the US to identify the factors that explain the punctuality of their microcredit repayments. Zhou et al. (2023) develop a behavioral heterogeneous agent model (HAM) comprising fundamentalists, chartists, and stabilizers to investigate investors’ dynamic switching mechanisms under government intervention.• Stock marketHtun et al. (2023) find that correlation criteria, random forest, principal component analysis, and autoencoder are the most widely used feature selection and extraction techniques with the best prediction accuracy for various stock market applications. Zhang et al. (2023) propose three novel strategies to address common issues in predicting high-frequency stock prices using machine learning methods. Cepoi et al. (2023) explore the impact of the COVID-19 pandemic on information asymmetry for the case of the Romanian capital market. Meng et al. (2023) examine the effect of stock market liberalization on market efficiency by using a recent stock market liberalization reform policy in China—the Stock Connect—as a quasi-natural experiment. Mensi et al. (2023) provide strong evidence of quantile dependence between gold and stock returns. Li and Chen (2023) conduct a theoretical analysis of low-price collusion in SBIC from the perspective of strategic interaction between institutional investors and the regulator. Mestre (2023) proposes a wavelets approach to estimating time–frequency-varying betas in the capital asset pricing model (CAPM) framework. Carrillo-Hidalgo et al. (2023) develop a dynamic regression model to predict the behavior of shares in the Spanish tourism sector according to the evolution of the COVID-19 pandemic in the medium term. It is confirmed that both the number of deaths and cases are good predictors of abnormal stock prices in the tourism sector.


Neurological disorders are a large and heterogeneous field of research that can be tackled through a variety of approaches, ranging from epidemiology to molecular biology, through clinical, biostatistical, and laboratory experiments. The objective of this article collection was to gather the most recent evidence on signaling and genetic regulation of major neurological disorders . The articles included in the collection offer interesting insights into a range of biological processes involved in neurodegeneration. In addition, one contribution described an in silico approach to develop drugs for Parkinson’s disease (PD). Barrera-Vaquez et al., 2023  sought tAlzheimer’s disease (AD) is certainly the best known neurodegenerative disorder. It is characterized by deficits in multiple cognitive domains always including the memory domain and always involving neurodegeneration in the hippocampus. Several hypotheses have been proposed to explain the complex pathophysiology of AD, including altered neurogenesis and neuroinflammation. Olabiyi et al., 2021 [1−42, caspase 3, caspase 9, and cytosolic phospholipase A2. To further test their findings, the authors performed an in vitro experiment by exposing HT22 cells to a 12/15-LOX shRNA and a p38 MAPK inhibitor in high-glucose medium. The finding that the 12/15-LOX pathway plays a role in diabetic brain damage by activating p38 MAPK to promote inflammation and neuronal apoptosis, and that this mechanism could be inactivated by 12/15-LOX inhibitors is worth future research, perhaps not only limited to diabetic cognitive impairment.The role of lipid-mediated inflammation in neurodegeneration was evaluated by Chen et al., 2022 . The autIn their contribution, Zhang et al., 2022  studied Jang et al., 2022  studied Neurodegeneration does not necessarily result in neuronal death. Indeed, brain cancer development can be a consequence of a neurodegenerative process that leads to loss of function, immortalization of cancer cells, and eventually, death of the individual. Oncogenesis shares pathways with neurodegeneration. For example, Chuang et al., 2021  found thNeurodegeneration is highly influenced by lifestyle habits, including alcohol (ab)use. A deeper understanding of the genetic basis of the risk of alcohol use and tendency to abuse is highly sought after. Al-Sabagh et al., 2022  tested tWhich aspect of neurodegeneration should be addressed first?


Xie et.al identify a homozygous missense variant in DND1 that causes non-obstructive azoospermia in humans . Aprea et.al. identify the pathogenic gene variants in CCDC39, CCDC40, RSPH1, RSPH9, HYDIN, and SPEF2 that cause defects of sperm flagella composition and male infertility. They find that immunofluorescence microscopy in sperm cells is a valuable tool to identify flagellar defects related to the axonemal ruler, radial spoke head, and the central pair apparatus . Yuan et al. finds a Gly684Ala substitution in the androgen receptor that causes azoospermia  and Fang et al. reports the phenotypic findings and genetic considerations of congenital absence of the vas deferens with hypospadias or without hypospadias: , which might advance the genetic diagnosis and clinical genetic counseling for male infertility. Zhu et al. also verifies that FISH could analyze numerical chromosomal abnormalities in the sperm of Robertsonian translocation der   carriers . Moreover, Wang et.al review various phenotypes resulting from different pathogenic genes, including sperm ultrastructure and encoding proteins with their location and functions as well as assisted reproductive technology outcomes, providing additional clinical views and broadening the understanding of this disease . Finally, Xu et al. reports a case of the birth of a boy after intracytoplasmic sperm injection using ejaculated spermatozoa from a non-mosaic KS man with normal sperm motility, which increases our knowledge of non-mosaic KS . The findings in these studies broaden our understanding of genetic factors in male infertility and were also included in our Research Topic scope.Our Research Topic is “Genetic Factors in Male Infertility” and the goal of this Research Topic is to collect more papers on the aspect of identifying different gene variants and various types of RNAs mainly focused on male infertility including azoospermia, oligozoospermia, teratozoospermia, and asthenozoospermia. In order to achieve this goal, we carefully reviewed every submitted manuscript and screened for highly qualified reviewers. Eventually, we accepted and published seven articles including four “Original Research” articles, one “Brief Research Report” article, one “Case Report” article, and one “Review”. These articles covered the genetic factors of non-obstructive azoospermia and teratozoospermia and the clinical outcomes of men with non-mosaic Klinefelter syndrome (KS).


