The pandemic SARS-CoV-2 has become an undying virus to spread a sustainable disease named COVID-19 for upcoming few years.Mortality rates are rising rapidly as approved drugs are not yet available.Isolation from the i...The pandemic SARS-CoV-2 has become an undying virus to spread a sustainable disease named COVID-19 for upcoming few years.Mortality rates are rising rapidly as approved drugs are not yet available.Isolation from the infected person or community is the preferred choice to protect our health.Since humans are the only carriers,it might be possible to control the positive rate if the infected population or host carriers are isolated from each other.Isolation alone may not be a proper solution.These are the resolutions of previous research work carried out on COVID-19 throughout the world.The present scenario of the world and public health is knocking hard with a big question of critical uncertainty of COVID-19 because of its imprecise database as per daily positive cases recorded all over the world and in India as well.In this research work,we have pre-sented an optimal control model for COVID-19 using granular differentiability based on fuzzy dynamical systems.In the first step,we created a fuzzy Susceptible-Exposed-Infected-Asymptomatic-Hospitalized-Recovered-Death(SEIAHRD)model for COVID-19,analyzed it using granular differentiability,and reported disease dynamics for time-independent disease control parameters.In the second step,we upgraded the fuzzy dynamical system and granular differentiability model related to time-dependent disease control parameters as an optimal control problem invader.Theoretical studies have been validated with some practical data from the epidemic COVID-19 related to the Indian perspective during first wave and early second wave.展开更多
This paper deals with Mckean-Vlasov backward stochastic differential equations with weak monotonicity coefficients.We first establish the existence and uniqueness of solutions to Mckean-Vlasov backward stochastic diff...This paper deals with Mckean-Vlasov backward stochastic differential equations with weak monotonicity coefficients.We first establish the existence and uniqueness of solutions to Mckean-Vlasov backward stochastic differential equations.Then we obtain a comparison theorem in one-dimensional situation.展开更多
The generation of synthetic trajectories has become essential in various fields for analyzing complex movement patterns.However,the use of real-world trajectory data poses significant privacy risks,such as location re...The generation of synthetic trajectories has become essential in various fields for analyzing complex movement patterns.However,the use of real-world trajectory data poses significant privacy risks,such as location reidentification and correlation attacks.To address these challenges,privacy-preserving trajectory generation methods are critical for applications relying on sensitive location data.This paper introduces DPIL-Traj,an advanced framework designed to generate synthetic trajectories while achieving a superior balance between data utility and privacy preservation.Firstly,the framework incorporates Differential Privacy Clustering,which anonymizes trajectory data by applying differential privacy techniques that add noise,ensuring the protection of sensitive user information.Secondly,Imitation Learning is used to replicate decision-making behaviors observed in real-world trajectories.By learning from expert trajectories,this component generates synthetic data that closely mimics real-world decision-making processes while optimizing the quality of the generated trajectories.Finally,Markov-based Trajectory Generation is employed to capture and maintain the inherent temporal dynamics of movement patterns.Extensive experiments conducted on the GeoLife trajectory dataset show that DPIL-Traj improves utility performance by an average of 19.85%,and in terms of privacy performance by an average of 12.51%,compared to state-of-the-art approaches.Ablation studies further reveal that DP clustering effectively safeguards privacy,imitation learning enhances utility under noise,and the Markov module strengthens temporal coherence.展开更多
With the popularization of smart devices,Location-Based Services(LBS)greatly facilitates users’life,but at the same time brings the risk of users’location privacy leakage.Existing location privacy protection methods...With the popularization of smart devices,Location-Based Services(LBS)greatly facilitates users’life,but at the same time brings the risk of users’location privacy leakage.Existing location privacy protection methods are deficient,failing to reasonably allocate the privacy budget for non-outlier location points and ignoring the critical location information that may be contained in the outlier points,leading to decreased data availability and privacy exposure problems.To address these problems,this paper proposes a Mix Location Privacy Preservation Method Based on Differential Privacy with