Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy ...Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy of Scytosiphon lomentaria fucoidan(SLF)in alleviating alcohol-induced liver injury was evaluated in a mouse model.It showed that SLF increased body weight and colon length,while reducing liver index,serum lipid,alanine aminotransferase,and aspartate aminotransferase in alcohol-treated mice.SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines.It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway.SLF modulated alcohol-induced dysbiosis of gut microbiota,including a reduction in Bacteroidetes and Proteobacteria,and improved metabolites profile,primarily affecting short chain fatty acids and amino acids metabolism.In addition,SLF reduced the level of total bile acids,regulated the profile of bile acids,and increased the levels of farnesoid X receptor(FXR)and AMP-activated protein kinase(AMPK),suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway.This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.展开更多
This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia(RC).Twenty-four female Wistar rats were assigned to 3 groups:CON group(normal saline by gavage)...This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia(RC).Twenty-four female Wistar rats were assigned to 3 groups:CON group(normal saline by gavage),CIA group(collagen-induced arthritis(CIA),normal saline by gavage),and CCFM1078 group(CIA,3×10^(9)CFU/(rat·day)B.breve CCFM1078 gavage).The results demonstrated that B.breve CCFM1078 not only improved skeletal muscle function in CIA rats,but also modulated the gut microbiota,skeletal muscle metabolism and hormone levels,reduced inflammation in the knee joint and skeletal muscles,decreased activity of the nuclear factor κB(NF-κB)inflammatory signaling pathway,enhanced the insulin receptor substrate 1(IRS1)/phosphatidylinositol 3-kinase/protein kinase(PI3K/Akt)signaling pathway,promoted skeletal muscle differentiation,and maintained skeletal muscle fiber diameter,consequently slowing down the progression of RC.These findings suggested that B.breve CCFM1078 may have a beneficial role as part of a dietary intervention for RC,enhancing overall therapeutic effects.展开更多
Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)indu...Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Microplastics are becoming well-known as chronic pollutants of terrestrial ecosystems,although their sources,dynamics of transportation,reliability of detection and ecological hazard are not evenly described.This revi...Microplastics are becoming well-known as chronic pollutants of terrestrial ecosystems,although their sources,dynamics of transportation,reliability of detection and ecological hazard are not evenly described.This review is a synthesis of the existing information about microplastics in soils,including analytical detection and characterization techniques,the major sources in the terrestrial environment,transport routes within the compartments and between compartments,and reported ecotoxicological consequences on soil biota,plants,and microbial communities.We also critically discuss the strengths and weaknesses of methodologies,making the distinction of sampling design differences,size detection limits,polymer identification methods,and quality assurance procedures on data comparability and uncertainty.An important outcome of this review is the systematic evaluation of the strength of evidence in three interrelated areas:measurement,environmental transport,and biological impacts,hence explaining which findings are strong and in which areas of research significant knowledge gaps still exist.We also suggest a conceptual framework that strongly connects the measurement uncertainty to the exposure estimation,interpretation of risk,and management relevance.This review uses mechanistic insights into transport and ecotoxicology alongside analysis constraints to add to the more comprehensive foundation of terrestrial risk assessment.Lastly,we determine research priorities,such as harmonized methodologies,realistic exposure scenarios,and cross-scale monitoring strategies,in order to assist in the science-based policies and mitigation action.展开更多
Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event ...Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event for the English edition of the book’s fifth volume on 3 December 2025 in Johannesburg,South Africa.展开更多
Pyrethroids are a class of novel broad-spectrum pesticides synthesized to mimic natural pyrethrins.Due to their high efficiency,low toxicity,and safety,pyrethroids have been widely used as alternatives to organophosph...Pyrethroids are a class of novel broad-spectrum pesticides synthesized to mimic natural pyrethrins.Due to their high efficiency,low toxicity,and safety,pyrethroids have been widely used as alternatives to organophosphate and carbamate insecticides in the control of agricultural and sanitary pests.However,with the increasing use of pyrethroid pesticides,the resulting pesticide residues have posed threats to both the environment and human health.Biodegradation is considered one of the most promising methods for the removal of pyrethroids,and significant research has been conducted in this area.This review summarizes recent advances in the biodegradation of pyrethroids,including degradation by single strains,microbial consortia,and enzymes.It provides an in-depth analysis of the biodegradation pathways and catalytic mechanisms involved in the degradation of pyrethroids and outlines enhancement strategies for improving the activity of pyrethroid-degrading enzymes.The review also identifies current challenges in pyrethroid biodegradation and offers perspectives for future research.This review serves as a valuable reference for subsequent studies on pyrethroid biodegradation.展开更多