Despite increasing awareness of the ubiquity of microplastics (MPs) in our environments, little is known about their risk of developmental toxicity. Even less is known about the environmental distribution and associated toxicity of nanoplastics (NPs). Here, we review the current literature on the capacity for MPs and NPs to be transported across the placental barrier and the potential to exert toxicity on the developing fetus.This review includes 11 research articles covering in vitro, in vivo, and ex vivo models, and observational studies. The current literature confirms the placental translocation of MPs and NPs, depending on physicochemical properties such as size, charge, and chemical modification as well as protein corona formation. Specific transport mechanisms for translocation remain unclear. There is emerging evidence of placental and fetal toxicity due to plastic particles based on animal and in vitro studies.Nine out of eleven studies examined in this review found that plastic particles were capable of placental translocation. In the future, more studies are needed to confirm and quantify the existence of MPs and NPs in human placentas. Additionally, translocation of different plastic particle types and heterogenous mixtures across the placenta, exposure at different periods of gestation, and associations with adverse birth and other developmental outcomes should also be investigated.The online version contains supplementary material available at 10.1007/s40572-023-00391-x. Since the production of plastics accelerated after the early 1950s, approximately 6300 million metric tons of plastic waste have been generated worldwide, over three-quarters of which have been discarded in various environments .The most commonly used plastic polymers are high- and low-density polyethylene, polyvinyl chloride, polyethylene terephthalate, polypropylene, and polystyrene . PrimarySince MPs and NPs are known to be widely present in food, water, and air, humans are most commonly exposed through ingestion and inhalation routes . A commoThe toxicity of micro- and nanosized plastic particles likely depends on their physicochemical properties including size, shape, molecular structure, functionalization, surface charge, and material type . There iThe potential for wide-ranging health risks associated with MP and NP exposure combined with the heightened susceptibility to environmental agents during fetal development underscores the importance of investigating the maternal-to-fetal transfer of such particles across the placenta. The role of the placenta is to facilitate essential nutrient, gas, and waste exchange for the fetus, but it is not impervious to environmental toxicants. The placental barrier consists of the syncytiotrophoblast layer, cytotrophoblast cells, and the endothelial cell layer of the fetal capillaries see Fig.  21•]. T•. T21•].Existing reviews cover the health risks posed by MPs, NPs, and other nanomaterials including placental transport, but none focus solely on the transport of plastic particles across the placenta , 27, 28.Articles were identified for review through a comprehensive literature search using PubMed and Web of Science databases. The search strategy utilized terms such as “placenta,” “transport,” “particle,” and “plastic” with Boolean operators  and Web of Science’s Core Collection (N = 435). A total of 146 duplicate articles were identified and removed using Endnote. Nineteen additional articles were retrieved from the reference lists of included reviews and other studies. Titles of all papers were screened, abstracts of 51 papers were screened, and 36 full-text papers were assessed for eligibility. Articles were excluded if they did not assess the transport of particles made of plastic across the placental barrier , if they did not explicitly investigate transport across the placental barrier, or if they were not primary research studies . The final selection of 11 primary research articles included 4 studies using in vitro human cell models, 2 in vivo animal studies, 1 study with both in vitro human cells and an in vivo animal model, 3 studies using ex vivo human placental perfusion models, and 1 observational study in humans. The study selection process is outlined in Fig. The literature search was conducted in July 2021 and updated in February 2022. A total of 752 articles were identified using PubMed  are provided for the translocation studies specifically. The reported “major findings” include results from toxicological investigations as well Table .Using an ex vivo human placental perfusion model, Wick et al. (2010) observed size-dependent maternal-to-fetal placental translocation of fluorescent polystyrene particles. After 180 min of perfusion, fluorescence measurements and transmission electron microscopy micrographs showed that beads sized 50, 80, and 240 nm were able to cross the placenta to the fetal compartment, while 500-nm beads did not •. LeveraUsing BeWo b30 cells, Kloet et al. (2015) observed that translocation of 50-nm polystyrene nanoparticles was not dependent on the surface charge of the particles. Translocation of three types of 50-nm polystyrene NPs, one positively charged and two negatively charged, was assessed [protein corona. Using the ex vivo human placental perfusion model, Gruber et al. (2020) found that dynamic protein coronas influenced the translocation of plain 80-nm polystyrene nanoparticles across the placental barrier. First, the group showed the addition of plasma to the perfusion medium increased the maternal-to-fetal transfer of NPs [It is plausible that the interaction of plastic particle surfaces with various endogenous biomolecules affects particle transport. In biological fluids, proteins can rapidly cover the surface of nanomaterials forming a r of NPs •. The cor of NPs •. For exr of NPs •. Using r of NPs •. Media r of NPs •. In allKloet et al. (2015) also investigated the role of specific transport mechanisms by assessing whether the distribution of NPs in the compartments changed in the presence of inhibitors of endocytosis and specific ATP-binding cassette transporters. They found that inhibitors of P-glycoprotein and breast cancer resistance protein had no effect on translocation of either NP and that an inhibitor of multidrug resistance protein 1 increased basolateral translocation of the positively charged NP and had no effect on the translocation of the negatively charged NP •. OveralIn contrast, Grafmueller et al. (2015) posit that the translocation