Clustering(MLDP).The method first utilizes the DBSCAN clustering algorithm to classify location points into non-outliers and outliers.For non-outliers,the scoring function is designed by combining geographic information and semantic information,and the privacy budget is allocated according to the heat intensity of the hotspot area;for outliers,the scoring function is constructed to allocate the privacy budget based on their correlation with the hotspot area.By comprehensively considering the geographic information,semantic information,and correlation with hotspot areas of the location points,a reasonable privacy budget is assigned to each location point,andfinallynoise is added throughthe Laplacemechanismto realizeprivacyprotection.Experimental results on tworeal trajectory datasets,Geolife and T-Drive,show that the MLDP approach significantly improves data availability while effectively protecting location privacy.Compared with the comparison methods,the maximum available data ratio of MLDP is 1.Moreover,compared with the RandomNoise method,its execution time is 0.056–0.061 s longer,and the logRE is 0.12951–0.62194 lower;compared with KemeansDP,QTK-DP,DPK-F,IDP-SC,and DPK-Means-up methods,it saves 0.114–0.296 s in execution time,and the logRE is 0.01112–0.38283 lower.展开更多
Let X be a real uniformly convex and uniformly smooth Banach space and C a nonempty closed and convex subset of X.Let Π_(C):X→C denote the generalized metric projection operator introduced by Alber in[1].In this pap...Let X be a real uniformly convex and uniformly smooth Banach space and C a nonempty closed and convex subset of X.Let Π_(C):X→C denote the generalized metric projection operator introduced by Alber in[1].In this paper,we define the Gâteaux directional differentiability of Π_(C).We investigate some properties of the Gâteaux directional differentiability of Π_(C).In particular,if C is a closed ball,or a closed and convex cone(including proper closed subspaces),or a closed and convex cylinder,then,we give the exact representations of the directional derivatives of Π_(C).By comparing the results in[12]and this paper,we see the significant difference between the directional derivatives of the generalized metric projection operator Π_(C) and the Gâteaux directional derivatives of the standard metric projection operator PC.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
Poly(phenylene oxide)(PPO)exhibits excellent dielectric properties,making it an ideal substrate for high-frequency,high-speed copper-clad laminates.The phenolic hydroxyl group at the end of PPO plays a key role in its...Poly(phenylene oxide)(PPO)exhibits excellent dielectric properties,making it an ideal substrate for high-frequency,high-speed copper-clad laminates.The phenolic hydroxyl group at the end of PPO plays a key role in its reactivity.Accurately quantifying the phenolic hydroxyl content in PPO is essential but challenging.In this study,we proposed a method for measuring the phenolic hydroxyl content of PPO using differential UV absorption spectroscopy.In alkaline solutions,the phenolic hydroxyl in PPO completely ionizes to form phenoxide ions,leading to a significant increase in UV absorbance at approximately 250 and 300 nm.Notably,the differential UV absorbance at approximately 300 nm was directly proportional to the phenolic hydroxyl concentration.Using 2,6-dimethylphenol as a standard,a calibration curve was established to relate the phenolic hydroxyl concentration to differential UV absorbance at approximately 300 nm,providing a precise and straightforward method for phenolic hydroxyl quantification in PPO with distinct advantages over conventional techniques.展开更多
In reliability analyses,the absence of a priori information on the most probable point of failure(MPP)may result in overlooking critical points,thereby leading to biased assessment outcomes.Moreover,second-order relia...In reliability analyses,the absence of a priori information on the most probable point of failure(MPP)may result in overlooking critical points,thereby leading to biased assessment outcomes.Moreover,second-order reliability methods exhibit limited accuracy in highly nonlinear scenarios.To overcome these challenges,a novel reliability analysis strategy based on a multimodal differential evolution algorithm and a hypersphere integration method is proposed.Initially,the penalty function method is employed to reformulate the MPP search problem as a conditionally constrained optimization task.Subsequently,a differential evolution algorithm incorporating a population delineation strategy is utilized to identify all MPPs.Finally,a paraboloid equation is constructed based on the curvature of the limit-state function at the MPPs,and the failure probability of the structure is calculated by using the hypersphere integration method.The localization effectiveness of the MPPs is compared through multiple numerical cases and two engineering examples,with accuracy comparisons of failure probabilities against the first-order reliability method(FORM)and the secondorder reliability method(SORM).The results indicate that the method effectively identifies existing MPPs and achieves higher solution precision.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
