China is carving out a distinctive development path which features urban-rural integration.This approach has not only yielded tangible results domestically but also drawn the attention of other countries.
China aims to build on its achievements of the past five years to accelerate rural revitalization during the 15th Five-Year Plan period.IN China,issues relating to agriculture,rural areas,and rural residents have alwa...China aims to build on its achievements of the past five years to accelerate rural revitalization during the 15th Five-Year Plan period.IN China,issues relating to agriculture,rural areas,and rural residents have always been a priority in national development.At its fourth plenary session held in October 2025,the 20th Central Committee of the Communist Party of China(CPC)once again emphasized the need to accelerate agricultural and rural modernization,and advance all-around rural revitalization over the next five years.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event ...Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event for the English edition of the book’s fifth volume on 3 December 2025 in Johannesburg,South Africa.展开更多
This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and cat...This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and categorised into different groups of main early-stage decisions.The present study stands in contrast to the contributions of the operations research and system engineering review articles,on the one hand,and the petroleum engineering review articles,on the other.This is because it does not focus on one methodological approach,nor does it limit the literature analysis by offshore oilfield characteristics.Consequently,the present analysis may offer valuable insights,for instance,by identifying environmental planning decisions as a recent yet highly significant concern that is currently being imposed on decision-making process.Thus,it is evident that the incorporation of safety criteria within the technical-economic decision-making process for the design of production systems would be a crucial requirement at development phase.展开更多
The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regul...The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a...Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a lipid-rich myelin sheath,which enables the saltatory conduction of action potentials.During development,oligodendrocyte progenitor cells(OPCs)emerge from neural stem cells in the ventricular zone.They then proliferate,increase their number,and migrate to their final destination where they encounter unmyelinated neuronal axons and differentiate in a stepwise fashion into myelinating oligodendrocytes(mOLs)under the influence of environmental stimuli.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
Developing deep fragmented soft coalbed methane(CBM)can significantly enhance domestic natural gas supplies,reduce reliance on imported energy,and bolster national energy security.This manuscript provides a comprehens...Developing deep fragmented soft coalbed methane(CBM)can significantly enhance domestic natural gas supplies,reduce reliance on imported energy,and bolster national energy security.This manuscript provides a comprehensive review of commonly employed coalbed methane extraction technologies.It then delves into several critical issues in the current stage of CBM exploration and development in China,including the compatibility of existing technologies with CBM reservoirs,the characteristics and occurrence states of CBM reservoirs,critical desorption pressure,and gas generation mechanisms.Our research indicates that current CBM exploration and development technologies in China have reached an internationally advanced level,yet the industry is facing unprecedented challenges.Despite progress in low-permeability,high-value coal seams,significant breakthroughs have not been achieved in exploring other types of coal seams.For different coal reservoirs,integrated extraction technologies have been developed,such as surface pre-depressurisation and segmented hydraulic fracturing of coal seam roof strata.Additionally,techniques like large-scale volume fracturing in horizontal wells have been established,significantly enhancing reservoir stimulation effects and coalbed methane recovery rates.However,all of these technologies are fundamentally based on permeation.These technologies lack direct methods aimed at enhancing the diffusion rate of CBM,thereby failing to fully reflect the unique characteristics of CBM.Current CBM exploration and development theories and technologies are not universally applicable to all coal seams.They do not adequately account for the predominantly adsorbed state of CBM,and the complex and variable gas generation mechanisms further constrain CBM development in China.Finally,continuous exploration of new deep CBM exploration technologies is necessary.Integrating more effective reservoir stimulation technologies is essential to enhance technical adaptability concerning CBM reservoir characteristics,gas occurrence states,and gas generation mechanisms,ultimately achieving efficient CBM development.We conclude that while China possesses a substantial foundation of deep fractured CBM resources,industry development is constrained and requires continuous exploration of new CBM exploration and development technologies to utilize these resources effectively.展开更多
The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and contin...The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.展开更多