V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating ene...V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.展开更多
The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were develop...The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.展开更多
Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates...Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.展开更多
Within contemporary healthcare systems, professional identity among specialized nurses serves as a pivotal intrinsic factor influencing the development of their core competencies. This review synthesizes existing rese...Within contemporary healthcare systems, professional identity among specialized nurses serves as a pivotal intrinsic factor influencing the development of their core competencies. This review synthesizes existing research, revealing that professional identity positively impacts the development of core competencies through multiple pathways, including psychological drive, behavioral facilitation, teamwork, and career stability. Building on this analysis, this paper proposes systematic enhancement strategies from four dimensions: education and training, organizational environment, cultural development, and individual growth, aiming to provide a reference for nursing practice and professional development.展开更多
Taohong Siwu Decoction(THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis(AS). This review examines the complex me...Taohong Siwu Decoction(THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis(AS). This review examines the complex mechanisms through which THSWD influences critical pathways, including nuclear factor kappa-B(NF-κB), phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(AKT), Toll-like receptor 4(TLR4), mitogen-activated protein kinase(MAPK), and mammalian target of rapamycin(mTOR), that play pivotal roles in AS pathogenesis. By synthesizing experimental evidence and existing literature, the review summarizes how THSWD and its bioactive constituents regulate these signaling cascades to ameliorate AS. Furthermore, it highlights the distinctive therapeutic advantages of traditional Chinese medicine(TCM) compounds in managing chronic diseases driven by multi-target and multifactorial mechanisms. Analyzing disease targets from the perspective of signaling pathways enhances the scientific validation of clinical efficacy for such formulations, thereby offering novel insights for future research.展开更多
Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and tr...Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.展开更多
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.展开更多
Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa&#...Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa's human capital and accelerating its structural transformation and modernization process.This paper employs“demand–supply–adaptation”as its core analytical framework and aims to systematically explore how the educational cooperation between China and Africa can serve Africa's goal of modernization more precisely and effectively.First,through reviewing and analyzing the domestic and international research literature,this paper clarifies the focus,paradigms,and shortcomings of existing research,identifying the knowledge contribution of this study.Second,utilizing detailed macro-level data,case studies,and comparative research methods,it comprehensively presents the multidimensional status,structural characteristics,and development trends of China–Africa educational cooperation in areas such as student exchanges,cooperative education,vocational and technical training,language and cultural exchange,and emerging digital education.This paper also deeply analyzes the pressing and specific demands placed on the education system by Africa's modernization development across key dimensions like economic diversification,industrialization,agricultural modernization,social governance upgrading,and digital transformation.Third,based on the cooperative principle of“Africa's needs and China's strengths,”this paper innovatively proposes systematic countermeasures and suggestions for constructing new,multi-level,high-quality,sustainable,and future-oriented pathways for China–Africa educational cooperation:(a)promoting the strategic focus of cooperation to extend from“hard infrastructure”support to empowering“soft infrastructure”;(b)deepening the integration of industry and education and school–enterprise collaboration to precisely align with Africa's industrial development needs;vigorously developing digital education and jointly building a smart education ecosystem to help Africa bridge the digital divide;(c)improving an evidence-based,third-party evaluation system for cooperative effectiveness and a full-process quality assurance system;and(d)promoting the collaborative participation of multiple actors including governments,schools,enterprises,think tanks,and social organizations to build a new cooperative pattern of coconstruction,co-governance,and shared benefits.展开更多
