Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LM...Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LMRB's terrestrial water storage anomaly(TWSA)and its spatio-temporal dynamics during 2002–2020.Considering the effects of natural factors and human activities,the respective contributions of climate variability and human activities to terrestrial water storage change(TWSC)were separated.Results showed that:(1)LMRB's TWSA decreased by 0.3158 cm/a.(2)TWSA showed a gradual increase in distribution from southwest of MRB to middle LMRB and from northeast of LRB to middle LMRB.TWSA positively changed in Myanmar while slightly changed in Laos and China.It negatively changed in Vietnam,Thailand and Cambodia.(3)TWSA components decreased in a descending order of soil moisture,groundwater and precipitation.(4)Natural factors had a substantial and spatial differentiated influence on TWSA over the LMRB.(5)Climate variability contributed 79%of TWSC in the LMRB while human activities contributed 21%with an increasing impact after 2008.The TWSC of upstream basin countries was found to be controlled by climate variability while Vietnam and Cambodia's TWSC has been controlled by human activities since 2012.展开更多
The Healthy China Initiative is a major health strategy being pursued by the country.To prevent and control different types of diseases as well as their complex variants,research on the spatio-temporal differentiation...The Healthy China Initiative is a major health strategy being pursued by the country.To prevent and control different types of diseases as well as their complex variants,research on the spatio-temporal differentiation among and mechanisms of influence of epidemic diseases is growing worldwide.This study analyzed monthly data on the incidence of influenza by using different methods,including Moran’s I,the hotspot analysis model,concentration analysis,and correlation analysis,to determine the characteristics of spatiotemporal differentiation in the incidence of influenza across prefecture-level cities in China from 2004 to 2017,and to examine its relationship with air pollution.According to the results,the overall incidence of influenza in China exhibited a trend of increase from 2004 to 2017,with small peaks in 2009 and 2014.More cases of influenza were recorded in the first and fourth quarters of each year.Regions with higher incidences of influenza were concentrated in northwestern and northern China,and in the coastal areas of southeastern China.Over time,the distribution of regions with a higher incidence of influenza has shifted from the west to the east of the country.A significant relationship was observed between the incidence of influenza and factors related to air pollution.The contents of five air pollutants(PM_(2.5),PM10,SO_(2),NO_(2),and CO)were significantly positively correlated with the incidence of influenza,with a decreasing order of contribution to it of SO_(2)>CO>NO_(2)>PM_(2.5)>PM_(10).The content of O_(3) in the air was negatively correlated with the incidence of influenza.The influence of air pollution-related factors on the incidence of influenza in different regions and seasons showed minor differences.The large-scale empirical results provided here can supply a scientific basis for governmental disease control authorities to formulate strategies for regional prevention and control.展开更多
Based on the adaptive analysis paradigm,this paper constructs an evaluation index system and an evaluation model of the level of industrial ecology of a restricted development zone from the perspective of the industri...Based on the adaptive analysis paradigm,this paper constructs an evaluation index system and an evaluation model of the level of industrial ecology of a restricted development zone from the perspective of the industrial system and of the environmental system,and studies the spatial-temporal differentiation characteristics and the driving factors of the level of industrial ecology of the restricted development zone of the Shandong Province,China,by using a variety of measurement methods.The results show that:1)In the temporal dimension,the level of industrial ecology of the research area increased from 2005 to 2017,while in the regional dimension,it was higher in the eastern coastal areas,followed by the northwestern area and the southwestern area;2)In the spatial dimension,from 2005 to 2017 the level of industrial ecology of the research area had a clear spatial dependence,and the regional spatial agglomeration of the restricted development zones with similar industrial ecology levels become increasingly evident;3)On the whole,the industrial ecology level in the study area had a clear spatial differentiation pattern,as it was higher in the north and in the east and lower in the south and in the west.Moreover,its evolution model changed from a‘three-core driven model’to a‘spatial scattered mosaic distribution model’,and then to a‘single-core driven model’;4)Industrial ecology was positively correlated with economic development,foreign investment,science and technology,and negatively correlated with the government role,while industrial structure and environmental regulation failed to pass the statistical significance test.展开更多
In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpf...In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpful for comprehensively appraising landscape spatial patterns and ecological functions, also, presents a new method for analyzing landscape features from multidimensional aspects. The practice process is demonstrated by taking Yan＇an region in northwestern China as a case. Firstly, the indices system including spatial attribute and functional attribute is established for assessing landscape ecological niche. Additionally, two-dimensional figures are drawn for comparing the spatio-temporal features of landscape ecological niche in 1987 and 2000 among the 13 administrative counties. The results show that from 1987 to 2000, towards Yan＇an region, spatial attribute value of landscape ecological niche changes from 1.000 to 1.178 with an obvious increment, and functional attribute value changes from 0.989 to 1.069 with a little increment, both of which enhance the regional landscape ecological niche. Towards each county, spatial attribute value of landscape ecological niche increases to different extent while functional attribute value changes dissimilarly with an increment or a decrement.展开更多