The reform stems from honesty and determination. Since 2005, organ donation and transplantation in China has undergone thorough reform, which complies with legislation requirements and ethical principles established b...The reform stems from honesty and determination. Since 2005, organ donation and transplantation in China has undergone thorough reform, which complies with legislation requirements and ethical principles established by the World Health Organization(WHO). Reform in China has demonstrated the unwavering confidence and utmost determination of the Chinese government and the Chinese transplantation community. The year 2015 marked a historic turning point when voluntary donations from Chinese citizens became the sole legitimate source for organ transplantation. Since 2015, China has gradually established and refined the “Chinese Mode” and “China System” for organ donation and transplantation, fulfilling its political pledge of reform, and has garnered international recognition, and fostered a social culture which promotes organ donation. This article reviewed the history of reform on organ donation and transplantation in China, presented a new pattern of establishment of organ donation system in the new era of the country, and the direction of advances in the future.展开更多
Dongyuemiao Member shale in the Sichuan Basin,China,is characterized by organic-rich shale intervals with different types of interbeds and accumulation modes.The aim of this study is to elucidate the impact of paleoen...Dongyuemiao Member shale in the Sichuan Basin,China,is characterized by organic-rich shale intervals with different types of interbeds and accumulation modes.The aim of this study is to elucidate the impact of paleoenvironmental indicators on interbed development.With this aim in mind,we established an interbed classification scheme and quantified the development of different types of interbeds and their frequencies.We categorized the shale interbeds into three types based on interbed type:silt interbeds(SIs),shell fragment interbeds(SFIs),and shell skeleton interbeds(SSIs).The SIs,SFIs,and SSIs are respectively the products of extrabasinal low-density turbidity currents,intrabasinal debris flow,and intrabasinal low-density turbidity currents.We propose that variations in paleoenvironmental conditions primarily influenced the types of interbeds that developed but had minimal impact on the frequency of their development.Models depicting the interbed development within the 1st Submember of Dongyuemiao Member indicate that during the early Dongyuemiao depositional period,under conditions of relatively aridity,weak weathering,high terrigenous input,and strong hydrodynamic activity,SSIs were well developed.In the middle depositional period,as the climate gradually transitioned to more humid conditions,and the weathering intensity and amount of terrestrial input increased,the development of SIs and SFIs significantly increased.During the late depositional period,with a continuous decrease in terrestrial inputs and sedimentation rates,the development of SIs decreased while that of SSIs increased.展开更多
Phenanthrene(Phe)is one of the common polycyclic aromatic hydrocarbons in the environment,and recent studies show that it can cause cardiac developmental toxicity and immunotoxicity.However,it is still unknown whether...Phenanthrene(Phe)is one of the common polycyclic aromatic hydrocarbons in the environment,and recent studies show that it can cause cardiac developmental toxicity and immunotoxicity.However,it is still unknown whether it can affect the hematopoietic development in aquatic organisms.To address this question,zebrafish(Danio rerio)were chronically exposed to Phe at different concentrations.We found that Phe caused structural damage to the renal tubules in the kidney,induced malformed erythrocytes in peripheral blood,and decreased the proportion of myeloid cells in adult zebrafish,suggesting possible negative impacts that Phe posed to hematopoietic development.Then,using in situ hybridization technology,we found that Phe decreased the expression of primitive hematopoietic marker genes,specifically gata1 and pu.1,accompanied by an obstruction of primitive erythrocyte circulation.Furthermore,Phe impaired definitive hematopoiesis,increased aberrations of the transient hematopoietic site(PBI),and reduced the generation of hematopoietic stem cells,ultimately influencing the number of erythrocytes and myeloid cells.The findings suggested that Phe could induce hematopoietic toxicity in zebrafish embryos and pose unknown ecological risks.展开更多
Artificial intelligence(AI)is revolutionizing traditional drug discovery and development models by seamlessly integrating data,computational power,and algorithms.This synergy enhances the efficiency,accuracy,and succe...Artificial intelligence(AI)is revolutionizing traditional drug discovery and development models by seamlessly integrating data,computational power,and algorithms.This synergy enhances the efficiency,accuracy,and success rates of drug research,shortens development timelines,and reduces costs.Coupled with machine learning(ML)and deep learning(DL),AI has demonstrated significant advancements across various domains,including drug characterization,target discovery and validation,small molecule drug design,and the acceleration of clinical trials.Through molecular generation techniques,AI facilitates the creation of novel drug molecules,predicting their properties and activities,while virtual screening(VS)optimizes drug candidates.Additionally,AI enhances clinical trial efficiency by predicting outcomes,designing trials,and enabling drug repositioning.However,AI's application in drug development faces challenges,including the need for robust data-sharing mechanisms and the establishment of more comprehensive intellectual property protections for algorithms.AI-driven pharmaceutical companies must also integrate biological sciences and algorithms effectively,ensuring the successful fusion of wet and dry laboratory experiments.Despite these challenges,the potential of AI in drug development remains undeniable.As AI technology evolves and these barriers are addressed,AI-driven therapeutics are poised for a broader and more impactful future in the pharmaceutical industry.展开更多