of polystyrene particles across the placenta mainly involves an active, energy-dependent transport pathway. The investigators used the ex vivo human placental perfusion model to assess the bidirectional transfer of both plain and carboxylate modified polystyrene particles with fluorescent labels 50–300 nm in diameter •. After Since there is accumulating evidence that plastic particles can cross the placental barrier, it is important to investigate the toxic potential of these particles. In the studies using ex vivo placental models by Grafmueller et al. (2015) and Wick et al. (2010), general measures of placental viability, functionality, and transfer were observed not to be affected by perfusion of plastic particles •, 35•. HIn different in vitro models, the human 3A-Sub-E trophoblast cell line and villous cytotrophoblasts derived from term placentas of normal pregnancies, Huang et al. (2015) did observe cytotoxicity of carboxylate-modified NPs. Following exposure to 20- and 40-nm particles in both trophoblast models, they observed elevated cleaved caspase 3, a marker of apoptosis induction, based on Western blot analysis •. They aInterestingly, Hesler et al. did not observe transport across a placental BeWo b30/HPEC-A2 co-culture model at either concentration tested (10 and 100 µg/mL) after 24 h of exposure. The researchers used a different detection system than previous studies, asymmetrical flow field-flow fractionation (AF4), and noted the possibility of translocated particles being present below the limit of detection •. Using Given some evidence of the toxicity of plastic particles on trophoblast and embryonic cell lines, the distribution of plastic particles in fetal organs after transport across the placenta warrants consideration. Kenesei et al. (2016) used an in vivo model to investigate the distribution of surface-modified fluorescent polystyrene nanoparticles after intravenous injection of pregnant mice. Using spectral imaging fluorescence microscopy, they found carboxylated NPs in the lacunas of the placenta 5 min after particle administration •. ParticIn a pilot observational study, Ragusa et al. (2021) were the first to report MPs found in human placenta samples, confirming the placental translocation of plastic particles observed in ex vivo and in vitro models. The researchers obtained placentas from 6 patients in Italy with uneventful pregnancies ••. SamplEleven studies investigating the capacity for MPs and NPs to cross the placental barrier were reviewed. Placental translocation of plastic particles was observed in multiple experimental models including in vitro cell cultures, in vivo animal models, and ex vivo human placental perfusion systems as well as in an observational study of MPs in human placentas after delivery. One study conducted in an in vitro co-culture context and one study conducted in mice did not observe placental translocation of the plastic particles tested. Given the wide variety of systems used, it is important to weigh the strengths and limitations of the different models when comparing study results.While in vitro models are easier to obtain and utilize for high-throughput studies, they can be over-simplified compared to an in vivo environment. Promisingly, translocation of compounds across in vitro models has been shown to correlate well with the ex vivo human placental perfusion model •, 39, 40In vivo studies of placental translocation of plastic particles in a whole-body system are valuable for understanding more realistic and comprehensive exposure conditions. As such, the study Fournier et al. (2020) conducted in rats provides insight into fetal deposition of NPs after maternal inhalation. Additionally, Kenesei et al. (2016) and Huang et al. (2015) investigated placental translocation of NPs in mice. However, extrapolation of findings from animal studies to humans is difficult due to significant interspecies differences in the placenta; rats show differences in placental morphology, yolk sac function, and steroid hormone biosynthesis, for example , 43.The ex vivo human placenta model used by Wick et al. (2010), Grafmeuller et al. (2015), and Gruber et al. (2020) provides advantages over animal models by more accurately representing the structure of the human placental barrier and over cell culture models by allowing for dynamic flow during exposure. The process of tissue degradation, however, limits experiments with these ex vivo models to a few hours •. BecausThe current literature suggests that the placental translocation and toxicity of MPs and NPs depend on physicochemical properties such as size, charge, and chemical modification. Wick et al. (2010), Cartwright et al. (2012), and Aengenheister et al. (2018) showed size-dependent transport of polystyrene particles across the placenta, while Kloet et al. (2015) found that polystyrene particles of the same size had different translocation properties likely dependent on functional groups. Kloet et al. (2015) also showed that functional groups and charge affect the cytotoxicity of polystyrene particles on placental trophoblast cells. This has implications for the risk assessment of the developmental toxicity of MPs and NPs—more characteristics modulating the translocation and toxicity of plastic particles justify the assessment of more variations and types. Furthermore, Gruber et al. (2020) showed dynamic protein coronas affect placental translocation of NPs, posing another variable in experimental risk assessment.Nine out of eleven studies examined in this review found that plastic particles were capable of placental translocation; observations of MPs in human placentas by Ragusa et al. (2021) make this consensus even more convincing. The mechanism that plastic particles use to cross the placenta remains unclear: Kloet et al. (2015) suggested it was passive diffusion and Grafmueller et al. (2015) suggested it was active transport. It is possible that these mechanisms are not mutually exclusive and the process depends on some combination of both.All of the experimental studies utilized mostly uniform, spherical, polystyrene particles. Polystyrene is widely used to package foods and has been found to be one of the most frequently detected plastic polymers in human blood •. MPs anGiven the evidence that MPs and NPs can not only translocate across the placenta but also subsequently deposit in fetal tissues and exert toxicity •, 34••, Supplementary file1 (DOCX 17 KB)Below is the link to the electronic supplementary material.