Background:The efficacy of standard 5-fluorouracil(5-FU)chemotherapy for colorectal cancer is limited by drug resistance and adverse effects,prompting research into esketamine,a potent ketamine variant with analgesic,...Background:The efficacy of standard 5-fluorouracil(5-FU)chemotherapy for colorectal cancer is limited by drug resistance and adverse effects,prompting research into esketamine,a potent ketamine variant with analgesic,antidepressant,and recently discovered anti-tumor properties,to determine if it can enhance 5-FU’s chemosensitivity.This study investigates whether esketamine synergizes with 5-FU to enhance therapeutic efficacy in colorectal adenocarcinoma cell models.Methods:We performed functional assays to evaluate proliferation(CCK-8),migration(wound healing),invasion(Transwell),and apoptosis(flow cytometry)in colorectal adenocarcinoma cell lines treated with 5-FU alone or in combination with esketamine.Transcriptomic profiling was conducted using RNA sequencing,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was employed to identify critical molecular targets and signaling networks.Protein-level validation of key pathway components was performed via western blotting.Results:Combination therapy with esketamine and 5-FU synergistically inhibited cellular proliferation,migration,and invasion while significantly inducing apoptosis compared to monotherapy.Mechanistically,esketamine potentiated 5-FU-driven AMP-activated protein kinase(AMPK)phosphorylation,leading to inhibition of both mammalian target of rapamycin(mTOR)and hyaluronan-mediated motility receptor(HMMR).Conclusion:Esketamine enhances 5-FU chemosensitivity in colorectal adenocarcinoma by activating the AMPK/mTOR/HMMR signaling axis,thereby suppressing tumor progression and metastatic potential.These findings position esketamine as a potential adjunctive therapy for 5-FU-based regimens,offering the dual benefit of enhancing chemotherapeutic efficacy while addressing cancer-associated comorbidities including pain and depression.展开更多
The increasing production and release of synthetic organic chemicals,including pharmaceuticals,into our envi-ronment has allowed these substances to accumulate in our surface water systems.Current purification technol...The increasing production and release of synthetic organic chemicals,including pharmaceuticals,into our envi-ronment has allowed these substances to accumulate in our surface water systems.Current purification technolo-gies have been unable to eliminate these pollutants,resulting in their ongoing release into aquatic ecosystems.This study focuses on cloperastine(CPS),a cough suppressant and antihistamine medication.The environmental impact of CPS usage has become a concern,mainly due to its increased detection during the COVID-19 pandemic.CPS has been found in wastewater treatment facilities,effluents from senior living residences,river waters,and sewage sludge.However,the photosensitivity of CPS and its photodegradation profile remain largely unknown.This study investigates the photodegradation process of CPS under simulated tertiary treatment conditions using UV photolysis,a method commonly applied in some wastewater treatment plants.Several transformation prod-ucts were identified,evaluating their kinetic profiles using chemometric approaches(i.e.,curve fitting and the hard-soft multivariate curve resolution-alternating least squares(HS-MCR-ALS)algorithm)and calculating the reaction quantum yield.As a result,three different transformation products have been detected and correctly identified.In addition,a comprehensive description of the kinetic pathway involved in the photodegradation process of the CPS drug has been provided,including observed kinetic rate constants.展开更多
Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation...Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.展开更多
Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed t...Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.展开更多
