The solar atmosphere is full of complicated transients manifesting the reconfiguration of the solar magnetic field and plasma. Solar jets represent collimated, beam-like plasma ejections; they are ubiquitous in the solar atmosphere and important for our understanding of solar activities at different scales, the magnetic reconnection process, particle acceleration, coronal heating, solar wind acceleration, as well as other related phenomena. Recent high-spatio-temporal-resolution, wide-temperature coverage and spectroscopic and stereoscopic observations taken by ground-based and space-borne solar telescopes have revealed many valuable new clues to restrict the development of theoretical models. This review aims at providing the reader with the main observational characteristics of solar jets, physical interpretations and models, as well as unsolved outstanding questions in future studies. Although these jet activities are observed at different scales and temperature ranges, they can be viewed as the same type of solar jets owing to their similar observational characteristics and generation mechanism, i.e. magnetic reconnection-dominated jet-like activities with an inverted-Y structure. For smaller, lower-energy jet-like activities such as spicules and dynamic fibrils, their generation mechanisms are still open questions. Previous studies have suggested that spicules and dynamic fibrils are possibly launched by upward-propagating shocked pressure-driven waves leaking from the photosphere ,11. Howeα telescopes and a few low-resolution space instruments such as Skylab (1991–2001) and SMM (1980–1989). Solar jets have been studied intensively since the 1990s owing to the launch of a series of space telescopes, including the Yohkoh satellite [Solar and Heliospheric Observatory [SOHO; 1995 to now), the Transition Region and Coronal Explorer [TRACE; 1998–2010), the Reuven Ramaty High Energy Solar Spectroscopic Imager [RHESSI; 2002–2018), the Hinode [Solar Terrestrial Relations Observatory [STEREO; 2006 to now), the Solar Dynamics Observatory [SDO; 2010 to now) and the Interface Region Imaging Spectrograph [IRIS; 2013 to now). Also, more and more ground-based large-aperture solar telescopes have been put into routine observation; for example, the Swedish Solar Telescope [The observation of solar jets dates back to the 1940s; they were dubbed surges in history . At the atellite , the Solervatory  α jets, extreme ultraviolet (EUV) jets and X-ray jets, depending on different observing wavebands. Nevertheless, since solar jets are often observed simultaneously at different wavebands covering a wide temperature range, and they can occur in all types of solar regions, it seems that the above classification methods are not very reasonable if one considers the physical properties and morphologies.Solar jets are generally described as collimated, beam-like ejecting plasma flows along straight or slightly oblique magnetic field lines. Because of the huge improvement in observing capabilities, solar jets can be imaged in a wide temperature range from the photosphere to the outer corona. According to different classification methods, solar jets were classified into different types in history. Firstly, solar jets were divided into photospheric jets, chromospheric jets (or surges), transition region jets, coronal jets and white-light jets, based on the temperature of the atmosphere in which they occur. Secondly, they were classified as coronal hole jets, active region jets and quiet-Sun region jets, based on regions where they occur. Thirdly, they were classified as Het al. [λ types, in which an inverted-Y (λ)-type jet was commonly interpreted as a small-scale magnetic bipole reconnecting with the ambient open coronal magnetic fields around the bipole top (footpoint). Hence, the different shapes could possibly be used to distinguish the reconnection sites in solar jets [Based on morphology, Shibata et al.  classifiet al. –49. Receet al. , which cet al. –60. A falar jets .Figure et al. [et al. [et al. [et al. [et al. [et al. [Moore et al.  classifi [et al.  found th [et al. . Sterlin [et al.  studied  [et al.  further  [et al.  to deter [et al. –68 they  [et al. ,69–84. R [et al. ,49,85,86 [et al. .Figure (b)It have been demonstrated that solar jets are launched from various pre-eruption structures, including satellite sunspots , mini-filaments, coronal bright points and mini-sigmoids. Observationally, these structures can be regarded as the progenitor of solar jets, and studying them can contribute to the prediction of the occurrence and evolution characteristics of solar jets.In the photosphere, satellite sunspots can be considered as a conspicuous progenitor for surges or many active region coronal jets. Rust  reportedet al. [Mini-filaments in the chromosphere and the corona can be recognized as an important progenitor for producing coronal jets. Mini-filaments were found to be eruptive in nature, and their eruption characteristics are similar to those evidenced in large-scale filament eruptions . Severalet al. ,69 studiet al. –84,97,98et al. ,65,99.et al. [Solar jets are frequently observed to be ejected from coronal bright points and micro-sigmoids. Coronal bright points represent a set of small-scale low-corona loops with enhanced emission in the EUV and X-ray spectra ,101, andet al.  found thHinode X-ray observations, Raouafi et al. [et al. [A coronal sigmoid consists of many differently oriented loops that all together form two opposite J-shaped bundles or an overall S-shaped structure , which ii et al.  identifi [et al.  reported [et al. .(c)(i)α images as a surge and in EUV or soft X-ray images as a coronal jet [et al. [α bright jet-like features. Jiang et al. [α component had a smaller size than the larger, hot one, and the former moved along the edges of the latter.Sometimes, cool and hot plasma flows can be identified simultaneously in a single jet. The co-existing cool and hot components can be observed in EUV images, or separately appear in Honal jet ,115–117.onal jet –120. Theonal jet , althougonal jet . Neverthonal jet ,124. Par [et al.  reportedet al. [Yohkoh X-ray data. Since solar jets can occur repeatedly from the same source region, and their lifetimes are usually of 40 min or less according to high-resolution observations, the 2 h time interval seems too long for a single jet. Hence, the cool surge and the hot X-ray jet in Zhang et al. [The cool component in a jet often appears a few minutes after the corresponding hot one ,125–127.a et al.  observeda et al. . This abg et al.  were verd5), several works have provided evidence that the cool component of jets is directly formed by the erupting mini-filaments confined within the jet base [et al. [The different spatial relationships can possibly be reconciled by considering the projection effect. In principle, observational results suggested that the two components are along different magnetic field lines and dynamically connected. Therefore, their spatial relationship should not be co-spatial but adjacent to each other. The co-spatial case can be expected when the two components overlap each other along the line of sight. For the delayed appearance of the cool component, one can understand it based on the formation mechanism of solar jets. Previously, the delayed appearance of the cool component was explained as the cooling of the earlier, hotter one ,117,125,figure 2jet base ,109,131. [et al. ,63,69, a [et al. ,109,131.(ii)et al. [H filtergram of the Hinode/Solar Optical Telescope (SOT), whose typical lifetime, size and intensity enhancement relative to the background are about 20–60 seconds, 0.3–1.5 Mm and 30%, respectively. Plasmoids have a multi-thermal (1.4–3.4 MK) structure with a number density in the range of IRIS, whose average size is about 0.57 Mm, and their ejecting speed ranges from 10 to 220 km s−1 [Supported by various observational indications , it has et al.  observed010 cm−3 ,133,134.0 km s−1 . Besides0 km s−1 ,136–139,0 km s−1   instability. According to this study, the observed discrete high-density features in solar jets could be either plasmoids or vortex structures at different wavebands. In 3D simulations, plasmoids were evidenced as twisted flux ropes resembling the shape of solenoids, and they are most likely formed as a result of the resistive tearing-mode instabilities in the current sheets located between closed and open fields [et al. [Numerical experiments also revealed the appearance of plasmoids in solar jets. Yokoyama & Shibata ,140 perfn fields ,145. Wyp [et al.  pointed (iii)KH instability is a basic physical process that occurs when there is velocity shear in a single continuous fluid, or when there is a velocity difference across the interface between two fluids . Recent IRIS observations, Li et al. [α observations taken by the NVST, Yuan et al. [Vortex structures caused by KH instability can be regarded as a basic fine structure of solar jets, which were frequently observed within or at the outer edges of solar jets ,155. Usii et al.  reportedn et al.  studied et al. [Theoretical and numerical works were performed to study the KH instability in rotating solar jets. Zaqarashvili et al.  found th(d)(i)Yohkoh soft X-ray observations, Shimojo et al. [5  the distribution of the lifetimes is a power law with an index of about 1.2; (v) most active region jets are observed to the west of the active regions; (vi) 76% of jets show constant or converging spires whose widths get narrower from the photosphere to the corona, and their intensity distribution often shows an exponential decrease with distance from the footpoints. In a subsequent paper [9 cm−3 with an average value of Hinode [−1, 5 × 104 km, 8 × 103 km and 10 min, respectively. In addition, the velocities of the transverse motions perpendicular to the jet axis ranged from Based on o et al.  describent paper , they fue Hinode . The autH broadband filter observations taken by the Hinode/SOT, Nishizuka et al. [Using Ca II a et al.  made a sa et al. . Differea et al. ,16 and da et al. , chromoset al. [STEREO observations; they found that the appearance of EUV jets is always correlated with small-scale chromospheric bright points. The typical lifetimes of the studied EUV jets are 20 (30) min at 171 (304) Å, while those of the white-light jets observed in coronagraphs peak at around 70–80 min. It was found that the speeds were 400 and 270 km s−1 for the hot 171 Å and cool 304 Å components, respectively. The speeds measured from 171 Å observations are comparable to those derived from coronagraph observations (390 km s−1). Mulay et al. [SDO; their results indicated that the lifetimes and velocities are in the ranges of 5–39 min and −1, respectively. Typically, all the studied jets were co-temporally associated with Hα jets and non-thermal type III radio bursts, and 50% (30%) of the events in their samples originated in the regions of flux cancellation (emergence). Other similar statistical studies based on STEREO and SDO observations can also be found in the literature [SOHO, the speeds of jets at the solar minimum of activity are in the range of 400–1100 km s−1 for the leading edge and 250 km s−1 for the bulk of their material, while the typical speeds at the maximum of activity are around 600 km s−1 [et al. [−1, respectively.Nisticò