The long-standing use of portable toilet cubicles by residents of Shanghai’s narrow,labyrinthine alleys came to an end in September 2025 after the city largely finished building public toilets to make up their lack o...The long-standing use of portable toilet cubicles by residents of Shanghai’s narrow,labyrinthine alleys came to an end in September 2025 after the city largely finished building public toilets to make up their lack of sanitation facilities.The project,targeting 14,082 households,started last year.展开更多
Unmanned Aerial Vehicles(UAVs)have become integral components in smart city infrastructures,supporting applications such as emergency response,surveillance,and data collection.However,the high mobility and dynamic top...Unmanned Aerial Vehicles(UAVs)have become integral components in smart city infrastructures,supporting applications such as emergency response,surveillance,and data collection.However,the high mobility and dynamic topology of Flying Ad Hoc Networks(FANETs)present significant challenges for maintaining reliable,low-latency communication.Conventional geographic routing protocols often struggle in situations where link quality varies and mobility patterns are unpredictable.To overcome these limitations,this paper proposes an improved routing protocol based on reinforcement learning.This new approach integrates Q-learning with mechanisms that are both link-aware and mobility-aware.The proposed method optimizes the selection of relay nodes by using an adaptive reward function that takes into account energy consumption,delay,and link quality.Additionally,a Kalman filter is integrated to predict UAV mobility,improving the stability of communication links under dynamic network conditions.Simulation experiments were conducted using realistic scenarios,varying the number of UAVs to assess scalability.An analysis was conducted on key performance metrics,including the packet delivery ratio,end-to-end delay,and total energy consumption.The results demonstrate that the proposed approach significantly improves the packet delivery ratio by 12%–15%and reduces delay by up to 25.5%when compared to conventional GEO and QGEO protocols.However,this improvement comes at the cost of higher energy consumption due to additional computations and control overhead.Despite this trade-off,the proposed solution ensures reliable and efficient communication,making it well-suited for large-scale UAV networks operating in complex urban environments.展开更多
At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduli...At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduling.It turned out that since the end of 2025,the company had successively secured bulk spindle orders from overseas clients in Bangladesh and other countries,coupled with continuous urgent requests for orders from domestic manufacturers.Faced with such a production peak right at the beginning of the year,Mr.Cao Xiucheng admitted,“It was truly unexpected.”展开更多
The rapid digitalization of urban infrastructure has made smart cities increasingly vulnerable to sophisticated cyber threats.In the evolving landscape of cybersecurity,the efficacy of Intrusion Detection Systems(IDS)...The rapid digitalization of urban infrastructure has made smart cities increasingly vulnerable to sophisticated cyber threats.In the evolving landscape of cybersecurity,the efficacy of Intrusion Detection Systems(IDS)is increasingly measured by technical performance,operational usability,and adaptability.This study introduces and rigorously evaluates a Human-Computer Interaction(HCI)-Integrated IDS with the utilization of Convolutional Neural Network(CNN),CNN-Long Short Term Memory(LSTM),and Random Forest(RF)against both a Baseline Machine Learning(ML)and a Traditional IDS model,through an extensive experimental framework encompassing many performance metrics,including detection latency,accuracy,alert prioritization,classification errors,system throughput,usability,ROC-AUC,precision-recall,confusion matrix analysis,and statistical accuracy measures.Our findings consistently demonstrate the superiority of the HCI-Integrated approach utilizing three major datasets(CICIDS 2017,KDD Cup 1999,and UNSW-NB15).Experimental results indicate that the HCI-Integrated model outperforms its counterparts,achieving an AUC-ROC of 0.99,a precision of 0.93,and a recall of 0.96,while maintaining the lowest false positive rate(0.03)and the fastest detection time(~1.5 s).These findings validate the efficacy of incorporating HCI to enhance anomaly detection capabilities,improve responsiveness,and reduce alert fatigue in critical smart city applications.It achieves markedly lower detection times,higher accuracy across all threat categories,reduced false positive and false negative rates,and enhanced system throughput under concurrent load conditions.The HCIIntegrated IDS excels in alert contextualization and prioritization,offering more actionable insights while minimizing analyst fatigue.Usability feedback underscores increased analyst confidence and operational clarity,reinforcing the importance of user-centered design.These results collectively position the HCI-Integrated IDS as a highly effective,scalable,and human-aligned solution for modern threat detection environments.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
