In the classroom,teachers usually find that students fail to remain focused and think actively.This relatively low classroom participation also affects students'reading and writing abilities.Therefore,it has been ...In the classroom,teachers usually find that students fail to remain focused and think actively.This relatively low classroom participation also affects students'reading and writing abilities.Therefore,it has been a common concern of educational researchers and practitioners worldwide to understand how students'initiative can be stimulated and how students can be fostered to become self-driven readers,thinkers,and writers.Catherine Snow is an expert on language and literacy development in children.展开更多
Questionnaires and interviews are employed in this paper to investigate and analyze the situation with respect to express packaging waste at the Graduate School of the Chinese Academy of Social Sciences(GCASS).The sur...Questionnaires and interviews are employed in this paper to investigate and analyze the situation with respect to express packaging waste at the Graduate School of the Chinese Academy of Social Sciences(GCASS).The survey results show that:(1)the campus receives a large number of express packages and there is,in turn,a considerable amount of packaging waste;(2)there are four main types of express packaging materials:paper packaging,plastic bags,wrapping tapes and package fillers;(3)neither the students nor the school perform well in the recycling of express packaging waste;(4)the samples investigated in this paper can be divided into four categories by cluster analysis,and the author infers from this that the colleges and universities with a large proportion of female students should pay more attention to the issue of recycling of express packaging waste.Several suggestions are presented based on the research results:(1)establishing a campus waste recycling system is the most efficient way to solve the problem of express packaging waste at GCASS;(2)we should advocate for green packaging and manage it from the source of waste generation because most of the express packaging material does not easily degrade naturally,and this represents a huge hidden danger to human health and the environment;(3)the school should cultivate student awareness of environmental protection.If education and penalties are implemented together,the recovery system will run better.展开更多
This study aims to investigate the current status of AI competencies among Chinese high school students using quantitative research methods.By integrating UNESCO’s AI Competency Framework for Students with China’s e...This study aims to investigate the current status of AI competencies among Chinese high school students using quantitative research methods.By integrating UNESCO’s AI Competency Framework for Students with China’s educational practices,a questionnaire was developed.Altogether,300 students from eight high schools joined the research.SPSS 26.0 was used for reliability and validity tests,exploratory factor analysis,and group difference analysis.The results show that the questionnaire has good reliability and validity(Cronbach’sα=0.974,KMO=0.912,Bartlett’s test of sphericity was significant with p<0.001,cumulative variance explained 72.0%).Besides,Chinese high school students’AI competencies exhibit a typical pattern of“strong in technology,weak in ethics,and insufficient in creativity”,with technical application ability(mean=3.7)significantly higher than ethical assessment(mean=3.0)and system design(mean=2.8).What’s more,students in the eastern region have significantly better overall competencies than those in the central and western regions(p<0.05),with the largest gap in the technical application dimension(mean difference=0.7)and the smallest gap in the ethical dimension(mean difference=0.3).The study recommends optimizing high school curricula by adding modules for ethical debates and interdisciplinary projects and promoting equitable distribution of educational resources.This research empirically supports global AI education standardization and offers a scientific basis for AI education policies and curriculum design in China’s high schools.展开更多
BACKGROUND Sex education was introduced early in foreign countries.For example,there is a more systematic sex education system abroad,which can better achieve the popularization of sex education.China's sex educat...BACKGROUND Sex education was introduced early in foreign countries.For example,there is a more systematic sex education system abroad,which can better achieve the popularization of sex education.China's sex education started relatively late,yet there are many problems in the development of sex education in China;for example,college students lack knowledge of sexuality.AIM To explore the perception of sex education among medical college students.METHODS Students majoring in medicine in a medical school were selected as the survey subjects.Anonymous online questionnaires were used to conduct the survey,and the results were analyzed using GraphPad Prism,SPSS,Microsoft Excel,and other software.The questionnaire was administered to understand the source of sexual knowledge,sexual responsibility,mastery of sexual knowledge,and distress caused by sexual problems.RESULTS Most students majoring in medicine had no formal sex education,lacked sexual knowledge,or had a biased understanding of sexual responsibility.This study analyzed future research trends in sex education based on relevant achievements in the Chinese context and abroad to further realize the practical significance and value of sex education popularization in China and provide recommendations for parents and schools at different levels.CONCLUSION Sex education should be conducted among college students,and medical colleges and universities should strengthen scientific sex education.展开更多
