Triterpenoids are valuable medicinal scaffolds,characterized by excellent pharmacological properties and the presence of hydroxyl and carboxyl groups that allow for further structural modifications.Expanding the scope...Triterpenoids are valuable medicinal scaffolds,characterized by excellent pharmacological properties and the presence of hydroxyl and carboxyl groups that allow for further structural modifications.Expanding the scope of oxidative modifications on these molecules is crucial for increasing their synthetic structural diversity and unlocking new potential pharmacological activities.However,the progress has been limited by the scarcity of suitable tailoring enzymes.Here,we reported a break-through in achieving targeted and remote dual-site oxidation of licorice triterpenoids using a single P450 mutant.This approach successfully enabled the selective synthesis of the rare triterpenoid,liquiritic acid and 24-OH-liquiritic acid.Our findings demonstrate that microenvironmental accessibility engineering of triterpenoid substrates within the P450 enzyme is essential for continuous and regioselective oxidation.This study not only sheds light on the mechanistic aspects of P450 catalysis but also expands the enzymatic toolkit for selective oxidative modifications in triterpenoid biosynthesis.展开更多
Background:Home accessibility modifi cations are crucial for promoting independent living and quality of life among persons with disabilities.While developed countries have established comprehensive policy frameworks,...Background:Home accessibility modifi cations are crucial for promoting independent living and quality of life among persons with disabilities.While developed countries have established comprehensive policy frameworks,developing nations like China face unique challenges in program design and implementation.Objective:This study conducts a systematic comparative analysis of home accessibility modification policies across China,Japan,Germany,and Sweden,identifying key policy dimensions and proposing evidence-based recommendations for strengthening China’s policy framework.Methods:We employed a multi-dimensional analytical framework examining legislative foundations,eligibility criteria,funding mechanisms,and service delivery models.Data were collected from primary legislation,governmental regulations,official statistics,and peer-reviewed literature.Results:Significant cross-national variations exist in policy approaches.Japan and Germany utilize social insurance models with standardized assessments,Sweden adopts a universal rights-based approach,while China employs a targeted assistance model focused on economically disadvantaged households.China completed 1.28 million household renovations during its 14th Five-Year Plan,demonstrating strong implementation capacity;future policy refi nement could draw on international experience to strengthen assessment standardization,broaden eff ective coverage,and improve the sustainability of fi nancing.Conclusions:China can benefi t from international experience in developing standardized assessment protocols,diversifying funding mechanisms,and establishing professional service delivery systems,while acknowledging contextual constraints unique to developing country settings.展开更多
Background Endometrial receptivity(ERE)is a transient uterine state that determines the success of blastocyst implantation;however,the epigenomic regulation underlying ERE establishment in goats remains unclear.Here,w...Background Endometrial receptivity(ERE)is a transient uterine state that determines the success of blastocyst implantation;however,the epigenomic regulation underlying ERE establishment in goats remains unclear.Here,we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats,utilizing RNA-seq,ATAC-seq,and H3 K27 ac CUT&Tag.Results A total of 3,143 differentially expressed genes(DEGs)were identified,accompanied by significant alterations in chromatin accessibility and H3 K27 ac modifications between receptive and non-receptive endometria.The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion,immune tolerance,and embryo attachment.Motif enrichment and transcription factor(TF)footprinting analyses identified members of the FOS/JUN,SOX,HNF1,CEBP,and BATF families as candidate regulators,implicating downstream genes involved in ERE establishment,including SPP1,FOXO1,KLF4/6,STAT1,IFI6,ITGB8,PLAC8,DUSP4,NR1D1,ISG15,RUFY4,and PIK3R3.In addition,numerous super-enhancers were identified,indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium.Integration of multi-omics datasets revealed a strong correlation(r>0.7)among chromatin accessibility,H3 K27 ac activation,and the expression of 172 DEGs.Furthermore,a set of hub genes(KLF6,IFI6,MCL1,SDC4,SUSD6,MAFF,and IL6R)that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.Conclusions Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation.These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.展开更多
The accessibility of urban public transit directly influences residents’quality of life,travel behavior,and social equity.Its correlation with housing prices has garnered significant attention across disciplines such...The accessibility of urban public transit directly influences residents’quality of life,travel behavior,and social equity.Its correlation with housing prices has garnered significant attention across disciplines such as geography,economics,and urban planning.Although much existing research focuses on the impact of individual transportation facilities on housing prices,there is a notable gap in comprehensive analyses that assess the influence of overall urban transit accessibility on housing market dynamics.This study selected the main urban area of Hefei,China,as a case to investigate the spatial distribution of housing prices and evaluate public transit accessibility in 2022.Employing techniques such as the optimized parameter geographical detector and local spatial regression models,the study aimed to elucidate the effects and underlying mechanisms of urban transit accessibility on housing prices.The findings revealed that:1)housing prices in Hefei exhibited a clustered spatial pattern,with high prices concentrated in the city center and lower prices in peripheral areas,forming three distinct high-price hotspots with a‘belt-like’distribution;2)public transit accessibility showed a‘coreperiphery’structure,with accessibility declining in a‘circumferential’pattern around the city center.Based on the‘housing price-accessibility’dimension,four categories were identified:high price-high accessibility(37.25%),high price-low accessibility(19.07%),low price-high accessibility(21.95%),and low price-low accessibility(21.73%);3)the impact of transit accessibility on housing prices was spatially heterogeneous,with bus travel showing the strongest explanatory power(0.692),followed by automobile,subway,and bicycle travel.The interaction of these transportation modes generated a synergistic effect on housing price differentiation,with most influencing factors contributing more than 25%.These findings offer valuable insights for optimizing the spatial distribution of public transit infrastructure and improving both urban housing quality and residents’living standards.展开更多
