Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),b...Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),but has received little attention.The pathway system and controlling factors of CO_(2)distribution in the Bohai Sea are analyzed using data on fault styles and information on the mantle and lithosphere.The relation between volcanic rocks and the distribution of mantle CO_(2)is reassessed using age data for CO_(2)accumulations.The distribution of mantle CO_(2)is controlled by uplift of the asthenosphere and upper mantle,magma conduits in the mantle and fault systems in the crust.Uplifted regions of the asthenosphere are accumulation areas for CO_(2).The area with uplift of the Moho exhibits accumulation of mantle CO_(2)at depth.CO_(2)was mainly derived from vertical migration through the upper mantle and lower crust.The fault style in the upper crust controls the distance of horizontal migration and the locations of CO_(2)concentrations.The distribution of mantle CO_(2)and volcanic rocks are not the same,but both probably followed the same pathways sometimes.Mantle CO_(2)in the Bohai Sea is concentrated in the Bozhong sag and the surrounding area,particularly in a trap that formed before 5.1 Ma and is connected to crustal faults(the Bozhang faults)and lithospheric faults(the Tanlu faults).展开更多
In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Creta...In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Cretaceous Yaojia Formation is the main hydrocarbon-bearing layer in the Fulaerji Oilfield. The hydrocarbon source of the oilfield is the Qijia-Gulong Sag which is about 80 km away from the Fulaerji Oilfield. The transport layer of long-distance hydrocarbon migration is the overlapped sandstone complex which fills the incised valley. The incised valley developed during the depositional period from the late Qingshankou Formation to the early Yaojia Formation of Cretaceous （SQqna-SQy0 was about 70 km long and 20 km wide, and extended in the NW-SE direction. The overlapped filling of the incised valley mainly occurred in the expanding system tract of the third-order sequence SQy23 （ESTy23）. Towards the basin, incised valley filling deposits overlapped on the delta developed in the early period, and towards the basin margin, incised valley filling deposits were covered by the shore-shallow lacustrine sandy beach bar developed in the maximum flooding period. All of the delta, the incised valley filling and the shore-shallow sandy beach bar are sandstone-rich, and have high porosity and permeability, and can form an effective hydrocarbon migration and accumulation system. Deltaic sand bodies collected and pumped hydrocarbon from the active source, incised valley filling depositional system completed the long-distance hydrocarbon migration, and lithological traps of shore-shallow lacustrine sandy beach bar accumulated hydrocarbon. The incised valley filling sequences are multi-cycle： an integrated shortterm filling cycle was developed on the erosion surface, and the sequences upward were mud-gravel stone, medium-fine sandstone containing terrigenous gravels and muddy pebbles with cross bedding, silty mudstone with ripple bedding, and mudstone. The incised valley filling deposits are characterized by a strong heterogeneity and the main hydrocarbon migration pathway is the medium-fine sandstone interval.展开更多
The large-scale exploitation of vanadium(Ⅴ) bearing minerals has led to a massive accumulation of Ⅴ tailings, of which Ⅴ pollution poses severe ecological risks. Although the mechanisms of Ⅴ stress to the microbia...The large-scale exploitation of vanadium(Ⅴ) bearing minerals has led to a massive accumulation of Ⅴ tailings, of which Ⅴ pollution poses severe ecological risks. Although the mechanisms of Ⅴ stress to the microbial community have been reported, the influential pathways in a multi-medium-containing system, for example, the soil-tailings-groundwater system,are unknown. The dynamic redox conditions and substance exchange within the system exhibited complex Ⅴ stress on the local microbial communities. In this study, the influence pathways of Ⅴ stress to the microbial community in the soil-tailings-groundwater system were first investigated. High Ⅴ contents were observed in groundwater(139.2 ± 0.15 μg/L) and soil(98.0–323.8 ± 0.02 mg/kg), respectively. Distinct microbial composition was observed for soil and groundwater, where soil showed the highest level of diversity and richness. Firmicutes, Proteobacteria, Actinobacteria, and Acidobacteria were dominant in soil and groundwater with a sum relative abundance of around 80 %. Based on redundancy analysis and structural equation models, Ⅴ was one of the vital driving factors affecting microbial communities. Groundwater microbial communities were influenced by Ⅴ via Cr, dissolved oxygen, and total nitrogen, while Fe, Mn, and total phosphorus were the key mediators for Ⅴ to affect soil microbial communities. Ⅴ affected the microbial community via metabolic pathways related to carbonaceous matter, which was involved in the establishment of survival strategies for metal stress. This study provides novel insights into the influence pathways of Ⅴ on the microorganisms in tailings reservoir for pollution bioremediation.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