Cold stress represents a critical constraint on crop productivity,particularly in temperate climates.Despite the established role of abscisic acid(ABA)in cold stress responses,the precise mechanisms through which tran...Cold stress represents a critical constraint on crop productivity,particularly in temperate climates.Despite the established role of abscisic acid(ABA)in cold stress responses,the precise mechanisms through which transcription factors mediate ABAdependent cold tolerance remain elusive.Here,we identify VaMYB4a,a MYB transcription factor from Vitis amurensis Rupr.(Amur grape),as a key regulator of cold tolerance.It integrates ABA signaling with the CBF(C-repeat binding factors)-COR(cold-regulated)pathway to orchestrate cold stress adaptation.Through a combination of overexpression and CRISPR/Cas9-mediated knockout lines in Arabidopsis thaliana,grape callus,and Vitis vinifera L.seedlings,we demonstrate that VaMYB4a enhances freezing tolerance by promoting osmotic regulation,reactive oxygen species(ROS)scavenging,and stomatal closure.VaMYB4a functions as a homo-dimer,with its C-terminal domain being essential for transcriptional activation.Mechanistically,VaMYB4a directly upregulates CBF and COR genes while fine-tuning ABA signaling components such as ABI1 and ABF4.Notably,ABA exhibits a dual role:enhancing VaMYB4a-mediated freezing tolerance under short-term stress but attenuating its effects during prolonged cold exposure,revealing an intricate regulatory crosstalk between cold and hormonal pathways.Our work not only advances the molecular understanding of cold adaptation but also provides a promising genetic target for developing stress-resilient grape varieties to mitigate the impacts of climate change.展开更多
文摘Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy of Scytosiphon lomentaria fucoidan(SLF)in alleviating alcohol-induced liver injury was evaluated in a mouse model.It showed that SLF increased body weight and colon length,while reducing liver index,serum lipid,alanine aminotransferase,and aspartate aminotransferase in alcohol-treated mice.SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines.It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway.SLF modulated alcohol-induced dysbiosis of gut microbiota,including a reduction in Bacteroidetes and Proteobacteria,and improved metabolites profile,primarily affecting short chain fatty acids and amino acids metabolism.In addition,SLF reduced the level of total bile acids,regulated the profile of bile acids,and increased the levels of farnesoid X receptor(FXR)and AMP-activated protein kinase(AMPK),suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway.This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.
基金supported by the National Natural Science Foundation of China(32021005)111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia(RC).Twenty-four female Wistar rats were assigned to 3 groups:CON group(normal saline by gavage),CIA group(collagen-induced arthritis(CIA),normal saline by gavage),and CCFM1078 group(CIA,3×10^(9)CFU/(rat·day)B.breve CCFM1078 gavage).The results demonstrated that B.breve CCFM1078 not only improved skeletal muscle function in CIA rats,but also modulated the gut microbiota,skeletal muscle metabolism and hormone levels,reduced inflammation in the knee joint and skeletal muscles,decreased activity of the nuclear factor κB(NF-κB)inflammatory signaling pathway,enhanced the insulin receptor substrate 1(IRS1)/phosphatidylinositol 3-kinase/protein kinase(PI3K/Akt)signaling pathway,promoted skeletal muscle differentiation,and maintained skeletal muscle fiber diameter,consequently slowing down the progression of RC.These findings suggested that B.breve CCFM1078 may have a beneficial role as part of a dietary intervention for RC,enhancing overall therapeutic effects.
基金funded by Yunnan Youth Top-notch Talent Support Program(YNWR-QNBJ2018-173)Agricultural Joint project of Yunnan Provincial S&T Programs(202301BD070001-195)+2 种基金S&T project of Yunnan provincial finance(K212020001-01)supported by Yunnan Province Education Department’s Engineering Research Center of Eco-friendly Products from Yunnan Characteristic Edible FungiYunnan Province Yongsheng County Farmer Academician Technology service station.
文摘Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
文摘Microplastics are becoming well-known as chronic pollutants of terrestrial ecosystems,although their sources,dynamics of transportation,reliability of detection and ecological hazard are not evenly described.This review is a synthesis of the existing information about microplastics in soils,including analytical detection and characterization techniques,the major sources in the terrestrial environment,transport routes within the compartments and between compartments,and reported ecotoxicological consequences on soil biota,plants,and microbial communities.We also critically discuss the strengths and weaknesses of methodologies,making the distinction of sampling design differences,size detection limits,polymer identification methods,and quality assurance procedures on data comparability and uncertainty.An important outcome of this review is the systematic evaluation of the strength of evidence in three interrelated areas:measurement,environmental transport,and biological impacts,hence explaining which findings are strong and in which areas of research significant knowledge gaps still exist.We also suggest a conceptual framework that strongly connects the measurement uncertainty to the exposure estimation,interpretation of risk,and management relevance.This review uses mechanistic insights into transport and ecotoxicology alongside analysis constraints to add to the more comprehensive foundation of terrestrial risk assessment.Lastly,we determine research priorities,such as harmonized methodologies,realistic exposure scenarios,and cross-scale monitoring strategies,in order to assist in the science-based policies and mitigation action.