Transforming urban spatial structures to promote green and low-carbon development is an effective strategy.Although prior studies have examined the impact of urban polycentricity on carbon emissions and economic devel...Transforming urban spatial structures to promote green and low-carbon development is an effective strategy.Although prior studies have examined the impact of urban polycentricity on carbon emissions and economic development,research on its role in the synergistic relationship between these factors regarding carbon emission efficiency is limited.Furthermore,existing literature often overlooks nonlinear effects and interactions with other urban variables.This paper analyzed data from 295 Chinese cities in 2020,calculating urban population polycentricity,population dispersion indices,and carbon emission efficiency.Utilizing local spatial autocorrelation tools,we reveal interactions among urban population polycentricity,dispersion,carbon emissions,and carbon emission efficiency.We then employ a gradient boosting decision tree model(GBDT)to explore nonlinear and synergistic effects of polycentric urbanization.Key findings include:1)polycentric urbanization in Chinese cities exhibits significant spatial differentiation characteristics.The Polycentricity index is relatively high in economically developed eastern coastal regions with an overall low level,carbon emissions are concentrated in industrialized north-central cities and some Yangtze River Delta hubs,and carbon emission efficiency is the highest in the Yangtze River Delta while relatively low in Northeast China;there are significant spatially heterogeneous interaction characteristics among population polycentricity,population dispersion,carbon emissions,and carbon emission efficiency.2)Urban population polycentricity contributes 9.42%to total carbon emissions and 6.24%to carbon emission efficiency.3)The polycentricity index has a nonlinear impact on carbon emissions and carbon emission efficiency:no significant effect when below 0.50 or above 0.55,increased carbon emissions in 0.50-0.53,and reduced carbon emissions with improved efficiency in 0.53-0.55.4)The polycentricity index has an interaction effect with other variables;specifically,when the polycentricity index is between 0.53 and 0.55,its interaction with urban gross domestic product(GDP),urban population,urban built-up area,green coverage rate in built-up areas,urban technological expenditure,and the proportion of the output value of the secondary industry will reduce carbon emissions and improve carbon emission efficiency.These findings enhance the understanding of urban spatial structures and carbon emissions,providing valuable insights for policymakers in developing green and low-carbon strategies.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 evolution of cities into digitally managed environments requires computational systems that can operate in real time while supporting predictive and adaptive infrastructure management.Earlier approaches have often...The evolution of cities into digitally managed environments requires computational systems that can operate in real time while supporting predictive and adaptive infrastructure management.Earlier approaches have often advanced one dimension—such as Internet of Things(IoT)-based data acquisition,Artificial Intelligence(AI)-driven analytics,or digital twin visualization—without fully integrating these strands into a single operational loop.As a result,many existing solutions encounter bottlenecks in responsiveness,interoperability,and scalability,while also leaving concerns about data privacy unresolved.This research introduces a hybrid AI–IoT–Digital Twin framework that combines continuous sensing,distributed intelligence,and simulation-based decision support.The design incorporates multi-source sensor data,lightweight edge inference through Convolutional Neural Networks(CNN)and Long ShortTerm Memory(LSTM)models,and federated learning enhanced with secure aggregation and differential privacy to maintain confidentiality.A digital twin layer extends these capabilities by simulating city assets such as traffic flows and water networks,generating what-if scenarios,and issuing actionable control signals.Complementary modules,including model compression and synchronization protocols,are embedded to ensure reliability in bandwidth-constrained and heterogeneous urban environments.The framework is validated in two urban domains:traffic management,where it adapts signal cycles based on real-time congestion patterns,and pipeline monitoring,where it anticipates leaks through pressure and vibration data.Experimental results show a 28%reduction in response time,a 35%decrease in maintenance costs,and a marked reduction in false positives relative to conventional baselines.The architecture also demonstrates stability across 50+edge devices under federated training and resilience to uneven node participation.The proposed system provides a scalable and privacy-aware foundation for predictive urban infrastructure management.By closing the loop between sensing,learning,and control,it reduces operator dependence,enhances resource efficiency,and supports transparent governance models for emerging smart cities.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
A key target of the overall strategy implementation for regional development since the 18th Party Congress of China has involved taking measures to narrow regional disparities. This is because resource-based cities...A key target of the overall strategy implementation for regional development since the 18th Party Congress of China has involved taking measures to narrow regional disparities. This is because resource-based cities' economic development has fallen below general levels due to resource exhaustion and an unbalanced industrial structure, among other factors. Further, an economic gap has long existed between Northeast China's large number of resource-based cities and non-resource-based cities. This article comprehensively studies the economic convergence of Northeast China's resource-based cities and non-resource-based cities from 1996 to 2015 by using a dynamic panel to analyze not only the economic development of different industries and types of cities, but also the main factors that influence economic development. The empirical results demonstrate that economic convergence exists in both resource-based and non-resource-based cities, but the economic gap between them has clearly narrowed since the implementation of a strategy to revitalize the Northeast's old industrial base. Shrinking cities are the fastest to converge, as mature cities are slower and regenerating cities are the slowest; regarding industry structure, the secondary industry dominates the economy in mature and shrinking cities, and the tertiary industry in regenerating cities. The primary stimulus in resource-based cities' economic development involves upgrading the industrial structure and investing in human capital. As China faces a ‘new normal' economy, resource-based cities in Northeast China should restructure the economy and perfect their market system to avoid again widening the economic gap.展开更多