Central nervous system(CNS) axons fail to regenerate following brain or spinal cord injury(SCI),which typically leads to permanent neurological deficits.Peripheral nervous system axons,howeve r,can regenerate followin...Central nervous system(CNS) axons fail to regenerate following brain or spinal cord injury(SCI),which typically leads to permanent neurological deficits.Peripheral nervous system axons,howeve r,can regenerate following injury.Understanding the mechanisms that underlie this difference is key to developing treatments for CNS neurological diseases and injuries characterized by axonal damage.To initiate repair after peripheral nerve injury,dorsal root ganglion(DRG) neurons mobilize a pro-regenerative gene expression program,which facilitates axon outgrowth.展开更多
Under the background of‘the Belt and Road’and‘China-Mongolia-Russia Economic Corridor’initiatives,this paper studied the urban accessibility level,regional accessibility pattern and regional spatial effects along ...Under the background of‘the Belt and Road’and‘China-Mongolia-Russia Economic Corridor’initiatives,this paper studied the urban accessibility level,regional accessibility pattern and regional spatial effects along the Primorsky No.1 and No.2 transportation corridors.First,the evaluation of urban accessibility level with and without Primorsky No.1 and No.2 high-speed rails(HSRs)opening was conducted with two indicators,i.e.,the weighted average travel time,and the economic potential.After the evaluation,the spatial differentiation pattern of the accessibility changes with and without Primorsky No.1 and No.2 HSRs opening was performed respectively using ArcGIS.On these bases,the regional spatial effects brought by Primorsky No.1 and No.2 HSRs opening were studied.The results are as following.First,the urban accessibility level will be greatly improved by the opening of Primorsky No.1 and No.2 HSRs.All adjacent cities will be integrated into‘1 h HSR communication circle’and the whole journey will be integrated into‘4 h HSR communication circle’along Primorsky No.1 and No.2 corridors,respectively.The HSR accessibility of Primorsky No.1 corridor is stronger than that of Primorsky No.2 corridor.But the HSR accessibility improvement degree of Primorsky No.1 corridor is weaker than that of Primorsky No.2 corridor.Second,spatially,along Primorsky No.1 and No.2 corridors,the HSR accessibility level of the cities which are located in China is stronger than those cities located in Russia,showing the‘High West,Low East’patterns.The HSR accessibility improvement degree of the cities which are located in Russia and Sino-Russian border is stronger than those cities located in China,showing the‘High East,Low West’patterns.Third,Primorsky No.1 and No.2 corridors could connect the China’s‘Heilongjiang Land Sea Silk Road Economic Belt’and‘Changchun-Jilin-Tumen Development Pilot Zone’respectively,gradually involving into the development of China’s Harbin-Changchun Megalopolis.Relying on Harbin(China)and Changchun(China),Primorsky No.1 and No.2 HSRs could connect Northeast China-Beijing HSR,accelerating the diffusion of population,economy and other flows from China’s Beijing-Tianjin-Hebei Urban Agglomeration to Northeast China,and then to Russia’s Far East Federal District.Relying on Suifenhe(China)and Hunchun(China),Primorsky No.1 and No.2 HSRs could be conducive to the development of the second largest sea channels for Northeast China,creating the Northeast Asian Urban Belt,and new sea-rail intermodal pattern among China,Russia,Democratic People’s Republic of Korea,Japan and Republic of Korea.Relying on Vladivostok(Russia)and Zarubino(Russia),Primorsky No.1 and No.2 corridors could connect the‘Ice Silk Road’,building the‘Sino-Russian Northern Maritime Corridor’and‘Sino-Russian Arctic Blue Economic Areas’.展开更多
Over the 80 years since the United Nations was founded,international human rights law has undergone a dynamic and increasingly enriched process of evolution from universal declarations to formal treaties,and from proc...Over the 80 years since the United Nations was founded,international human rights law has undergone a dynamic and increasingly enriched process of evolution from universal declarations to formal treaties,and from proclamations of rights to institutionalized safeguards.As an integral part of the human rights system,the affirmation of the rights of persons with disabilities and the promotion of accessibility mark new breakthroughs and developments in international human rights law since the advent of the new century.展开更多
Since the 1970s,a series of international and national sources have supported the principle of accessibility,which slowly has become a statuary norm and a legislative obligation.Each country has implemented accessibil...Since the 1970s,a series of international and national sources have supported the principle of accessibility,which slowly has become a statuary norm and a legislative obligation.Each country has implemented accessibility through a singular policy.But in addition to the accessibility of a place or an activity,to inform about what is accessible is very important as well,and has not really taken off.Indeed,for disabled people,the difficulty lies not only with access to places and the use of resources,but also with the visibility of these resources.This means that information concerning accessibility has to be disclosed and provided effectively to disabled people,those involved with them and the relevant institutions.In different countries all over the world,many labels and pictograms have been created for this purpose and give information relating to accessibility.Using a socio-historical approach,we will present and analyze the different types of icons,symbols,pictograms and labels that have been put in place around the world and in France:what are they used for and for whom are they made?We will show that they are pointers which firstly reflect the diversity and range within the target group concerned by accessibility,and secondly the evolution of accessibility as a dynamic and ecological principle.展开更多