文摘Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event for the English edition of the book’s fifth volume on 3 December 2025 in Johannesburg,South Africa.
基金supported by grants from the National Natural Science Foundation of China(No.42207148)the Science and Technology Plan Project of Quanzhou,China(Nos.2025QZNS002 and 2022N030)+2 种基金the Natural Science Foundation of Fujian Province,China(No.2022J01573)the Educational Research Project for Young and Middle-Aged Teachers in Fujian Province,China(No.JAT210042)the Open Project Fund of Key Laboratory of Marine Biological Resources,Ministry of Natural Resources of China(Nos.HY202201 and HY202202)。
文摘Pyrethroids are a class of novel broad-spectrum pesticides synthesized to mimic natural pyrethrins.Due to their high efficiency,low toxicity,and safety,pyrethroids have been widely used as alternatives to organophosphate and carbamate insecticides in the control of agricultural and sanitary pests.However,with the increasing use of pyrethroid pesticides,the resulting pesticide residues have posed threats to both the environment and human health.Biodegradation is considered one of the most promising methods for the removal of pyrethroids,and significant research has been conducted in this area.This review summarizes recent advances in the biodegradation of pyrethroids,including degradation by single strains,microbial consortia,and enzymes.It provides an in-depth analysis of the biodegradation pathways and catalytic mechanisms involved in the degradation of pyrethroids and outlines enhancement strategies for improving the activity of pyrethroid-degrading enzymes.The review also identifies current challenges in pyrethroid biodegradation and offers perspectives for future research.This review serves as a valuable reference for subsequent studies on pyrethroid biodegradation.
基金support from various sources,including the National Natural Science Foundation of China(Grant Nos.81570774,82070872,92049118,and 82370854)the Junior Thousand Talents Program of China,and the Nanjing Medical University Startup Fund(All awarded to J.L.)support provided by Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(Grant No.JSSCTD2021)(All awarded to J.L.).
文摘V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.
基金supported by the National Natural Science Foundation of China(82372552)the Excellent Youth of Natural Science Research Projects in Anhui Province Universities(2023AH030060)+1 种基金Anhui Provincial Natural Science Foundation(2408085Y016)Anhui Province Excellent Research and Innovation Team Project(2024AH010013)。
文摘The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.
基金funded by the Sichuan Science and Technology Program(2021ZDZX0009)the earmarked fund from the National Natural Science Foundation of China(31972577)。
文摘Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.
文摘Within contemporary healthcare systems, professional identity among specialized nurses serves as a pivotal intrinsic factor influencing the development of their core competencies. This review synthesizes existing research, revealing that professional identity positively impacts the development of core competencies through multiple pathways, including psychological drive, behavioral facilitation, teamwork, and career stability. Building on this analysis, this paper proposes systematic enhancement strategies from four dimensions: education and training, organizational environment, cultural development, and individual growth, aiming to provide a reference for nursing practice and professional development.
基金supported by the National Natural Science Foundation of China (Nos. 82104430 and 82274133)the Shanghai Sailing Program (No. 21YF1447600)the Future Plan for Traditional Chinese Medicine Development of Science and Technology of Shanghai Municipal Hospital of Traditional Chinese Medicine (No. WL-HBQN-2022002K)。
文摘Taohong Siwu Decoction(THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis(AS). This review examines the complex mechanisms through which THSWD influences critical pathways, including nuclear factor kappa-B(NF-κB), phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(AKT), Toll-like receptor 4(TLR4), mitogen-activated protein kinase(MAPK), and mammalian target of rapamycin(mTOR), that play pivotal roles in AS pathogenesis. By synthesizing experimental evidence and existing literature, the review summarizes how THSWD and its bioactive constituents regulate these signaling cascades to ameliorate AS. Furthermore, it highlights the distinctive therapeutic advantages of traditional Chinese medicine(TCM) compounds in managing chronic diseases driven by multi-target and multifactorial mechanisms. Analyzing disease targets from the perspective of signaling pathways enhances the scientific validation of clinical efficacy for such formulations, thereby offering novel insights for future research.