A total of 18 cities and counties in Hainan from 2012 to 2015 were selected as the basic research units to construct an index system for evaluating the ability of sustainable development that includes four guidelines ...A total of 18 cities and counties in Hainan from 2012 to 2015 were selected as the basic research units to construct an index system for evaluating the ability of sustainable development that includes four guidelines of economic development capacity, population development capacity, social support capacity, and resource utilization and environmental protection capacity. The improved entropy method was used to determine the weight, the Technique for Order of Preference by Similarity to Ideal Solution(TDPSIS) was used to calculate the capacity for sustainable development of the cities and counties and sort these cities and counties, and Arcgis10.2 was used to draw the provincewide distribution of the four guidelines. Thereupon, the author reached following conclusions: there was no big regional difference in the sustainable development capacity of cities and counties in Hainan, and they were basically in a general state of intermediate stage in the past four years; Haikou City and Sanya City, as the key cities, had a higher ability of sustainable development and had shown a remarkable capacity to drive the sustainable development of surrounding areas; according to the development level, the four guidelines were in the following order: resource utilization and environmental protection capacity, population development capacity, social support capacity, and economic development capacity.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
This paper addresses urban sustainability challenges amid global urbanization, emphasizing the need for innova tive approaches aligned with the Sustainable Development Goals. While traditional tools and linear models ...This paper addresses urban sustainability challenges amid global urbanization, emphasizing the need for innova tive approaches aligned with the Sustainable Development Goals. While traditional tools and linear models offer insights, they fall short in presenting a holistic view of complex urban challenges. System dynamics (SD) models that are often utilized to provide holistic, systematic understanding of a research subject, like the urban system, emerge as valuable tools, but data scarcity and theoretical inadequacy pose challenges. The research reviews relevant papers on recent SD model applications in urban sustainability since 2018, categorizing them based on nine key indicators. Among the reviewed papers, data limitations and model assumptions were identified as ma jor challenges in applying SD models to urban sustainability. This led to exploring the transformative potential of big data analytics, a rare approach in this field as identified by this study, to enhance SD models’ empirical foundation. Integrating big data could provide data-driven calibration, potentially improving predictive accuracy and reducing reliance on simplified assumptions. The paper concludes by advocating for new approaches that reduce assumptions and promote real-time applicable models, contributing to a comprehensive understanding of urban sustainability through the synergy of big data and SD models.展开更多
The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with t...The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with the advantage of being environmental-friendly.As one of the organic acids produced by biological metabolism,citric acid was used to leach REEs and explore the performance and process.The results demonstrate that citric acid exhibits higher leaching efficiency(96.00%)for REEs at a relatively low concentration of 0.01 mol/L compared with(NH_(4))_(2)SO_(4)(84.29%,0.1 mol/L)and MgSO_(4)(83.99%,0.1 mol/L).Citric acid shows a preference for leaching heavy rare earth elements,with 99%leaching efficiency in IAREO,which shows higher capacity than(NH_(4))_(2)SO_(4)and MgSO_(4)(as inorganic leaching agents).Kinetic analysis indicates that the leaching process of REEs with citric acid is controlled by both the internal diffusion kinetics and chemical reaction kinetics,which is different from inorganic leaching agents.Visual Minteq calculations confirm that RE-Citrate is the main constituent of the extract solution in the leaching process of the IAREO,thereby enhancing the leaching efficiency of REEs from the IAREO.It suggests that citric acid may be used as a promising organic leaching agent for the environmentalfriendly extraction of REEs from IAREO.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate ...Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.展开更多
文摘The long-standing use of portable toilet cubicles by residents of Shanghai’s narrow,labyrinthine alleys came to an end in September 2025 after the city largely finished building public toilets to make up their lack of sanitation facilities.The project,targeting 14,082 households,started last year.