et al.  performey et al.  studied terature ,163. In 0 km s−1 ,165. In  [et al.  carried (ii)et al. [α spectral observations. With the improvements in the quality of imaging and spectral observations, rotating motion was widely observed in Hα surges [Rotating motion is a typical dynamic characteristic of solar jets. Earlier observations demonstrated the appearance of rotating motion in prominences like a tornado –169, andet al.  detectedα surges ,178,179,α surges ,180,181 α surges ,183. Somα surges ,174,184,α surges . In suchα surges ,88,179.STEREO imaged the fine helical structure of the rotating jets, which exhibited different morphologies when they were observed from different viewing angles [STEREO observations indicated that at least half of EUV jets exhibited a helical magnetic field structure [SDO data, Shen et al. [et al. [Stereoscopic observations taken by g angles . A statitructure . Using tn et al.  studied  [et al. ,186 foun [et al. –190, and [et al. ,191,192.et al. [−1, respectively. Cheung et al. [−1, and the magnetic twists needed for the helical jets were found to be supplied by emerging current-carrying magnetic fields et al. [et al. [−1) and fast (20 km s−1) lateral expansions in an X-ray jet, in which the slow expanding stage was explained as the loop escaping from the anti-parallel magnetic field, while the fast stage corresponded to the whip-like motion of the reconnected field lines. By contrast, Chandrashekhar et al. [−1) and fast (135 km s−1) expanding motions of loop systems were also observed in small chromospheric anemone jets [Lateral expansion is a typical characteristic of solar jets, which manifests as the whip-like upward motion of the newly formed field lines ,129. Theet al.  found th [et al.  reportedr et al.  proposedone jets , in whicet al. [−1), fast (25 km s−1) and constant stages. Both the slow and fast expansion stages lasted for about 12 min, and the jet kept a constant width of about 4 × 104 km during the constant stage (a–f ). The fast transition from the slow to the fast expansion stage was explained as the sudden acceleration of the magnetic reconnection between the emerging arch and the ambient open field. In other words, the slow expansion stage corresponded to the emerging period of the arch, during which its reconnection with the ambient open field was slow, while the fast expansion stage manifested as the impulsive reconnection between the two magnetic systems. The constant stage indicated the full opening of the closed arch and the end of the twist transfer into the open fields, and its width corresponded to the distance between the footpoints of the open field line and the remote footpoint of the closed arch. In a statistical study [Shen et al.  reportednt stage a–f . Theal study , the autg). Cirtain et al. [et al. [et al. [Transverse oscillation is another distinct characteristic of solar jets g. Cirtain et al.  proposedn et al. , Morton  [et al.  estimater et al.  estimate00–536 s ,201–203,00–536 s ,88.. 3(a)Coronal plumes are thin ray-like structures that are pervasive within polar and equatorial coronal holes, as well as quiet-Sun regions –206; theet al. [et al. [Lites et al.  observedet al. . Raouafi [et al.  studied  [et al.  further (b)Solar jets are tightly associated with filaments. On the one hand, as has been discussed in §§et al. [et al. [et al. [Luna et al.  reportedet al. . A simil [et al. , in whic [et al.  reported [et al. ; it was  [et al. ,219. It et al. [et al. [et al. [et al. [Solar jets not only supply sufficient mass for filament formation but also cause the instability and eruption of large-scale filaments. Zirin  reportedet al.  reported [et al.  studied  [et al. ,222. All [et al.  reported [et al.  found th(c)et al. [et al. [et al. [Solar jets are closely related to magnetohydrodynamic (MHD) waves. Observational studies indicated that solar jets can act as a driver to excite torsion Alfvén waves in themselves ° or less are typically associated with solar jets [a), but also standard broad CMEs with a typical three-part structure [b).CMEs represent large-scale plasma and magnetic fields being released from the Sun into the interplanetary space –237. CMElar jets . Observalar jets  3He/4He ratios and high ionization states and tightly correlated with type III radio bursts [Solar energetic particles (SEPs) carry important information about the particle energization inside the solar corona, as well as the properties of the acceleration volume. SEP events are divided into ‘gradual’ and ‘impulsive’ types. Gradual SEP events are long-lasting, intense, more closely correlated with CMEs and characterized by the abundances and charge states of the solar wind. Therefore, they are thought to be accelerated by CME-driven coronal/interplanetary shock waves. By contrast, impulsive SEP events are short lived, less intense, closely related to flaring active regions, characterized by high o bursts .et al. [3He-rich events and found that their sources lie close to coronal holes and are characterized by jet-like ejections along Earth-directed open field lines. Some studies suggested that impulsive SEP events are associated with narrow jet-like CMEs [et al. [3He-rich SEPs were also observed to be associated with helical jets [Flaring regions accompanied by solar jets are found to be the most possible candidate solar source for producing impulsive SEP events , since tet al.  investigike CMEs –266. Nit [et al.  found thcal jets , and thecal jets ,266,268,cal jets  and sunscal jets ,271.ne is the electron number density) by the Langmuir waves generated by the electron beam instabilities [et al. [A type III radio burst is an important diagnostic tool for SEPs. It is a signature of propagating non-thermal electron beams in a wide range of heights of the solar atmosphere (from the low corona to the interplanetary space), and is excited at the fundamental and second harmonic of the local electron plasma frequency −1 for slow and fast solar winds [The problems of coronal heating and the acceleration of solar wind are two highly controversial topics in solar physics. Since energy must come from the solar interior, it is hard to understand why the coronal temperature is far hotter than the solar surface. The problem is primarily concerned with how energy is continuously transported up into the corona through non-thermal processes from the solar interior and then converted into heat within a few solar radii. In the last half-century, many coronal heating theories have been proposed, but two theories have remained as the most likely candidates: wave heating and magnetic reconnection . The solar winds . Previouar winds . Recent ar winds .−1, whose energy and mass can satisfy the power (6 × 1027 erg s−1) and mass flux (2 × 1012g~s−1) requirements of the corona and solar wind if one assumes a birth rate of 24 events per second over the whole Sun [et al. [et al. [Ultraviolet spectrum observations have revealed prevalent high-energy jets in the corona at an average speed of 400 km sscenario . The onescenario ; this sha et al.  found tha et al. ,153.Figet al. [−1) and the other is near the speed of sound (approx. 200 km s−1). The authors claimed that a large number of X-ray jets with high velocities may contribute to high-speed solar wind. McIntosh et al. [et al. [et al. [et al. [IRIS observations also reveled the prevalence of small-scale jets from the networks of the solar transition region and chromosphere [−1. They were thought to be an intermittent but persistent source of mass and energy for solar wind.Alfvén waves, which propagate along magnetic field lines over large distances and transport magneto-convective energy from near the photosphere into the corona, have been invoked as a possible candidate to heat coronal plasma to millions of degrees and to accelerate the solar wind to hundreds of kilometres per second. Transverse oscillations of spicular jets were regarded as the presence or passage of Alfvén waves; the energy carried by these Alfvén waves was found to be enough to accelerate solar wind and to heat the quiet corona –288. Ciret al.  detectedh et al.  found th [et al.  found tw [et al.  and Thre [et al. ). Recent−1 at heliocentric distances of a few solar radii. These observational facts may imply that the moving jets have been incorporated into the ambient solar wind [et al. [−1; they found a ubiquitous presence in polar coronal regions at about 100-fold mass and energy greater than the coronal response itself. This suggests that the primary acceleration of the solar wind should induce the dissipation of high-speed solar jets [For big jets that often reach up to a few solar radii and can be observed as white-light jets or jet-like CMEs, their contribution to solar wind often exhibits as microstreams or speed enhancements ,293–295.lar wind ,241. Yu  [et al.  found thlar jets .. 4With the unceasing improvement of solar telescopes and numerical modelling, the physical interpretation of solar jets has achieved significant progress in recent years. In theoretical studies, the mechanism of flux emergence and the onset of instability or loss of equilibrium were investigated in detail, in which the slingshot effect, untwisting and chromospheric evaporation were considered as the possible acceleration mechanisms . As more(a)et al. [et al. [α surges are generated by magnetic reconnection between emerging fluxes and ambient pre-existing magnetic fields et al. [et al. [Pariat et al.  proposedet al. , the helet al. ,63,180 aet al. ,199. It et al. . In such [et al.  found th [et al. , plasma  [et al. , gravity [et al.  and the  [et al. . In addi [et al.  and the  [et al. , microst [et al.  were als(c)The magnetic breakout model was originally proposed to interpret the initiation of large-scale CMEs, in which magnetic reconnection between the unsheared field and neighbouring flux systems decreases the amount of the overlying field and, thereby, allows the low-lying sheared flux to break out . So far,et al. [Recently, high-resolution observational and statistical studies suggested that all coronal jets are probably driven by mini-filament eruptions, and they share many common characteristics with large-scale eruptions. Therefore, coronal jets are proposed to be the miniature version of large-scale eruptions ,186,247.et al.  performeet al. , and theet al. –321.Fig(d)To obtain realistic numerical results that are more comparable to real observations, some works managed to use multi-wavelength observations in tandem with MHD simulations to investigate the formation and evolution of solar jets. Such simulations are known as data-driven models, which use continuously time-varying solar observations as the input to reproduce solar jets. By contrast, if one use only an instantaneous cadence of observation as the input, it should be called data-constrained modelling.et al. [Jiang et al.  simulateet al. ,301. In et al. [Using an extrapolated non-force-free magnetic field as the initial condition, Nayak et al.  performeet al.  and the et al. .et al. [et al. [Cheung et al.  presenteet al.  to carry [et al.  presente(e)Most previous simulations were performed within small numerical domains in Cartesian geometry to study the generation mechanism and evolution process. So far, only a few publications have considered a large