Over the last few decades, great efforts have been dedicated to the discovery of various nanomaterials. Due to their unique optical, magnetic, and electrical properties (among others), they have found applications in medicine (drug delivery), agriculture, electronics, catalysis, etc. Thus, due to the increasing possibilities, the need to design and fabricate novel nanoparticles is rapidly increasing. In this Special Issue “Advanced Nanomaterials in Biomedical Application”, a total of seventeen articles—including five reviews—have been published, addressing the most recent advances in nanomaterials in terms of both synthesis and characterization as well as technological applications. In the following, we provide a brief overview of the key findings presented in this Special Issue.50 values were more than 1000 times lower compared to cisplatin. Furthermore, the derivative with the highest activity cisplatin–diacetyl caffeate conjugate and its MSNs induced apoptotic cell death by causing potent caspase activation. Moreover, in vivo studies conducted using BALB/c mouse models with breast tumors showed that the same compound and its MSNs exhibit tumor growth inhibition with a reduced necrotic area and lowered mitotic rate. The review paper by Spoială  and containing 72 Mo(VI) and 60 Mo(V), to the existing states of the human papillomavirus (HPV) major capsid protein, L1-pentamer (L1-p), and virus-like particles (VLPs). The color responses result from the different binding modes between [Mo132] and the capsid protein. This straightforward colorimetry approach is of importance to estimating the existing states of the HPV capsid protein and could be used in the future to analyze the quality of the HPV vaccine and the existing states of other viruses.The studies conducted by Xue et al.  have shoMany studies have shown that CSC chemokine receptor 4 (CXCR4) is a promising target for cancer therapies, and intracellular siRNA delivery to suppress CXCR4 expression in cancer cells is an effective therapeutic strategy. Thus, Cao et al.  synthesiMin and co-authors  presenteThe work of Tyubaeva et al.  exploresRen and coauthors  summarizDing et al.  designedIn their review article addressing SARS-CoV-2, a hot topic lately, Kianpout et al.  gave an A new nano-emulsion adjuvant based on squalane  containing CpG was prepared, and its in vivo properties were examined . The SNAS35A  with poly acid (PLGA) nanoparticles, the selective delivery of cytotoxin to macrophages, in comparison to epithelial cells, was suggested. This drug delivery system presents anti-inflammatory effects.Harada et al., reported a useful technique for protein delivery to macrophages . By applIn the study by Wen et al. , osteoim


They confirmed that [NiFe] large subunits dimerize in the absence of their small subunit (Hartmann et al., Kisgeropoulos et al. investigated the effect of amino acid exchanges of the primary proteinaceous proton acceptor in [FeFe]-hydrogenase. The data expand previous work (Cornish et al., Ka of the proton acceptor is one factor controlling the catalytic bias of the enzyme. Three further articles dealt with functional aspects of hydrogenases. Morra reviewed the identification and characterization of novel [FeFe]-hydrogenases, described their functional roles, and recent findings regarding their O2 tolerance. Kpebe et al. reported on the essential role of a bifurcating [FeFe]-hydrogenase in the sulfate reducer Solidesulfovibrio fructosivorans, showing that during ethanol oxidation, the hydrogenase confurcates electrons from NADH and reduced ferredoxin to produce H2, which is later on used for energy conservation using sulfate as electron acceptor. The function of a bidirectional [NiFe]-hydrogenase in Synechocystis sp. PCC 6803 was investigated by Burgstaller et al.. They showed that this hydrogenase is essential for growth on arginine and glucose in the presence of light and O2, and interestingly this function seems to be unrelated to H2 catalysis. Instead, an H2-independent role for the transfer of electrons into the photosynthetic electron transfer chain is proposed, which is an important hypothesis that may also be relevant for certain multisubunit hydrogenases in other species.This Research Topic comprises 11 articles that aimed to bring together recent advances in hydrogenase research, including structure, function, maturation, and application. In terms of structural investigation, Haase and Sawers investigated residues that contribute to [NiFe]-hydrogenase maturation. They found a histidine residue in a HypC-type chaperone that is important for efficient binding to its maturation partner HypD (Blokesch and Böck, Fan et al. significantly improved the [NiFe]-cofactor incorporation in the course of heterologous production of a [NiFe]-hydrogenase from Cupriavidus necator in Escherichia coli. Previously, cofactor