The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
Long-life energy storage batteries are integral to energy storage systems and electric vehicles,with lithium-ion batteries(LIBs)currently being the preferred option for extended usage-life energy storage.To further ex...Long-life energy storage batteries are integral to energy storage systems and electric vehicles,with lithium-ion batteries(LIBs)currently being the preferred option for extended usage-life energy storage.To further extend the life span of LIBs,it is essential to intensify investments in battery design,manufacturing processes,and the advancement of ancillary materials.The pursuit of long durability introduces new challenges for battery energy density.The advent of electrode material offers effective support in enhancing the battery’s long-duration performance.Often underestimated as part of the cathode composition,the binder plays a pivotal role in the longevity and electrochemical performance of the electrode.Maintaining the mechanical integrity of the electrode through judicious binder design is a fundamental requirement for achieving consistent long-life cycles and high energy density.This paper primarily concentrates on the commonly employed cathode systems in lithium-ion batteries,elucidates the significance of binders for both,discusses the application status,strengths,and weaknesses of novel binders,and ultimately puts forth corresponding optimization strategies.It underscores the critical function of binders in enhancing battery performance and advancing the sustainable development of lithium-ion batteries,aiming to offer fresh insights and perspectives for the design of high-performance LIBs.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
Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.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
As African economies continue to expand their trade networks,digital transformation and e-commerce have emerged as key drivers of economic development.Ethiopia has embraced this trend,aiming to modernise its logistics...As African economies continue to expand their trade networks,digital transformation and e-commerce have emerged as key drivers of economic development.Ethiopia has embraced this trend,aiming to modernise its logistics and aviation infrastructure to meet the growing demand.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
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 critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a pati...The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.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
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
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
Brassinosteroids(BRs),a class of plant-specific steroidal hormones,play crucial roles in regulating various plant physiological functions,such as growth,development,and adaptability to the environment.Despite this bro...Brassinosteroids(BRs),a class of plant-specific steroidal hormones,play crucial roles in regulating various plant physiological functions,such as growth,development,and adaptability to the environment.Despite this broader role of BRs,previously published reviews mainly focused on the molecular mechanisms of BR-mediated regulation of vegetative and reproductive growth of model plants like Arabidopsis and some food crops,such as rice,maize,and wheat.While horticultural plants hold significant economic importance in modern agriculture,less attention has been paid to understanding the role of BRs in regulating the physiological functions of these plants.Given the lack of relevant reviews,this article aims to discuss the major roles of BRs in horticultural plants,particularly fruit and leaf development,whole plant architecture,and adaptive stress response.We also highlight key challenges and provide some future research directions for genetically improving horticultural plants by altering the BR signaling pathway.展开更多
In the wave of digital and intelligent applications,artificial intelligence(AI)is transforming the development trajectories of industries across the globe.Traditional Chinese medicine(TCM),as a cultural treasure of th...In the wave of digital and intelligent applications,artificial intelligence(AI)is transforming the development trajectories of industries across the globe.Traditional Chinese medicine(TCM),as a cultural treasure of the Chinese nation,carries thousands of years of wisdom and practical experience.However,in the context of the rapid advancements in modern medicine and technology,TCM faces dual challenges:preserving its heritage while innovating.DeepSeek,a major achievement in the field of AI,offers a new opportunity for the development of TCM with its powerful technological capabilities.Exploring the integration of DeepSeek with TCM not only helps modernize the practice but also promises unique contributions to global health.展开更多
The rapid urbanization and increasing challenges are faced by cities globally,including climate change,population growth,and resource constraints.Sustainable smart city(also referred to as“smart sustainable city”)ca...The rapid urbanization and increasing challenges are faced by cities globally,including climate change,population growth,and resource constraints.Sustainable smart city(also referred to as“smart sustainable city”)can offer innovative solutions by integrating advanced technologies to build smarter,greener,and more livable urban environments with significant benefits.Using the Web of Science(WoS)database,this study examined:(i)the mainstream approaches and current research trends in the literature of sustainable smart city;(ii)the extent to which the research of sustainable smart city aligns with Sustainable Development Goals(SDGs);(iii)the current topics and collaboration patterns in sustainable smart city research;and(iv)the potential opportunities for future research on the sustainable smart city field.The findings indicated that research on sustainable smart city began in 2010 and gained significant momentum in 2013,with China leading,followed by Italy and Spain.Moreover,59.00%of the selected publications on the research of sustainable smart city focus on SDG 11(Sustainable Cities and Communities).Bibliometric analysis outcome revealed that artificial intelligence(AI),big data,machine learning,and deep learning are emerging research fields.The terms smart city,smart cities,and sustainability emerged as the top three co-occurring keywords with the highest link strength,followed by frequently co-occurring keywords such as AI,innovation,big data,urban governance,resilience,machine learning,and Internet of Things(IoT).The clustering results indicated that current studies explored the theoretical foundation,challenges,and future prospects of sustainable smart city,with an emphasis on sustainability.To further support urban sustainability and the attainment of SDGs,the future research of sustainable smart city should explore the application and implications of AI and big data on urban development including cybersecurity and governance challenges.展开更多
Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination...Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion.This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence,aiming to provide general guidance on appropriate imaging examination selection,comprehensive and accurate imaging assessment for early orthodontic treatment patients.展开更多
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
基金We would like to show gratitude to the Yunnan Province Basic Research Major Project(202501BC070006(Y.Wang))Key Industry Science and Technology Projects for University Services in Yunnan Province(FWCY ZNT2024002(Y.Wang))+3 种基金National Natural Science Foundation of China(22279070(L.Wang))and(U21A20170(X.He))the Ministry of Science and Technology of China(2019YFA0705703(L.Wang))Beijing Natural Science Foundation(L242005(X.He))Key Industry Science and Technology Projects for University Services in Yunnan Province(FWCY BSPY2024011(T.Lai)).