文摘Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
基金supported by the National Natural Science Foundation of China (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
文摘Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa's human capital and accelerating its structural transformation and modernization process.This paper employs“demand–supply–adaptation”as its core analytical framework and aims to systematically explore how the educational cooperation between China and Africa can serve Africa's goal of modernization more precisely and effectively.First,through reviewing and analyzing the domestic and international research literature,this paper clarifies the focus,paradigms,and shortcomings of existing research,identifying the knowledge contribution of this study.Second,utilizing detailed macro-level data,case studies,and comparative research methods,it comprehensively presents the multidimensional status,structural characteristics,and development trends of China–Africa educational cooperation in areas such as student exchanges,cooperative education,vocational and technical training,language and cultural exchange,and emerging digital education.This paper also deeply analyzes the pressing and specific demands placed on the education system by Africa's modernization development across key dimensions like economic diversification,industrialization,agricultural modernization,social governance upgrading,and digital transformation.Third,based on the cooperative principle of“Africa's needs and China's strengths,”this paper innovatively proposes systematic countermeasures and suggestions for constructing new,multi-level,high-quality,sustainable,and future-oriented pathways for China–Africa educational cooperation:(a)promoting the strategic focus of cooperation to extend from“hard infrastructure”support to empowering“soft infrastructure”;(b)deepening the integration of industry and education and school–enterprise collaboration to precisely align with Africa's industrial development needs;vigorously developing digital education and jointly building a smart education ecosystem to help Africa bridge the digital divide;(c)improving an evidence-based,third-party evaluation system for cooperative effectiveness and a full-process quality assurance system;and(d)promoting the collaborative participation of multiple actors including governments,schools,enterprises,think tanks,and social organizations to build a new cooperative pattern of coconstruction,co-governance,and shared benefits.
基金funded by the Natural Science Foundation of Guangdong Provice(2022A1515012543).
文摘Background:The efficacy of standard 5-fluorouracil(5-FU)chemotherapy for colorectal cancer is limited by drug resistance and adverse effects,prompting research into esketamine,a potent ketamine variant with analgesic,antidepressant,and recently discovered anti-tumor properties,to determine if it can enhance 5-FU’s chemosensitivity.This study investigates whether esketamine synergizes with 5-FU to enhance therapeutic efficacy in colorectal adenocarcinoma cell models.Methods:We performed functional assays to evaluate proliferation(CCK-8),migration(wound healing),invasion(Transwell),and apoptosis(flow cytometry)in colorectal adenocarcinoma cell lines treated with 5-FU alone or in combination with esketamine.Transcriptomic profiling was conducted using RNA sequencing,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was employed to identify critical molecular targets and signaling networks.Protein-level validation of key pathway components was performed via western blotting.Results:Combination therapy with esketamine and 5-FU synergistically inhibited cellular proliferation,migration,and invasion while significantly inducing apoptosis compared to monotherapy.Mechanistically,esketamine potentiated 5-FU-driven AMP-activated protein kinase(AMPK)phosphorylation,leading to inhibition of both mammalian target of rapamycin(mTOR)and hyaluronan-mediated motility receptor(HMMR).Conclusion:Esketamine enhances 5-FU chemosensitivity in colorectal adenocarcinoma by activating the AMPK/mTOR/HMMR signaling axis,thereby suppressing tumor progression and metastatic potential.These findings position esketamine as a potential adjunctive therapy for 5-FU-based regimens,offering the dual benefit of enhancing chemotherapeutic efficacy while addressing cancer-associated comorbidities including pain and depression.