Ensuring the provision of accessible,affordable,and high-quality public services to all individuals aligns with one of the paramount aims of the United Nations’Sustainable Development Goals(SDGs).In the face of esca ...Ensuring the provision of accessible,affordable,and high-quality public services to all individuals aligns with one of the paramount aims of the United Nations’Sustainable Development Goals(SDGs).In the face of esca lating urbanization and a dwindling rural populace in China,reconstructing rural settlements to enhance public service accessibility has become a fundamental strategy for achieving the SDGs in rural areas.However,few stud ies have examined the optimal methods for rural settlement reconstruction that ensure accessible and equitable public services while considering multiple existing facilities and service provisions.This paper focuses on rural settlement reconstruction in the context of the SDGs,employing an inverted MCLP-CC(maximal coverage loca tion problem for complementary coverage)model to identify optimal rural settlements and a rank-based method for their relocation.Conducted in Changyuan,a county-level city in Henan Province,China,this study observed significant enhancements in both accessibility and equity following rural settlement reconstruction by utilizing the MH3SFCA(modified Huff 3-step floating catchment area)and the spatial Lorenz curve method.Remarkably,these improvements were achieved without the addition of new facilities,with the accessibility increasing by 44.21%,4.97%,and 3.11%;Gini coefficients decreasing by 19.53%,1.64%,and 3.18%;Ricci-Schutz coef-ficients decreasing by 21.09%,2.09%,and 4.33%for educational,medical,and cultural and sports facilities,respectively.It indicated that rural settlement reconstruction can bolster the accessibility and equity of public ser-vices by leveraging existing facilities.This paper provides a new framework for stakeholders to better reconstruct rural settlements and promote sustainable development in rural areas in China.展开更多
Multicriteria Decision Analysis(MCDA)has been integrated with GIS modelling by many studies to aid the decision-making process.This integration enhances modelling by incorporating spatial relationships and using advan...Multicriteria Decision Analysis(MCDA)has been integrated with GIS modelling by many studies to aid the decision-making process.This integration enhances modelling by incorporating spatial relationships and using advanced techniques,including the combination of Frequency Ratio(FR)and Analytical Hierarchical Process(AHP),also known as FR-AHP.Although methods like Two-Steps Floating Catchment Area(2SFCA),AHP,and FR are widely applied in measuring accessibility,they have limitations in terms of threshold sensitivity and subjectivity.Hence,this study used FR-AHP,which combines the data-driven strength of FR and the structured decision-making technique of AHP to provide a more reliable evaluation of spatial accessibility.This study aims to integrate FR-AHP with GIS to derive campus spatial accessibility in Shah Alam.Campus spatial accessibility can be measured by using location and distance between origin and destination,topological accessibility for nodes and paths,and contiguous accessibility for surfaces.Understanding these concepts is crucial for determining the appropriate technique.This study utilizedMCDA,GIS-basedFR,andAHPmethods tomodel spatial accessibility in activemobility andpublic transport areas,calculating estimation index values and analyzing comparisons between physical factors.A sample survey was conducted among the university’s students to gather information on their origin and destination,as well as the type of transportation used by students.The data were used in calculating the weightage of each physical factor using the FR-AHP method.Then,the Campus Spatial Accessibility Index(CSAI)was determined by using GIS IndexModelling.By using the model,the index was classified into five(5)classes from Very Low to Very High.The results show that Section 2 has the highest accessibility,while the area with the lowest accessibility index is Jalan Zamrud and Jalan Permata,located in Section 7.To analyze the efficiency of FR-AHP,the CSAI was also derived using theweightage derived fromFR only.The comparisons revealed that the results derived using FR-AHP are closer to reality than those derived using FR only,as it incorporates human preferences in accessibility.Hence,the findings suggest that the integration of FR-AHP could provide better CSAI than FR only.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is notorious for its aggressive progression and dismal prognosis,with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.AIM To dissect how multi...BACKGROUND Hepatocellular carcinoma(HCC)is notorious for its aggressive progression and dismal prognosis,with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.AIM To dissect how multilayered chromatin regulation sustains oncogenic transcription and tumor-stroma crosstalk in HCC,we combined multiomics single cell analysis.METHODS We integrated single-cell RNA sequencing and paired single-cell assay for transposase-accessible chromatin with sequencing data of HCC samples,complemented by bulk RNA sequencing validation across The Cancer Genome Atlas,Liver Cancer Institute,and GSE25907 cohorts.Cell type-specific chromatin architectures were resolved via ArchR,with regulatory hubs identified through peak-to-gene linkages and coaccessibility networks.Functional validation employed A485-mediated histone 3 lysine 27 acetylation suppression and small interfering RNA targeting DGAT1.RESULTS Malignant hepatocytes exhibited expanded chromatin accessibility profiles,characterized by increased numbers of accessible peaks and larger physical regions despite reduced peak intensity.Enhancer-like peaks enriched in malignant regulation,forming long-range hubs.Eighteen enhancer-like peak-related genes showed tumor-specific overexpression and diagnostic accuracy,correlating with poor prognosis.Intercellular coaccessibility analysis revealed tumor-stroma symbiosis via shared chromatin states.Pharmacological histone 3 lysine 27 acetylation inhibition paradoxically downregulated DGAT1,the hub gene most strongly regulated by chromatin accessibility.DGAT1 knockdown suppressed cell proliferation.CONCLUSION Multilayered chromatin reprogramming sustains HCC progression through tumor-stroma crosstalk and DGAT1-related oncogenic transcription,defining targetable epigenetic vulnerabilities.展开更多
Objective:The scarcity of healthcare resources and inadequate access to medical services in rural and remote areas are pervasive challenges many countries face,particularly in the developing world.Telemedicine,with it...Objective:The scarcity of healthcare resources and inadequate access to medical services in rural and remote areas are pervasive challenges many countries face,particularly in the developing world.Telemedicine,with its capacity to overcome geographical barriers and provide patients with real‐time medical services,has shown considerable potential in addressing these issues,attracting wide-spread attention.Compact medical communities and family doctor systems play important roles in improving healthcare accessibility.However,despite the critical nature of patients'perceptions of healthcare accessibility,research in this domain is sparse.This study aimed to explore the impact of telemedicine on rural residents'perceived healthcare accessibility in China,analyze the mechanisms underpinning this relationship,and elucidate the roles of compact medical communities and the family doctor system.Methods:Survey data from 3311 rural residents were analyzed using a probit model,instrumental