insertion was not functional, resulting in production of inactive hydrogenases (Fan et al., On the subtopic of hydrogenase maturation, Hogendoorn et al. isolated the novel strain “Candidatus Hydrogenisulfobacillus filiaventi” R50 gen. nov., sp., nov. which was characterized as a chemolithoautotrophic thermoacidophilic aerobic H2-oxidizing bacterium. This strain excretes about half of the fixed CO2 in the form of amino acids, which makes it a promising candidate for the industrial production of organic compounds from CO2, using H2 as energy source. H2 oxidation in this strain is facilitated by two [NiFe]-hydrogenases from the groups 1b and 1h, with the latter conferring high affinity toward H2 (Søndergaard et al., Kobayashi et al. engineered the acetogenic bacterium Moorella thermoacetica for enhanced acetate, ethanol and acetone production. They found that H2 supplementation under mixotrophic conditions increases NADH levels but can inhibit growth due to an unbalanced redox status. This study emphasized the role of a reversible electron-bifurcating group A3 [FeFe]-hydrogenase for balancing the cellular redox state. These observations may also be exploited for biohydrogen production by that strain. Another way to produce H2 was analyzed by Barahona et al.. In order to enhance nitrogenase-driven H2 production in Rhodobacter capsulatus, they used a sensory hydrogenase coupled to the production of a fluorescence signal. By inducing genome-wide mutations and using high-throughput fluorescence-activated cell sorting, they were able to generate mutants with elevated H2 evolution capabilities. Finally, Schumann et al. reviewed current state-of-the-art and future perspectives for efficient light-driven H2 production using phototrophic microorganisms. This technology potentially enables conversion of solar energy into a chemical compound that enables storage and transport. However, as discussed by the authors, extensive engineering is required for this technology to be efficient and scalable.Another four articles explore the application of hydrogenases. 2-based biologically green technologies.Taken together, the Research Topic advances our knowledge especially on the function and application of hydrogenases and provides important perspectives for future HSF: Writing—original draft, Writing—review and editing. CP: Writing—review and editing. FV: Writing—review and editing. CG: Writing—review and editing.


Metastasis and resistance to cancer therapeutics are critical barriers to curing cancer. This special issue entitled “Cancer Metastasis and Therapeutic Resistance” contains nine original contributions. The articles span a variety of human cancers, including breast, lung, brain, prostate, and skin and touch upon significant areas of interest such as cancer stem cell function, cancer immunology, and glycosylation. This special issue contains one review article by Kilmister et al., which touches on the important topic of cancer stem cells (CSC) . These sSriratanasak et al. also tackle important aspects of CSC regulation in a research article that examines the impact of cisplatin-induced senescence on lung cancer cells . TypicalThis issue had a significant set of original research, tackling different aspects of breast cancer. The article by Barutello et al. examines a combination of methods to target the cystine-glutamate antiporter xCT and p53 using the drug APR-246, which restores the wild-type function of p53 in mutant p53 tumors . FindingThe research article by Cheng et al. looks more distinctly at guanylate binding protein 5 (GBP5) and its expression in triple-negative breast cancer (TNBC) . This stPrior studies have shown that fucosylation, a type of glycosylation, promotes metastatic phenotypes and signaling in breast cancer cells ,10. DoudRhosin is a RhoGTPase RhoA/C-yes associated protein (YAP) pathway inhibitor . TsubakiPenas-Martínez et al. provided an interesting brief study about the effect of antithrombin (AT) on glioblastoma . RecentlSpine magnetic resonance imaging (MRI) can be typically used to guide treatment for vertebral metastasis. Pichon et al. aimed to improve imaging techniques for metastatic breast and medullary thyroid cancers with metastasis of the spine . The stuIuliani et al. contributed a brief report investigating the effect of an agent abiraterone (ABI), which is a selective inhibitor of androgen biosynthesis, on the osteoblast secretome . These sArticles in this special issue span many topics, all aimed to increase knowledge in the area of metastasis and therapeutic resistance. Common themes include areas of significance in understanding the CSC function as well as breast cancer biology. The overall aim of this issue is to provide a broad representation of research areas that examine mechanisms and approaches for confronting metastasis and the failure of cancer treatments.