基金supported by the grants PID2020-113371RA-C22 and TED2021-130845A-C32,funded by MCIN/AEI/10.13039/501100011033.M.Marín-García,R.González-OlmosC.Gómez-Canela are members of the GESPA group(Grup d’Enginyeria i Simulacióde Processos Ambientals)at IQS-URL,which has been acknowledged as a Consolidated Research Group by the Government of Catalonia(No.2021-SGR-00321)+1 种基金In addition,M.Marín-García has been awarded a public grant for the Investigo Programme,aimed at hiring young job seekers to undertake research and innovation projects under the Recovery,Transformation,and Resilience Plan(PRTR),European Union Next Generation,for the year 2022,through the Government of Catalonia and the Spanish Ministry for Work and Social Economy(No.100045ID16)Ana Belén Cuenca for her support and expertise,which helped to confirm the proposed reaction mechanism involved in the UV photolysis of cloperastine.
文摘The increasing production and release of synthetic organic chemicals,including pharmaceuticals,into our envi-ronment has allowed these substances to accumulate in our surface water systems.Current purification technolo-gies have been unable to eliminate these pollutants,resulting in their ongoing release into aquatic ecosystems.This study focuses on cloperastine(CPS),a cough suppressant and antihistamine medication.The environmental impact of CPS usage has become a concern,mainly due to its increased detection during the COVID-19 pandemic.CPS has been found in wastewater treatment facilities,effluents from senior living residences,river waters,and sewage sludge.However,the photosensitivity of CPS and its photodegradation profile remain largely unknown.This study investigates the photodegradation process of CPS under simulated tertiary treatment conditions using UV photolysis,a method commonly applied in some wastewater treatment plants.Several transformation prod-ucts were identified,evaluating their kinetic profiles using chemometric approaches(i.e.,curve fitting and the hard-soft multivariate curve resolution-alternating least squares(HS-MCR-ALS)algorithm)and calculating the reaction quantum yield.As a result,three different transformation products have been detected and correctly identified.In addition,a comprehensive description of the kinetic pathway involved in the photodegradation process of the CPS drug has been provided,including observed kinetic rate constants.
基金supported by grant provided by the Sao Paulo Research Foundation-FAPESP.Grant#2023/15750-7。
文摘Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.
基金financially supported by the Major Science and Technology Special Projects in Henan Province(231100310200)the Key R&D Projects in Henan Province(241111314200)+1 种基金the National Natural Science Foundation of China(32302172)the Natural Science Foundation of Henan Province(252300423038).
文摘Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.
基金supported by the Ningxia Hui Autonomous Region Key R&D Program,China(2023BCF01003)the National Natural Science Foundation of China(32472711 and 32060672)the Agricultural Breeding Project of Ningxia Hui Autonomous Region,China(NXNYYZ202101)。
文摘Cold stress represents a critical constraint on crop productivity,particularly in temperate climates.Despite the established role of abscisic acid(ABA)in cold stress responses,the precise mechanisms through which transcription factors mediate ABAdependent cold tolerance remain elusive.Here,we identify VaMYB4a,a MYB transcription factor from Vitis amurensis Rupr.(Amur grape),as a key regulator of cold tolerance.It integrates ABA signaling with the CBF(C-repeat binding factors)-COR(cold-regulated)pathway to orchestrate cold stress adaptation.Through a combination of overexpression and CRISPR/Cas9-mediated knockout lines in Arabidopsis thaliana,grape callus,and Vitis vinifera L.seedlings,we demonstrate that VaMYB4a enhances freezing tolerance by promoting osmotic regulation,reactive oxygen species(ROS)scavenging,and stomatal closure.VaMYB4a functions as a homo-dimer,with its C-terminal domain being essential for transcriptional activation.Mechanistically,VaMYB4a directly upregulates CBF and COR genes while fine-tuning ABA signaling components such as ABI1 and ABF4.Notably,ABA exhibits a dual role:enhancing VaMYB4a-mediated freezing tolerance under short-term stress but attenuating its effects during prolonged cold exposure,revealing an intricate regulatory crosstalk between cold and hormonal pathways.Our work not only advances the molecular understanding of cold adaptation but also provides a promising genetic target for developing stress-resilient grape varieties to mitigate the impacts of climate change.