基金funded by Hung Yen University of Technology and Education under grand number UTEHY.L.2025.62.
文摘Unmanned Aerial Vehicles(UAVs)have become integral components in smart city infrastructures,supporting applications such as emergency response,surveillance,and data collection.However,the high mobility and dynamic topology of Flying Ad Hoc Networks(FANETs)present significant challenges for maintaining reliable,low-latency communication.Conventional geographic routing protocols often struggle in situations where link quality varies and mobility patterns are unpredictable.To overcome these limitations,this paper proposes an improved routing protocol based on reinforcement learning.This new approach integrates Q-learning with mechanisms that are both link-aware and mobility-aware.The proposed method optimizes the selection of relay nodes by using an adaptive reward function that takes into account energy consumption,delay,and link quality.Additionally,a Kalman filter is integrated to predict UAV mobility,improving the stability of communication links under dynamic network conditions.Simulation experiments were conducted using realistic scenarios,varying the number of UAVs to assess scalability.An analysis was conducted on key performance metrics,including the packet delivery ratio,end-to-end delay,and total energy consumption.The results demonstrate that the proposed approach significantly improves the packet delivery ratio by 12%–15%and reduces delay by up to 25.5%when compared to conventional GEO and QGEO protocols.However,this improvement comes at the cost of higher energy consumption due to additional computations and control overhead.Despite this trade-off,the proposed solution ensures reliable and efficient communication,making it well-suited for large-scale UAV networks operating in complex urban environments.
文摘At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduling.It turned out that since the end of 2025,the company had successively secured bulk spindle orders from overseas clients in Bangladesh and other countries,coupled with continuous urgent requests for orders from domestic manufacturers.Faced with such a production peak right at the beginning of the year,Mr.Cao Xiucheng admitted,“It was truly unexpected.”
基金funded and supported by the Ongoing Research Funding program(ORF-2025-314),King Saud University,Riyadh,Saudi Arabia.
文摘The rapid digitalization of urban infrastructure has made smart cities increasingly vulnerable to sophisticated cyber threats.In the evolving landscape of cybersecurity,the efficacy of Intrusion Detection Systems(IDS)is increasingly measured by technical performance,operational usability,and adaptability.This study introduces and rigorously evaluates a Human-Computer Interaction(HCI)-Integrated IDS with the utilization of Convolutional Neural Network(CNN),CNN-Long Short Term Memory(LSTM),and Random Forest(RF)against both a Baseline Machine Learning(ML)and a Traditional IDS model,through an extensive experimental framework encompassing many performance metrics,including detection latency,accuracy,alert prioritization,classification errors,system throughput,usability,ROC-AUC,precision-recall,confusion matrix analysis,and statistical accuracy measures.Our findings consistently demonstrate the superiority of the HCI-Integrated approach utilizing three major datasets(CICIDS 2017,KDD Cup 1999,and UNSW-NB15).Experimental results indicate that the HCI-Integrated model outperforms its counterparts,achieving an AUC-ROC of 0.99,a precision of 0.93,and a recall of 0.96,while maintaining the lowest false positive rate(0.03)and the fastest detection time(~1.5 s).These findings validate the efficacy of incorporating HCI to enhance anomaly detection capabilities,improve responsiveness,and reduce alert fatigue in critical smart city applications.It achieves markedly lower detection times,higher accuracy across all threat categories,reduced false positive and false negative rates,and enhanced system throughput under concurrent load conditions.The HCIIntegrated IDS excels in alert contextualization and prioritization,offering more actionable insights while minimizing analyst fatigue.Usability feedback underscores increased analyst confidence and operational clarity,reinforcing the importance of user-centered design.These results collectively position the HCI-Integrated IDS as a highly effective,scalable,and human-aligned solution for modern threat detection environments.