The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient uti...The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient utilization of lepidolite as a lithium source.Therefore,the processes for the flotation of lepidolite have been studied in depth,particularly the development and use of lepidolite flotation collectors and the action mechanism of the collectors on the lepidolite surface.Based on the crystal-structure characteristics of lepidolite minerals,this review focuses on the application of anionic collectors,amine cationic collectors(primary amines,quaternary ammonium salts,ether amines,and Gemini amines),and combined collectors to the flotation behavior of lepidolite as well as the adsorption mechanisms.New directions and technologies for the controllable flotation of lepidolite are proposed,including process improvement,reagent synthesis,and mechanistic research.This analysis demonstrates the need for the further study of the complex environment inside lepidolite and pulp.By using modern analytical detection methods and quantum chemical calculations,research on reagents for the flotation of lepidolite has expanded,providing new concepts and references for the efficient flotation recovery and utilization of lepidolite.展开更多
This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to...This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.展开更多
To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical nee...To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.展开更多
Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination syst...Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination system for Connected and Automated Vehicles(CAVs)at single-lane intersections,particularly in the context of left-hand side driving on roads.The goal is to facilitate smooth right turns for certain vehicles without creating bottlenecks.We consider that all approaching vehicles share relevant information through vehicular communications.The Intersection Coordination Unit(ICU)processes this information and communicates the optimal crossing or turning times to the vehicles.The primary objective of this coordination is to minimize overall traffic delays,which also helps improve the fuel consumption of vehicles.By considering information from upcoming vehicles at the intersection,the coordination system solves an optimization problem to determine the best timing for executing right turns,ultimately minimizing the total delay for all vehicles.The proposed coordination system is evaluated at a typical urban intersection,and its performance is compared to traditional traffic systems.Numerical simulation results indicate that the proposed coordination system significantly enhances the average traffic speed and fuel consumption compared to the traditional traffic system in various scenarios.展开更多
BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.展开更多
The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory ...The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.展开更多
TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing Ti...TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing TiB_(2)coatings have disadvantages such as high equipment costs,complicated processes,and highly toxic gas emissions.This paper proposes an environmentally friendly method,which requires inexpensive equipment and simple processing,for preparing TiB_(2)coating on molybdenum via electrophoretic deposition within Na3AlF6-based molten salts.The produced TiB_(2)layer had an approximate thickness of 60μm and exhibited high density,outstanding hardness(38.2 GPa)and robust adhesion strength(51 N).Additionally,high-temperature oxidation experiments revealed that,at900℃,the TiB_(2)coating provided effective protection to the molybdenum substrate against oxidation for 3 h.This result indicates that the TiB_(2)coating prepared on molybdenum using molten salt electrophoretic deposition possesses good high-temperature oxidation resistance.展开更多
The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in ...The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).展开更多
Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML...Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.展开更多
Aging is a complex biological process characterized by nine hallmarks,including genomic instability,mitochondrial dysfunction,and chronic inflammation,which collectively drive the progression of age-related chronic no...Aging is a complex biological process characterized by nine hallmarks,including genomic instability,mitochondrial dysfunction,and chronic inflammation,which collectively drive the progression of age-related chronic non-communicable diseases.Phytonutrients,a class of bioactive secondary metabolites abundant in plants,have emerged as a promising research focus for intervening in the aging process due to their multifaceted biological activities.This review systematically elaborates on the molecular mechanisms,key signaling pathways,specifically SIRT1,Nrf2/ARE,and AMPK/mTOR,and the synergistic anti-aging effects of four typical phytonutrient categories:polyphenols(e.g.,resveratrol,quercetin),carotenoids(e.g.,lycopene,astaxanthin),sulfur compounds(e.g.,α-lipoic acid,ergothioneine),and phytoestrogens(e.g.,soybean isoflavones).The evidence indicates that these compounds combat aging through a multidimensional network involving direct antioxidant actions,free radical scavenging,metal chelation,promotion of autophagy,and modulation of inflammatory and epigenetic pathways.Crucially,the review highlights that synergistic interactions between different phytonutrients can significantly enhance their efficacy beyond the effect of any single compound.The aim is to consolidate the anti-aging evidence of phytonutrients and address the current translational challenges,such as bioavailability and a lack of robust human trials,thereby providing a comprehensive theoretical framework for developing effective,diet-centered strategies to promote healthy aging and reduce the global burden of non-communicable diseases.展开更多