variables,and subgroup regression analyses to ascertain causal effects,perform heterogeneity analysis,examine mechanisms,and ascertain the robustness of the findings.Results:Telemedicine significantly enhanced rural residents'perceived healthcare accessibility,with particularly notable benefits for those in sparsely populated areas,regions with high‐speed internet access,within the purview of compact healthcare consortiums,and those with access to family doctor services.Furthermore,telemedicine improved rural residents'perceived healthcare accessibility by encouraging the use of primary care services.Conclusion:Telemedicine in China has played a significant role in improving the perceived healthcare accessibility among rural residents and aiding in the reduction of disparities in accessibility across different demographic groups.This is consistent with the broader objective of achieving universal health coverage.However,the efficacy of telemedicine in enhancing healthcare accessibility is contingent upon certain preconditions.Policymakers must confront local infrastructure challenges,particularly regarding internet connectivity,when expanding telemedicine services to ensure their effective operation.The synergistic interaction observed between telemedicine,the family doctor system,and compact medical communities highlights the importance of integrating telemedicine into existing healthcare systems.Such integration could enhance collaboration with current healthcare frameworks,ensuring the provision of safe,accessible,and affordable healthcare services,and promoting the health and well‐being of local populations.展开更多
This study analyzes the spatial accessibility of key services in Caen,France,focusing on how different transport modes(car,bicycle,and public transit)influence access to essential services across the urban and suburba...This study analyzes the spatial accessibility of key services in Caen,France,focusing on how different transport modes(car,bicycle,and public transit)influence access to essential services across the urban and suburban landscape.Indeed,the introduction of traffic restrictions in towns with low emission zones encourages a detailed study,on a fine spatial scale,of the differences in accessibility between different modes of transport,for different services and for different journey times.Using spatial analysis techniques,we examine accessibility patterns in relation to services such as shops,healthcare,education,and tourism,highlighting significant disparities between transport modes.The findings reveal that car travel provides the highest accessibility across all service categories,particularly for healthcare and recreational services,while bicycle and public transit accessibility is more limited,especially in peripheral areas.A Principal Component Analysis(PCA)synthesizes the multimodal accessibility data,and hierarchical clustering identifies distinct patterns of accessibility using different transport modes across the city.The study further explores temporal trends in accessibility,showing how different modes perform over varying travel times.Based on these findings,we propose targeted policy interventions aimed at improving public transit,enhancing cycling infrastructure,decentralizing essential services,and promoting mixed-use urban development.Future research directions include examining socio-economic disparities,the impact of emerging mobility technologies,and the environmental implications of accessibility patterns.This research provides valuable insights for urban planners seeking to improve mobility equity and sustainability in urban areas.展开更多
In this paper,we propose a random access scheme termed sign-compute diversity slotted ALOHA(SCDSA).The SCDSA scheme combines diversity transmission with compute-and-forward.Without considering the capture effect and m...In this paper,we propose a random access scheme termed sign-compute diversity slotted ALOHA(SCDSA).The SCDSA scheme combines diversity transmission with compute-and-forward.Without considering the capture effect and multiple user detection techniques,our scheme can reach a high throughput of 0.98 without feedback under finite frame size settings,where the upper bound on performance is 1.Moreover,a lower bound on throughput performance is derived,which is tight in some parameter settings and can be used to approximate theoretical performance.Simulation results validate our analysis and confirm the advantages of our proposed scheme.展开更多
The performance of data restore is one of the key indicators of user experience for backup storage systems.Compared to the traditional offline restore process,online restore reduces downtime during backup restoration,...The performance of data restore is one of the key indicators of user experience for backup storage systems.Compared to the traditional offline restore process,online restore reduces downtime during backup restoration,allowing users to operate on already restored files while other files are still being restored.This approach improves availability during restoration tasks but suffers from a critical limitation:inconsistencies between the access sequence and the restore sequence.In many cases,the file a user needs to access at a given moment may not yet be restored,resulting in significant delays and poor user experience.To this end,we present Histore,which builds on the user’s historical access sequence to schedule the restore sequence,in order to reduce users’access delayed time.Histore includes three restore approaches:(i)the frequency-based approach,which restores files based on historical file access frequencies and prioritizes ensuring the availability of frequently accessed files;(ii)the graph-based approach,which preferentially restores the frequently accessed files as well as their correlated files based on historical access patterns,and(iii)the trie-based approach,which restores particular files based on both users’real-time and historical access patterns to deduce and restore the files to be accessed in the near future.We implement a prototype of Histore and evaluate its performance from multiple perspectives.Trace-driven experiments on two datasets show that Histore significantly reduces users’delay time by 4-700×with only 1.0%-14.5%additional performance overhead.展开更多
Avery significant event in China’s political calendar took place in Beijing in early March,and,as usual,it was more than optics.The fourth sessions of the 14th National People’s Congress(NPC)and the 14th National Co...Avery significant event in China’s political calendar took place in Beijing in early March,and,as usual,it was more than optics.The fourth sessions of the 14th National People’s Congress(NPC)and the 14th National Committee of the Chinese People’s Political Consultative Conference(CPPCC),the country’s top legislative and advisory bodies,are expected to set the course for China’s direction over the year and beyond.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.22108154,22138006,32171430).