The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:tho...The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:those containing LRR domains along with other structural elements,which are further subdivided into five groups,LRR receptor-like kinases,LRR receptor-like proteins,nucleotide-binding site LRR proteins,LRR-extensin proteins,and polygalacturonase-inhibiting proteins,and those containing only LRR domains.Functionally,various LRR proteins are primarily involved in plant development and responses to environmental stress.Notably,the LRR protein family plays a central role in signal transduction pathways related to stress adaptation.In this review,we classify and analyze the functions of LRR proteins in plants.While extensive research has been conducted on the roles of LRR proteins in disease resistance signaling,these proteins also play important roles in abiotic stress responses.This review highlights recent advances in understanding how LRR proteins mediate responses to biotic and abiotic stresses.Building upon these insights,further exploration of the roles of LRR proteins in abiotic stress resistance may aid efforts to develop rice varieties with enhanced stress and disease tolerance.展开更多
The mountainous rural regions of China are undergoing enormous changes in space and time.To a certain extent,this change has increased the difficulties in our understanding of rural development in mountainous areas an...The mountainous rural regions of China are undergoing enormous changes in space and time.To a certain extent,this change has increased the difficulties in our understanding of rural development in mountainous areas and brought challenges to development policies and revitalization strategies in mountainous rural regions,especially in karst mountainous areas.In light of the difficulty in and as the key to the development of China's mountainous rural areas,the scientific and systematic construction of indicators for evaluating the level of rural revitalization development and clarifying the level of rural revitalization development and influential factors in karst mountainous areas are of great significance to the implementation of the development of the strategy for the revitalization of the rural areas in karst mountainous areas in China.This study constructed an evaluation index system of the rural regional system and rural revitalization development(RTSRD)from the perspective of rural regional system theory,assessed the spatial differentiation patterns and influential factors of RTSRD,and refined a typical territorial model of rural revitalization development in karst mountainous areas by taking Guizhou Province,a typical karst mountainous region,as a case study area.The evaluation and spatial analyses show that the RTSRD indices of karst mountainous areas in the system perspective show a linear growth trend in all single dimensions,with industrial revitalization(IR)showing the most significant increase each year.In time,the RTSRD of karst mountainous regions has developed from low to high,with evident improvement;spatially,the RTSRD shows the characteristics of‘high in the middle and low in the surroundings,and low in the plateau and low in the depression,'with apparent spatial heterogeneity.In addition,this study found that the spatial and temporal differences in RTSRD result from a combination of endogenous push and exogenous pull in the rural system.In particular,this study has refined a typical regional model of rural revitalization development in karst mountainous regions,which provides theoretical support and case practice for rural development in other karst mountainous regions.At the same time,it provides a basis for decision-making for the county level government and rural development planning.展开更多
Investigations into rail corrugation within metro systems have traditionally focused on specific mechanisms,thereby limiting the generalizability of proposed theories.Understanding the commonalities in rail corrugatio...Investigations into rail corrugation within metro systems have traditionally focused on specific mechanisms,thereby limiting the generalizability of proposed theories.Understanding the commonalities in rail corrugation across diverse metro lines remains pivotal for elucidating its underlying mechanisms.The present study conducted extensive field surveys and tracking tests across 14 Chinese metro lines.By employing t-distributed stochastic neighbor embedding(t-SNE)for dimensional reduction and employing the unsupervised clustering algorithm DBSCAN,the research redefines the classification of metro rail corrugation based on characteristic information.The analysis encompassed spatial distribution and temporal