[Objective]As wireless power transfer(WPT)technology is increasingly deployed in scenarios such as electric vehicles,metallic foreign objects in the WPT area may cause local overheating and energy loss.Existing method...[Objective]As wireless power transfer(WPT)technology is increasingly deployed in scenarios such as electric vehicles,metallic foreign objects in the WPT area may cause local overheating and energy loss.Existing methods still suffer from poor edge/corner sensitivity,misjudgment due to fixed thresholds,and limited ability to extract position information.This work proposes a wireless power transfer-foreign object detection(WPT-FOD)method based on channel differential response and a dynamic-threshold corner-enhancement strategy,aiming to improve detection sensitivity,localization accuracy,and robustness without altering the overall coil layout.[Method]A multi-channel detection coil array is designed,and the self-inductance disturbance response of each channel coil is modeled.A channel-difference mapping mechanism is introduced to build a 2-D sensitivity matrix to characterize spatial position correlation.A corner-enhancement algorithm is developed to weight and amplify the collaborative response of adjacent channels,and a dynamic threshold adjustment mechanism is integrated to adapt to varying interference levels.Validation is carried out on a self-built 64-channel FOD platform by moving a typical metallic foreign object across central,edge,and corner regions,and by conducting comparative tests under different interference intensities.[Result]When a typical metallic foreign object moves to corner regions,the self-inductance disturbance of the detection coil increases from less than 0.02μH to more than 0.06μH,significantly enhancing the discrimination capability at corners.Under varying interference strengths,the dynamic threshold mechanism reduces the number of false positives from 13 to 2,demonstrating good environmental adaptability and stability.[Conclusion]By combining channel differential response,corner enhancement,and dynamic thresholding,the proposed WPT-FOD effectively mitigates edge/corner blind spots and fixed-threshold misjudgment,while providing localization capability and robustness.It markedly improves the accuracy of metallic foreign object detection in WPT systems and offers a feasible path and method reference for the safe application and engineering deployment of WPT systems.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
By investigating the evolution of shale gas generation,storage,adjustment and accumulation under different structural settings in superimposed basins,this study elucidates the differential accumulation mechanisms of s...By investigating the evolution of shale gas generation,storage,adjustment and accumulation under different structural settings in superimposed basins,this study elucidates the differential accumulation mechanisms of shale gas.An improved evaluation method of shale gas content evolution in superimposed basins is proposed.This method incorporates the coupling effect of key geological factors such as temperature,pressure,organic matter abundance,maturity,and pore characteristics on the content and occurrence state of shale gas,as well as the configuration relationship between shale gas generation and storage throughout geological history.Using this approach,the gas evolution histories of the Longmaxi Formation shales in wells N201 and PY1 are reconstructed under varying geological conditions.The Longmaxi Formation shales in these wells are dominated by typeⅠkerogen,with original total organic carbon(TOC_(o))contents of 6.20 wt% and 4.92 wt%,respectively,indicating differences in the initial material basis for gas generation.At the maximum burial depth of approximately 5000 m,the Longmaxi Formation shale in well N201 exhibits a formation pressure coefficient of 2.05,an organic matter maturity of 2.2%,and organic pores accounting for 68%of the total porosity.The gas generation quantity(Q_(g))reaches 19.24 m^(3)/t,while the gas storage capacity(Q_(s))is 4.30 m^(3)/t.The actual total gas content(Q_(a)),constrained by Q_(s),is 4.30 m^(3)/t,with free gas comprising 94%.Following relatively moderate tectonic uplift,the Q_(a) in well N201 decreases to 4.03 m^(3)/t,with free gas accounting for 63%.In contrast,the Longmaxi Formation shale in well PY1 reached a maximum burial depth of 6300 m,associated with a formation pressure coefficient of 1.62,organic matter maturity of 2.5%,and organic pore proportion of 67%.Here,Q_(g) is 16.87 m^(3)/t,and both Q_(s) and Q_(a) are 3.65 m^(3)/t,with free gas accounting for 98%.After intense tectonic uplift,Q_(a) declines to 2.72 m^(3)/t,and the proportion of free gas drops to51%.Finally,a four-stage differential accumulation model of shale gas is established:Slow gas generation and only adsorbed gas occur in stageⅠ,which is primarily controlled by TOC content;both adsorbed gas and free gas present in stageⅡ,with free gas becoming dominant;rapid gas generation and free gas predominance are controlled by temperature and porosity in stageⅢ;and gas adjustment and accumulation are primarily controlled by temperature and pressure in stageⅣ.展开更多