simulation domain extension to the interplanetary space using spherical geometry to investigate the interplanetary effects caused by solar jets.et al. [et al. [Török et al.  and Lion [et al.  performen models . A whiteet al. [in situ in the solar wind. Using another code that employs Alfvén wave dissipation to produce a realistic solar wind background, Szente et al. [et al. [° in latitude and out to To investigate the influence of solar jets on the solar wind, Karpen et al.  extendedet al.  by inclue et al.  studied  [et al.  was gene results ,298, the. 5High-spatio-temporal-resolution imaging and spectroscopic and stereoscopic observations covering a wide temperature range over the last several decades have significantly improved our understanding of solar jets, including various aspects such as their triggering, formation, evolution, fine structure, relationships with other solar eruptive activities, and their possible contribution to the coronal heating and acceleration of solar wind. Nowadays, we recognize that the basic energy release mechanism in solar jets is magnetic reconnection; they are triggered by photospheric magnetic activities exhibiting as flux–flux cancellations and shearing motions of opposite polarities, and are accelerated alone or in combination by possible mechanisms of untwisting, chromospheric evaporation and slingshot effects. Observationally, solar jets can be divided into eruptive jets and confined jets, or straight anemone jets and two-sided-loop jets; they can evolve from different progenitors including satellite sunspots , mini-filaments, coronal bright points and mini-sigmoids; they can exhibit various fine structures including cool and hot components, plasmoids and KH vortex structures; and they can show interesting rotating and transverse oscillation motions. Solar jets not only provide the necessary mass and energy to the corona and solar wind, triggering other eruptive phenomena such as EUV waves, filament and loop oscillations and CMEs, but also significantly affect the interplanetary space through launching CMEs and energetic particles. Among the new knowledge that we have gained in recent years is that solar jets are often driven by mini-filament eruptions in association with photospheric magnetic flux cancellations; in addition to narrow white-light jets, broad CMEs with typical three-part structures and simultaneous paired narrow and broad CMEs are found to be dynamically associated with solar jets. These findings lead to an important conclusion that solar jets may represent the miniature version of large-scale solar eruptions, and they probably hint at a scale invariance of solar eruptions. In this sense, investigating solar jets can provide important clues to understanding complicated large-scale solar eruptions (e.g. CMEs) and currently indistinguishable small-scale transients (e.g. spicules).Numerical modelling of solar jets has also achieved many significant advances in recent years. MHD models of solar jets have been developed from one to three dimensions with different scenarios such as the emerging-reconnection and onset of instability mechanisms, which can be applied to interpret the formation, evolution, morphology and plasma properties of standard and blowout jets in coronal holes and active regions. Recently, some numerical works have further considered the effects of heat conduction, radiative losses and background heating, and more realistic data-constrained and data-driven MHD simulations are being developed to understand solar jets. These great efforts make the obtained numerical results more morphologically and quantifiably comparable to real observations. In addition, numerical works that consider a large domain extension to the interplanetary space using spherical geometry are also being developed to aid our understanding of the interplanetary disturbances resulting from solar jets.Observations have shown that solar jets are tightly associated with magnetic flux cancellation, especially in mini-filament-driven jets. Nevertheless, what kind of physical process takes place during the triggering stage is still unclear. Physically, flux cancellation represents three possible processes: emergence of U-shaped loops, submergence of Ω-shaped loops and reconnection in the magnetogram layer . TherefoObservational studies have indicated that solar jets not only cause narrow white-light jets in the outer corona, but they can also result in broad CMEs with a typical three-part structure. Sometimes, a single mini-filament-driven jet can cause a pair of simultaneous narrow and broad CMEs . Narrow Although more and more observational studies have shown the similarity between small-scale solar jets and large-scale filament/CME eruptions, the possible scale invariance of solar eruptions should be further tested theoretically and observationally. It should be made a priority to check whether the current jet models can be applied to small-scale explosions such as spicules and nano-flares, which are believed to be important for coronal heating. On the other hand, it is also important to check if the current jet models are suitable for explaining complicated large-scale solar eruptions and astrophysical jets.The contribution of solar jets to coronal heating and to the formation and acceleration of solar wind as well as the jet-associated acceleration mechanism of SEPs should be investigated in depth. There are too many assumptions and uncertainties in the existing studies on these topics.Most of the current MHD simulations only deal with idealized boundary and initial conditions using a relatively small numerical domain. Future investigations should consider more realistic data-constrained and data-driven MHD simulations, using a large simulation domain so that one can study the interplanetary disturbances caused by solar jets.Despite the great advances achieved in previous observational and numerical studies, there are still many aspects of solar jets that deserve further investigation. The following is a list of some outstanding questions.Parker Solar Probe , launch Orbiter , launche Orbiter , which iy (ASO-S ), which Click here for additional data file.


The WHO has identified vaccine hesitancy as one of the 10 threats to global health. One of the biggest causes of vaccine hesitancy is an inaccurate understanding of infectious diseases and vaccines. Currently, a new strain of coronavirus has spread around the world. People have a great fear of new coronavirus infections. A protective vaccine against coronavirus would be widely well received, even if there are inevitable severe or unknown adverse reactions. Awareness of various kinds of infectious diseases, preventive behavior against infectious diseases including vaccination, and various kinds of bias towards the recognition of infectious diseases and vaccines might be a potential focus.Dr. Foteini Malli et al.  presenteDr. Adam Palanica et al.  examinedDr. Abanoub Riad et al.  conducteDr. Georgios Marinos et al.  conducteDr. Elham Kateeb et al.  assessedDr. Abanoub Riad et al.  investigDr. Yen-Ju Lin et al.  comparedThe editor believes that these findings will provide a rationale for more effective dissemination of vaccines against COVID-19 and hopes that this Special Issue “Human Consciousness and Behavior towards Infectious Diseases and Vaccines 2.0” will contribute to the improvement of health of people around the world.


Microsurgical anatomy is not only the backbone for neurosurgical operations, but also for technological innovations, novel surgical techniques, a better understanding of the etiopathogenesis of pathologies, and translational medicine from neuroscience to daily clinical practice.The overarching goal of this Special Issue was to build a bridge between research and patient care studies and to bring neuroscientists and clinicians together.This Special Issue contains 16 individual papers that are categorized into research laboratory investigations; clinical case series, including those of the brain and spine regarding updated intraoperative technologies; novel neurosurgical tenets; and molecular anatomy.Wysiadecki et al.  contribuThe article published by Poblete et al. , simplifAnterior petrosectomy provides excellent exposure to the petroclival region, but its related morbidity is non-negligible. The paper published by Flores-Justa et al.  notes saThe article published by Çevik et al.  examinesGöksu et al.  publisheThe paper published by Kim et al.  is a cliRevascularization procedures are considered to be the most effective treatment modality that can be implemented to diminish the risk of intracranial hemorrhages in hemorrhagic moyamoya disease. On the other hand, delayed anastomotic occlusion is a common long-term complication after direct vascularization procedures. In the article published by Chen et al. , the autExtreme lateral interbody fusion (XLIF) has become a standard technique for the fusion of the thoracic and lumbar spine . It is aThe article published by Pojskić et al.  is a proThe paper “Do Orthopedic Surgeons or Neurosurgeons Detect More Hip Disorders in Patients with Hip-Spine Syndrome? A Nationwide Database Study” by Yin et al.  pointed Soldozy et al.  systemic“Spontaneous Resolution of Late-Onset, Symptomatic Fluid Collection Localized in the Meningioma Resection Cavity: A Case Report and Suggestion of Possible Pathogenesis” is the contribution by Kim et al. . The autTranscranial MR-guided focused ultrasound has been adopted as a noninvasive ablative procedure for the treatment of movement disorders and psychiatric disorders . Additio“Common Challenges and Solutions Associated with the Preparation of Silicone-Injected Human Head and Neck Vessels for Anatomical Study”, the article in this Special Issue published by Çırak et al. , reportsSince the beginning of this century, the portion of the central nervous system that is associated with lymphatics has gained popularity after the proven existence and functionality of the lymphatic structures for cleaning waste products from cerebrospinal fluid in animal studies . Animal


That O. setnai was recovered as the sister group of all other ricefishes in a molecular phylogenetic analysis with high branch support, therefore, is not surprising and possibly reflects a long branch attraction artefact et al. co dataset , in whicO. setnai, Yamahira et al. [To explain the exceptionally long branch of a et al.  invoked . 4Lithopoecilus brouweri, a fossil of Miocene age from Sulawesi described by de Beaufort [Oryzias and the Sulawesi endemic Adrianichthys. Like Rosen [et al. [Lithopoecilus to calibrate the internal node between Oryzias sarasinorum and Oryzias eversi, citing Horoiwa et al. [Lithopoecilus to represent the last common ancestor of these two recent species without any supporting evidence. Its use for calibration of this internal node is unfounded.The authors employed three fossil calibrations including †Beaufort  as interke Rosen , Parentike Rosen  included [et al.  used †Lia et al. . The latIn conclusion, the ‘out-of-India' dispersal hypothesis to explain modern ricefish biogeography is unsupported and vicariance, the fragmentation of a coastal widely distributed ancestral species by tectonic and climatological events, a better explanation for the historical biogeography of ricefishes.