文摘Long-life energy storage batteries are integral to energy storage systems and electric vehicles,with lithium-ion batteries(LIBs)currently being the preferred option for extended usage-life energy storage.To further extend the life span of LIBs,it is essential to intensify investments in battery design,manufacturing processes,and the advancement of ancillary materials.The pursuit of long durability introduces new challenges for battery energy density.The advent of electrode material offers effective support in enhancing the battery’s long-duration performance.Often underestimated as part of the cathode composition,the binder plays a pivotal role in the longevity and electrochemical performance of the electrode.Maintaining the mechanical integrity of the electrode through judicious binder design is a fundamental requirement for achieving consistent long-life cycles and high energy density.This paper primarily concentrates on the commonly employed cathode systems in lithium-ion batteries,elucidates the significance of binders for both,discusses the application status,strengths,and weaknesses of novel binders,and ultimately puts forth corresponding optimization strategies.It underscores the critical function of binders in enhancing battery performance and advancing the sustainable development of lithium-ion batteries,aiming to offer fresh insights and perspectives for the design of high-performance LIBs.
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 Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
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.
文摘As African economies continue to expand their trade networks,digital transformation and e-commerce have emerged as key drivers of economic development.Ethiopia has embraced this trend,aiming to modernise its logistics and aviation infrastructure to meet the growing demand.
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,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 critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.
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 National Natural Science Foundation of China(grants 32030005,32470325,32400288)GuangDong Basic and Applied Basic Research Foundation(grant 2023A1515110339)internal funding from Guangzhou University.
文摘Brassinosteroids(BRs),a class of plant-specific steroidal hormones,play crucial roles in regulating various plant physiological functions,such as growth,development,and adaptability to the environment.Despite this broader role of BRs,previously published reviews mainly focused on the molecular mechanisms of BR-mediated regulation of vegetative and reproductive growth of model plants like Arabidopsis and some food crops,such as rice,maize,and wheat.While horticultural plants hold significant economic importance in modern agriculture,less attention has been paid to understanding the role of BRs in regulating the physiological functions of these plants.Given the lack of relevant reviews,this article aims to discuss the major roles of BRs in horticultural plants,particularly fruit and leaf development,whole plant architecture,and adaptive stress response.We also highlight key challenges and provide some future research directions for genetically improving horticultural plants by altering the BR signaling pathway.
文摘In the wave of digital and intelligent applications,artificial intelligence(AI)is transforming the development trajectories of industries across the globe.Traditional Chinese medicine(TCM),as a cultural treasure of the Chinese nation,carries thousands of years of wisdom and practical experience.However,in the context of the rapid advancements in modern medicine and technology,TCM faces dual challenges:preserving its heritage while innovating.DeepSeek,a major achievement in the field of AI,offers a new opportunity for the development of TCM with its powerful technological capabilities.Exploring the integration of DeepSeek with TCM not only helps modernize the practice but also promises unique contributions to global health.
文摘The rapid urbanization and increasing challenges are faced by cities globally,including climate change,population growth,and resource constraints.Sustainable smart city(also referred to as“smart sustainable city”)can offer innovative solutions by integrating advanced technologies to build smarter,greener,and more livable urban environments with significant benefits.Using the Web of Science(WoS)database,this study examined:(i)the mainstream approaches and current research trends in the literature of sustainable smart city;(ii)the extent to which the research of sustainable smart city aligns with Sustainable Development Goals(SDGs);(iii)the current topics and collaboration patterns in sustainable smart city research;and(iv)the potential opportunities for future research on the sustainable smart city field.The findings indicated that research on sustainable smart city began in 2010 and gained significant momentum in 2013,with China leading,followed by Italy and Spain.Moreover,59.00%of the selected publications on the research of sustainable smart city focus on SDG 11(Sustainable Cities and Communities).Bibliometric analysis outcome revealed that artificial intelligence(AI),big data,machine learning,and deep learning are emerging research fields.The terms smart city,smart cities,and sustainability emerged as the top three co-occurring keywords with the highest link strength,followed by frequently co-occurring keywords such as AI,innovation,big data,urban governance,resilience,machine learning,and Internet of Things(IoT).The clustering results indicated that current studies explored the theoretical foundation,challenges,and future prospects of sustainable smart city,with an emphasis on sustainability.To further support urban sustainability and the attainment of SDGs,the future research of sustainable smart city should explore the application and implications of AI and big data on urban development including cybersecurity and governance challenges.
基金supports by the National Natural Science Foundation of China(Nos.82201135)"2015"Cultivation Program for Reserve Talents for Academic Leaders of Nanjing Stomatological School,Medical School of Nanjing University(No.0223A204).
文摘Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion.This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence,aiming to provide general guidance on appropriate imaging examination selection,comprehensive and accurate imaging assessment for early orthodontic treatment patients.