Welding deformation adversely affects the quality and precision of structural components,and traditional methods require significant material resources and time.Machine learning has demonstrated exceptional ac-curacy ...Welding deformation adversely affects the quality and precision of structural components,and traditional methods require significant material resources and time.Machine learning has demonstrated exceptional ac-curacy and efficiency in solving complex problems.Thus,the use of machine learning to predict welding de-formations is a novel approach.In this study,laser welding experiments were conducted on a TC4 titanium alloy to establish a welding deformation dataset.The deep neural network(DNN)and convolutional neural network(CNN)models were designed and constructed,with average prediction errors of 0.85 mm and 0.94 mm on the validation set,respectively.To further optimize the network parameters,a differential evolution algorithm was employed through mutation,crossover,and selection.The results indicated that after optimization,the pre-diction errors of the DNN and CNN models reduced to 0.75 mm and 0.85 mm,respectively.These represent accuracy improvements of 14.8%and 9.6%,respectively.The optimized models exhibited superior predictive performances for the validation set.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
Selective Laser Melting(SLM),an advanced metal additive manufacturing technology,offers high precision and personalized customization advantages.However,selecting reasonable SLM parameters is challenging due to comple...Selective Laser Melting(SLM),an advanced metal additive manufacturing technology,offers high precision and personalized customization advantages.However,selecting reasonable SLM parameters is challenging due to complex relationships.This study proposes a method for identifying the optimal process window by combining the simulation model with an optimization algorithm.JAYA is guided by the principle of preferential behavior towards best solutions and avoidance of worst ones,but it is prone to premature convergence thus leading to insufficient global search.To overcome limitations,this research proposes a Differential Evolution-framed JAYA algorithm(DEJAYA).DEJAYA incorporates four key enhancements to improve the flexibility of the original algorithm,which include DE framework design,horizontal crossover operator,longitudinal crossover operator,and global greedy strategy.The effectiveness of DEJAYA is rigorously evaluated by a suite of 23 distinct benchmark functions.Furthermore,the numerical simulation establishes AlSi10Mg single-track formation models,and DEJAYA successfully identified the optimal process window for this problem.Experimental results validate that DEJAYA effectively guides SLM parameter selection for AlSi10Mg.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
Addressing the limitations of inadequate stochastic disturbance characterization during wind turbine degradation processes that result in constrained modeling accuracy,replacement-based maintenance practices that devi...Addressing the limitations of inadequate stochastic disturbance characterization during wind turbine degradation processes that result in constrained modeling accuracy,replacement-based maintenance practices that deviate from actual operational conditions,and static maintenance strategies that fail to adapt to accelerated deterioration trends leading to suboptimal remaining useful life utilization,this study proposes a Time-Based Incomplete Maintenance(TBIM)strategy incorporating reliability constraints through stochastic differential equations(SDE).By quantifying stochastic interference via Brownian motion terms and characterizing nonlinear degradation features through state influence rate functions,a high-precision SDE degradation model is constructed,achieving 16%residual reduction compared to conventional ordinary differential equation(ODE)methods.The introduction of age reduction factors and failure rate growth factors establishes an incomplete maintenance mechanism that transcends traditional“as-good-as-new”assumptions,with the TBIM model demonstrating an additional 8.5%residual reduction relative to baseline SDE approaches.A dynamic maintenance interval optimization model driven by dual parameters—preventive maintenance threshold R_(p) and replacement threshold R_(r)—is designed to achieve synergistic optimization of equipment reliability and maintenance economics.Experimental validation demonstrates that the optimized TBIM extends equipment lifespan by 4.4%and reducesmaintenance costs by 4.16%at R_(p)=0.80,while achieving 17.2%lifespan enhancement and 14.6%cost reduction at R_(p)=0.90.This methodology provides a solution for wind turbine preventive maintenance that integrates condition sensitivity with strategic foresight.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