Based on SPOT5 satellite remote sensing images and land use data in five time phases covering the period 1988–2012, the distribution characteristics, spatial differentiation processes, and driving mechanisms affectin...Based on SPOT5 satellite remote sensing images and land use data in five time phases covering the period 1988–2012, the distribution characteristics, spatial differentiation processes, and driving mechanisms affecting the residential land of the Jinshitan Tourist Resort were studied. The work included a combination of GIS technology, adoption of the differentiation index D, and the multi-group differentiation-measure model D(m). The results provided a basis for the following conclusions: 1) From 1988 to 2012, the degree of differentiation of the rural residential land first decreased, and then increased. The general residential, commercial residential and garden-house land-types all showed declining trends, of which the garden-house type presented the most intense volatility. 2) The overall background of the traditional residential land type was gradually replaced by a new residential land type, and the total area of residential land increased year by year, significantly improving the overall residential conditions. The areas of the new residential land type showed growth, and were increasingly widely distributed in the coastal tourist resorts, transportation corridors, and scenic areas. 3) Government policy, social differentiation, market mechanisms, and individual choices(along with other factors) were mutually promoted, although still restrained. However, all of these factors interacted to constrain the developmental direction and the processes affecting tourism real estate in the Dalian Jinshitan Tourist Resort.展开更多
Large amounts of data accumulated in ecology and related environmental sciences arouses urgent need to explore useful patterns and information in it.Here we propose coclustering-based methods and a temperatures-photop...Large amounts of data accumulated in ecology and related environmental sciences arouses urgent need to explore useful patterns and information in it.Here we propose coclustering-based methods and a temperatures-photoperiod driven phenological model to explore spatio-temporal differentiation in long-term spring phenology in China.First,we created the first bloom date(FBD)dataset in China from 1979 to 2018 using the extended spring indices and China Meteorological Forcing Dataset.Then we analyzed the dataset using Bregman block average co-clustering algorithm with I-divergence(BBAC_I)and kmeans algorithm.Such analysis delineated the spatially-continuous phenoregions in China for the first time.Results showed three spatial patterns of FBD in China and their temporal dynamics for 40 years(1979–2018).More specifically,overall late spring onsets occur in 1979–1996,in which areas located in Jiangxi,northern Xinjiang and middle Inner Mongolia experienced constant changing spring onsets.Overall increasingly earlier spring onsets occur in 1997–2012,in which areas located in Fujian,Hunan and eastern Heilongjiang experienced the most variable spring onsets.Stable early spring onsets over China occur after 2012.Results also showed 15 temporal patterns of spring phenology over the study period and their spatial delineation in China.More specifically,most areas in China have the same FBD category for 40 years while northern Guizhou,Hunan and southern Hubei have the same category in 1979–1997 and then fluctuate between different categories.Finally,our results have certain directive significance on the design of existing observational sites in Chinese Phenological Network.展开更多
Green and plaza land(GPL)is one of the basic elements of urban construction,and is also the most basic public space to meet the needs of citizens for a better life.The exploration on its internal development laws can ...Green and plaza land(GPL)is one of the basic elements of urban construction,and is also the most basic public space to meet the needs of citizens for a better life.The exploration on its internal development laws can provide theoretical foundations for the planning of GPL and creating good human settlements.Taking 612 cities in China as the study area and from the"people-land"perspective,this paper selects the total GPL area,the per capita GPL area,and the land use proportion of per capita GPL as indicators to analyze the spatio-temporal differentiation characteristics and evolution rules of the construction level of GPL in China from 1996 to 2016,by using mathematical statistics and spatial analysis methods.The result shows:(1)from a national perspective,the construction level of GPL in China has been rapidly improved along with the temporal evolution,but there is still a big gap from the upper limit of the standard.In terms of the spatial distribution,regional differences have always been great,and the cities scoring below the standard are concentrated in the eastern and central regions,while high-scoring cities are more concentrated in the western region;the distribution of the land use proportion of per capita GPL is in a pattern that the eastern region has the highest proportion,followed by the western region,central region,and northeastern region successively.(2)From the perspective of scale,differences between cities of different sizes exist over a long period of time,and there is an obvious imbalance in the per capita GPL area as well as the land use proportion of per capita GPL between different cities.The construction level shows that small cities have the highest level,followed by medium-sized cities and then large cities.展开更多
Traffic flow prediction constitutes a fundamental component of Intelligent Transportation Systems(ITS),playing a pivotal role in mitigating congestion,enhancing route optimization,and improving the utilization efficie...Traffic flow prediction constitutes a fundamental component of Intelligent Transportation Systems(ITS),playing a pivotal role in mitigating congestion,enhancing route optimization,and improving the utilization efficiency of roadway infrastructure.However,existingmethods struggle in complex traffic scenarios due to static spatio-temporal embedding,restricted multi-scale temporal modeling,and weak representation of local spatial interactions.This study proposes Bi-STAT+,an enhanced bidirectional spatio-temporal attention framework to address existing limitations through three principal contributions:(1)an adaptive spatio-temporal embedding module that dynamically adjusts embeddings to capture complex traffic variations;(2)frequency-domain analysis in the temporal dimension for simultaneous high-frequency details and low-frequency trend extraction;and(3)an agent attention mechanism in the spatial dimension that enhances local feature extraction through dynamic weight allocation.Extensive experiments were performed on four distinct datasets,including two publicly benchmark datasets(PEMS04 and PEMS08)and two private datasets collected from Baotou and Chengdu,China.The results demonstrate that Bi-STAT+consistently outperforms existing methods in terms of MAE,RMSE,and MAPE,while maintaining strong robustness against missing data and noise.Furthermore,the results highlight that prediction accuracy improves significantly with higher sampling rates,providing crucial insights for optimizing real-world deployment scenarios.展开更多