Chlorinated paraffins (CPs) have been applied as additives in a wide range of consumer products, including polyvinyl chloride (PVC) products, mining conveyor belts, paints, sealants, adhesives and as flame retardants. Consequently, CPs have been found in many matrices. Of all the CP groups, short-chain chlorinated paraffins (SCCPs) have raised an alarming concern globally due to their toxicity, persistence and long-range transportation in the environment. As a result, SCCPs were listed in the Stockholm Convention on Persistent Organic Pollutants (POPs) in May 2017. Additionally, a limit for the presence of SCCPs in other CP mixtures was set at 1% by weight. CPs can be released into the environment throughout their life cycle; therefore, it becomes crucial to assess their effects in different matrices. Although about 199 studies on SCCP concentration in different matrices have been published in other continents; however, there are scarce/or limited studies on SCCP concentration in Africa, particularly on consumer products, landfill leachates and sediment samples. So far, published studies on SCCP concentration in the continent include SCCPs in egg samples, e-waste recycling area and indoor dust in Ghana and South Africa, despite absence of any production of SCCPs in Africa. However, there still remains a huge research gap in the continent of Africa on SCCPs. Consequently, there is a need to develop robust SCCP inventories in Africa since the Stockholm Convention has already developed guidance document in this respect. This review, therefore, examines the state of knowledge pertaining to the levels and trends of these contaminants in Africa and further provides research gaps that need to be considered in order to better understand the global scale of the contaminant. Since all CP mixtures detected had a SCCP content significantly above 1% , the used mixtures would also be classified as POPs , and in seven of these, oven SCCP content was below the limit of quantification meeting the European Union and Stockholm Convention requirement of a SCCP content of less than 1% in MCCP. However, in 3 cases, the SCCP content was 2.8%, 5.0% and 14.4% of the total CP content  were used, and an average migration efficiency of 12% and 1.5% for SCCPs and MCCPs were reported, respectively. SCCPs (C10) and lower chlorinated (C6 and C7) showed the highest migration. With these findings, it is important to highlight that since there is lack of CP regulations on uses in most African countries, SCCP oils might enter sensitive uses like lubricants in food production sector leading to a larger population exposed to their toxicological effects.Considering the use of SCCPs as additives in diverse consumer applications, continuous human exposure is likely to occur from this route. The major routes of exposure to SCCPs in human include air inhalation, dust ingestion and dermal absorption EFSA . Despite−1 day−1 after the 100th week, and that of rats at 312 mg kg−1 day−1 after the 90th week, which were significantly less than those of respective controls. Another study by Wang et al.  for 28 days caused immune cell infiltration in the liver, which indicated a potential of liver damage although the liver weight was not affected. The International Agency for Research on Cancer (IARC 10-SCCPs (60% chlorination) were found to be carcinogenic to experimental animals and possibly carcinogenic to humans. Wang et al. (9-13-CPs (vehicle corn oil) altered the expression of cancer-related genes, implying that these cancer-related genes may be involved in SCCP-induced carcinogenicity. Furthermore, SCCPs are known to be endocrine disruptors. Treatment of male rats with chlorowax 500C and cerclor 56 L at 1 g kg−1 day−1 (vehicle corn oil) by gavage for 14 days significantly reduced the levels of plasma thyroid hormone (TH), 32% and 39% lower for free thyroxine (FT4) and 26% and 35% lower for total T4 (TT4), respectively  for 28 days showed decreased levels of plasma FT4, free triiodothyronine (FT3) and hepatic T4 and increased levels of plasma TSH and hepatic T3.The toxicity of SCCPs has raised an alarming public concern globally leading to a number of research studies reviewed by Wang et al. . Accordig et al.  demonstrcer IARC  reportedg et al.  also demDifferent studies have indicated the ubiquity of SCCPs in diverse environments and matrices, including industrialized regions as well as remote areas . Compared with previous atmospheric SCCP concentration, only Huang et al.  were below MDL and if ∑SCCP concentration above MDL, ranged from 11 (RU5) to 170 (RU1) ng/sampler with ∑SCCP concentration of 61 ng/sampler. The ∑SCCP concentrations were 28-fold higher than those of PCBs measured with the same sampler at the same site in 2012 , which was attributed to the use pattern of commercial CP formulations in China. Thus, Shanghai aquatic system is mainly contaminated by MCCPs than SCCPs. Another study by Pan et al.  which were in the same order of magnitude with those reported by Saborido Basconcillo et al.  from three natural protected areas in Spain . SCCP concentration determined in egg samples of Larus michahellis ranged from 1.78 to 3.70 ng g−1 ww, which were notably lower than those that were determined in Larus audouinii ranging from 4.40 to 5.08 ng g−1 ww. Morales et al. (Larus michahellis and Larus audouinii) from the Ebro delta Natural Park, and SCCP concentrations were detected at 4536 ± 40 pgg−1 ww in Larus michahellis and 6364 ± 20 pg g−1 ww in Larus audouinii.In Africa, Adu-Kumi-Jonathan et al.  analysedg et al.  determinez Prats  analyseds et al.  also con−1—10% of the product weight . Furthermore, a number of studies conducted on landfills in China have focused on SCCP concentration that are determined in soil and sediment samples of e-waste dismantling areas than in landfill leachate and sediment samples. Different research studies have shown that concentrations of SCCPs in e-waste dismantling areas are significantly higher than in other sampling areas (Kalinowska et al. −1 dw. Xu et al. (5 ng g−1 and 32.5 to 1.29 × 104 ng g−1, respectively. Concentrations of SCCPs in soil samples were higher than in sediment samples, which were attributed to the distance between sampling points around the e-waste dismantling centres. Concentrations of SCCPs in soil and sediment samples may vary based on factors such as land-use type, proximity to sources and soil profile (Kalinowska et al. Guida et al.  stated tu et al.  determin−1 and 145 to 28.000 ng g−1 were determined in Kingtom and Agbogbloshie e-waste waste sites, respectively. Compared to literature data, the lowest SCCP concentration determined in the Agbogbloshie and Kingtom samples was similar to slightly higher than concentrations determined in ambient soils in China, UK and Norway (Xu et al. According to Möckel et al. , it can According to Xia et al. , there i−1 ww in breast milk samples from China. Compared with other studies, the concentrations were of the same magnitude with those reported by Yang et al. (−1 lw and 65.6 to 2310 ng g−1 lw in 2007 and 2011, respectively. The obtained results varied by about three orders of magnitude. Cao et al. (−1 lw. In the UK, Thomas et al. (−1 lw.Recently, Liu et al.  reportedg et al. . Xia et g et al.  also deto et al.  also dets et al.  determin−1 and 70.0 ng mL−1, respectively, which were in the same range with those reported by Aamir et al. (−1 ww, which were comparable with those previously reported in blood samples (Qiao et al. −1 were determined by Zhou et al. (−1 ww. The concentrations obtained were lower than those obtained in human, maternal and cord serum samples from China (Zhou et al. Liu et al.  reportedr et al.  and Qiaor et al. . Ding etr et al.  also detu et al. , which wu et al.  and humau et al. . In Austu et al.  showed S2, including over 54 countries and a population of about 1.17 billion people (UNDP Africa is the second largest continent in the world covering over 30 million kmple UNDP . Apart fple UNDP , it remaple UNDP . Consideple UNDP .In comparing SCCP studies done in Africa so far with those published in other continents, it is clear that there remains a huge gap in CP studies. There are limited published studies on the determination of SCCP concentration in consumer products and landfills as well as in other different matrices in the continent, and as such, further research studies are necessary in order to tackle those research gaps. Additionally, very few studies have so far reported on SCCP concentration in landfill leachate and sediment globally. Nearly all imports of CPs and CP-containing waste end up in dump sites or landfills in Africa. The lack of resources on intensive analytical methods and elaborate sampling techniques required may be the reason for fewer SCCP studies in Africa; therefore, attention should be given to this area. Temperature is one of the key meteorological parameters that can severely influence the global distribution of SCCPs in the environment. Due to the hot climate experienced in Africa, SCCPs can be evaporated and thereby influence the re-emission and distribution of SCCPs to other regions. In view of the effects of SCCPs globally, the use of SCCPs needs to be legally restricted/banned and not used in many exempted applications as prescribed by the Stockholm Convention. Robust SCCP inventories and other CPs containing SCCPs are overdue in Africa and, therefore, require some attentions. It is, therefore, important to gather comparable data on concentrations of SCCPs in consumer products and other matrices in all the continents in order to have a global overview of the state SCCPs. It is also crucial to study SCCPs in Africa in order to understand the impacts of the Stockholm Convention to reduce POPs in Africa and to assess their distribution and influence of other continents to the environmental burden of SCCPs in Africa, and vice versa.