文摘The pandemic SARS-CoV-2 has become an undying virus to spread a sustainable disease named COVID-19 for upcoming few years.Mortality rates are rising rapidly as approved drugs are not yet available.Isolation from the infected person or community is the preferred choice to protect our health.Since humans are the only carriers,it might be possible to control the positive rate if the infected population or host carriers are isolated from each other.Isolation alone may not be a proper solution.These are the resolutions of previous research work carried out on COVID-19 throughout the world.The present scenario of the world and public health is knocking hard with a big question of critical uncertainty of COVID-19 because of its imprecise database as per daily positive cases recorded all over the world and in India as well.In this research work,we have pre-sented an optimal control model for COVID-19 using granular differentiability based on fuzzy dynamical systems.In the first step,we created a fuzzy Susceptible-Exposed-Infected-Asymptomatic-Hospitalized-Recovered-Death(SEIAHRD)model for COVID-19,analyzed it using granular differentiability,and reported disease dynamics for time-independent disease control parameters.In the second step,we upgraded the fuzzy dynamical system and granular differentiability model related to time-dependent disease control parameters as an optimal control problem invader.Theoretical studies have been validated with some practical data from the epidemic COVID-19 related to the Indian perspective during first wave and early second wave.
基金Supported by the National Natural Science Foundation of China(12001074)the Research Innovation Program of Graduate Students in Hunan Province(CX20220258)+1 种基金the Research Innovation Program of Graduate Students of Central South University(1053320214147)the Key Scientific Research Project of Higher Education Institutions in Henan Province(25B110025)。
文摘This paper deals with Mckean-Vlasov backward stochastic differential equations with weak monotonicity coefficients.We first establish the existence and uniqueness of solutions to Mckean-Vlasov backward stochastic differential equations.Then we obtain a comparison theorem in one-dimensional situation.
基金supported by the Natural Science Foundation of Fujian Province of China(2025J01380)National Natural Science Foundation of China(No.62471139)+3 种基金the Major Health Research Project of Fujian Province(2021ZD01001)Fujian Provincial Units Special Funds for Education and Research(2022639)Fujian University of Technology Research Start-up Fund(GY-S24002)Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare(GY-H-24179).
文摘The generation of synthetic trajectories has become essential in various fields for analyzing complex movement patterns.However,the use of real-world trajectory data poses significant privacy risks,such as location reidentification and correlation attacks.To address these challenges,privacy-preserving trajectory generation methods are critical for applications relying on sensitive location data.This paper introduces DPIL-Traj,an advanced framework designed to generate synthetic trajectories while achieving a superior balance between data utility and privacy preservation.Firstly,the framework incorporates Differential Privacy Clustering,which anonymizes trajectory data by applying differential privacy techniques that add noise,ensuring the protection of sensitive user information.Secondly,Imitation Learning is used to replicate decision-making behaviors observed in real-world trajectories.By learning from expert trajectories,this component generates synthetic data that closely mimics real-world decision-making processes while optimizing the quality of the generated trajectories.Finally,Markov-based Trajectory Generation is employed to capture and maintain the inherent temporal dynamics of movement patterns.Extensive experiments conducted on the GeoLife trajectory dataset show that DPIL-Traj improves utility performance by an average of 19.85%,and in terms of privacy performance by an average of 12.51%,compared to state-of-the-art approaches.Ablation studies further reveal that DP clustering effectively safeguards privacy,imitation learning enhances utility under noise,and the Markov module strengthens temporal coherence.
基金supported in part by the National Natural Science Foundation of China(Grant No.61971291)the Basic Scientific Research Project of the Liaoning Provincial Department of Education(LJ212410144013)+2 种基金the Leading Talent of the‘Xing Liao Ying Cai Plan’(XLYC2202013)the Shenyang Natural Science Foundation(22-315-6-10)the Guangxuan Scholar of Shenyang Ligong University(SYLUGXXZ202205).