The pseudo-two-dimensional(P2D)model plays an important role in exploring physicochemical mechanisms,predicting the state of health,and improving the fast charge capability for Li-ion batteries(LIBs).However,the fast ...The pseudo-two-dimensional(P2D)model plays an important role in exploring physicochemical mechanisms,predicting the state of health,and improving the fast charge capability for Li-ion batteries(LIBs).However,the fast charge leads to the lithium concentration gradient in the solid and electrolyte phases and the non-uniform electrochemical reaction at the solid/electrolyte interface.In order to decouple charge transfer reactions in LIBs under dynamic conditions,understanding the spatio-temporal resolution of the P2D model is urgently required.Till now,the study of this aspect is still insufficient.This work studies the spatio-temporal resolution for dynamic/static electrochemical impedance spectroscopy(DEIS/SEIS)on multiple scales.In detail,DEIS and SEIS with spatio-temporal resolutions are used to decouple charge transfer reactions in LIBs based on the numerical solution of the P2D model in the frequency domain.The calculated results indicate that decoupling solid diffusion requires a high spatial resolution along the r-direction in particles,decoupling electrolyte diffusion and interfacial transfer reaction requires a high spatial resolution along the x-direction,and decoupling charge transfer reactions in LIBs at an extremely low state of charge(SOC)requires an extremely high temporal resolution along the t-direction.Finally,the optimal range of spatio-temporal resolutions for DEIS/SEIS is derived,and the method to decouple charge transfer reactions with spatio-temporal resolutions is developed.展开更多
This study proposes a novel forecasting framework that simultaneously captures the strong periodicity and irregular meteorological fluctuations inherent in solar radiation time series.Existing approaches typically def...This study proposes a novel forecasting framework that simultaneously captures the strong periodicity and irregular meteorological fluctuations inherent in solar radiation time series.Existing approaches typically define inter-regional correlations using either simple correlation coefficients or distance-based measures when applying spatio-temporal graph neural networks(STGNNs).However,such definitions are prone to generating spurious correlations due to the dominance of periodic structures.To address this limitation,we adopt the Elastic-Band Transform(EBT)to decompose solar radiation into periodic and amplitude-modulated components,which are then modeled independently with separate graph neural networks.The periodic component,characterized by strong nationwide correlations,is learned with a relatively simple architecture,whereas the amplitude-modulated component is modeled with more complex STGNNs that capture climatological similarities between regions.The predictions from the two components are subsequently recombined to yield final forecasts that integrate both periodic patterns and aperiodic variability.The proposed framework is validated with multiple STGNN architectures,and experimental results demonstrate improved predictive accuracy and interpretability compared to conventional methods.展开更多
Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning f...Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning framework enhanced by knowledge graphs.Methods We developed Agent-GNN,a three-stage decoupled learning framework,and validated it on the Traditional Chinese Medicine Syndrome Diagnosis(TCM-SD)dataset containing 54152 clinical records across 148 syndrome categories.First,we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system.Second,we proposed a Functional Patient Profiling(FPP)method that utilizes large language models(LLMs)combined with Graph Retrieval-Augmented Generation(RAG)to extract structured symptom-etiology-pathogenesis subgraphs from medical records.Third,we employed heterogeneous graph neural networks to learn structured combination patterns explicitly.We compared our method against multiple baselines including BERT,ZY-BERT,ZY-BERT+Know,GAT,and GPT-4 Few-shot,using macro-F1 score as the primary evaluation metric.Additionally,ablation experiments were conducted to validate the contribution of each key component to model performance.Results Agent-GNN achieved an overall macro-F1 score of 72.4%,representing an 8.7 percentage points improvement over ZY-BERT+Know(63.7%),the strongest baseline among traditional methods.For long-tail syndromes with fewer than 10 samples,Agent-GNN reached a macro-F1 score of 58.6%,compared with 39.3%for ZY-BERT+Know and 41.2%for GPT-4 Few-shot,representing relative improvements of 49.2%and 42.2%,respectively.Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.Conclusion This study proposes Agent-GNN,a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation.By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs,our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.展开更多
Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteobla...Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteoblast proliferation and differentiation,investigating its viability as a bone-healing agent.Methods This study employed various cellular and molecular biology experiments to assess the effects of LA on the viability,proliferation,cell cycle,apoptosis,differentiation,mineralization,and migration of MC3T3-E1 osteoblasts.Immunofluorescence and Western blot analyses were conducted to detect the expression of proteins related to the Wnt/β-catenin signaling pathway,investigating the regulatory mechanisms by which LA promotes osteoblast proliferation and differentiation.Additionally,Wnt inhibitor dickkopf-1(DKK-1)andβ-catenin-silenced cell models were used to further validate the role of LA in modulating this signaling pathway.Results LA significantly promoted osteoblast proliferation without apparent cytotoxicity.Flow cytometry showed that LA regulated the cell cycle by reducing G0/G1 phase arrest and promoting G2/M phase progression.Western blot results indicated that LA upregulated the expression of proteins associated with cell proliferation and enhanced osteoblast differentiation and mineralization.Immunofluorescence and Western blot analyses further confirmed that LA markedly increased the expression of Wnt andβ-catenin,facilitatingβ-catenin nuclear translocation.Treatment with the DKK-1 inhibitor significantly diminished the proliferative and differentiation-promoting effects of LA,confirming the critical role of this pathway.β-catenin knockdown experiments further substantiated its central role in LA-mediated regulation.Conclusion This study confirms that LA promotes osteoblast proliferation,differentiation,mineralization,and migration by activating the Wnt/β-catenin signaling pathway.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,w...Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.展开更多
The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a d...The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