文摘Triterpenoids are valuable medicinal scaffolds,characterized by excellent pharmacological properties and the presence of hydroxyl and carboxyl groups that allow for further structural modifications.Expanding the scope of oxidative modifications on these molecules is crucial for increasing their synthetic structural diversity and unlocking new potential pharmacological activities.However,the progress has been limited by the scarcity of suitable tailoring enzymes.Here,we reported a break-through in achieving targeted and remote dual-site oxidation of licorice triterpenoids using a single P450 mutant.This approach successfully enabled the selective synthesis of the rare triterpenoid,liquiritic acid and 24-OH-liquiritic acid.Our findings demonstrate that microenvironmental accessibility engineering of triterpenoid substrates within the P450 enzyme is essential for continuous and regioselective oxidation.This study not only sheds light on the mechanistic aspects of P450 catalysis but also expands the enzymatic toolkit for selective oxidative modifications in triterpenoid biosynthesis.
基金funded by the China Disabled Persons’Federation under its 2024 research project(Grant No.2024CDPFAT-47)the Yancheng Social Science Foundation(Grant No.25skB252).
文摘Background:Home accessibility modifi cations are crucial for promoting independent living and quality of life among persons with disabilities.While developed countries have established comprehensive policy frameworks,developing nations like China face unique challenges in program design and implementation.Objective:This study conducts a systematic comparative analysis of home accessibility modification policies across China,Japan,Germany,and Sweden,identifying key policy dimensions and proposing evidence-based recommendations for strengthening China’s policy framework.Methods:We employed a multi-dimensional analytical framework examining legislative foundations,eligibility criteria,funding mechanisms,and service delivery models.Data were collected from primary legislation,governmental regulations,official statistics,and peer-reviewed literature.Results:Significant cross-national variations exist in policy approaches.Japan and Germany utilize social insurance models with standardized assessments,Sweden adopts a universal rights-based approach,while China employs a targeted assistance model focused on economically disadvantaged households.China completed 1.28 million household renovations during its 14th Five-Year Plan,demonstrating strong implementation capacity;future policy refi nement could draw on international experience to strengthen assessment standardization,broaden eff ective coverage,and improve the sustainability of fi nancing.Conclusions:China can benefi t from international experience in developing standardized assessment protocols,diversifying funding mechanisms,and establishing professional service delivery systems,while acknowledging contextual constraints unique to developing country settings.
基金financially supported by the National Natural Science Foundation of China(No.32502862)the Collection,Utilization and Innovation of Animal Resources by Research Institutes and Enterprises of Chongqing(No.Cqnyncwkqlhtxm)+1 种基金the Chongqing Modern Agricultural Industry Technology System(CQMAITS202513)the Key Project of Chongqing Technology Innovation and Application Development Special Program(CTSB2025TIAD-KPX0079)。
文摘Background Endometrial receptivity(ERE)is a transient uterine state that determines the success of blastocyst implantation;however,the epigenomic regulation underlying ERE establishment in goats remains unclear.Here,we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats,utilizing RNA-seq,ATAC-seq,and H3 K27 ac CUT&Tag.Results A total of 3,143 differentially expressed genes(DEGs)were identified,accompanied by significant alterations in chromatin accessibility and H3 K27 ac modifications between receptive and non-receptive endometria.The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion,immune tolerance,and embryo attachment.Motif enrichment and transcription factor(TF)footprinting analyses identified members of the FOS/JUN,SOX,HNF1,CEBP,and BATF families as candidate regulators,implicating downstream genes involved in ERE establishment,including SPP1,FOXO1,KLF4/6,STAT1,IFI6,ITGB8,PLAC8,DUSP4,NR1D1,ISG15,RUFY4,and PIK3R3.In addition,numerous super-enhancers were identified,indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium.Integration of multi-omics datasets revealed a strong correlation(r>0.7)among chromatin accessibility,H3 K27 ac activation,and the expression of 172 DEGs.Furthermore,a set of hub genes(KLF6,IFI6,MCL1,SDC4,SUSD6,MAFF,and IL6R)that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.Conclusions Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation.These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.
基金Under the auspices of the National Natural Science Foundation of China(No.42271224,41901193)Ministry of Edu cation Humanities and Social Sciences Research Planning Fund Project of China(No.24YJAZH190)+1 种基金Anhui Province Excellent Youth Research Project in Universities(No.2022AH030019)Anhui Social Sciences Innovation Development Research Project(No.2024CXQ503)。
文摘The accessibility of urban public transit directly influences residents’quality of life,travel behavior,and social equity.Its correlation with housing prices has garnered significant attention across disciplines such as geography,economics,and urban planning.Although much existing research focuses on the impact of individual transportation facilities on housing prices,there is a notable gap in comprehensive analyses that assess the influence of overall urban transit accessibility on housing market dynamics.This study selected the main urban area of Hefei,China,as a case to investigate the spatial distribution of housing prices and evaluate public transit accessibility in 2022.Employing techniques such as the optimized parameter geographical detector and local spatial regression models,the study aimed to elucidate the effects and underlying mechanisms of urban transit accessibility on housing prices.The findings revealed that:1)housing prices in Hefei exhibited a clustered spatial pattern,with high prices concentrated in the city center and lower prices in peripheral areas,forming three distinct high-price hotspots with a‘belt-like’distribution;2)public transit accessibility showed a‘coreperiphery’structure,with accessibility declining in a‘circumferential’pattern around the city center.Based on the‘housing price-accessibility’dimension,four categories were identified:high price-high accessibility(37.25%),high price-low accessibility(19.07%),low price-high accessibility(21.95%),and low price-low accessibility(21.73%);3)the impact of transit accessibility on housing prices was spatially heterogeneous,with bus travel showing the strongest explanatory power(0.692),followed by automobile,subway,and bicycle travel.The interaction of these transportation modes generated a synergistic effect on housing price differentiation,with most influencing factors contributing more than 25%.These findings offer valuable insights for optimizing the spatial distribution of public transit infrastructure and improving both urban housing quality and residents’living standards.