Perrier et al. conducted NGS in six patients with leukodystrophy and described a range of pathogenic variants  of leukodystrophies. Ek et al. emphasized that a genome-wide analysis, with variant calling strategies extended to structural variants (SV) and short tandem repeat expansions (STRs) in addition to single nucleotide variants and small insertions/deletions (SNVs/INDELs), was critical to enhance diagnostic yield for neuromuscular disorders (NMDs). Corroborating literature review and genomic sequencing, Bar et al. identified 22 candidate genes for cyclic vomiting syndromes (CVS), which further suggests a cellular model of the disease mechanism.Next-generation sequencing (NGS) has propelled the diagnosis of neurological disorders, the discovery of new candidate disease loci, and precision therapy. He et al. performed whole-exome sequencing and Sanger sequencing in three patients with adrenomyeloneuropathy (AMN) and identified one known mutation (c.1415_1416delAG) and two novel ABCD1 variants (c.217C>T and c.160_170delACGCAGGAGGC) in the Chinese population, indicating the importance of ABCD1 gene analysis in the diagnosis of patients with spastic paraplegia. Zambrano et al. used NGS to describe two Ecuadorian siblings with muscular dystrophy and deafness who carried EMD and EYA4 mutations associated with phenotypes. Genotypes are also linked to clinical manifestations and laboratory tests. Yang et al. identified differences in serum ceruloplasmin levels correlated to the age of symptom onset and genotypes (ATP7B variant); the authors established the cutoff value (0.13 g/L) of serum ceruloplasmin levels for the diagnosis of Wilson disease (WD) in a Chinese cohort with high sensitivity and specificity. It is hoped that diagnosing and treating neurogenetic illnesses will become easier with the advancement of diagnostic methods.In studying several rare diseases of the nervous system, SM and CL prepared the original draft. BY, LY, and HS critically review and edit the manuscript. All authors have reviewed and approved of the final manuscript.


Jin  Despite the implementation of numerous weight loss initiatives by various governments, the global prevalence of obesity continues to rise . This noet al [et al [Since its rediscovery in adult humans, research into thermogenic fat has increased tremendously . This iset al  and Yadal [et al  now provet al [In the first study by Jin et al  VSG and et al . When thet al , again ret al [Firmicutes and decreased the fecal abundance of Bacteriodetes, associated with stabilization of the intestinal epithelial barrier. Mass spectrometry analysis then revealed that 3 metabolites were increased in the feces of VSG-operated mice: licoricidin, muramic acid, and 3-hydroxybutyryl carnitine. Moreover, fecal licoricidin not only negatively correlated with various gut microbiota known to promote metabolic disease, but circulating licoricidin levels were doubled in VSG-operated mice suggesting that it could communicate directly with subcutaneous white fat. To formally test if gut microbiota-derived products contribute to thermogenesis in subcutaneous white fat after VSG, mice were treated with a broad spectrum antibiotic cocktail via their drinking water for 2 weeks. Strikingly, this not only prevented the weight loss and metabolic benefits associated with VSG similar to a previous study in diet-induced obese mice [per se contributes to the activation of thermogenesis in subcutaneous white fat after VSG.Jin et al  then reaese mice , but it et al [Next, Jin et al  determinet al , 21 and et al , respectet al , are neeet al [et al [et al [et al [18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging experiments to determine if brown fat contributes to increased energy expenditure in mice receiving post-RYGB fecal microbiota. This revealed that brown fat 18F-FDG uptake in response to overnight cold exposure, the natural stimulus for brown fat, almost doubles in mice receiving post-RYGB feces compared with mice receiving pre-RYGB feces. Accordingly, brown fat UCP1 protein expression was also markedly enhanced.In the other study by Yadav et al  stool sal [et al  apart frl [et al  is that l [et al  found th18F-FDG uptake. This could have provided evidence that post-RYGB microbiota enhance blood glucose clearance in response to insulin treatment through using brown fat as a glucose sink. It would have also been interesting to determine if the patients themselves showed increased oxygen consumption and brown fat 18F-FDG uptake after RYGB, which would have provided the key evidence that this beneficial metabolic change in the host is potentially gut microbiota-mediated and is transmissable to germ-free mice.Considering that the post-RYGB feces-treated mice showed enhanced insulin sensitivity in the absence of any differences in body weight, it would have been interesting to determine if insulin increases brown fat et al performed metabolomic analyses of their feces. This revealed that thermogenic molecules like the short chain fatty acid butyrate [et al [Finally, after showing that differences in patient fecal microbiota after RYGB can be transferred to germ-free mice, such as an increase in Akkermansia municiphila, Yadav butyrate , 25 and butyrate  were incbutyrate  were redbutyrate . Considee [et al . It woulet al [et al [Figure 1). Notably, changes in bile acid metabolism by gut microbiota after VSG leads to the generation of cholic acid-7-sulfate in the liver and its accumulation in the gut [While we are witnessing the dawn of a new era for obesity pharmacotherapy with gut hormone preperations causing unprecendented levels of weight loss, bariatric surgery remains the most effective . The higet al  and Yadal [et al  are grou the gut , which h the gut . Thus, uet al [et al [The findings of Jin et al  and Yadal [et al  demonstrl [et al , and actl [et al .