evolution of this phenomenon.Findings revealed that floating slab tracks exhibited the highest proportion of rail corrugation at 47%.Notably,ordinary monolithic bed tracks employing damping fasteners were more prone to inducing rail corrugation.Corrugation primarily manifested in curve sections with radii between 300 and 500 m,featuring ordinary monolithic bed track and steel-spring floating slab track structures,with wavelengths typically between 30 and 120 mm.Stick–slip vibrations of the wheel–rail system maybe led to short-wavelength corrugations(40–60 mm),while longer wavelengths(200–300 mm)exhibited distinct fatigue damage characteristics,mainly observed in steel-spring floating slab tracks and small-radius curve sections of ordinary monolithic bed tracks and ladder sleeper tracks.A classification system comprising 57 correlated features categorized metro rail corrugation into four distinct types.These research outcomes serve as critical benchmarks for validating various theories pertaining to rail corrugation formation.展开更多
This study investigates the coordination between regional economic growth and ecological sustainability within the context of high-quality town economy development.To address the challenges of balancing economic expan...This study investigates the coordination between regional economic growth and ecological sustainability within the context of high-quality town economy development.To address the challenges of balancing economic expansion with environmental protection,a comprehensive evaluation index system is constructed,encompassing two key dimensions:regional economy and ecological environment.Using panel data from 2013 to 2022,the coupling coordination degree model is employed to quantify the interactions and synergy between these dimensions.Additionally,spatial econometric methods are applied to calculate both global and local Moran’s Index,revealing spatial clustering patterns,regional disparities,and heterogeneity.The relative development model further identifies critical factors influencing regional coordination,with a focus on the lagging development of basic infrastructure and public services.The findings demonstrate a positive temporal trend toward improved regional coordination and reduced development gaps,with a spatial pattern characterized by higher coupling degrees in eastern and central regions compared to western areas.Based on these results,this study proposes actionable strategies to enhance coordinated development,emphasizing ecological conservation,the establishment of green production and consumption systems,ecological restoration,and strengthened municipal collaboration.This revised abstract emphasizes the study’s purpose,methods,and key findings more clearly while maintaining a professional and concise tone.Finally,based on the above analysis results,the corresponding coordinated development suggestions of regional economy and ecological environment are given from the aspects of ecological environment protection measures,green production and consumption system construction,ecological environment restoration and municipal coordination.展开更多
DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Ca...DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Camellia sinensis).In this study,we combined the methylome,transcriptome,and metabolome to investigate the dynamic changes in DNA methylation and its potential regulatory roles in secondary metabolite biosynthesis.In this study,the level of genomic DNA methylation increased as leaf development progressed from tender to old leaf.It additionally exhibited a similar distribution across the genomic background at the two distinct developmental stages studied.Notably,integrated analysis of transcriptomic and methylomic data showed that DNA hypermethylation primarily occurred in genes of the phenylpropanoid,flavonoid,and terpenoid biosynthesis pathways.The effect of methylation on transcription of these secondary metabolite biosynthesis genes was dependent on the location of methylation(i.e.,in the promoter,gene or intergenic regions)and the sequence context(i.e.,CpG,CHG,or CHH).Changes in the content of catechins and terpenoids were consistent with the changes in gene transcription and the methylation state of structural genes,such as serine carboxypeptidase-like acyltransferases 1A(SCPL1A),leucoanthocyanidin reductase(LAR),and nerolidol synthase(NES).Our study provides valuable information for dissecting the effects of DNA methylation on regulation of genes involved in secondary metabolism during tea leaf development.展开更多
文摘China is carving out a distinctive development path which features urban-rural integration.This approach has not only yielded tangible results domestically but also drawn the attention of other countries.
文摘China aims to build on its achievements of the past five years to accelerate rural revitalization during the 15th Five-Year Plan period.IN China,issues relating to agriculture,rural areas,and rural residents have always been a priority in national development.At its fourth plenary session held in October 2025,the 20th Central Committee of the Communist Party of China(CPC)once again emphasized the need to accelerate agricultural and rural modernization,and advance all-around rural revitalization over the next five years.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
文摘Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event for the English edition of the book’s fifth volume on 3 December 2025 in Johannesburg,South Africa.