基金supported by the Canada Foundation for Innovation (Project#44220)the Natural Sciences and Engineering Research Council of Canada (RGPIN-2024-03986)+3 种基金the Michael Smith Foundation for Health Research BCthe financial support of Health Canada,through the Canada Brain Research Fund,an innovative partnership between the Government of Canada (through Health Canada),Brain Canada Foundationthe Azrieli Foundationsupported by a Canadian Institutes of Health Research (CIHR) Canada Graduate Scholarship–Master’s Award。
文摘Central nervous system(CNS) axons fail to regenerate following brain or spinal cord injury(SCI),which typically leads to permanent neurological deficits.Peripheral nervous system axons,howeve r,can regenerate following injury.Understanding the mechanisms that underlie this difference is key to developing treatments for CNS neurological diseases and injuries characterized by axonal damage.To initiate repair after peripheral nerve injury,dorsal root ganglion(DRG) neurons mobilize a pro-regenerative gene expression program,which facilitates axon outgrowth.
基金Under the auspices of Heilongjiang Provincial Natural Science Foundation of China(No.YQ2024D012),National Natural Science Foundation of China(No.42071162,42101165,42501220)。
文摘Under the background of‘the Belt and Road’and‘China-Mongolia-Russia Economic Corridor’initiatives,this paper studied the urban accessibility level,regional accessibility pattern and regional spatial effects along the Primorsky No.1 and No.2 transportation corridors.First,the evaluation of urban accessibility level with and without Primorsky No.1 and No.2 high-speed rails(HSRs)opening was conducted with two indicators,i.e.,the weighted average travel time,and the economic potential.After the evaluation,the spatial differentiation pattern of the accessibility changes with and without Primorsky No.1 and No.2 HSRs opening was performed respectively using ArcGIS.On these bases,the regional spatial effects brought by Primorsky No.1 and No.2 HSRs opening were studied.The results are as following.First,the urban accessibility level will be greatly improved by the opening of Primorsky No.1 and No.2 HSRs.All adjacent cities will be integrated into‘1 h HSR communication circle’and the whole journey will be integrated into‘4 h HSR communication circle’along Primorsky No.1 and No.2 corridors,respectively.The HSR accessibility of Primorsky No.1 corridor is stronger than that of Primorsky No.2 corridor.But the HSR accessibility improvement degree of Primorsky No.1 corridor is weaker than that of Primorsky No.2 corridor.Second,spatially,along Primorsky No.1 and No.2 corridors,the HSR accessibility level of the cities which are located in China is stronger than those cities located in Russia,showing the‘High West,Low East’patterns.The HSR accessibility improvement degree of the cities which are located in Russia and Sino-Russian border is stronger than those cities located in China,showing the‘High East,Low West’patterns.Third,Primorsky No.1 and No.2 corridors could connect the China’s‘Heilongjiang Land Sea Silk Road Economic Belt’and‘Changchun-Jilin-Tumen Development Pilot Zone’respectively,gradually involving into the development of China’s Harbin-Changchun Megalopolis.Relying on Harbin(China)and Changchun(China),Primorsky No.1 and No.2 HSRs could connect Northeast China-Beijing HSR,accelerating the diffusion of population,economy and other flows from China’s Beijing-Tianjin-Hebei Urban Agglomeration to Northeast China,and then to Russia’s Far East Federal District.Relying on Suifenhe(China)and Hunchun(China),Primorsky No.1 and No.2 HSRs could be conducive to the development of the second largest sea channels for Northeast China,creating the Northeast Asian Urban Belt,and new sea-rail intermodal pattern among China,Russia,Democratic People’s Republic of Korea,Japan and Republic of Korea.Relying on Vladivostok(Russia)and Zarubino(Russia),Primorsky No.1 and No.2 corridors could connect the‘Ice Silk Road’,building the‘Sino-Russian Northern Maritime Corridor’and‘Sino-Russian Arctic Blue Economic Areas’.
文摘Over the 80 years since the United Nations was founded,international human rights law has undergone a dynamic and increasingly enriched process of evolution from universal declarations to formal treaties,and from proclamations of rights to institutionalized safeguards.As an integral part of the human rights system,the affirmation of the rights of persons with disabilities and the promotion of accessibility mark new breakthroughs and developments in international human rights law since the advent of the new century.
文摘Since the 1970s,a series of international and national sources have supported the principle of accessibility,which slowly has become a statuary norm and a legislative obligation.Each country has implemented accessibility through a singular policy.But in addition to the accessibility of a place or an activity,to inform about what is accessible is very important as well,and has not really taken off.Indeed,for disabled people,the difficulty lies not only with access to places and the use of resources,but also with the visibility of these resources.This means that information concerning accessibility has to be disclosed and provided effectively to disabled people,those involved with them and the relevant institutions.In different countries all over the world,many labels and pictograms have been created for this purpose and give information relating to accessibility.Using a socio-historical approach,we will present and analyze the different types of icons,symbols,pictograms and labels that have been put in place around the world and in France:what are they used for and for whom are they made?We will show that they are pointers which firstly reflect the diversity and range within the target group concerned by accessibility,and secondly the evolution of accessibility as a dynamic and ecological principle.