Mountain area accounts for a high proportion of the land area in China,and it is the focal area to solve the contradiction of imbalanced regional development,as well as an important source of ecosystem services.Theref...Mountain area accounts for a high proportion of the land area in China,and it is the focal area to solve the contradiction of imbalanced regional development,as well as an important source of ecosystem services.Therefore,this area has been facing long-term pressure and challenges in economic development and ecological protection.In this paper,we selected a rocky desertification mountain area,an active mountain area of new tectonic movement and a typical northern earth-rock mountain area,as Qian-Gui karst Mountain area,Hengduan Mountain area and Taihang Mountain area,as examples to represent three main types of mountain areas.Three representative types of ecosystem services,including NPP(Net Primary Productivity)as a support service,water conservation as a regulation service,and agricultural produce as a supply service,were incorporated into this study.Linear regression,correlation analysis and other methods were then used to investigate the spatial-temporal characteristics of the trade-offs and synergies in each of the three kinds of mountain areas during 1990-2015 in China.The analysis yielded three main conclusions for the three mountainous areas.(1)The agricultural produce supply service decreased relatively,while the support and regulation services of NPP and hydrological regulation increased significantly.(2)There was a synergistic relationship between NPP and the hydrological regulation services in the three mountainous areas.The synergistic relation in Qian-Gui karst Mountain area became enhanced,while those in Hengduan and Taihang Mountain areas became weakened,and the former was weakened to a greater extent.There was a trade-off between NPP,the hydrological regulation service and the agricultural produce supply service among the three mountainous areas.In particular,the trade-off between NPP and the agricultural produce supply service in Qian-Gui karst Mountain area became weaker,while those in Hengduan and Taihang Mountain areas were enhanced,and the latter was enhanced to a greater degree.(3)Significant spatial differentiation was evident in the trade-offs and synergies of ecosystem services among the three mountain areas.展开更多
Cultivated land pressure is often used to reflect the shortage of cultivated land resources. By using the methods of the Cultivated Land Pressure Index, coefficient of variation and cold-hot spot analysis, this paper ...Cultivated land pressure is often used to reflect the shortage of cultivated land resources. By using the methods of the Cultivated Land Pressure Index, coefficient of variation and cold-hot spot analysis, this paper analyzes the spatial-temporal differentiation pattern and dynamic change processes of cultivated land pressure in the counties of the Pearl River-Xijiang Economic Zone from 2008 to 2017, and measures the factors which influence cultivated land pressure by using Principal Component Analysis. The results show that the cultivated land pressure in the Pearl River-Xijiang Economic Zone has been in a “high pressure” state, and the Cultivated Land Pressure Index has been rising continuously from 2008 to 2017. The coefficient of variation of the Cultivated Land Pressure Index in the Pearl River-Xijiang Economic Zone and various prefecture-level cities is fluctuating and rising, which indicates that the overall spatial differences in the cultivated land pressure in this region are expanding and polarization is obvious. In addition, the area where the municipal district of the provincial capital city is located is the core area of urban development and also the area with the greatest cultivated land pressure. The spatial pattern of cultivated land pressure cold-hot spots in the Pearl River-Xijiang Economic Zone is obviously heterogeneous, in which the Pearl River Economic Zone is the main hot spot gathering area and the Xijiang Economic Zone is the main cold spot gathering area. Farmers’ income, investment in fixed assets, GDP, population and other socio-economic factors are the main factors driving the changes in the cultivated land pressure in the Pearl River-Xijiang Economic Zone. Furthermore, farming production factors, such as the multiple cropping index and grain yield per unit area,will also have an important impact on the changes in the cultivated land pressure.展开更多
Sloping farmland,particularly in mountainous and hilly areas,constitutes a significant component of regional farmland resources.An investigation into the spatio-temporal pattern of sloping farmland and its influencing...Sloping farmland,particularly in mountainous and hilly areas,constitutes a significant component of regional farmland resources.An investigation into the spatio-temporal pattern of sloping farmland and its influencing factors in China is imperative for the efficient utilization of farmland and the optimization of land space.We used land use transfer matrix,geographically weighted regression model and geographical detector to conduct this study.Results showed that sloping farmland in China firstly decreased and then increased from 2000 to 2020.The proportion of sloping farmland decreased radially outward from Sichuan basin to the surrounding areas.Change rates of sloping farmland with different slopes varied and the slope with 6°-15°underwent the fastest changes.The influencing factors of farmland at various slope degrees were different.For sloping farmland below 15°,land use intensity and elevation had the greatest contribution.For sloping farmland between 15°and 25°,elevation,land use intensity,and population density were the main influencing factors.Sloping farmland above 25°was mostly affected by natural factors.This study can provide scientific basis for rational development and protection of sloping farmland.展开更多
基金National Natural Science Foundation of China,No.42161006Yunnan Fundamental Research Projects No.202201AT070094,No.202301BF070001-004+1 种基金Special Project for High-level Talents of Yunnan Province for Young Top Talents,No.C6213001159European Research Council(ERC)Starting-Grant STORIES,No.101040939。
文摘Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LMRB's terrestrial water storage anomaly(TWSA)and its spatio-temporal dynamics during 2002–2020.Considering the effects of natural factors and human activities,the respective contributions of climate variability and human activities to terrestrial water storage change(TWSC)were separated.Results showed that:(1)LMRB's TWSA decreased by 0.3158 cm/a.(2)TWSA showed a gradual increase in distribution from southwest of MRB to middle LMRB and from northeast of LRB to middle LMRB.TWSA positively changed in Myanmar while slightly changed in Laos and China.It negatively changed in Vietnam,Thailand and Cambodia.(3)TWSA components decreased in a descending order of soil moisture,groundwater and precipitation.(4)Natural factors had a substantial and spatial differentiated influence on TWSA over the LMRB.(5)Climate variability contributed 79%of TWSC in the LMRB while human activities contributed 21%with an increasing impact after 2008.The TWSC of upstream basin countries was found to be controlled by climate variability while Vietnam and Cambodia's TWSC has been controlled by human activities since 2012.