Liver diseases are currently diagnosed through liver biopsy. Its invasiveness, costs, and relatively low diagnostic accuracy require new techniques to be sought. Analysis of volatile organic compounds (VOCs) in human bio-matrices has received a lot of attention. It is known that a musty odour characterises liver impairment, resulting in the elucidation of volatile chemicals in the breath and other body fluids such as urine and stool, which may serve as biomarkers of a disease. Aims: This study aims to review all the studies found in the literature regarding VOCs in liver diseases, and to summarise all the identified compounds that could be used as diagnostic or prognostic biomarkers. The literature search was conducted on ScienceDirect and PubMed, and each eligible publication was qualitatively assessed by two independent evaluators using the SANRA critical appraisal tool. Results: In the search, 58 publications were found, and 28 were kept for inclusion: 23 were about VOCs in the breath, one in the bile, three in urine, and one in faeces. Each publication was graded from zero to ten. A graphical summary of the metabolic pathways showcasing the known liver disease-related VOCs and suggestions on how VOC analysis on liver impairment could be applied in clinical practice are given. Fetor hepaticus, a musty breath aroma, has been among the most prominent liver insufficiency signs available to clinicians, and it was in the 1970s when Chen et al. . HoweverA wide variety of viral, immune-mediated, cholestatic, and toxic conditions may cause chronic liver tissue inflammation. In response to this, the liver accumulates extracellular matrix components, leading to fibrous tissue and scarring ,7. In prIn the past few decades, several noninvasive biomarkers have entered the liver research field, some of which have already been used in clinical trials, and the most widely used are the enhanced liver fibrosis score (ELF) , the FibHelicobacter pylori infection via the C13 urea breath test ) OR ((Diagnosis/Broad[filter]) AND (“Liver Diseases”[Mesh])))) AND ((volatile organic compounds) OR “Volatile Organic Compounds”[Mesh])) AND  OR “Breath Tests” [Mesh]).The search terms for faeces were:(((((“Liver Diseases”[Mesh]) OR liver disease) OR ((Diagnosis/Broad[filter]) AND (“Liver Diseases”[Mesh])))) AND ((volatile organic compounds) OR “Volatile Organic Compounds”[Mesh])) AND  OR faecal analysis) OR “Feces” [Mesh]).Replacing the word “Diagnosis” with “Prognosis” or “Monitoring” yielded the same results for both biological matrices. Additional studies cited by the initially identified research papers were also included and discussed in this review. These additional studies examined liver diseases related to VOCs in the breath and faeces and other body fluids such as urine, blood, and bile. The number of the latter was minimal; therefore, it was decided to discuss these as well. Only articles published in English, reporting original research in humans, and focused on different VOC patterns between healthy and diseased liver subjects were included. Engineering or technical studies were excluded since they fall outside the scope of this review. Finally, no year of publication criterion was imposed as an exclusion criterion. An overview of the literature search and the exact numbers of the publications found and used herein can be seen in the Results section in Two independent evaluators assessed the eligible studies using the Scale for the Assessment of Narrative Review Articles (SANRA) . SANRA iThe literature search performed in both PubMed and ScienceDirect resulted in 58 hits in total, of which 1 was not accessible, 16 were either engineering or technical, and 13 were reviews. Thus, the final number of papers to be discussed here was 28. From these 28 articles, 23 found VOCs in the breath, one in the bile, three in urine, and one in faeces.Pauling et al. pioneered breath testing with their unprecedented study published in 1971 . Since tVan den Velde et al.  and DadaIn 2015, Del Rio et al.  also comPijls et al.  stratifiDe Vincentis et al.  also comIn 2015, Eng et al.  conducteThe most significant compounds, and the ones that the aforementioned literature  seems toIn 2013, Alkhouri et al.  assessedHepatic encephalopathy (HE) was investigated by Khalid et al. . They saIn 2016, O’Hara et al. , a folloQin et al.  comparedFerrandino et al.  followedIn 2020, another broader scale HCC study was reported by Miller-Atkins et al. . They saArasaradnam et al.  investigBreath analysis has also been implemented to examine obesity-related liver diseases. Solga et al.  comparedIn 2013, Verdam et al.  investigAlkhouri et al.  examinedMillonig et al.  demonstrIn 2020, Sinha et al.  were theLetteron et al.  conducteHanouneh et al.  publisheThe key compounds and their metabolic pathways discussed in the aforementioned literature  can be sRaman et al.  sampled In 2015, Navaneethan et al.  publisheNavaneethan et al.  publisheArasaradnam et al.  publisheFinally, Bannaga et al.  publisheVOC analysis might greatly benefit liver disease diagnosis and prognosis; however, it is apparent from the literature findings that implementation of the VOC analysis in clinical liver practices is not ready yet for routine applications since much more research is needed. All conducted studies are either proof-of-concept studies or of a small sample size. Furthermore, many of the studies presented here did not perform any internal or external validation of their findings. The correction of possible confounding factors was also not considered, and this might have affected their results. Nevertheless, some key concept can be kept from the present review that may point towards the eventual implementation of the VOC analysis in clinical liver practices. Several VOCs have been found in several studies, and as indicated in


This new alternative combines an improved quantification of intracellular fungal components with a lower hazard risk at a lower cost.Arbuscular mycorrhizal (AM) fungi are one of the most common fungal organisms to exist in symbiosis with terrestrial plants, facilitating the growth and maintenance of arable crops. Wheat has been studied extensively for AM fungal symbiosis using the carcinogen trypan blue as the identifying stain for fungal components, namely arbuscles, vesicles and hyphal structures. The present study uses Sheaffer blue ink with a lower risk as an alternative to this carcinogenic stain. Justification for this is determined by stained wheat root sections ( Arbuscular mycorrhizal (AM) fungi are the most common fungal organisms to exist symbiotically with the root structures of vascular plants . It is c37H27N3Na2O9S3) is one of several stains that has been widely utilized for many years [34H28N6O14S4), originally developed by Philips and Hayman (1970) [Current staining procedures target arbuscules, vesicles and hyphal structures within the root cortex. Staining of target structures is performed for rapid, simple and cost-effective assessment of fungal symbiosis. Using light microscopy, the required skill sets are lower and the procedure can be performed with ease. Lactophenol cotton blue (Cn (1970) . With thet al. [Many widely used fungal root stains, including trypan blue, are known carcinogens . As a coet al.  investig3COOH). The constituents of commercially available fountain pen ink were reported by [et al. [Phaseolus vulgaris), barley (Hordeum vulgare), cucumber (Cucumis sativus) and wheat (Triticum aestivum). Vierheilig et al. [et al.’s work [Rhizoctonia cerealis inoculation were stated as being observable on wheat roots, but the authors do not present the data in any further detail. Another potential factor that may explain the lack of more wide-scale adoption is that in subsequent years, focus shifted toward the immunological identification of characteristic intracellular root cortical fungal structures [The use of an ink–vinegar stain has been proposed as a safer alternative. The chemical composition of the ink–vinegar stain is not stated by , althougorted by  as being [et al. . They ing et al.  reported.’s work . The reaructures .et al. [Immunohistochemical (IHC) methodologies are advantageous due to their higher specificity and the reduced damage caused to histological architecture . When pret al.  has remaThe present study compares the efficacy of trypan blue and Sheaffer blue ink as stains of intracellular AM fungal components in the root sections of two varieties of winter wheat (Zulu and Siskin). The focus is on image clarity, quantifiable structures (arbuscules and vesicles) and the potential for the substitution of a hazardous staining material with a safer alternative.et al. [Winter wheat (variety: Siskin), 98 % germination rate, with no chemical pretreatment was supplied by KWS UK Ltd. A second winter wheat variety (Zulu) was sourced from a farm in central Hertfordshire as farm-saved seed. The percentage of organic matter of the adjusted soil was confirmed via modified loss on ignition (LOI) methodologies obtained from Myrbo et al. , using 5Individual seeds were introduced into 300 g of adjusted, pre-purchased, top soils (J Arthur Bowers) and kept in controlled growth room conditions at 25 °C, 1770 lm and a humidity of 35 %.n=60) and Siskin (n=60) wheat varieties in controlled growth conditions. The samples were viewed initially at a total magnification of 40× using a Vickers compound microscope. The counting of stained root vesicles and arbuscules was performed at a total magnification of 100×, and fungal components were counted and recorded with the focus on arbuscule and vesicle quantity. Images of samples were taken with a Bresser HD microscope camera.Intracellular root arbuscules and vesicles were examined after the roots were left fully submerged in a formaldehyde, acetic acid, alcohol (FAA) and deionized water solution, 10 : 5 : 50 : 35, respectively, for 24 h. Roots were removed and rinsed with deionized water prior to autoclaving. Root systems, containing small quantities of soils, were subject to sonication at 42 kHz for 10 min and rinsed in deionized water. If small amounts of soils still adhered to root systems, a soft fine paint brush was used to remove debris. Root systems were submerged in 5 % hydrochloric acid for 30 min and incubated at 60 °C in a water bath. After cooling to room temperature, root material was sectioned into 1 cm pieces, with adjacent sections subjected to different stains. Five 1 cm root sections were each allowed to stain in 0.4 % trypan blue in phosphate-buffered saline (PBS) (Fisher Scientific) and 10 % Sheaffer blue ink in 25 % glacial acetic acid  for 3 mit-tests were employed for null hypothesis testing of differences between trypan blue and Sheaffer blue staining. Statistical significance was determined by P values ≤0.05.Standard errors and means were calculated from raw data for each week of sample collection. Paired The difference in clarity of the stained root sample between the trypan blue and Sheaffer blue ink approaches can be seen in n=120), staining with trypan blue did not produce sufficient clarity  in comparison to staining with Sheaffer blue for the two varieties of winter wheat investigated. Quantification of fungal spores is possible from the images presented in From the samples examined (t-test for Zulu (degrees of freedom (df)=5, t value=−4.5, P=0.003) and Siskin  (sem) for those samples stained with trypan blue   varietiepan blue  reflectsThe present study has identified a statistically significant difference between staining techniques with respect to observable intracellular root cortical fungal components. The employment of Sheaffer blue ink over trypan blue is more favourable in terms of both improved image clarity and reduction of the user’s exposure risk to chemicals with potential long-term health hazards. As an azo stain, trypan blue is a known carcinogen . Sheaffeet al. [Rhizoctonia cerealis, but did not present the data or images to substantiate the comment in any further detail. Vierheilig et al. [Although subject to scrutiny in previous studies, the use of ink–vinegar as a staining method has not been adopted widely. In 1998, Vierheilig et al.  investigg et al.  also useet al. [et al. [et al. [et al. [Cottet et al.  compared [et al.  studied  [et al. , and tho [et al. , who anaet al. [et al. [et al. [The clearing of soil materials from roots is an important first step in the preparation of stained samples due to the desired components being potentially obscured by debris. The present study used adjacent root sections. This negates any differences from root clearing. In most cases, roots are cleared with the use of 10 % w/v potassium hydroxide . Whilst et al. , the emp [et al. , Kobae [ [et al.  and CottAn area of limitation within the method used arises from the manual counting of stained fungal components and the time input required. Although potentially faster approaches exist for the quantification of fungal structures, employing image analysis software, the programs are only able to scan the field of view for objects that are different to the background image. There is a high risk of misidentification and classification of structures and hence this was not considered to be a sufficiently reliable approach for the purpose of the current study.et al. [Ford and Becker  producedet al.  investigIn conclusion, the employment of Sheaffer blue staining allows for the effective, safe and low-cost quantification of fungal components in commercially important plant species such as wheat. The manual handling of slides, whether old or new, comes with reduced long-term health risks when stained with Sheaffer blue as opposed to the carcinogenic azo dye trypan blue. Further, the number of fungal components that obstruct viewing are limited, resulting in a more reliable quantification of the established AM fungal infection and symbiosis within the roots of wheat plants.