Heart disease remains a leading cause of mortality worldwide,emphasizing the urgent need for reliable and interpretable predictive models to support early diagnosis and timely intervention.However,existing Deep Learni...Heart disease remains a leading cause of mortality worldwide,emphasizing the urgent need for reliable and interpretable predictive models to support early diagnosis and timely intervention.However,existing Deep Learning(DL)approaches often face several limitations,including inefficient feature extraction,class imbalance,suboptimal classification performance,and limited interpretability,which collectively hinder their deployment in clinical settings.To address these challenges,we propose a novel DL framework for heart disease prediction that integrates a comprehensive preprocessing pipeline with an advanced classification architecture.The preprocessing stage involves label encoding and feature scaling.To address the issue of class imbalance inherent in the personal key indicators of the heart disease dataset,the localized random affine shadowsampling technique is employed,which enhances minority class representation while minimizing overfitting.At the core of the framework lies the Deep Residual Network(DeepResNet),which employs hierarchical residual transformations to facilitate efficient feature extraction and capture complex,non-linear relationships in the data.Experimental results demonstrate that the proposed model significantly outperforms existing techniques,achieving improvements of 3.26%in accuracy,3.16%in area under the receiver operating characteristics,1.09%in recall,and 1.07%in F1-score.Furthermore,robustness is validated using 10-fold crossvalidation,confirming the model’s generalizability across diverse data distributions.Moreover,model interpretability is ensured through the integration of Shapley additive explanations and local interpretable model-agnostic explanations,offering valuable insights into the contribution of individual features to model predictions.Overall,the proposed DL framework presents a robust,interpretable,and clinically applicable solution for heart disease prediction.展开更多
Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accom...Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to...BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.展开更多
BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,...BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
文摘In the classroom,teachers usually find that students fail to remain focused and think actively.This relatively low classroom participation also affects students'reading and writing abilities.Therefore,it has been a common concern of educational researchers and practitioners worldwide to understand how students'initiative can be stimulated and how students can be fostered to become self-driven readers,thinkers,and writers.Catherine Snow is an expert on language and literacy development in children.
文摘Questionnaires and interviews are employed in this paper to investigate and analyze the situation with respect to express packaging waste at the Graduate School of the Chinese Academy of Social Sciences(GCASS).The survey results show that:(1)the campus receives a large number of express packages and there is,in turn,a considerable amount of packaging waste;(2)there are four main types of express packaging materials:paper packaging,plastic bags,wrapping tapes and package fillers;(3)neither the students nor the school perform well in the recycling of express packaging waste;(4)the samples investigated in this paper can be divided into four categories by cluster analysis,and the author infers from this that the colleges and universities with a large proportion of female students should pay more attention to the issue of recycling of express packaging waste.Several suggestions are presented based on the research results:(1)establishing a campus waste recycling system is the most efficient way to solve the problem of express packaging waste at GCASS;(2)we should advocate for green packaging and manage it from the source of waste generation because most of the express packaging material does not easily degrade naturally,and this represents a huge hidden danger to human health and the environment;(3)the school should cultivate student awareness of environmental protection.If education and penalties are implemented together,the recovery system will run better.
基金supported by Research Project on Humanities and Social Sciences in Higher Education Institutions of Guizhou Provincial Department of Education(No.24RWZX060).
文摘This study aims to investigate the current status of AI competencies among Chinese high school students using quantitative research methods.By integrating UNESCO’s AI Competency Framework for Students with China’s educational practices,a questionnaire was developed.Altogether,300 students from eight high schools joined the research.SPSS 26.0 was used for reliability and validity tests,exploratory factor analysis,and group difference analysis.The results show that the questionnaire has good reliability and validity(Cronbach’sα=0.974,KMO=0.912,Bartlett’s test of sphericity was significant with p<0.001,cumulative variance explained 72.0%).Besides,Chinese high school students’AI competencies exhibit a typical pattern of“strong in technology,weak in ethics,and insufficient in creativity”,with technical application ability(mean=3.7)significantly higher than ethical assessment(mean=3.0)and system design(mean=2.8).What’s more,students in the eastern region have significantly better overall competencies than those in the central and western regions(p<0.05),with the largest gap in the technical application dimension(mean difference=0.7)and the smallest gap in the ethical dimension(mean difference=0.3).The study recommends optimizing high school curricula by adding modules for ethical debates and interdisciplinary projects and promoting equitable distribution of educational resources.This research empirically supports global AI education standardization and offers a scientific basis for AI education policies and curriculum design in China’s high schools.