基金Under the auspices of Key Program of National Natural Science Foundation of China(No.41630749)Program of the National Social Science Fund of China(No.17BJL051)Fundamental Research Funds for the Central Universities(No.1709103,2412020FZ001)。
文摘The Healthy China Initiative is a major health strategy being pursued by the country.To prevent and control different types of diseases as well as their complex variants,research on the spatio-temporal differentiation among and mechanisms of influence of epidemic diseases is growing worldwide.This study analyzed monthly data on the incidence of influenza by using different methods,including Moran’s I,the hotspot analysis model,concentration analysis,and correlation analysis,to determine the characteristics of spatiotemporal differentiation in the incidence of influenza across prefecture-level cities in China from 2004 to 2017,and to examine its relationship with air pollution.According to the results,the overall incidence of influenza in China exhibited a trend of increase from 2004 to 2017,with small peaks in 2009 and 2014.More cases of influenza were recorded in the first and fourth quarters of each year.Regions with higher incidences of influenza were concentrated in northwestern and northern China,and in the coastal areas of southeastern China.Over time,the distribution of regions with a higher incidence of influenza has shifted from the west to the east of the country.A significant relationship was observed between the incidence of influenza and factors related to air pollution.The contents of five air pollutants(PM_(2.5),PM10,SO_(2),NO_(2),and CO)were significantly positively correlated with the incidence of influenza,with a decreasing order of contribution to it of SO_(2)>CO>NO_(2)>PM_(2.5)>PM_(10).The content of O_(3) in the air was negatively correlated with the incidence of influenza.The influence of air pollution-related factors on the incidence of influenza in different regions and seasons showed minor differences.The large-scale empirical results provided here can supply a scientific basis for governmental disease control authorities to formulate strategies for regional prevention and control.
基金Under the auspices of National Natural Science Foundation of China(No.41801105,41771138)National Natural Science Foundation of Shandong(No.ZR2018BD002)Social Science Planning Research Project of Shandong(No.18DJJJ14)。
文摘Based on the adaptive analysis paradigm,this paper constructs an evaluation index system and an evaluation model of the level of industrial ecology of a restricted development zone from the perspective of the industrial system and of the environmental system,and studies the spatial-temporal differentiation characteristics and the driving factors of the level of industrial ecology of the restricted development zone of the Shandong Province,China,by using a variety of measurement methods.The results show that:1)In the temporal dimension,the level of industrial ecology of the research area increased from 2005 to 2017,while in the regional dimension,it was higher in the eastern coastal areas,followed by the northwestern area and the southwestern area;2)In the spatial dimension,from 2005 to 2017 the level of industrial ecology of the research area had a clear spatial dependence,and the regional spatial agglomeration of the restricted development zones with similar industrial ecology levels become increasingly evident;3)On the whole,the industrial ecology level in the study area had a clear spatial differentiation pattern,as it was higher in the north and in the east and lower in the south and in the west.Moreover,its evolution model changed from a‘three-core driven model’to a‘spatial scattered mosaic distribution model’,and then to a‘single-core driven model’;4)Industrial ecology was positively correlated with economic development,foreign investment,science and technology,and negatively correlated with the government role,while industrial structure and environmental regulation failed to pass the statistical significance test.
基金National Natural Science Foundation of China, No.40371003 Innovation Foundation of Shaanxi Normal University
文摘In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpful for comprehensively appraising landscape spatial patterns and ecological functions, also, presents a new method for analyzing landscape features from multidimensional aspects. The practice process is demonstrated by taking Yan＇an region in northwestern China as a case. Firstly, the indices system including spatial attribute and functional attribute is established for assessing landscape ecological niche. Additionally, two-dimensional figures are drawn for comparing the spatio-temporal features of landscape ecological niche in 1987 and 2000 among the 13 administrative counties. The results show that from 1987 to 2000, towards Yan＇an region, spatial attribute value of landscape ecological niche changes from 1.000 to 1.178 with an obvious increment, and functional attribute value changes from 0.989 to 1.069 with a little increment, both of which enhance the regional landscape ecological niche. Towards each county, spatial attribute value of landscape ecological niche increases to different extent while functional attribute value changes dissimilarly with an increment or a decrement.
基金Under the auspices of National Natural Science Foundation of China(No.41471140)Outstanding Youth Program of Liaoning Province(No.LJQ2015058)
文摘Based on SPOT5 satellite remote sensing images and land use data in five time phases covering the period 1988–2012, the distribution characteristics, spatial differentiation processes, and driving mechanisms affecting the residential land of the Jinshitan Tourist Resort were studied. The work included a combination of GIS technology, adoption of the differentiation index D, and the multi-group differentiation-measure model D(m). The results provided a basis for the following conclusions: 1) From 1988 to 2012, the degree of differentiation of the rural residential land first decreased, and then increased. The general residential, commercial residential and garden-house land-types all showed declining trends, of which the garden-house type presented the most intense volatility. 2) The overall background of the traditional residential land type was gradually replaced by a new residential land type, and the total area of residential land increased year by year, significantly improving the overall residential conditions. The areas of the new residential land type showed growth, and were increasingly widely distributed in the coastal tourist resorts, transportation corridors, and scenic areas. 3) Government policy, social differentiation, market mechanisms, and individual choices(along with other factors) were mutually promoted, although still restrained. However, all of these factors interacted to constrain the developmental direction and the processes affecting tourism real estate in the Dalian Jinshitan Tourist Resort.