基金the Strategic Research Plan of the Centre for Marine Technology and Ocean Engineering(CENTEC),which is financed by the Portuguese Foundation for Science and Technology(Fundação para a Ciência e a Tecnologia FCT)under contract UIDB/UIDP/00134/2020.
文摘This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and categorised into different groups of main early-stage decisions.The present study stands in contrast to the contributions of the operations research and system engineering review articles,on the one hand,and the petroleum engineering review articles,on the other.This is because it does not focus on one methodological approach,nor does it limit the literature analysis by offshore oilfield characteristics.Consequently,the present analysis may offer valuable insights,for instance,by identifying environmental planning decisions as a recent yet highly significant concern that is currently being imposed on decision-making process.Thus,it is evident that the incorporation of safety criteria within the technical-economic decision-making process for the design of production systems would be a crucial requirement at development phase.
基金supported by grants from Simons Foundation (SFARI 479754),CIHR (PJT-180565)the Scottish Rite Charitable Foundation of Canada (to YL)funding from the Canada Research Chairs program。
文摘The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
基金supported by grants from the Deutsche Forschungsgemeinschaft(DFG)to MW.
文摘Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a lipid-rich myelin sheath,which enables the saltatory conduction of action potentials.During development,oligodendrocyte progenitor cells(OPCs)emerge from neural stem cells in the ventricular zone.They then proliferate,increase their number,and migrate to their final destination where they encounter unmyelinated neuronal axons and differentiate in a stepwise fashion into myelinating oligodendrocytes(mOLs)under the influence of environmental stimuli.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
基金supported by the National Natural Science Foundation of China(52074045,52274074)the Science Fund for Distinguished Young Scholars of Chongqing(CSTB2022NSCQ-JQX0028).
文摘Developing deep fragmented soft coalbed methane(CBM)can significantly enhance domestic natural gas supplies,reduce reliance on imported energy,and bolster national energy security.This manuscript provides a comprehensive review of commonly employed coalbed methane extraction technologies.It then delves into several critical issues in the current stage of CBM exploration and development in China,including the compatibility of existing technologies with CBM reservoirs,the characteristics and occurrence states of CBM reservoirs,critical desorption pressure,and gas generation mechanisms.Our research indicates that current CBM exploration and development technologies in China have reached an internationally advanced level,yet the industry is facing unprecedented challenges.Despite progress in low-permeability,high-value coal seams,significant breakthroughs have not been achieved in exploring other types of coal seams.For different coal reservoirs,integrated extraction technologies have been developed,such as surface pre-depressurisation and segmented hydraulic fracturing of coal seam roof strata.Additionally,techniques like large-scale volume fracturing in horizontal wells have been established,significantly enhancing reservoir stimulation effects and coalbed methane recovery rates.However,all of these technologies are fundamentally based on permeation.These technologies lack direct methods aimed at enhancing the diffusion rate of CBM,thereby failing to fully reflect the unique characteristics of CBM.Current CBM exploration and development theories and technologies are not universally applicable to all coal seams.They do not adequately account for the predominantly adsorbed state of CBM,and the complex and variable gas generation mechanisms further constrain CBM development in China.Finally,continuous exploration of new deep CBM exploration technologies is necessary.Integrating more effective reservoir stimulation technologies is essential to enhance technical adaptability concerning CBM reservoir characteristics,gas occurrence states,and gas generation mechanisms,ultimately achieving efficient CBM development.We conclude that while China possesses a substantial foundation of deep fractured CBM resources,industry development is constrained and requires continuous exploration of new CBM exploration and development technologies to utilize these resources effectively.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.
文摘The reform stems from honesty and determination. Since 2005, organ donation and transplantation in China has undergone thorough reform, which complies with legislation requirements and ethical principles established by the World Health Organization(WHO). Reform in China has demonstrated the unwavering confidence and utmost determination of the Chinese government and the Chinese transplantation community. The year 2015 marked a historic turning point when voluntary donations from Chinese citizens became the sole legitimate source for organ transplantation. Since 2015, China has gradually established and refined the “Chinese Mode” and “China System” for organ donation and transplantation, fulfilling its political pledge of reform, and has garnered international recognition, and fostered a social culture which promotes organ donation. This article reviewed the history of reform on organ donation and transplantation in China, presented a new pattern of establishment of organ donation system in the new era of the country, and the direction of advances in the future.