Mycobacterium tuberculosis enable the bacterium to acquire lipids from the host cells. Asthana et al.  present the first structural insights into the potential assembly of Mce1 and Mce4, advancing our understanding of lipid transport by the human pathogen that causes tuberculosis.The mammalian-cell-entry (Mce) proteins of  Mycobacterium tuberculosis, the bacterium that causes tuberculosis , the ‘white plague’ or consumption, tuberculosis appears as a common theme in art, music and literature, and has shaped many elements of human social history  multiprotein complexes that are proposed to play crucial roles in translocating various lipid molecules across the cell envelope , and importing cholesterol from the host cells (Mce4)  that act as substrate-binding proteins (SBPs)  domain, the MCE domain, a helical domain and a tail domain of variable size. They also showed that all these individual domains, except for the MCE domain, require detergents for solubility and stability. Interestingly, the full-length and individual domains of M. tuberculosis Mce1A and Mce4A are predominantly present as monomers in solution. This was further confirmed by the crystal structure of the single MCE domain present in Mce4A (Mce4A39–140), indicating that this domain could not form homo-hexamers due to steric clashes between monomers. This is a notable difference from the previously reported hexameric SBPs observed in E. coli (Ekiert et al., 2017et al., 2020et al., 2020et al., 2020A. baumannii (Kamischke et al., 2019et al., 2020The results presented by Asthana  al. 2021 reveal sM. tuberculosis (Asthana et al., 2021Ec-Pqi (Ekiert et al., 2017M. tuberculosis.These results have consequently led to a proposed model on the likely assembly of the Mce proteins in et al. (2021M. tuberculosis. Such endeavours may also facilitate the development of specific compounds to target cholesterol import as a therapeutic intervention, particularly restricting M. tuberculosis growth and survival during persistence.The proposed model by Asthana  al. 2021 establis


Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome engineering and related technologies have revolutionized biotechnology over the last decade by enhancing the efficiency of sophisticated biological systems. Cas12a (Cpf1) is an RNA-guided endonuclease associated to the CRISPR adaptive immune system found in many prokaryotes. Contrary to its more prominent counterpart Cas9, Cas12a recognizes A/T rich DNA sequences and is able to process its corresponding guide RNA directly, rendering it a versatile tool for multiplex genome editing efforts and other applications in biotechnology. While Cas12a has been extensively used in eukaryotic cell systems, microbial applications are still limited. In this review, we highlight the mechanistic and functional differences between Cas12a and Cas9 and focus on recent advances of applications using Cas12a in bacterial hosts. Furthermore, we discuss advantages as well as current challenges and give a future outlook for this promising alternative CRISPR-Cas system for bacterial genome editing and beyond.Cas12a is a powerful tool for genome engineering and transcriptional perturbation• Cas12a causes less toxic side effects in bacteria than Cas9• Self-processing of crRNA arrays facilitates multiplexing approaches•  Streptococcus pyogenes is still by far the most studied and well characterized. Based on the architecture of the genomic loci, it is classified as a Class 2 type II-A CRISPR system for its single, large effector Cas9 protein , Acidaminococcus sp. BV3L6 (AsCas12a), Lachnospiraceae bacterium ND2006 (LbCas12a), and Moraxella bovoculi AAX11_00205 (MbCas12a). Thus far, the Cas12a orthologs are shown to be able to mediate genome editing in human cells  variants Fig. . For thiE. coli, Bacillus subtilis, Streptomyces coelicolor, and Paenibacillus polymyxa (Zhang et al. . A clear strand bias of the repression efficiency by dCas12a was observed, especially when aiming for interference during transcription elongation. Different studies reported that efficiency of transcriptional perturbation significantly increases when the template strand is targeted (Zhang et al. S. coelicolor, repression efficiency of dFnCas12a targeting the template strand can achieve up to 88% whereas it was much less effective when targeting the non-template strand (Li et al. Compared to gene editing, dCas12a-mediated gene regulation in bacteria was reported less frequently although some studies demonstrated its high efficiency for gene interference (Table B. subtilis and P. polymyxa (Schilling et al. . These studies demonstrated that linking dCas12a to transcription activation domain like RemA or SoxS resulted in higher expression levels of the target genes. Contrary to eukaryotic organisms, for which CRISPRa is primarily based on chromatin rearrangements (Gilbert et al. Besides CRISPRi, dCas12a can also be employed for activation of gene expression by linking it to a transcription activator domain. Upon dCas12a binding to the target region, the activator domain facilitates recruitment of RNA polymerase leading to higher expression levels of the gene of interest. Gene activation facilitated by the dCas12a has been well explored in mammalian cells (Campa et al. While Cas12a is of importance for bacterial strains in which Cas9 expression shows toxic effects, its simplicity for multiplex targeting remains the most attractive property of Cas12a. To realize multiplex targeting, the spacers-containing crRNAs can either be delivered individually in separate plasmids or in form of a crRNAs array. Nonetheless, it has been reported that supplying the crRNAs in one array is as efficient as supplying them individually (Ao et al. E. coli, B. subtilis, Clostridium difficile, S. coelicolor, and P. polymyxa (Zhang et al. . Nevertheless, the studies demonstrated the functionality of Cas12a multiplexing with reasonably high efficiency. In bacteria, the highest degree of multiplexing that has been investigated thus far was regulation of four genes in E. coli and P. polymyxa (Zhang et al. . While efficiency of transcriptional perturbation is usually not heavily influenced by an increasing number of targets, efficacy of genome editing via homology-directed repair can decrease (Zhang et al. C. difficile resulted in an efficiency of 25% which was significantly lower than the efficiency of targeted single gene deletion (Hong et al. E. coli, where single-site chromosomal integration showed an efficiency close to 100%, it dropped to 40% and 20% when two and three loci were targeted for simultaneous integrations (Ao et al. S. coelicolor (Li et al. .Despite the great potential, Cas12a-based multiplexing has only been investigated in few bacteria: There are different strategies that can be employed to achieve higher activity of Cas12a in the desired bacterial host. An important aspect is to ensure adequate expression of Cas12a. Since each organism has distinct codon usage preference (Quax et al. Various studies also investigated different possibilities to enhance the activity of Cas12a. It is reported that engineered AsCas12a variant with E174R/S542R/K548R mutations has twofold higher editing efficiency in human cells than the wild-type variant (Kleinstiver et al. First characterized in 2015, Cas12a has emerged as a promising genetic tool and many studies have exploited its potential since then. With the rapidly growing research, there will be several improvements that we can anticipate in the upcoming years which will boost the use of Cas12a for bacterial genome engineering.acr genes. For example, Listeria monocytogenes encodes acr for Cas9. Consequently, it severely inhibits commonly used SpCas9 (Marino et al. As often seen in biological systems, there exist antagonistic mechanisms to keep the balance of the natural condition. Recently, it was described that some proteins can act as natural inhibitor of Cas nucleases (Pawluk et al. To broaden Cas12a application, it will also be interesting to analyze its utilization as a highly efficient base editing tool in bacteria. As described for Cas9, fusing the dead or nickase variant with a cytidine deaminase protein could direct the conversion of cytosine to thymidine within a particular editing window (Komor et al. . This variant will certainly be a beneficial add-on for extended applications of Cas12a.Finally, we also anticipate the development of other Cas12a variants including the nickase which only induces ssDNA breaks, while still triggering the repair mechanism. The mutated variants will particularly be of interest for applications in bacteria which are deficient of the dsDNA break repair mechanism (Song et al.