基金Supported by Scientific Research Project of College Students in Liaoning Province,No.S202410164004.
文摘BACKGROUND Sex education was introduced early in foreign countries.For example,there is a more systematic sex education system abroad,which can better achieve the popularization of sex education.China's sex education started relatively late,yet there are many problems in the development of sex education in China;for example,college students lack knowledge of sexuality.AIM To explore the perception of sex education among medical college students.METHODS Students majoring in medicine in a medical school were selected as the survey subjects.Anonymous online questionnaires were used to conduct the survey,and the results were analyzed using GraphPad Prism,SPSS,Microsoft Excel,and other software.The questionnaire was administered to understand the source of sexual knowledge,sexual responsibility,mastery of sexual knowledge,and distress caused by sexual problems.RESULTS Most students majoring in medicine had no formal sex education,lacked sexual knowledge,or had a biased understanding of sexual responsibility.This study analyzed future research trends in sex education based on relevant achievements in the Chinese context and abroad to further realize the practical significance and value of sex education popularization in China and provide recommendations for parents and schools at different levels.CONCLUSION Sex education should be conducted among college students,and medical colleges and universities should strengthen scientific sex education.
基金financially supported by the Excellent Youth Scholars Program of State Key Laboratory of Complex Nonferrous Metal Resource Clean Utilization,Kunming University of Science and Technology,China(No.YXQN-2024003)the Central Government-Guided Local Science and Technology Development Fund Project,China(No.202407AB110022)。
文摘The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient utilization of lepidolite as a lithium source.Therefore,the processes for the flotation of lepidolite have been studied in depth,particularly the development and use of lepidolite flotation collectors and the action mechanism of the collectors on the lepidolite surface.Based on the crystal-structure characteristics of lepidolite minerals,this review focuses on the application of anionic collectors,amine cationic collectors(primary amines,quaternary ammonium salts,ether amines,and Gemini amines),and combined collectors to the flotation behavior of lepidolite as well as the adsorption mechanisms.New directions and technologies for the controllable flotation of lepidolite are proposed,including process improvement,reagent synthesis,and mechanistic research.This analysis demonstrates the need for the further study of the complex environment inside lepidolite and pulp.By using modern analytical detection methods and quantum chemical calculations,research on reagents for the flotation of lepidolite has expanded,providing new concepts and references for the efficient flotation recovery and utilization of lepidolite.
基金Supported by Japan Society for the Promotion of Science,No.24K11935.
文摘This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.
基金Supported by Japan Society for the Promotion of Science KAKENHI,No.25K11274.
文摘To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.
基金supported by the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid for Scientific Research(C)23K03898.
文摘Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination system for Connected and Automated Vehicles(CAVs)at single-lane intersections,particularly in the context of left-hand side driving on roads.The goal is to facilitate smooth right turns for certain vehicles without creating bottlenecks.We consider that all approaching vehicles share relevant information through vehicular communications.The Intersection Coordination Unit(ICU)processes this information and communicates the optimal crossing or turning times to the vehicles.The primary objective of this coordination is to minimize overall traffic delays,which also helps improve the fuel consumption of vehicles.By considering information from upcoming vehicles at the intersection,the coordination system solves an optimization problem to determine the best timing for executing right turns,ultimately minimizing the total delay for all vehicles.The proposed coordination system is evaluated at a typical urban intersection,and its performance is compared to traditional traffic systems.Numerical simulation results indicate that the proposed coordination system significantly enhances the average traffic speed and fuel consumption compared to the traditional traffic system in various scenarios.
基金Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
基金supported by the Deutsche Forschungsgemeinschaft(DFG),TRR274(Project ID 408885537,Sy Nergy,EXC 2145/ID 390857198,to FMB)。
文摘The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
基金supported by the Original Exploratory Program of the National Natural Science Foundation of China(No.52450012)。
文摘TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing TiB_(2)coatings have disadvantages such as high equipment costs,complicated processes,and highly toxic gas emissions.This paper proposes an environmentally friendly method,which requires inexpensive equipment and simple processing,for preparing TiB_(2)coating on molybdenum via electrophoretic deposition within Na3AlF6-based molten salts.The produced TiB_(2)layer had an approximate thickness of 60μm and exhibited high density,outstanding hardness(38.2 GPa)and robust adhesion strength(51 N).Additionally,high-temperature oxidation experiments revealed that,at900℃,the TiB_(2)coating provided effective protection to the molybdenum substrate against oxidation for 3 h.This result indicates that the TiB_(2)coating prepared on molybdenum using molten salt electrophoretic deposition possesses good high-temperature oxidation resistance.