基金funded by the National Nat-ural Science Foundation of China(Grants No.42371433,U2443214)National Key Project of High-Resolution Earth Observation System of China(Grant No.80Y50G19900122/23)Foundation of Key Laboratory of Soil andWater Conservation on the Loess Plateau ofMinistry ofWater Resources(Grant No.WSCLP202301).
文摘Ensuring the provision of accessible,affordable,and high-quality public services to all individuals aligns with one of the paramount aims of the United Nations’Sustainable Development Goals(SDGs).In the face of esca lating urbanization and a dwindling rural populace in China,reconstructing rural settlements to enhance public service accessibility has become a fundamental strategy for achieving the SDGs in rural areas.However,few stud ies have examined the optimal methods for rural settlement reconstruction that ensure accessible and equitable public services while considering multiple existing facilities and service provisions.This paper focuses on rural settlement reconstruction in the context of the SDGs,employing an inverted MCLP-CC(maximal coverage loca tion problem for complementary coverage)model to identify optimal rural settlements and a rank-based method for their relocation.Conducted in Changyuan,a county-level city in Henan Province,China,this study observed significant enhancements in both accessibility and equity following rural settlement reconstruction by utilizing the MH3SFCA(modified Huff 3-step floating catchment area)and the spatial Lorenz curve method.Remarkably,these improvements were achieved without the addition of new facilities,with the accessibility increasing by 44.21%,4.97%,and 3.11%;Gini coefficients decreasing by 19.53%,1.64%,and 3.18%;Ricci-Schutz coef-ficients decreasing by 21.09%,2.09%,and 4.33%for educational,medical,and cultural and sports facilities,respectively.It indicated that rural settlement reconstruction can bolster the accessibility and equity of public ser-vices by leveraging existing facilities.This paper provides a new framework for stakeholders to better reconstruct rural settlements and promote sustainable development in rural areas in China.
文摘Multicriteria Decision Analysis(MCDA)has been integrated with GIS modelling by many studies to aid the decision-making process.This integration enhances modelling by incorporating spatial relationships and using advanced techniques,including the combination of Frequency Ratio(FR)and Analytical Hierarchical Process(AHP),also known as FR-AHP.Although methods like Two-Steps Floating Catchment Area(2SFCA),AHP,and FR are widely applied in measuring accessibility,they have limitations in terms of threshold sensitivity and subjectivity.Hence,this study used FR-AHP,which combines the data-driven strength of FR and the structured decision-making technique of AHP to provide a more reliable evaluation of spatial accessibility.This study aims to integrate FR-AHP with GIS to derive campus spatial accessibility in Shah Alam.Campus spatial accessibility can be measured by using location and distance between origin and destination,topological accessibility for nodes and paths,and contiguous accessibility for surfaces.Understanding these concepts is crucial for determining the appropriate technique.This study utilizedMCDA,GIS-basedFR,andAHPmethods tomodel spatial accessibility in activemobility andpublic transport areas,calculating estimation index values and analyzing comparisons between physical factors.A sample survey was conducted among the university’s students to gather information on their origin and destination,as well as the type of transportation used by students.The data were used in calculating the weightage of each physical factor using the FR-AHP method.Then,the Campus Spatial Accessibility Index(CSAI)was determined by using GIS IndexModelling.By using the model,the index was classified into five(5)classes from Very Low to Very High.The results show that Section 2 has the highest accessibility,while the area with the lowest accessibility index is Jalan Zamrud and Jalan Permata,located in Section 7.To analyze the efficiency of FR-AHP,the CSAI was also derived using theweightage derived fromFR only.The comparisons revealed that the results derived using FR-AHP are closer to reality than those derived using FR only,as it incorporates human preferences in accessibility.Hence,the findings suggest that the integration of FR-AHP could provide better CSAI than FR only.
基金Supported by the Science and Technology Planning Project of Guangzhou,No.2024A03J0102the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar,No.2022B1515020024+1 种基金National Natural Science Foundation of China,No.82070574the Key Research and Development Program of Guangzhou,No.2023B03J1298.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is notorious for its aggressive progression and dismal prognosis,with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.AIM To dissect how multilayered chromatin regulation sustains oncogenic transcription and tumor-stroma crosstalk in HCC,we combined multiomics single cell analysis.METHODS We integrated single-cell RNA sequencing and paired single-cell assay for transposase-accessible chromatin with sequencing data of HCC samples,complemented by bulk RNA sequencing validation across The Cancer Genome Atlas,Liver Cancer Institute,and GSE25907 cohorts.Cell type-specific chromatin architectures were resolved via ArchR,with regulatory hubs identified through peak-to-gene linkages and coaccessibility networks.Functional validation employed A485-mediated histone 3 lysine 27 acetylation suppression and small interfering RNA targeting DGAT1.RESULTS Malignant hepatocytes exhibited expanded chromatin accessibility profiles,characterized by increased numbers of accessible peaks and larger physical regions despite reduced peak intensity.Enhancer-like peaks enriched in malignant regulation,forming long-range hubs.Eighteen enhancer-like peak-related genes showed tumor-specific overexpression and diagnostic accuracy,correlating with poor prognosis.Intercellular coaccessibility analysis revealed tumor-stroma symbiosis via shared chromatin states.Pharmacological histone 3 lysine 27 acetylation inhibition paradoxically downregulated DGAT1,the hub gene most strongly regulated by chromatin accessibility.DGAT1 knockdown suppressed cell proliferation.CONCLUSION Multilayered chromatin reprogramming sustains HCC progression through tumor-stroma crosstalk and DGAT1-related oncogenic transcription,defining targetable epigenetic vulnerabilities.