基金supported by the National Key R&D Program of China(Grant No.2019YFA0606901)the National Natural Science Foundation of China(Grant No.41901317)the China Postdoctoral Science Foundation(Grant No.2018M641246)。
文摘Large amounts of data accumulated in ecology and related environmental sciences arouses urgent need to explore useful patterns and information in it.Here we propose coclustering-based methods and a temperatures-photoperiod driven phenological model to explore spatio-temporal differentiation in long-term spring phenology in China.First,we created the first bloom date(FBD)dataset in China from 1979 to 2018 using the extended spring indices and China Meteorological Forcing Dataset.Then we analyzed the dataset using Bregman block average co-clustering algorithm with I-divergence(BBAC_I)and kmeans algorithm.Such analysis delineated the spatially-continuous phenoregions in China for the first time.Results showed three spatial patterns of FBD in China and their temporal dynamics for 40 years(1979–2018).More specifically,overall late spring onsets occur in 1979–1996,in which areas located in Jiangxi,northern Xinjiang and middle Inner Mongolia experienced constant changing spring onsets.Overall increasingly earlier spring onsets occur in 1997–2012,in which areas located in Fujian,Hunan and eastern Heilongjiang experienced the most variable spring onsets.Stable early spring onsets over China occur after 2012.Results also showed 15 temporal patterns of spring phenology over the study period and their spatial delineation in China.More specifically,most areas in China have the same FBD category for 40 years while northern Guizhou,Hunan and southern Hubei have the same category in 1979–1997 and then fluctuate between different categories.Finally,our results have certain directive significance on the design of existing observational sites in Chinese Phenological Network.
基金co-funded by the National Natural Science Foundation of China(No.51778389)the“Qing Lan Project”of Colleges and Universities of Jiangsu Province+1 种基金the Enterprise-Postgraduate Studio of Jiangsu Provincethe Project of Disciplinary Construction of Landscape Architecture at Suzhou University of Science and Technology。
文摘Green and plaza land(GPL)is one of the basic elements of urban construction,and is also the most basic public space to meet the needs of citizens for a better life.The exploration on its internal development laws can provide theoretical foundations for the planning of GPL and creating good human settlements.Taking 612 cities in China as the study area and from the"people-land"perspective,this paper selects the total GPL area,the per capita GPL area,and the land use proportion of per capita GPL as indicators to analyze the spatio-temporal differentiation characteristics and evolution rules of the construction level of GPL in China from 1996 to 2016,by using mathematical statistics and spatial analysis methods.The result shows:(1)from a national perspective,the construction level of GPL in China has been rapidly improved along with the temporal evolution,but there is still a big gap from the upper limit of the standard.In terms of the spatial distribution,regional differences have always been great,and the cities scoring below the standard are concentrated in the eastern and central regions,while high-scoring cities are more concentrated in the western region;the distribution of the land use proportion of per capita GPL is in a pattern that the eastern region has the highest proportion,followed by the western region,central region,and northeastern region successively.(2)From the perspective of scale,differences between cities of different sizes exist over a long period of time,and there is an obvious imbalance in the per capita GPL area as well as the land use proportion of per capita GPL between different cities.The construction level shows that small cities have the highest level,followed by medium-sized cities and then large cities.
基金partly supported by the Youth Foundation of the Inner Mongolia Natural Science Foundation[grant number 2024QN06017 and 2025MS06022]the Basic Scientific Research Business Fee Project for Universities in Inner Mongolia[grant numbers 2023XKJX019 and 2023XKJX024]the Central Guidance on Local Science and Technology Development Fund through[grant number 2024ZY0084].
文摘Traffic flow prediction constitutes a fundamental component of Intelligent Transportation Systems(ITS),playing a pivotal role in mitigating congestion,enhancing route optimization,and improving the utilization efficiency of roadway infrastructure.However,existingmethods struggle in complex traffic scenarios due to static spatio-temporal embedding,restricted multi-scale temporal modeling,and weak representation of local spatial interactions.This study proposes Bi-STAT+,an enhanced bidirectional spatio-temporal attention framework to address existing limitations through three principal contributions:(1)an adaptive spatio-temporal embedding module that dynamically adjusts embeddings to capture complex traffic variations;(2)frequency-domain analysis in the temporal dimension for simultaneous high-frequency details and low-frequency trend extraction;and(3)an agent attention mechanism in the spatial dimension that enhances local feature extraction through dynamic weight allocation.Extensive experiments were performed on four distinct datasets,including two publicly benchmark datasets(PEMS04 and PEMS08)and two private datasets collected from Baotou and Chengdu,China.The results demonstrate that Bi-STAT+consistently outperforms existing methods in terms of MAE,RMSE,and MAPE,while maintaining strong robustness against missing data and noise.Furthermore,the results highlight that prediction accuracy improves significantly with higher sampling rates,providing crucial insights for optimizing real-world deployment scenarios.