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Under the auspices of National Natural Science Foundation of China(No.42571300)。
文摘Transforming urban spatial structures to promote green and low-carbon development is an effective strategy.Although prior studies have examined the impact of urban polycentricity on carbon emissions and economic development,research on its role in the synergistic relationship between these factors regarding carbon emission efficiency is limited.Furthermore,existing literature often overlooks nonlinear effects and interactions with other urban variables.This paper analyzed data from 295 Chinese cities in 2020,calculating urban population polycentricity,population dispersion indices,and carbon emission efficiency.Utilizing local spatial autocorrelation tools,we reveal interactions among urban population polycentricity,dispersion,carbon emissions,and carbon emission efficiency.We then employ a gradient boosting decision tree model(GBDT)to explore nonlinear and synergistic effects of polycentric urbanization.Key findings include:1)polycentric urbanization in Chinese cities exhibits significant spatial differentiation characteristics.The Polycentricity index is relatively high in economically developed eastern coastal regions with an overall low level,carbon emissions are concentrated in industrialized north-central cities and some Yangtze River Delta hubs,and carbon emission efficiency is the highest in the Yangtze River Delta while relatively low in Northeast China;there are significant spatially heterogeneous interaction characteristics among population polycentricity,population dispersion,carbon emissions,and carbon emission efficiency.2)Urban population polycentricity contributes 9.42%to total carbon emissions and 6.24%to carbon emission efficiency.3)The polycentricity index has a nonlinear impact on carbon emissions and carbon emission efficiency:no significant effect when below 0.50 or above 0.55,increased carbon emissions in 0.50-0.53,and reduced carbon emissions with improved efficiency in 0.53-0.55.4)The polycentricity index has an interaction effect with other variables;specifically,when the polycentricity index is between 0.53 and 0.55,its interaction with urban gross domestic product(GDP),urban population,urban built-up area,green coverage rate in built-up areas,urban technological expenditure,and the proportion of the output value of the secondary industry will reduce carbon emissions and improve carbon emission efficiency.These findings enhance the understanding of urban spatial structures and carbon emissions,providing valuable insights for policymakers in developing green and low-carbon strategies.
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The researchers would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2025)。
文摘The evolution of cities into digitally managed environments requires computational systems that can operate in real time while supporting predictive and adaptive infrastructure management.Earlier approaches have often advanced one dimension—such as Internet of Things(IoT)-based data acquisition,Artificial Intelligence(AI)-driven analytics,or digital twin visualization—without fully integrating these strands into a single operational loop.As a result,many existing solutions encounter bottlenecks in responsiveness,interoperability,and scalability,while also leaving concerns about data privacy unresolved.This research introduces a hybrid AI–IoT–Digital Twin framework that combines continuous sensing,distributed intelligence,and simulation-based decision support.The design incorporates multi-source sensor data,lightweight edge inference through Convolutional Neural Networks(CNN)and Long ShortTerm Memory(LSTM)models,and federated learning enhanced with secure aggregation and differential privacy to maintain confidentiality.A digital twin layer extends these capabilities by simulating city assets such as traffic flows and water networks,generating what-if scenarios,and issuing actionable control signals.Complementary modules,including model compression and synchronization protocols,are embedded to ensure reliability in bandwidth-constrained and heterogeneous urban environments.The framework is validated in two urban domains:traffic management,where it adapts signal cycles based on real-time congestion patterns,and pipeline monitoring,where it anticipates leaks through pressure and vibration data.Experimental results show a 28%reduction in response time,a 35%decrease in maintenance costs,and a marked reduction in false positives relative to conventional baselines.The architecture also demonstrates stability across 50+edge devices under federated training and resilience to uneven node participation.The proposed system provides a scalable and privacy-aware foundation for predictive urban infrastructure management.By closing the loop between sensing,learning,and control,it reduces operator dependence,enhances resource efficiency,and supports transparent governance models for emerging smart cities.
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Under the auspices of National Natural Science Foundation of China(No.41471111)China’s Postdoctoral Science Foundation(No.2017M621191)Fundamental Research Funds for the Central Universities(No.2412017QD020)
文摘A key target of the overall strategy implementation for regional development since the 18th Party Congress of China has involved taking measures to narrow regional disparities. This is because resource-based cities' economic development has fallen below general levels due to resource exhaustion and an unbalanced industrial structure, among other factors. Further, an economic gap has long existed between Northeast China's large number of resource-based cities and non-resource-based cities. This article comprehensively studies the economic convergence of Northeast China's resource-based cities and non-resource-based cities from 1996 to 2015 by using a dynamic panel to analyze not only the economic development of different industries and types of cities, but also the main factors that influence economic development. The empirical results demonstrate that economic convergence exists in both resource-based and non-resource-based cities, but the economic gap between them has clearly narrowed since the implementation of a strategy to revitalize the Northeast's old industrial base. Shrinking cities are the fastest to converge, as mature cities are slower and regenerating cities are the slowest; regarding industry structure, the secondary industry dominates the economy in mature and shrinking cities, and the tertiary industry in regenerating cities. The primary stimulus in resource-based cities' economic development involves upgrading the industrial structure and investing in human capital. As China faces a ‘new normal' economy, resource-based cities in Northeast China should restructure the economy and perfect their market system to avoid again widening the economic gap.