Radiomics is a quantitative and high-throughput radiological method that can aid in clinical decision-making, like treatment modality selection, and treatment plan optimization. By extracting plentiful of parameters from standard images, plenty of information that cannot be discovered by human naked eyes can be explored. Based on the hypothesis that these extra data provide additional information related to gene, protein and tumor phenotype, radiomics has gained increasing attention in cancer research. Meanwhile, because of the rich amount of data obtained in radiomics, sophisticated image analysis tools are required to analyze it. Many image-based signatures have been constructed by computer algorithms. Herein, this Research Topic recruited studies that exploring the usage of radiomics and artificial intelligence assisting clinical decision-making of tumors.We are very glad to see that many excellent works were submitted to our Research Topic. In the end, a total of 36 papers were published, among which 34 were original studies and two were reviews. The researches were carried out in different countries, including China, USA, UK and France, and most of them were retrospective studies. They used various methods to explore the role of imaging in clinical decision-making. The methods used to select high-throughput imaging parameters can be divided into three levels, including the mathematical formulas level, Machine Learning level and Deep Learning level which belongs to Machine Learning but is more automatic. These kinds of analysis methods are constantly evolving to mimic the thinking patterns of the human brain, gaining the ability to analyze increasingly complicated data. However, for the lack of open platform of images and non-uniform manual feature extraction, there is still a long way to go till a standard or a series of standardized radiomics signatures can be constructed.Xu X. et al.; Xu H. et al.; Gao et al.; Hu et al.; Wang J. et al.; Zhou X. et al.; Zhang Y. et al.; Zhong et al.; Wu J. et al.; Zhang P. et al.; Chen W. et al.; Dong Y. et al.; Mai et al.; Li et al.). For instance, Zhang P. et al. differentiated seminomas and nonseminomas by MRI radiomics. Features were selected by comparing their heterogeneity among different groups and by assessing their relevance and redundancy. Then, Least Absolute Shrinkage and Selection Operator (LASSO), a regression analysis method, was used to select features to improve the mode prediction accuracy and interpretability . Mai et al. focused on the differentiation of phyllodes tumors and fibroadenoma with breast MRI texture analysis. They used a combination of a linear discriminant analysis and the K-Nearest Neighbor classifier to construct differentiative models .As for the first level, using mathematical formulas, some studies generally extract parameters from images, then use statistical methods, like Mann–Whitney U-test, Spearman’s rank correlation test, etc., to compare the internal and external differences of parameters, and then select the most heterogeneous data in different groups. After selecting the appropriate features, Machine Learning algorithms will be used to build models. This kind of studies included in the Research Topic used textures extracted from various images, like Positron Emission Tomography–Computed Tomography (PET/CT), CT, Magnetic Resonance Imaging (MRI), etc., to improve the accuracy of disease differentiation or prognosis prediction . Machine Learning algorithms build prediction models based on patterns in the training data and make predictions by comparing new instances to previous similar events, and they can be divided into supervised, unsupervised and semi-supervised learning algorithms, based on whether the data are labeled. Some studies selected one kind of algorithms to process data. Fei Wang et al. used LASSO to select features and Support Vector Machine (SVM) algorithm to constructed a predictive model and drew a nomogram to improve the preoperative T category accuracy . Huang et al. used LASSO regression model to select features and a multivariable logistic regression to develop predicting models. In addition, a nomogram was drawn by radiomics and clinical features to evaluate peritoneal metastasis status in gastric cancer . Yi et al. predicted treatment response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Three aspects of the treatment response: not only partial clinical remission and good response, but also down-staging were evaluated. They used SVM rather than LASSO or Random Forest (RF) to regress features into a two-dimensional plane .At the second analysis level, studies mainly used Machine Learning algorithms to select and classify radiomics features -based models represented better performances than SVM-based models and Logistic Regression (LR)-based models . Similar results were found in other studies that compared different combinations . For example, Yang Zhang et al. used five selection methods and nine classifiers. The combination of LASSO and LDA represented the best comprehensive performance . LDA is a linear classifier whose decision boundary is a plane or a line, while SVM is a non-linear classifier with a decision boundary of a surface or a curved line. Although the above studies showed that LDA was superior to SVM, other studies uncovered the opposite results . Zhang Y. et al. differentiated anaplastic oligodendroglioma from atypical low-grade oligodendroglioma. The best-performed combinations were various according to different image parameters. The combination of LASSO and RF classifier was the best for T1 images, while the combination of GBDT and RF classifier was the best for the fluid attenuated inversion recovery images . In addition, Payabvash et al. differentiated posterior fossa tumors by using different Machine Learning classifiers, and also found RF models achieved greater accuracy. Delzell et al. used three types of classifying methods, including linear, nonlinear, and ensemble predictive classifying models, and found Elastic Net and SVM performed the best, while RF and Bagged Trees were the worst. It is impossible to draw firm conclusions about which method is the best, because there are too many influencing factors, such as sample size, parameter acquisition, extraction method, etc. However, at the very least, all the relevant articles show that Machine Learning methods are superior to manual methods, so more research on Machine Learning is necessary.Some other studies used multiple methods for feature selection and classification, as there are many kinds of Machine Learning methods with different advantages and drawbacks. They found the choice of classification methods accounted more than selection methods. Moawad et al. explored the feasibility of volumetric assessment of pre- and post- Transhepatic Arterial Chemotherapy And Embolization hepatocellular carcinoma using fully automated segmentation that based on a Convolutional Neural Network (CNN) approach (U-Net). For automated segmentation, attenuation of adjacent organs and the small size of lesions were the main challenges. According to the assessment of response evaluation criteria in solid tumors, automated segmentation was a good substitute for manual segmentation . Sun et al. compared the deep CNN model based on breast ultrasound parameters with the radiomics model. Radiomics can be regarded as an accurate phenotypic analysis of medical images in which the imaging features are carefully defined in advance according to expert opinion. However, Deep Learning uses the raw data and analyzes the pixels and the voxel values by themselves. With convolution techniques, imaging features are automatically defined in the network. Thus, Deep Learning is the most artificial intelligent tool among these three analyzing levels. It is closest to human mode of thinking and can extract features and analyze them automatically.Deep Learning is a subclass of Machine Learning that extends Deep Neural Networks to create complex neural architectures to solve difficult problems which would be impossible with traditional programming based on mathematical logic. Lacroix et al. optimized MR images before process with N4ITK bias field correction and normalizing voxel intensities with fat as a reference region. The results showed that correction of magnetic field heterogeneity and normalization of voxel values can promote the usage of radiomic features . Wu W. et al. decomposed data by a non-linear kernelization method, Kernel Principal Component Analysis (KPCA), to find a new set of candidates and maximize the use of data. Lu et al. used concordance correlation coefficients to measure the fidelity in repeated experiments. A lot of features with good repeatability were found and their repeatability can be improved by using specific lesion-drawing methods. Zormpas-Petridis et al. proposed a novel multi-resolution hierarchical framework (SuperCRF) which can introduce the spatial context of a cell as additional information and improve the single cell classification algorithms. In other researches, topics related to radiomics and Machine Learning were discussed. Dong J. et al. and Ge et al. reviewed the usage of radiomics and Machine Learning in the management of cancers, and summarized computer-aided clinical decision-making as a promising solution.Moreover, there are some included studies focusing on optimizing the original features to promote the analysis results. http://www.predictcancer.org need to be built. Secondly, based on open image sources, algorithms of lesion delineation, feature extraction and signature construction require more standard reference to increase the generalization of the results. Thirdly, more studies that based on uniform data and algorithms and comparing the efficiency of computer-aid and conventional clinical decision-making, are required to better promote the usage of Artificial Intelligence in clinic.In conclusion, the combination of radiomics and Machine Learning can provide clinical practice convenience, as long as some obstacles can be solved. The limitations of Machine Learning-based radiological decision-making mainly lie in the following aspects: Firstly, the data quality is uneven, and thus open data-platforms like This Research Topic involved many studies, which used the combination of radiomics and Machine Learning in tumor management. We appreciate all the reviewers and authors for their contributions to this Research Topic. We hope this Research Topic can arouse more attention in the related fields.HX and LD wrote the first draft of the manuscript. RT and XM contributed to manuscript revision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Archer et al., Chem. Sci., 2019, 10, 3502–3513.Correction for ‘A dinuclear ruthenium( The authors regret that incorrect details were given for ref. 41 in the original article. The correct details for ref. 41 are given below as The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


It is erroneously stated that the European Synchrotron Radiation Facility developed the FlexED8 sample-changer. However, it has been pointed out that it was the EMBL-Grenoble Instrumentation team who actually developed the FlexED8 sample-changer, as shown in the paper by Papp et al. (2017In the paper by  al. 2017.et al., 2017et al., 2006et al., 2017The correct sentence should read: ‘Across the pond, Diamond Light Source achieved one of the fastest sample exchange times with BART, a six-axis robotic arm system (O’Hea