基金supported by the National Natural Science Foundation of China(Nos.22479092 and 22078190)。
文摘The pseudo-two-dimensional(P2D)model plays an important role in exploring physicochemical mechanisms,predicting the state of health,and improving the fast charge capability for Li-ion batteries(LIBs).However,the fast charge leads to the lithium concentration gradient in the solid and electrolyte phases and the non-uniform electrochemical reaction at the solid/electrolyte interface.In order to decouple charge transfer reactions in LIBs under dynamic conditions,understanding the spatio-temporal resolution of the P2D model is urgently required.Till now,the study of this aspect is still insufficient.This work studies the spatio-temporal resolution for dynamic/static electrochemical impedance spectroscopy(DEIS/SEIS)on multiple scales.In detail,DEIS and SEIS with spatio-temporal resolutions are used to decouple charge transfer reactions in LIBs based on the numerical solution of the P2D model in the frequency domain.The calculated results indicate that decoupling solid diffusion requires a high spatial resolution along the r-direction in particles,decoupling electrolyte diffusion and interfacial transfer reaction requires a high spatial resolution along the x-direction,and decoupling charge transfer reactions in LIBs at an extremely low state of charge(SOC)requires an extremely high temporal resolution along the t-direction.Finally,the optimal range of spatio-temporal resolutions for DEIS/SEIS is derived,and the method to decouple charge transfer reactions with spatio-temporal resolutions is developed.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(RS-2023-00249743).
文摘This study proposes a novel forecasting framework that simultaneously captures the strong periodicity and irregular meteorological fluctuations inherent in solar radiation time series.Existing approaches typically define inter-regional correlations using either simple correlation coefficients or distance-based measures when applying spatio-temporal graph neural networks(STGNNs).However,such definitions are prone to generating spurious correlations due to the dominance of periodic structures.To address this limitation,we adopt the Elastic-Band Transform(EBT)to decompose solar radiation into periodic and amplitude-modulated components,which are then modeled independently with separate graph neural networks.The periodic component,characterized by strong nationwide correlations,is learned with a relatively simple architecture,whereas the amplitude-modulated component is modeled with more complex STGNNs that capture climatological similarities between regions.The predictions from the two components are subsequently recombined to yield final forecasts that integrate both periodic patterns and aperiodic variability.The proposed framework is validated with multiple STGNN architectures,and experimental results demonstrate improved predictive accuracy and interpretability compared to conventional methods.
基金Sichuan TCM Culture Coordinated Development Research Center Project(2023XT131)National Key Science and Technology Project of China(2023ZD0509405)National Natural Science Foundation of China(82174236).
文摘Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning framework enhanced by knowledge graphs.Methods We developed Agent-GNN,a three-stage decoupled learning framework,and validated it on the Traditional Chinese Medicine Syndrome Diagnosis(TCM-SD)dataset containing 54152 clinical records across 148 syndrome categories.First,we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system.Second,we proposed a Functional Patient Profiling(FPP)method that utilizes large language models(LLMs)combined with Graph Retrieval-Augmented Generation(RAG)to extract structured symptom-etiology-pathogenesis subgraphs from medical records.Third,we employed heterogeneous graph neural networks to learn structured combination patterns explicitly.We compared our method against multiple baselines including BERT,ZY-BERT,ZY-BERT+Know,GAT,and GPT-4 Few-shot,using macro-F1 score as the primary evaluation metric.Additionally,ablation experiments were conducted to validate the contribution of each key component to model performance.Results Agent-GNN achieved an overall macro-F1 score of 72.4%,representing an 8.7 percentage points improvement over ZY-BERT+Know(63.7%),the strongest baseline among traditional methods.For long-tail syndromes with fewer than 10 samples,Agent-GNN reached a macro-F1 score of 58.6%,compared with 39.3%for ZY-BERT+Know and 41.2%for GPT-4 Few-shot,representing relative improvements of 49.2%and 42.2%,respectively.Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.Conclusion This study proposes Agent-GNN,a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation.By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs,our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.
基金funded by Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2023ZL128)Zhejiang Province Medical and Health Science and Technology Project(2022504276)Hangzhou Municipal Health and Family Planning Science and Technology Program General Project(A20210086).
文摘Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteoblast proliferation and differentiation,investigating its viability as a bone-healing agent.Methods This study employed various cellular and molecular biology experiments to assess the effects of LA on the viability,proliferation,cell cycle,apoptosis,differentiation,mineralization,and migration of MC3T3-E1 osteoblasts.Immunofluorescence and Western blot analyses were conducted to detect the expression of proteins related to the Wnt/β-catenin signaling pathway,investigating the regulatory mechanisms by which LA promotes osteoblast proliferation and differentiation.Additionally,Wnt inhibitor dickkopf-1(DKK-1)andβ-catenin-silenced cell models were used to further validate the role of LA in modulating this signaling pathway.Results LA significantly promoted osteoblast proliferation without apparent cytotoxicity.Flow cytometry showed that LA regulated the cell cycle by reducing G0/G1 phase arrest and promoting G2/M phase progression.Western blot results indicated that LA upregulated the expression of proteins associated with cell proliferation and enhanced osteoblast differentiation and mineralization.Immunofluorescence and Western blot analyses further confirmed that LA markedly increased the expression of Wnt andβ-catenin,facilitatingβ-catenin nuclear translocation.Treatment with the DKK-1 inhibitor significantly diminished the proliferative and differentiation-promoting effects of LA,confirming the critical role of this pathway.β-catenin knockdown experiments further substantiated its central role in LA-mediated regulation.Conclusion This study confirms that LA promotes osteoblast proliferation,differentiation,mineralization,and migration by activating the Wnt/β-catenin signaling pathway.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金supported by the National Natural Science Foundation of China(82271159,82071049,82425018,and 82101219)the STI2030-Major Projects(2022ZD0205400).