基金supported by the China National Health Development Rescarch Center Study on Total Health Insurance Package Payment and National Office for Philosophy and Social Sciences,National Social Science Fund of China(17ZDA121)Tsinghua University Dushi Program(2024Z11DSZ001).
文摘Objective:The scarcity of healthcare resources and inadequate access to medical services in rural and remote areas are pervasive challenges many countries face,particularly in the developing world.Telemedicine,with its capacity to overcome geographical barriers and provide patients with real‐time medical services,has shown considerable potential in addressing these issues,attracting wide-spread attention.Compact medical communities and family doctor systems play important roles in improving healthcare accessibility.However,despite the critical nature of patients'perceptions of healthcare accessibility,research in this domain is sparse.This study aimed to explore the impact of telemedicine on rural residents'perceived healthcare accessibility in China,analyze the mechanisms underpinning this relationship,and elucidate the roles of compact medical communities and the family doctor system.Methods:Survey data from 3311 rural residents were analyzed using a probit model,instrumental variables,and subgroup regression analyses to ascertain causal effects,perform heterogeneity analysis,examine mechanisms,and ascertain the robustness of the findings.Results:Telemedicine significantly enhanced rural residents'perceived healthcare accessibility,with particularly notable benefits for those in sparsely populated areas,regions with high‐speed internet access,within the purview of compact healthcare consortiums,and those with access to family doctor services.Furthermore,telemedicine improved rural residents'perceived healthcare accessibility by encouraging the use of primary care services.Conclusion:Telemedicine in China has played a significant role in improving the perceived healthcare accessibility among rural residents and aiding in the reduction of disparities in accessibility across different demographic groups.This is consistent with the broader objective of achieving universal health coverage.However,the efficacy of telemedicine in enhancing healthcare accessibility is contingent upon certain preconditions.Policymakers must confront local infrastructure challenges,particularly regarding internet connectivity,when expanding telemedicine services to ensure their effective operation.The synergistic interaction observed between telemedicine,the family doctor system,and compact medical communities highlights the importance of integrating telemedicine into existing healthcare systems.Such integration could enhance collaboration with current healthcare frameworks,ensuring the provision of safe,accessible,and affordable healthcare services,and promoting the health and well‐being of local populations.
文摘This study analyzes the spatial accessibility of key services in Caen,France,focusing on how different transport modes(car,bicycle,and public transit)influence access to essential services across the urban and suburban landscape.Indeed,the introduction of traffic restrictions in towns with low emission zones encourages a detailed study,on a fine spatial scale,of the differences in accessibility between different modes of transport,for different services and for different journey times.Using spatial analysis techniques,we examine accessibility patterns in relation to services such as shops,healthcare,education,and tourism,highlighting significant disparities between transport modes.The findings reveal that car travel provides the highest accessibility across all service categories,particularly for healthcare and recreational services,while bicycle and public transit accessibility is more limited,especially in peripheral areas.A Principal Component Analysis(PCA)synthesizes the multimodal accessibility data,and hierarchical clustering identifies distinct patterns of accessibility using different transport modes across the city.The study further explores temporal trends in accessibility,showing how different modes perform over varying travel times.Based on these findings,we propose targeted policy interventions aimed at improving public transit,enhancing cycling infrastructure,decentralizing essential services,and promoting mixed-use urban development.Future research directions include examining socio-economic disparities,the impact of emerging mobility technologies,and the environmental implications of accessibility patterns.This research provides valuable insights for urban planners seeking to improve mobility equity and sustainability in urban areas.
文摘In this paper,we propose a random access scheme termed sign-compute diversity slotted ALOHA(SCDSA).The SCDSA scheme combines diversity transmission with compute-and-forward.Without considering the capture effect and multiple user detection techniques,our scheme can reach a high throughput of 0.98 without feedback under finite frame size settings,where the upper bound on performance is 1.Moreover,a lower bound on throughput performance is derived,which is tight in some parameter settings and can be used to approximate theoretical performance.Simulation results validate our analysis and confirm the advantages of our proposed scheme.
基金supported in part by National Key R&D Program of China(2022YFB4501200),National Natural Science Foundation of China(62332018)Science and Technology Program(2024NSFTD0031,2024YFHZ0339 and 2025ZNSFSC0497).
文摘The performance of data restore is one of the key indicators of user experience for backup storage systems.Compared to the traditional offline restore process,online restore reduces downtime during backup restoration,allowing users to operate on already restored files while other files are still being restored.This approach improves availability during restoration tasks but suffers from a critical limitation:inconsistencies between the access sequence and the restore sequence.In many cases,the file a user needs to access at a given moment may not yet be restored,resulting in significant delays and poor user experience.To this end,we present Histore,which builds on the user’s historical access sequence to schedule the restore sequence,in order to reduce users’access delayed time.Histore includes three restore approaches:(i)the frequency-based approach,which restores files based on historical file access frequencies and prioritizes ensuring the availability of frequently accessed files;(ii)the graph-based approach,which preferentially restores the frequently accessed files as well as their correlated files based on historical access patterns,and(iii)the trie-based approach,which restores particular files based on both users’real-time and historical access patterns to deduce and restore the files to be accessed in the near future.We implement a prototype of Histore and evaluate its performance from multiple perspectives.Trace-driven experiments on two datasets show that Histore significantly reduces users’delay time by 4-700×with only 1.0%-14.5%additional performance overhead.
文摘Avery significant event in China’s political calendar took place in Beijing in early March,and,as usual,it was more than optics.The fourth sessions of the 14th National People’s Congress(NPC)and the 14th National Committee of the Chinese People’s Political Consultative Conference(CPPCC),the country’s top legislative and advisory bodies,are expected to set the course for China’s direction over the year and beyond.