Estimating the coronavirus disease-2019 (COVID-19) infection fatality rate (IFR) has proven to be particularly challenging –and rather controversial– due to the fact that both the data on deaths and the data on the number of individuals infected are subject to many different biases. We consider a Bayesian evidence synthesis approach which, while simple enough for researchers to understand and use, accounts for many important sources of uncertainty inherent in both the seroprevalence and mortality data. With the understanding that the results of one's evidence synthesis analysis may be largely driven by which studies are included and which are excluded, we conduct two separate parallel analyses based on two lists of eligible studies obtained from two different research teams. The results from both analyses are rather similar. With the first analysis, we estimate the COVID-19 IFR to be 0.31% [95% credible interval (CrI) of ] for a typical community-dwelling population where 9% of the population is aged over 65 years and where the gross-domestic-product at purchasing-power-parity (GDP at PPP) per capita is $17.8k (the approximate worldwide average). With the second analysis, we obtain 0.32% [95% CrI of ]. Our results suggest that, as one might expect, lower IFRs are associated with younger populations . For a typical community-dwelling population with the age and wealth of the United States we obtain IFR estimates of 0.43% and 0.41%; and with the age and wealth of the European Union, we obtain IFR estimates of 0.67% and 0.51%. Above all, what's needed is humility in the face of an intricately evolving body of evidence. The pandemic could well drift or shift into something that defies our best efforts to model and characterise it.The New YorkerSiddhartha Mukherjee, 22 February 2021The infection fatality ratio (IFR), defined as the proportion of individuals infected who will go on to die as a result of their infection, is a crucial statistic for understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ongoing coronavirus disease-2019 (COVID-19) pandemic. Estimating the COVID-19 IFR has proven to be particularly challenging –and rather controversial– due to the fact that both the data on deaths and the data on the number of individuals infected are subject to many different biases.et al.  . In the published version of their article , an alternative interval “accounting for uncertainty in the number of recorded deaths” is provided. This alternative interval, which essentially takes into account the D|C binomial distribution, is substantially wider: . In a very similar way, Levin et al.  per capita (GDPk), respectively.Having established simple binomial distributions for the study-specific IRs and IFRs, we define a simple random-effects model such that, for et al. . The spread of COVID-19 is substantially different in LTC facilities than in the general population and residents of LTC facilities are particularly vulnerable to severe illness and death from infection; see Danis et al. . With th ; see ‘World’, ‘USA’ and ‘EU’ rows in et al.-based analysis, an across-population average IFR estimate of 0.31%, with a 95% CrI of . With the Serotracker-based analysis, we obtain a similar estimate of 0.32%, with a 95% CrI of . For 65yo = 16% and GDP = $ 65 298, the USA values, we obtain across-population average IFR estimates of 0.43%, with a 95% CrI of   and of 0.41%, with a 95% CrI of  . Finally, for 65yo = 20% and GDP = $ 47 828, the EU values, we obtain across-population average IFR estimates 0.67%, with a 95% CrI of   and of 0.51%, with a 95% CrI of  . Note that for the ‘World’ predictions, the Serotracker-based analysis has the more precise estimates, while the Chen et al.-based estimates are more precise for the ‘USA’ predictions. This is likely due to the fact that the Serotracker-based analysis considers several younger and less wealthy populations, whereas the Chen et al.-based analysis considers fewer outliers.We can infer , the moet al. [et al. [et al. [et al. [et al. [et al. [et al. [Our estimates are somewhat similar to those obtained in other analyses. Brazeau et al. , using d [et al.  obtain a [et al. , using d [et al. , who res [et al.  estimate [et al.  estimate [et al.  and the  [et al.  . On the other hand, those individuals who have reason to believe they may have been infected, may be more likely to volunteer to participate in a seroprevalence study . It is aet al. [et al. [The need to improve the quality and reporting of seroprevalence studies cannot be overemphasised.et al.  review tet al. . Novel m [et al.  proposedOutside of biased data, perhaps the foremost challenge in evidence synthesis using observational data is that necessarily one is forced to make an array of design choices around inclusion/exclusion criteria, statistical modelling approaches and prior specifications . With thet al. [Reducing the uncertainty around the severity of COVID-19 was of great importance to policy makers and the public during the early stages of the pandemic –93 and iet al. ). And yeet al. , identifet al. , 95.We prioritised simplicity in our modelling so as to promote transparency in our findings and to facilitate adaptations to similar, but not identical, data structures. While ‘simple’ is a relative term, note that the entire dataset used for our analyses fits on a single page in  and 4 anet al. [Including age-stratification in the model could represent a substantial improvement given that infection in some populations is far from homogeneous (e.g. about 95% of Singapore's COVID-19 infections were among young migrant workers (as of September 2020), which explains the incredibly low case fatality rate ). If a fet al.  for estiFinally, we must emphasise that the IFR is a moving target. As the pandemic changes, so to does the IFR. Our estimates are based on data from 2020, most of which were obtained more than a year ago. It is likely that, with continual viral mutation of SARS-CoV-2, advances in treatment and the availability of vaccines, the current IFR in many places is now markedly different than it was earlier in 2020 , 99, 100The COVID-19 IFR is estimated to be about 0.32% for a typical community-dwelling population where 9% of individuals are over 65 years old and where the GDP per capita is $17.8k (the approximate worldwide averages). For a typical community-dwelling population with the age and wealth of the United States we estimate the IFR to be approximately 0.42%.Any estimation of the COVID-19 IFR should take into account the various uncertainties and potential biases in both the mortality data and the seroprevalence data.Bayesian methods with interval censoring are well suited for complex evidence synthesis tasks such as estimating the COVID-19 IFR.


P-wave velocity perturbations (dVp) [et al. [et al. [Recent studies have shown the extent and nature of the South China Sea (SCS) at the end of spreading by unfolding  the Manila slab, which is the subducted part of the SCS, and by identifying the nature of the crust-lithosphere  from mid-slab ns (dVp) ,2. The ons (dVp) ,4) until [et al.  introduc [et al.  and cons [et al. ,6), but  [et al. ).The Manila subduction zone along the eastern boundary of the present-day SCS has undoubtedly played an important role in the evolutionary history of the SCS; however, the details are unclear because the eastern part of the SCS has already subducted. What did the SCS look like at the end of seafloor spreading (i.e. between 15.5 and 20 Ma) ,9? What dVp values within the mapped slab, slightly negative areas (in green) roughly correspond to thinned continental crust and positive areas (in blue) to oceanic crust. Thus, S1 corresponds to the northeastern portion of the northern COB within the slab, S3 is the portion of the northern COB defined by Liu et al. [Figure u et al.  and sligu et al. .et al.’s [et al. [et al. [Based on spreading flow-lines   with NNE–SSW trending (30°–45°) small rift basins ,15. The The first episode of the SCS rifting (56.0–40.0 Ma) corresponds to the first phase of the PSP seafloor spreading (~53.2–42.5 Ma). The second episode of the SCS rifting (40.0–33.0 Ma) corresponds to the second phase of the PSP spreading (~40.4–33.7 Ma). Therefore, during Eocene, similar-age tensional tectonic phases are observed on the SCS continental margin and in the oceanic PSP basin. We propose a simple sketch for the 56- to 33-Ma period, in which the two tensional domains of the SCS continental margins and of the PSP oceanic basin are connected by a left-lateral shear fault. We suggest that this fault is a large shear-plate boundary, which was active from 56 Ma up to now  and locaIf paleo-latitude variations give the correct magnitude of the PSP northward component of the motion through time, the variations of paleo-magnetic declinations (synthesized in ) give thet al. [et al. [Since 56 Ma, a straightforward link between the SCS and PSP is not easily established given their 2200-km separation and the smaller size of the PSP relative to the present. Our interpreted large shear-plate boundary does not necessarily follow the same geological features through time. For example, magnetic lineations that show different trends across either side of the Gagua ridge indicate this boundary was not only a fracture zone (e.g. ), but a et al.  and Desc [et al.  confirm  [et al. . Though An early Cretaceous age was proposed for the HB based on radiometric dating of gabbros belonging to the 115- to 125-Ma oceanic crust uplifted by the Miocene Luzon arc and the 115-Ma age of radiolarians deposited on this oceanic crust , suggestet al. [This paper only considers a fairly narrow class of allowable solutions amongst the many plate models. For example, our proposed reconstruction model of Fig. et al.  and Hallet al. . The lefet al. .Despite ample evidence the HB was formed during the early Cretaceous ,7,20,21,


Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that includes mTOR complex (mTORC) 1 and mTORC2. The mTOR pathway is activated in viral hepatitis, including hepatitis B virus (HBV) infection-induced hepatitis. Currently, chronic HBV infection remains one of the most serious public health issues worldwide. The unavailability of effective therapeutic strategies for HBV suggests that clarification of the pathogenesis of HBV infection is urgently required. Increasing evidence has shown that HBV infection can activate the mTOR pathway, indicating that HBV utilizes or hijacks the mTOR pathway to benefit its own replication. Therefore, the mTOR signaling pathway might be a crucial target for controlling HBV infection. Here, we summarize and discuss the latest findings from model biology research regarding the interaction between the mTOR signaling pathway and HBV replication. Patients with chronic HBV infection are prone to cirrhosis, liver failure, and hepatocellular carcinoma (HCC)  signaling pathway -related kinase (PIKK) family. mTOR is the catalytic subunit of two complexes, mTORC1 and mTORC2 . Under nutrient-rich conditions or insulin stimulation, mTOR activation leads to the phosphorylation and activation of SREBP1, thereby enhancing lipogenesis , another major metabolic sensor. AMPK is activated in response to the increased AMP/ATP ratio, for example, after starvation of glucose. Importantly, AMPK directly or indirectly inhibits mTOR activity  Semenza  and promet al.et al.et al.Akt, serum and glucocorticoid-induced protein kinase 1 (SGK1) and protein kinase C-α (PKC-α). mTORC2 directly activates Akt by phosphorylating the hydrophobic motif (Ser473) of Akt, which is required for the maximum activation of Akt .et al.et al.et al.et al.et al.et al.et al.et al.et al.The HBx protein, the product of the smallest of the four overlapping open reading frames of the HBV genome, plays a vital role in HBV replication and the pathogenesis of HBV-associated HCC. HBx transfection in hepatoma cells increases the expression of mTOR  as a functional receptor for HBV, the role of HBV in cellular metabolism has been placed at the forefront. Yan etal. showed that HBx acts as a positive regulator of gluconeogenesis  or siRNA that targets the PtdIns3K or ATG7 gene to disrupt the initiation of autophagy  and late  phase of autophagy, HBV assembly and release through enhanced autophagy are still beneficial for the production HBV particles despite the degradation by lysosomes. Recent findings also showed that HBV replication can interfere with the lysosomal functions and thereby evade the autophagic degradation process  increased the transcription of 3.5-kb and 2.4-kb viral RNA as well as the replication of HBV DNA (Guo et al.et al.et al.invitro or invivo (Raney et al.et al.et al.et al.et al.et al.Different concentrations of PI3K, Akt and mTOR inhibitors have different effects on HBV transcription and replication. Guo et al.et al.et al.et al.etal. reported that naïve T cells fail to differentiate into Th1, and Th17 cells in mTOR or Rheb gene knockout mice (Delgoffe et al.+ T cell responses (Pearce et al. + T cell differentiation (Araki et al.Recently, increasing evidence has indicated that the mTOR signaling pathway plays multiple roles in immunity (Weichhart Despite recent advances in drug discovery and development, effective antiviral drugs against HBV are still very limited, especially for the cure of chronic HBV infection. Thus, the development of effective, well-tolerated and affordable antiviral treatments is necessary and urgent. The HBV-induced abnormalities in the expression of PI3K/Akt/mTOR and its downstream regulators and alteration in host metabolism make mTOR a potential target for drug development.