文摘Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.
基金supported by the National Natural Science Foundation of China(82170951,82470961)the Beijing Natural Science Foundation (7222079)+4 种基金the Beijing Hospital Authority"Dengfeng"Talent Training Plan (DFL 20221301)the Beijing Stomatological HospitalCapital Medical University Young Scientist Program (No.YSP202401)the Laboratory for Clinical Medicine and the Central Laboratory of Capital Medical University for their technical support and fundingthe Japan China Sasakawa Medical Fellowship for their generous support and funding。
文摘The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
基金The National Natural Science Foundation of China(41771115)National Key Basic Research and Development Program(2015CB452706)Guizhou Science and Technology Fund(Guizhou Technology Cooperation Basis 20181116)。
文摘Mountain area accounts for a high proportion of the land area in China,and it is the focal area to solve the contradiction of imbalanced regional development,as well as an important source of ecosystem services.Therefore,this area has been facing long-term pressure and challenges in economic development and ecological protection.In this paper,we selected a rocky desertification mountain area,an active mountain area of new tectonic movement and a typical northern earth-rock mountain area,as Qian-Gui karst Mountain area,Hengduan Mountain area and Taihang Mountain area,as examples to represent three main types of mountain areas.Three representative types of ecosystem services,including NPP(Net Primary Productivity)as a support service,water conservation as a regulation service,and agricultural produce as a supply service,were incorporated into this study.Linear regression,correlation analysis and other methods were then used to investigate the spatial-temporal characteristics of the trade-offs and synergies in each of the three kinds of mountain areas during 1990-2015 in China.The analysis yielded three main conclusions for the three mountainous areas.(1)The agricultural produce supply service decreased relatively,while the support and regulation services of NPP and hydrological regulation increased significantly.(2)There was a synergistic relationship between NPP and the hydrological regulation services in the three mountainous areas.The synergistic relation in Qian-Gui karst Mountain area became enhanced,while those in Hengduan and Taihang Mountain areas became weakened,and the former was weakened to a greater extent.There was a trade-off between NPP,the hydrological regulation service and the agricultural produce supply service among the three mountainous areas.In particular,the trade-off between NPP and the agricultural produce supply service in Qian-Gui karst Mountain area became weaker,while those in Hengduan and Taihang Mountain areas were enhanced,and the latter was enhanced to a greater degree.(3)Significant spatial differentiation was evident in the trade-offs and synergies of ecosystem services among the three mountain areas.
基金The Guangdong Education Science Planning Project(2019GXJK080)The Guangdong Philosophy and Social Science Planning Project(GD19YYJ03)The Guangdong Coastal Economic Belt Development Research Institute 2020 Special Project(YJY202002).
文摘Cultivated land pressure is often used to reflect the shortage of cultivated land resources. By using the methods of the Cultivated Land Pressure Index, coefficient of variation and cold-hot spot analysis, this paper analyzes the spatial-temporal differentiation pattern and dynamic change processes of cultivated land pressure in the counties of the Pearl River-Xijiang Economic Zone from 2008 to 2017, and measures the factors which influence cultivated land pressure by using Principal Component Analysis. The results show that the cultivated land pressure in the Pearl River-Xijiang Economic Zone has been in a “high pressure” state, and the Cultivated Land Pressure Index has been rising continuously from 2008 to 2017. The coefficient of variation of the Cultivated Land Pressure Index in the Pearl River-Xijiang Economic Zone and various prefecture-level cities is fluctuating and rising, which indicates that the overall spatial differences in the cultivated land pressure in this region are expanding and polarization is obvious. In addition, the area where the municipal district of the provincial capital city is located is the core area of urban development and also the area with the greatest cultivated land pressure. The spatial pattern of cultivated land pressure cold-hot spots in the Pearl River-Xijiang Economic Zone is obviously heterogeneous, in which the Pearl River Economic Zone is the main hot spot gathering area and the Xijiang Economic Zone is the main cold spot gathering area. Farmers’ income, investment in fixed assets, GDP, population and other socio-economic factors are the main factors driving the changes in the cultivated land pressure in the Pearl River-Xijiang Economic Zone. Furthermore, farming production factors, such as the multiple cropping index and grain yield per unit area,will also have an important impact on the changes in the cultivated land pressure.
基金supported by the Key Laboratory of Natural Resources Monitoring and Supervision in Southern Hilly Region,Ministry of Natural Resources(NRMSSHR2023Y02)Yunnan Key Laboratory of Plateau Geographic Processes and Environmental Changes,Faculty of Geography,Yunnan Normal University(PGPEC2304)China Scholarship Council。
文摘Sloping farmland,particularly in mountainous and hilly areas,constitutes a significant component of regional farmland resources.An investigation into the spatio-temporal pattern of sloping farmland and its influencing factors in China is imperative for the efficient utilization of farmland and the optimization of land space.We used land use transfer matrix,geographically weighted regression model and geographical detector to conduct this study.Results showed that sloping farmland in China firstly decreased and then increased from 2000 to 2020.The proportion of sloping farmland decreased radially outward from Sichuan basin to the surrounding areas.Change rates of sloping farmland with different slopes varied and the slope with 6°-15°underwent the fastest changes.The influencing factors of farmland at various slope degrees were different.For sloping farmland below 15°,land use intensity and elevation had the greatest contribution.For sloping farmland between 15°and 25°,elevation,land use intensity,and population density were the main influencing factors.Sloping farmland above 25°was mostly affected by natural factors.This study can provide scientific basis for rational development and protection of sloping farmland.