基金Sponsored by Scientific Research Projects of Colleges and Universities in Hainan Province(Hnky2015-54)
文摘A total of 18 cities and counties in Hainan from 2012 to 2015 were selected as the basic research units to construct an index system for evaluating the ability of sustainable development that includes four guidelines of economic development capacity, population development capacity, social support capacity, and resource utilization and environmental protection capacity. The improved entropy method was used to determine the weight, the Technique for Order of Preference by Similarity to Ideal Solution(TDPSIS) was used to calculate the capacity for sustainable development of the cities and counties and sort these cities and counties, and Arcgis10.2 was used to draw the provincewide distribution of the four guidelines. Thereupon, the author reached following conclusions: there was no big regional difference in the sustainable development capacity of cities and counties in Hainan, and they were basically in a general state of intermediate stage in the past four years; Haikou City and Sanya City, as the key cities, had a higher ability of sustainable development and had shown a remarkable capacity to drive the sustainable development of surrounding areas; according to the development level, the four guidelines were in the following order: resource utilization and environmental protection capacity, population development capacity, social support capacity, and economic development capacity.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
基金sponsored by the U.S.Department of Housing and Urban Development(Grant No.NJLTS0027-22)The opinions expressed in this study are the authors alone,and do not represent the U.S.Depart-ment of HUD’s opinions.
文摘This paper addresses urban sustainability challenges amid global urbanization, emphasizing the need for innova tive approaches aligned with the Sustainable Development Goals. While traditional tools and linear models offer insights, they fall short in presenting a holistic view of complex urban challenges. System dynamics (SD) models that are often utilized to provide holistic, systematic understanding of a research subject, like the urban system, emerge as valuable tools, but data scarcity and theoretical inadequacy pose challenges. The research reviews relevant papers on recent SD model applications in urban sustainability since 2018, categorizing them based on nine key indicators. Among the reviewed papers, data limitations and model assumptions were identified as ma jor challenges in applying SD models to urban sustainability. This led to exploring the transformative potential of big data analytics, a rare approach in this field as identified by this study, to enhance SD models’ empirical foundation. Integrating big data could provide data-driven calibration, potentially improving predictive accuracy and reducing reliance on simplified assumptions. The paper concludes by advocating for new approaches that reduce assumptions and promote real-time applicable models, contributing to a comprehensive understanding of urban sustainability through the synergy of big data and SD models.
基金Project supported by the Thousand Talents Program of Jiangxi Province,China(JXSQ2023201003)National Natural Science Foundation of China(42107254)+4 种基金Science and Technology Major Program of Ordos City(2022EEDSKJZDZX014-2)Technological Innovation Guidance Program of Jiangxi Province(20212BDH81029)Rare Earth Industry Fund(IAGM2020DB06)Selfdeployed Projects of Ganjiang Innovation Academy,Chinese Academy of Sciences(E055A01)the Key Research Program of the Chinese Academy of Sciences(ZDRW-CN-2021-3-3)。
文摘The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with the advantage of being environmental-friendly.As one of the organic acids produced by biological metabolism,citric acid was used to leach REEs and explore the performance and process.The results demonstrate that citric acid exhibits higher leaching efficiency(96.00%)for REEs at a relatively low concentration of 0.01 mol/L compared with(NH_(4))_(2)SO_(4)(84.29%,0.1 mol/L)and MgSO_(4)(83.99%,0.1 mol/L).Citric acid shows a preference for leaching heavy rare earth elements,with 99%leaching efficiency in IAREO,which shows higher capacity than(NH_(4))_(2)SO_(4)and MgSO_(4)(as inorganic leaching agents).Kinetic analysis indicates that the leaching process of REEs with citric acid is controlled by both the internal diffusion kinetics and chemical reaction kinetics,which is different from inorganic leaching agents.Visual Minteq calculations confirm that RE-Citrate is the main constituent of the extract solution in the leaching process of the IAREO,thereby enhancing the leaching efficiency of REEs from the IAREO.It suggests that citric acid may be used as a promising organic leaching agent for the environmentalfriendly extraction of REEs from IAREO.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金supported by the project of Central Funds Guiding the Local Science and Technology Development(No.20212ZDD02010)。
文摘Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