基金sponsored by the National Natural Science Foundation of China,China(No.42272171)National Science and Technology Major Project of China,China(No.2017ZX05036).
文摘Dongyuemiao Member shale in the Sichuan Basin,China,is characterized by organic-rich shale intervals with different types of interbeds and accumulation modes.The aim of this study is to elucidate the impact of paleoenvironmental indicators on interbed development.With this aim in mind,we established an interbed classification scheme and quantified the development of different types of interbeds and their frequencies.We categorized the shale interbeds into three types based on interbed type:silt interbeds(SIs),shell fragment interbeds(SFIs),and shell skeleton interbeds(SSIs).The SIs,SFIs,and SSIs are respectively the products of extrabasinal low-density turbidity currents,intrabasinal debris flow,and intrabasinal low-density turbidity currents.We propose that variations in paleoenvironmental conditions primarily influenced the types of interbeds that developed but had minimal impact on the frequency of their development.Models depicting the interbed development within the 1st Submember of Dongyuemiao Member indicate that during the early Dongyuemiao depositional period,under conditions of relatively aridity,weak weathering,high terrigenous input,and strong hydrodynamic activity,SSIs were well developed.In the middle depositional period,as the climate gradually transitioned to more humid conditions,and the weathering intensity and amount of terrestrial input increased,the development of SIs and SFIs significantly increased.During the late depositional period,with a continuous decrease in terrestrial inputs and sedimentation rates,the development of SIs decreased while that of SSIs increased.
基金supported by the National Natural Science Foundation of China(Nos.22276117 and 22076108)the Science and Technology Innovation Talent Team Project of Shanxi Province(No.202204051002024).
文摘Phenanthrene(Phe)is one of the common polycyclic aromatic hydrocarbons in the environment,and recent studies show that it can cause cardiac developmental toxicity and immunotoxicity.However,it is still unknown whether it can affect the hematopoietic development in aquatic organisms.To address this question,zebrafish(Danio rerio)were chronically exposed to Phe at different concentrations.We found that Phe caused structural damage to the renal tubules in the kidney,induced malformed erythrocytes in peripheral blood,and decreased the proportion of myeloid cells in adult zebrafish,suggesting possible negative impacts that Phe posed to hematopoietic development.Then,using in situ hybridization technology,we found that Phe decreased the expression of primitive hematopoietic marker genes,specifically gata1 and pu.1,accompanied by an obstruction of primitive erythrocyte circulation.Furthermore,Phe impaired definitive hematopoiesis,increased aberrations of the transient hematopoietic site(PBI),and reduced the generation of hematopoietic stem cells,ultimately influencing the number of erythrocytes and myeloid cells.The findings suggested that Phe could induce hematopoietic toxicity in zebrafish embryos and pose unknown ecological risks.
基金supported by the National Natural Science Foundation of China(Grant No.:82304564)the Liaoning Province Education Department Scientific Research Funding Project(Grant No.:LJKZ0777).
文摘Artificial intelligence(AI)is revolutionizing traditional drug discovery and development models by seamlessly integrating data,computational power,and algorithms.This synergy enhances the efficiency,accuracy,and success rates of drug research,shortens development timelines,and reduces costs.Coupled with machine learning(ML)and deep learning(DL),AI has demonstrated significant advancements across various domains,including drug characterization,target discovery and validation,small molecule drug design,and the acceleration of clinical trials.Through molecular generation techniques,AI facilitates the creation of novel drug molecules,predicting their properties and activities,while virtual screening(VS)optimizes drug candidates.Additionally,AI enhances clinical trial efficiency by predicting outcomes,designing trials,and enabling drug repositioning.However,AI's application in drug development faces challenges,including the need for robust data-sharing mechanisms and the establishment of more comprehensive intellectual property protections for algorithms.AI-driven pharmaceutical companies must also integrate biological sciences and algorithms effectively,ensuring the successful fusion of wet and dry laboratory experiments.Despite these challenges,the potential of AI in drug development remains undeniable.As AI technology evolves and these barriers are addressed,AI-driven therapeutics are poised for a broader and more impactful future in the pharmaceutical industry.