文摘With the popularization of smart devices,Location-Based Services(LBS)greatly facilitates users’life,but at the same time brings the risk of users’location privacy leakage.Existing location privacy protection methods are deficient,failing to reasonably allocate the privacy budget for non-outlier location points and ignoring the critical location information that may be contained in the outlier points,leading to decreased data availability and privacy exposure problems.To address these problems,this paper proposes a Mix Location Privacy Preservation Method Based on Differential Privacy with Clustering(MLDP).The method first utilizes the DBSCAN clustering algorithm to classify location points into non-outliers and outliers.For non-outliers,the scoring function is designed by combining geographic information and semantic information,and the privacy budget is allocated according to the heat intensity of the hotspot area;for outliers,the scoring function is constructed to allocate the privacy budget based on their correlation with the hotspot area.By comprehensively considering the geographic information,semantic information,and correlation with hotspot areas of the location points,a reasonable privacy budget is assigned to each location point,andfinallynoise is added throughthe Laplacemechanismto realizeprivacyprotection.Experimental results on tworeal trajectory datasets,Geolife and T-Drive,show that the MLDP approach significantly improves data availability while effectively protecting location privacy.Compared with the comparison methods,the maximum available data ratio of MLDP is 1.Moreover,compared with the RandomNoise method,its execution time is 0.056–0.061 s longer,and the logRE is 0.12951–0.62194 lower;compared with KemeansDP,QTK-DP,DPK-F,IDP-SC,and DPK-Means-up methods,it saves 0.114–0.296 s in execution time,and the logRE is 0.01112–0.38283 lower.
文摘Let X be a real uniformly convex and uniformly smooth Banach space and C a nonempty closed and convex subset of X.Let Π_(C):X→C denote the generalized metric projection operator introduced by Alber in[1].In this paper,we define the Gâteaux directional differentiability of Π_(C).We investigate some properties of the Gâteaux directional differentiability of Π_(C).In particular,if C is a closed ball,or a closed and convex cone(including proper closed subspaces),or a closed and convex cylinder,then,we give the exact representations of the directional derivatives of Π_(C).By comparing the results in[12]and this paper,we see the significant difference between the directional derivatives of the generalized metric projection operator Π_(C) and the Gâteaux directional derivatives of the standard metric projection operator PC.
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the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2023C01072)the Institute of Zhejiang University-Quzhou for their financial support。
文摘Poly(phenylene oxide)(PPO)exhibits excellent dielectric properties,making it an ideal substrate for high-frequency,high-speed copper-clad laminates.The phenolic hydroxyl group at the end of PPO plays a key role in its reactivity.Accurately quantifying the phenolic hydroxyl content in PPO is essential but challenging.In this study,we proposed a method for measuring the phenolic hydroxyl content of PPO using differential UV absorption spectroscopy.In alkaline solutions,the phenolic hydroxyl in PPO completely ionizes to form phenoxide ions,leading to a significant increase in UV absorbance at approximately 250 and 300 nm.Notably,the differential UV absorbance at approximately 300 nm was directly proportional to the phenolic hydroxyl concentration.Using 2,6-dimethylphenol as a standard,a calibration curve was established to relate the phenolic hydroxyl concentration to differential UV absorbance at approximately 300 nm,providing a precise and straightforward method for phenolic hydroxyl quantification in PPO with distinct advantages over conventional techniques.
基金National Natural Science Foundation of China(No.52375236)Fundamental Research Funds for the Central Universities of China(No.23D110316)。
文摘In reliability analyses,the absence of a priori information on the most probable point of failure(MPP)may result in overlooking critical points,thereby leading to biased assessment outcomes.Moreover,second-order reliability methods exhibit limited accuracy in highly nonlinear scenarios.To overcome these challenges,a novel reliability analysis strategy based on a multimodal differential evolution algorithm and a hypersphere integration method is proposed.Initially,the penalty function method is employed to reformulate the MPP search problem as a conditionally constrained optimization task.Subsequently,a differential evolution algorithm incorporating a population delineation strategy is utilized to identify all MPPs.Finally,a paraboloid equation is constructed based on the curvature of the limit-state function at the MPPs,and the failure probability of the structure is calculated by using the hypersphere integration method.The localization effectiveness of the MPPs is compared through multiple numerical cases and two engineering examples,with accuracy comparisons of failure probabilities against the first-order reliability method(FORM)and the secondorder reliability method(SORM).The results indicate that the method effectively identifies existing MPPs and achieves higher solution precision.