This is a Research Topic on thoracic oncology. Thoracic malignancy is a term used to describe any cancer presented in organs, glands, or structures within the thoracic cavity. Lung cancer is the second most frequent malignancy after breast cancer, accounting for 2.21 million cases annually, and the leading cause of cancer mortality worldwide (1.8 million deaths) for women and men combined  inhibitor and is administered as first-line treatment to ALK-positive metastatic non-small cell lung adenocarcinoma patients. Xing et al., systematically reviewed the efficacy and safety of Brigatinib. Tyrosine kinase inhibitors is another type of lung cancer targeted treatment. Currently, mutation status is determined by examining lung tumor tissue biopsies. Hu et al., discuss the advances of PET/CT in establishing EGFR mutation status in lung cancer and their clinical significance.Better understanding of the disease has advanced and improved lung cancer treatment and clinical management. Patients may receive chemotherapy, radiotherapy, targeted therapy, immunotherapy, and surgery. Mizuno et al., discuss the current status and future perspectives of PD-1/PD-L1 immune checkpoint blockade in lung cancer. ICIs may cause immune-related adverse events. Hao et al., present the pathogenesis, risk factors, and clinical presentation of immune checkpoint inhibitor-related pneumonitis. Non-small cell lung cancer patients with mutations on the MET pathway present poor clinical outcomes. The development of targeted tyrosine kinase inhibitors and bispecific antibodies for MET genetic alterations have benefited this cohort of patients. Michaels and Bestvina discuss the evolution and current state of MET selective therapy. Surgery remains the first-line treatment for early stage lung cancer patients with resectable tumors. The surgical methods have developed resulting to smaller surgical traumas, fewer complications, and quicker post-operational recovery periods. Fuzhi et al., outline the importance of evaluating pulmonary function in individuals who have undergone surgery for lung cancer, as well as the alterations in pulmonary function that occur after surgery. Additionally, they discuss strategies for effective rehabilitation of pulmonary function and factors that may affect the success of such rehabilitation.The introduction of immune checkpoint inhibitors (ICI) revolutionized cancer treatment and extended survival. However, not all patients respond to ICI therapy and benefit in terms of survival. It is still not clear which is the cohort of patients that would benefit the most. Addala et al., 2022; Zhao et al., 2022). Parotid and gastric metastases for patients with lung cancer are rare and thus not very well studied. Wang et al., and Tang et al., present two reviews on primary lung cancer with parotid and gastric metastases.Metastasis is a major factor that leads to mortality, and approximately 90% of cancer deaths are attributed to metastases. Malignant pleural effusion (MPE) is a common clinical problem for patients with lung cancer. The conduction of large-scale randomized clinical trials advanced diagnosis and clinical management. However, treatment focuses on symptom relief and control of fluid accumulation (Boulanger et al., reviewed the connection between financial toxicity, quality of life, and survival in high value care.Financial toxicity refers to the adverse impact of cancer treatment expenses on a patient’s quality of life. Lung cancer survivors often experience a rise in unemployment, psychological stress and a decrease in wages, indicating the persistent impact of financial toxicity. Carcinogen derived thoracic cancers including lung and oesophageal are amongst the most frequently diagnosed malignancies worldwide. Despite advances like the introduction of ICIs the clinical management of these patients remains challenging. Endotyping of lung cancer patients in combination with targeted treatments has improved survival. Metastases are common and more studies are necessary to understand the underlying biology. Finally, the effect of cancer on the financial sustainability and stability of patients is an important factor we need to investigate and gather more data.The author confirms being the sole contributor of this work and has approved it for publication.


Wu H. et al., Wu H.-N. et al., Li et al.).Multidrug-resistant (MDR) microbes infection for critically ill patients is a big challenge in clinical practice and is associated with greatly increased mortality . This ReWu H.-N. et al. retrospectively analyzed the distribution and antibiotic resistance of pathogens based on the clinical data of intensive care patients with bloodstream infections presented to a Chinese tertiary hospital and explored the value of procalcitonin (PCT) for the differentiated diagnosis of bloodstream infections caused by various pathogens. Gram-negative bacteria were the most frequently isolated microorganisms and were associated with a higher percentage of complications such as brain dysfunction, acute kidney injury, and thrombocytopenia. It was observed that PCT was a not good biomarker to distinguish bloodstream infections caused by various pathogens or fungi. Given that the mortality for patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection is reported to be as high as 30%−70%, Wu H. et al. used a logistic analysis to assess the association between the neutrophil-to-lymphocyte ratio (NLR) on 4th-day and 28th-day mortality. After balancing the confounders, NLR on the 4th day was associated with the 28th-day mortality, whereas the appropriate initial therapy was an independent protective factor. Moreover, the authors suggested that the trend of the NLR during therapy may help to evaluate the efficacy of different anti-infection therapy strategies at an early stage. In another article, Li et al. described their experience in the management of post-neurosurgical central nervous system infection caused by MDR Gram-negative bacteria with combined intraventricular and intravenous polymyxin B administration. After a mean duration of 14 days of treatment, all six cases caused by CRKP or carbapenem-resistant Acinetobacter baumannii (CRAB) were cured and no obvious kidney injury occurred.Karlsson et al., Yoon et al., Casarotta et al.). Yoon et al. demonstrated that bacterial superinfections