基金supported by the National Natural Science Foundation of China(Grant Nos.32072048 and U2004204)National Key Research and Development Program of China(Grant No.2023YFF1001200)+2 种基金China Rice Research Institute Basal Research Fund(Grant No.CPSIBRF-CNRRI-202404)Academician Workstation of National Nanfan Research Institute(Sanya),Chinese Agricultural Academic Science(CAAS),(Grant Nos.YBXM2422 and YBXM2423)Agricultural Science and Technology Innovation Program of CAAS,China.
文摘The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:those containing LRR domains along with other structural elements,which are further subdivided into five groups,LRR receptor-like kinases,LRR receptor-like proteins,nucleotide-binding site LRR proteins,LRR-extensin proteins,and polygalacturonase-inhibiting proteins,and those containing only LRR domains.Functionally,various LRR proteins are primarily involved in plant development and responses to environmental stress.Notably,the LRR protein family plays a central role in signal transduction pathways related to stress adaptation.In this review,we classify and analyze the functions of LRR proteins in plants.While extensive research has been conducted on the roles of LRR proteins in disease resistance signaling,these proteins also play important roles in abiotic stress responses.This review highlights recent advances in understanding how LRR proteins mediate responses to biotic and abiotic stresses.Building upon these insights,further exploration of the roles of LRR proteins in abiotic stress resistance may aid efforts to develop rice varieties with enhanced stress and disease tolerance.
基金supported by the National Natural Science Foundation of China(Grant No.42061035)the Guizhou Provincial Program on Commercialization of Scientific and Technological Achievements([2022]010)。
文摘The mountainous rural regions of China are undergoing enormous changes in space and time.To a certain extent,this change has increased the difficulties in our understanding of rural development in mountainous areas and brought challenges to development policies and revitalization strategies in mountainous rural regions,especially in karst mountainous areas.In light of the difficulty in and as the key to the development of China's mountainous rural areas,the scientific and systematic construction of indicators for evaluating the level of rural revitalization development and clarifying the level of rural revitalization development and influential factors in karst mountainous areas are of great significance to the implementation of the development of the strategy for the revitalization of the rural areas in karst mountainous areas in China.This study constructed an evaluation index system of the rural regional system and rural revitalization development(RTSRD)from the perspective of rural regional system theory,assessed the spatial differentiation patterns and influential factors of RTSRD,and refined a typical territorial model of rural revitalization development in karst mountainous areas by taking Guizhou Province,a typical karst mountainous region,as a case study area.The evaluation and spatial analyses show that the RTSRD indices of karst mountainous areas in the system perspective show a linear growth trend in all single dimensions,with industrial revitalization(IR)showing the most significant increase each year.In time,the RTSRD of karst mountainous regions has developed from low to high,with evident improvement;spatially,the RTSRD shows the characteristics of‘high in the middle and low in the surroundings,and low in the plateau and low in the depression,'with apparent spatial heterogeneity.In addition,this study found that the spatial and temporal differences in RTSRD result from a combination of endogenous push and exogenous pull in the rural system.In particular,this study has refined a typical regional model of rural revitalization development in karst mountainous regions,which provides theoretical support and case practice for rural development in other karst mountainous regions.At the same time,it provides a basis for decision-making for the county level government and rural development planning.