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.
文摘[Objective]As wireless power transfer(WPT)technology is increasingly deployed in scenarios such as electric vehicles,metallic foreign objects in the WPT area may cause local overheating and energy loss.Existing methods still suffer from poor edge/corner sensitivity,misjudgment due to fixed thresholds,and limited ability to extract position information.This work proposes a wireless power transfer-foreign object detection(WPT-FOD)method based on channel differential response and a dynamic-threshold corner-enhancement strategy,aiming to improve detection sensitivity,localization accuracy,and robustness without altering the overall coil layout.[Method]A multi-channel detection coil array is designed,and the self-inductance disturbance response of each channel coil is modeled.A channel-difference mapping mechanism is introduced to build a 2-D sensitivity matrix to characterize spatial position correlation.A corner-enhancement algorithm is developed to weight and amplify the collaborative response of adjacent channels,and a dynamic threshold adjustment mechanism is integrated to adapt to varying interference levels.Validation is carried out on a self-built 64-channel FOD platform by moving a typical metallic foreign object across central,edge,and corner regions,and by conducting comparative tests under different interference intensities.[Result]When a typical metallic foreign object moves to corner regions,the self-inductance disturbance of the detection coil increases from less than 0.02μH to more than 0.06μH,significantly enhancing the discrimination capability at corners.Under varying interference strengths,the dynamic threshold mechanism reduces the number of false positives from 13 to 2,demonstrating good environmental adaptability and stability.[Conclusion]By combining channel differential response,corner enhancement,and dynamic thresholding,the proposed WPT-FOD effectively mitigates edge/corner blind spots and fixed-threshold misjudgment,while providing localization capability and robustness.It markedly improves the accuracy of metallic foreign object detection in WPT systems and offers a feasible path and method reference for the safe application and engineering deployment of WPT systems.
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funded by the Sinopec Science and Technology Project(No.P23132)the AAPG Foundation Grants-inAid Program(No.18644937)。
文摘By investigating the evolution of shale gas generation,storage,adjustment and accumulation under different structural settings in superimposed basins,this study elucidates the differential accumulation mechanisms of shale gas.An improved evaluation method of shale gas content evolution in superimposed basins is proposed.This method incorporates the coupling effect of key geological factors such as temperature,pressure,organic matter abundance,maturity,and pore characteristics on the content and occurrence state of shale gas,as well as the configuration relationship between shale gas generation and storage throughout geological history.Using this approach,the gas evolution histories of the Longmaxi Formation shales in wells N201 and PY1 are reconstructed under varying geological conditions.The Longmaxi Formation shales in these wells are dominated by typeⅠkerogen,with original total organic carbon(TOC_(o))contents of 6.20 wt% and 4.92 wt%,respectively,indicating differences in the initial material basis for gas generation.At the maximum burial depth of approximately 5000 m,the Longmaxi Formation shale in well N201 exhibits a formation pressure coefficient of 2.05,an organic matter maturity of 2.2%,and organic pores accounting for 68%of the total porosity.The gas generation quantity(Q_(g))reaches 19.24 m^(3)/t,while the gas storage capacity(Q_(s))is 4.30 m^(3)/t.The actual total gas content(Q_(a)),constrained by Q_(s),is 4.30 m^(3)/t,with free gas comprising 94%.Following relatively moderate tectonic uplift,the Q_(a) in well N201 decreases to 4.03 m^(3)/t,with free gas accounting for 63%.In contrast,the Longmaxi Formation shale in well PY1 reached a maximum burial depth of 6300 m,associated with a formation pressure coefficient of 1.62,organic matter maturity of 2.5%,and organic pore proportion of 67%.Here,Q_(g) is 16.87 m^(3)/t,and both Q_(s) and Q_(a) are 3.65 m^(3)/t,with free gas accounting for 98%.After intense tectonic uplift,Q_(a) declines to 2.72 m^(3)/t,and the proportion of free gas drops to51%.Finally,a four-stage differential accumulation model of shale gas is established:Slow gas generation and only adsorbed gas occur in stageⅠ,which is primarily controlled by TOC content;both adsorbed gas and free gas present in stageⅡ,with free gas becoming dominant;rapid gas generation and free gas predominance are controlled by temperature and porosity in stageⅢ;and gas adjustment and accumulation are primarily controlled by temperature and pressure in stageⅣ.