基金supported by a grant from the Japan Foundation for applied enzymology (to NT)the Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (26430059, 17K08272, and 20K07014 to NT)+1 种基金the establishment of university fellowships toward the creation of science technology innovation (JPMJFS2128)a Grant-in-Aid for JSPS Fellows (23KJ1603)(to MK)。
文摘The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).
文摘Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.
基金supported by the Shanghai Sailing Program(No.21YF1418500)the Shanghai Chenguang Program(No.21CGA70)+1 种基金the three-year action plan for strengthening the construction of the public health system in Shanghai(No.GWVI-11.2-YQ12)Additionally,we would like to thank the Shanghai Oriental Talents Program-Youth Project(Education Platform)for its support of this study.
文摘Aging is a complex biological process characterized by nine hallmarks,including genomic instability,mitochondrial dysfunction,and chronic inflammation,which collectively drive the progression of age-related chronic non-communicable diseases.Phytonutrients,a class of bioactive secondary metabolites abundant in plants,have emerged as a promising research focus for intervening in the aging process due to their multifaceted biological activities.This review systematically elaborates on the molecular mechanisms,key signaling pathways,specifically SIRT1,Nrf2/ARE,and AMPK/mTOR,and the synergistic anti-aging effects of four typical phytonutrient categories:polyphenols(e.g.,resveratrol,quercetin),carotenoids(e.g.,lycopene,astaxanthin),sulfur compounds(e.g.,α-lipoic acid,ergothioneine),and phytoestrogens(e.g.,soybean isoflavones).The evidence indicates that these compounds combat aging through a multidimensional network involving direct antioxidant actions,free radical scavenging,metal chelation,promotion of autophagy,and modulation of inflammatory and epigenetic pathways.Crucially,the review highlights that synergistic interactions between different phytonutrients can significantly enhance their efficacy beyond the effect of any single compound.The aim is to consolidate the anti-aging evidence of phytonutrients and address the current translational challenges,such as bioavailability and a lack of robust human trials,thereby providing a comprehensive theoretical framework for developing effective,diet-centered strategies to promote healthy aging and reduce the global burden of non-communicable diseases.
基金funded by Ongoing Research Funding Program for Project number(ORF-2025-648),King Saud University,Riyadh,Saudi Arabia.
文摘Heart disease remains a leading cause of mortality worldwide,emphasizing the urgent need for reliable and interpretable predictive models to support early diagnosis and timely intervention.However,existing Deep Learning(DL)approaches often face several limitations,including inefficient feature extraction,class imbalance,suboptimal classification performance,and limited interpretability,which collectively hinder their deployment in clinical settings.To address these challenges,we propose a novel DL framework for heart disease prediction that integrates a comprehensive preprocessing pipeline with an advanced classification architecture.The preprocessing stage involves label encoding and feature scaling.To address the issue of class imbalance inherent in the personal key indicators of the heart disease dataset,the localized random affine shadowsampling technique is employed,which enhances minority class representation while minimizing overfitting.At the core of the framework lies the Deep Residual Network(DeepResNet),which employs hierarchical residual transformations to facilitate efficient feature extraction and capture complex,non-linear relationships in the data.Experimental results demonstrate that the proposed model significantly outperforms existing techniques,achieving improvements of 3.26%in accuracy,3.16%in area under the receiver operating characteristics,1.09%in recall,and 1.07%in F1-score.Furthermore,robustness is validated using 10-fold crossvalidation,confirming the model’s generalizability across diverse data distributions.Moreover,model interpretability is ensured through the integration of Shapley additive explanations and local interpretable model-agnostic explanations,offering valuable insights into the contribution of individual features to model predictions.Overall,the proposed DL framework presents a robust,interpretable,and clinically applicable solution for heart disease prediction.
基金supported by The Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(RS-2023-00244901)(to RB)。
文摘Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
文摘BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.
基金Supported by the National Natural Science Foundation of China,No.81860843Guangxi Administration of Traditional Chinese Medicine Project,No.GZSY23-36 and No.GXZYA20240150。
文摘BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