基金support extended by the Joint Funds of Beijing Municipal Natural Science Foundation and Fengtai Rail Transit Frontier Research(Grant No.L211006)the Fundamental Research Funds for the Central Universities(Science and technology leading talent team project,Grant No.2022JBXT010)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.2023YJS052)the National Natural Science Foundation of China(Grant No.52308426)。
文摘Investigations into rail corrugation within metro systems have traditionally focused on specific mechanisms,thereby limiting the generalizability of proposed theories.Understanding the commonalities in rail corrugation across diverse metro lines remains pivotal for elucidating its underlying mechanisms.The present study conducted extensive field surveys and tracking tests across 14 Chinese metro lines.By employing t-distributed stochastic neighbor embedding(t-SNE)for dimensional reduction and employing the unsupervised clustering algorithm DBSCAN,the research redefines the classification of metro rail corrugation based on characteristic information.The analysis encompassed spatial distribution and temporal evolution of this phenomenon.Findings revealed that floating slab tracks exhibited the highest proportion of rail corrugation at 47%.Notably,ordinary monolithic bed tracks employing damping fasteners were more prone to inducing rail corrugation.Corrugation primarily manifested in curve sections with radii between 300 and 500 m,featuring ordinary monolithic bed track and steel-spring floating slab track structures,with wavelengths typically between 30 and 120 mm.Stick–slip vibrations of the wheel–rail system maybe led to short-wavelength corrugations(40–60 mm),while longer wavelengths(200–300 mm)exhibited distinct fatigue damage characteristics,mainly observed in steel-spring floating slab tracks and small-radius curve sections of ordinary monolithic bed tracks and ladder sleeper tracks.A classification system comprising 57 correlated features categorized metro rail corrugation into four distinct types.These research outcomes serve as critical benchmarks for validating various theories pertaining to rail corrugation formation.
基金support from Guangdong Science and Technology(20230505)Guangdong Provincial Philosophy and Social Science Planning Project(GD20SQ25)Guangdong Provincial Special Fund for Science and Technology Innovation Strategy in 2024(Cultivation of College Students’Science and Technology Innovation)(pdjh2024a391)during preparation of this manuscript.
文摘This study investigates the coordination between regional economic growth and ecological sustainability within the context of high-quality town economy development.To address the challenges of balancing economic expansion with environmental protection,a comprehensive evaluation index system is constructed,encompassing two key dimensions:regional economy and ecological environment.Using panel data from 2013 to 2022,the coupling coordination degree model is employed to quantify the interactions and synergy between these dimensions.Additionally,spatial econometric methods are applied to calculate both global and local Moran’s Index,revealing spatial clustering patterns,regional disparities,and heterogeneity.The relative development model further identifies critical factors influencing regional coordination,with a focus on the lagging development of basic infrastructure and public services.The findings demonstrate a positive temporal trend toward improved regional coordination and reduced development gaps,with a spatial pattern characterized by higher coupling degrees in eastern and central regions compared to western areas.Based on these results,this study proposes actionable strategies to enhance coordinated development,emphasizing ecological conservation,the establishment of green production and consumption systems,ecological restoration,and strengthened municipal collaboration.This revised abstract emphasizes the study’s purpose,methods,and key findings more clearly while maintaining a professional and concise tone.Finally,based on the above analysis results,the corresponding coordinated development suggestions of regional economy and ecological environment are given from the aspects of ecological environment protection measures,green production and consumption system construction,ecological environment restoration and municipal coordination.
基金supported by the Natural Science Foundation of Guangdong Province(Grant Nos.2022A1515111141 and 2023A1515010786)。
文摘DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Camellia sinensis).In this study,we combined the methylome,transcriptome,and metabolome to investigate the dynamic changes in DNA methylation and its potential regulatory roles in secondary metabolite biosynthesis.In this study,the level of genomic DNA methylation increased as leaf development progressed from tender to old leaf.It additionally exhibited a similar distribution across the genomic background at the two distinct developmental stages studied.Notably,integrated analysis of transcriptomic and methylomic data showed that DNA hypermethylation primarily occurred in genes of the phenylpropanoid,flavonoid,and terpenoid biosynthesis pathways.The effect of methylation on transcription of these secondary metabolite biosynthesis genes was dependent on the location of methylation(i.e.,in the promoter,gene or intergenic regions)and the sequence context(i.e.,CpG,CHG,or CHH).Changes in the content of catechins and terpenoids were consistent with the changes in gene transcription and the methylation state of structural genes,such as serine carboxypeptidase-like acyltransferases 1A(SCPL1A),leucoanthocyanidin reductase(LAR),and nerolidol synthase(NES).Our study provides valuable information for dissecting the effects of DNA methylation on regulation of genes involved in secondary metabolism during tea leaf development.