基金Supported by Defense Industrial Technology Development Program of China(Grant No.JCKY2021605B015).
文摘Welding deformation adversely affects the quality and precision of structural components,and traditional methods require significant material resources and time.Machine learning has demonstrated exceptional ac-curacy and efficiency in solving complex problems.Thus,the use of machine learning to predict welding de-formations is a novel approach.In this study,laser welding experiments were conducted on a TC4 titanium alloy to establish a welding deformation dataset.The deep neural network(DNN)and convolutional neural network(CNN)models were designed and constructed,with average prediction errors of 0.85 mm and 0.94 mm on the validation set,respectively.To further optimize the network parameters,a differential evolution algorithm was employed through mutation,crossover,and selection.The results indicated that after optimization,the pre-diction errors of the DNN and CNN models reduced to 0.75 mm and 0.85 mm,respectively.These represent accuracy improvements of 14.8%and 9.6%,respectively.The optimized models exhibited superior predictive performances for the validation set.
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.
文摘Selective Laser Melting(SLM),an advanced metal additive manufacturing technology,offers high precision and personalized customization advantages.However,selecting reasonable SLM parameters is challenging due to complex relationships.This study proposes a method for identifying the optimal process window by combining the simulation model with an optimization algorithm.JAYA is guided by the principle of preferential behavior towards best solutions and avoidance of worst ones,but it is prone to premature convergence thus leading to insufficient global search.To overcome limitations,this research proposes a Differential Evolution-framed JAYA algorithm(DEJAYA).DEJAYA incorporates four key enhancements to improve the flexibility of the original algorithm,which include DE framework design,horizontal crossover operator,longitudinal crossover operator,and global greedy strategy.The effectiveness of DEJAYA is rigorously evaluated by a suite of 23 distinct benchmark functions.Furthermore,the numerical simulation establishes AlSi10Mg single-track formation models,and DEJAYA successfully identified the optimal process window for this problem.Experimental results validate that DEJAYA effectively guides SLM parameter selection for AlSi10Mg.
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.
基金supported in part by the National Natural Science Foundation of China(No.52467008)Gansu Provincial Depatment of Education Youth Doctoral Suppo Project(2024QB-051).
文摘Addressing the limitations of inadequate stochastic disturbance characterization during wind turbine degradation processes that result in constrained modeling accuracy,replacement-based maintenance practices that deviate from actual operational conditions,and static maintenance strategies that fail to adapt to accelerated deterioration trends leading to suboptimal remaining useful life utilization,this study proposes a Time-Based Incomplete Maintenance(TBIM)strategy incorporating reliability constraints through stochastic differential equations(SDE).By quantifying stochastic interference via Brownian motion terms and characterizing nonlinear degradation features through state influence rate functions,a high-precision SDE degradation model is constructed,achieving 16%residual reduction compared to conventional ordinary differential equation(ODE)methods.The introduction of age reduction factors and failure rate growth factors establishes an incomplete maintenance mechanism that transcends traditional“as-good-as-new”assumptions,with the TBIM model demonstrating an additional 8.5%residual reduction relative to baseline SDE approaches.A dynamic maintenance interval optimization model driven by dual parameters—preventive maintenance threshold R_(p) and replacement threshold R_(r)—is designed to achieve synergistic optimization of equipment reliability and maintenance economics.Experimental validation demonstrates that the optimized TBIM extends equipment lifespan by 4.4%and reducesmaintenance costs by 4.16%at R_(p)=0.80,while achieving 17.2%lifespan enhancement and 14.6%cost reduction at R_(p)=0.90.This methodology provides a solution for wind turbine preventive maintenance that integrates condition sensitivity with strategic foresight.
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.
