With the basic characteristics of conventional horizontal wells,the so-called complex wells including horizontal extended-reach wells,multi-lateral horizontal wells,U-shaped wells,cluster horizontal wells,etc.,are adv...With the basic characteristics of conventional horizontal wells,the so-called complex wells including horizontal extended-reach wells,multi-lateral horizontal wells,U-shaped wells,cluster horizontal wells,etc.,are advanced well types for the efficient development of low-permeability,unconventional,deep-water,and deep oil and gas reservoirs,which have been highly concerned all over the world.Significant progress at home and abroad has been made in relevant researches and practices and is expected to play an important role in the efficient development of shale oil and gas.To meet the basic needs of environment&safety,land conservation,cost reducing and efficiency improving,it is urgent to create a unique and efficient mode for developing shale gas.Therefore,an efficient shale gas development mode for mountainous areas and an engineering and technical support system are presented based on large cluster horizontal-well engineering.An equation is thus obtained for calculating the maximum number of horizontal wells arranged allowably in“Well Factory”on a single platform.The general research and development of large extended-reach well technology are analyzed by expounding the basic concept of an extended-reach well and its drilling extension limit.And a calculation method is thus established to predict the maximum measured depth of open hole in extended-reach drilling.Moreover,some relevant research results and their significance for downhole tubular mechanics&mechanical extension limits in extended-reach drilling are also briefly introduced in this paper.The conclusions are drawn that,by following the idea of“integration of geology and engineering”in oil and gas development,these research results have a foreseeable application prospect in shale gas development in the mountainous areas in the future,and will contribute to new progress in China's“Shale Revolution”.展开更多
Through literature analysis and case study, the introduction history, variety selection (high bush, half high bush, low bush) and regional cultivation techniques of blueberry in China were summarized, and the practica...Through literature analysis and case study, the introduction history, variety selection (high bush, half high bush, low bush) and regional cultivation techniques of blueberry in China were summarized, and the practical effects of precision cultivation (water and fertilizer integration, wild planting) and under-forest economic model (forest-blueberry-fungus system, ecological tourism) were evaluated. It provided a technical reference for expanding the planting scale of blueberry and improving the fruit quality.展开更多
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
The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base edit...The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.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
基金supported by National Natural Science Foundation of China(Grant numbers:51821092 and U1762214)。
文摘With the basic characteristics of conventional horizontal wells,the so-called complex wells including horizontal extended-reach wells,multi-lateral horizontal wells,U-shaped wells,cluster horizontal wells,etc.,are advanced well types for the efficient development of low-permeability,unconventional,deep-water,and deep oil and gas reservoirs,which have been highly concerned all over the world.Significant progress at home and abroad has been made in relevant researches and practices and is expected to play an important role in the efficient development of shale oil and gas.To meet the basic needs of environment&safety,land conservation,cost reducing and efficiency improving,it is urgent to create a unique and efficient mode for developing shale gas.Therefore,an efficient shale gas development mode for mountainous areas and an engineering and technical support system are presented based on large cluster horizontal-well engineering.An equation is thus obtained for calculating the maximum number of horizontal wells arranged allowably in“Well Factory”on a single platform.The general research and development of large extended-reach well technology are analyzed by expounding the basic concept of an extended-reach well and its drilling extension limit.And a calculation method is thus established to predict the maximum measured depth of open hole in extended-reach drilling.Moreover,some relevant research results and their significance for downhole tubular mechanics&mechanical extension limits in extended-reach drilling are also briefly introduced in this paper.The conclusions are drawn that,by following the idea of“integration of geology and engineering”in oil and gas development,these research results have a foreseeable application prospect in shale gas development in the mountainous areas in the future,and will contribute to new progress in China's“Shale Revolution”.
文摘Through literature analysis and case study, the introduction history, variety selection (high bush, half high bush, low bush) and regional cultivation techniques of blueberry in China were summarized, and the practical effects of precision cultivation (water and fertilizer integration, wild planting) and under-forest economic model (forest-blueberry-fungus system, ecological tourism) were evaluated. It provided a technical reference for expanding the planting scale of blueberry and improving the fruit quality.
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 Beijing Scholars Program[BSP041]。
文摘The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.
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.