were common in a tertiary Korean academic hospital and that more than one-third of the bacterial superinfection cases were caused by multidrug-resistant pathogens. Moreover, bacterial superinfection was associated with significantly fewer ventilator-free days, longer ICU and hospital stays. As many studies reported that a CRAB-associated bloodstream infection was the crucial risk factor for death in patients with COVID-19 . In a prospective longitudinal study in Sweden conducted by Karlsson et al., the authors evaluated the complicated bacteriuria and antibiotic resistance for ICU-admitted COVID-19 patients. They found that the vast majority of patients received antibiotics on ICU admission. Longer stays in ICUs linearly correlated with bacteriuria, and the authors proposed that biofilms in urinary catheters act as a reservoir of pathogenic bacteria with the potential to develop and disseminate antibiotic resistance.This Research Topic also includes three articles on the superinfection of patients with SARS-CoV-2 infection who were admitted to the ICU  study, given that CPR scenarios are at high risk for healthcare-associated infections. By studying Advanced Cardiovascular Life Support (ACLS) courses in a manikin simulation, they found more than half of hand-cleaning indications could have been accomplished without delaying patient resuscitation and they concluded that hand disinfection can be implemented without compromising quality in acute care. In patients with severe acute pancreatitis (SAP), secondary MDR pathogen infection plays a vital role in increased mortality and prolonged hospital and ICU stays  to enhance the resolution of late-phase organizing pneumonia caused by CRKP. Organizing pneumonia is a pattern of lung-tissue repair after injury and it can be cryptogenic or a response to a specific lung injury in many diverse clinical contexts. Given the therapy for organizing pneumonia is empirical and few therapies have been confirmed besides systemic glucocorticoid therapy (This Research Topic also includes an original study by  therapy , they deQL: Writing—original draft. S-JZ: Writing—review and editing. J-CZ: Writing—original draft, Writing—review and editing.


Methodological advancements have played a pivotal role in driving progress within the field of biomedicine. A striking illustration of this trend is the groundbreaking discovery of the CRISPR/Cas9 technology by Emmanuelle Charpentier and Jennifer A. Doudna in 2012, a feat that earned them the Nobel Prize in Chemistry in 2020. This innovation, which facilitates precise gene editing, has revolutionized the capability to incorporate gene sequences into genomes with an unprecedented level of accuracy and efficiency (Jinek et al., Streptococcus pyogenes. Within this context, Charpentier uncovered an entirely novel molecule, tracrRNA, which constitutes a crucial component of the bacterium's innate defense mechanism aimed at neutralizing viruses by cleaving their DNA strands (Deltcheva et al., The genesis of the CRISPR/Cas9 technology emerged unexpectedly from investigations into Consequently, the CRISPR/Cas9 technology has emerged as a cornerstone of modern biotechnology over the past decade. Its global utilization across bioscience domains underscores its impact and significance, and it applications have extended far into the field of clinical neurosciences. So far, CRISPR/Cas9 has inseminated Cellular Neuropathology in the following ways:Treating Genetic Disorders: CRISPR/Cas9 technology holds promise for treating genetic disorders in the nervous system. Researchers have been exploring its potential for correcting mutations associated with neurodegenerative diseases such as Huntington's disease (Morelli et al., Modeling Neurological Disorders: CRISPR/Cas9 has been used to generate cellular and animal models of various neurological disorders. This allows scientists to study disease mechanisms more accurately, potentially leading to insights into the underlying causes of disorders like Alzheimer's disease (Schrauben et al., Understanding Neurodevelopment: By precisely manipulating genes in developing organisms, researchers have been able to uncover the roles of specific genes in brain development (Zhang et al., Functional Genomics: CRISPR/Cas9 technology has enabled scientists to perform large-scale functional genomics studies in neural cells (Sandberg et al., Pain Management: Researchers have explored the use of CRISPR/Cas9 technology to modulate pain perception by targeting specific genes involved in pain pathways (Reese et al., Gene Therapies for Neurological Disorders: CRISPR/Cas9-based gene therapies have shown promise in preclinical studies for various neurological disorders (Ou et al., Regenerative Medicine: CRISPR/Cas9 technology has been investigated for promoting neuronal regeneration after CNS injuries (Keatinge et al., It is important to note that while CRISPR/Cas9 technology holds immense potential, there are also challenges to overcome, including off-target effects, delivery methods, and the need for rigorous safety assessments before any clinical applications can be more widely adopted. The use of CRISPR/Cas9 in clinical neuroscience has also brought about important ethical discussions. Ensuring the safety and specificity of gene editing techniques in the complex and delicate nervous system is a critical consideration.in vitro and in vivo. With this Research Topic, we would like to expand current knowledge in the field functional genomics and gain further insight into neurodevelopmental disorders. This Research Topic is open for all disease areas. Papers outlining limitations and challenges of CRISPR/Cas9 technologies are particularly invited. In this search for the best ideas and concepts, Original research, Reviews, Perspectives and Opinions are envisaged. Papers will be reviewed based on excellence, originality and innovation potential. Outstanding papers will be featured in an editorial. We are looking forward to your contributions to this new Research Topic.In an effort to identify the most promising concepts in translational neurosciences, the Cellular Neuropathology section of Frontiers in Cellular Neurosciences recently launched a platform, the Hot Topics hub Hermann, . Within DH: Conceptualization, Investigation, Writing—original draft, Writing—review and editing.