This article investigates the development process and current status of policy-based agricultural insurance in Chongqing.Based on recent data-including premium income,compensation amounts,the number of insured househo...This article investigates the development process and current status of policy-based agricultural insurance in Chongqing.Based on recent data-including premium income,compensation amounts,the number of insured households,and insurance penetration,the article analyzes the primary challenges faced in the system's operation and proposes recommendations from two dimensions:institutional optimization and practical interventions.These recommendations include establishing a differentiated participation incentive mechanism,optimizing the composition of insurance products,enhancing risk diversification and reinsurance systems,creating an agricultural disaster risk reserve fund,developing a dynamic fiscal subsidy distribution mechanism based on risk and performance,improving information-sharing platforms,strengthening the rural grassroots power grid infrastructure,and accelerating the adoption of modern technologies in underwriting and claims settlement processes.The findings suggest that the coordinated advancement of institutional optimization and technological empowerment can substantially enhance the inclusiveness,sustainability,and operational efficiency of policy-based agricultural insurance in Chongqing,thereby providing substantial support for agricultural modernization and the Rural Revitalization Strategy.展开更多
The latent heat thermal energy storage system with solid-liquid phase-change material(SLPCM-LHTES)as energy storage medium provides outstanding advantages such as system simplicity,stable temperature control,and high ...The latent heat thermal energy storage system with solid-liquid phase-change material(SLPCM-LHTES)as energy storage medium provides outstanding advantages such as system simplicity,stable temperature control,and high energy storage density,showing great potential toward addressing the energy storage problems associated with decentralized,intermittent,and unstable renewable energy sources.Notably,effective heat transfer within the SLPCM-LHTES is crucial for extending its application potential.Therefore,a comprehensive understanding of the heat transfer processes in SLPCM-LHTES from a theoretical perspective is necessary.In this review,we propose a three-stage heat transfer pathway in SLPCM-LHTES,including external heating,interfacial heat transfer,and intrinsic phase transition processes.From the perspective of this three-stage pathway,the theoretical basis of heat transfer processes and typical efficiency enhancement strategies in SLPCM-LHTES are summarized.Moreover,an overview of the typical applications of SLPCM-LHTES in various fields,such as building energy efficiency,textiles and garments,and battery thermal management,is presented.Finally,the remaining challenges and possible avenues of research in this burgeoning field will also be discussed.展开更多
Farmland ecosystems are the primary ecosystem type in inland river basins,providing the biological and material basis for human development and survival.The foundation for monetizing the value of agricultural ecologic...Farmland ecosystems are the primary ecosystem type in inland river basins,providing the biological and material basis for human development and survival.The foundation for monetizing the value of agricultural ecological products and transforming green mountains into gold mountains is the precise assessment of ecosystem products in specific geographic units(VEP)within farmland ecosystems,which elucidates regional agricultural resource endowments and spatial distribution.However,agricultural ecological products face challenges in valuation,trading,and monetization,and research on pathways for their value transformation remains limited.This study uses Zhangye City in inland river basins as an example to construct a catalog of farmland ecosystem ecological products and explores VEP accounting methods based on multi-source data,including statistical,remote sensing,and monitoring data,at the city and county scales,and analyzes differentiated value transformation pathways according to the attributes of various agricultural ecological products.The results show that material supply value ranks highest among the VEP of farmland ecosystems in inland river basins,followed by regulatory services,while recreational agriculture value ranks lowest.The ranking of VEP varies from the ranking of farmland ecosystem area,with available agricultural water being a major constraint on the VEP of farmland ecosystems in inland river basins.Regional climate,geographic position,and transportation are linked to the value of agricultural ecosystem products within material supply products.Precipitation,soil structure,and cropping patterns are linked to the value of agricultural ecosystem products within regulatory services.The local cultural resources and tourism infrastructure are linked to the value of agricultural ecosystem products within cultural services.Regarding the pathways for achieving the value of agricultural ecological products,market-oriented strategies dominate the mainstay of material supply products,government-led mechanisms are pivotal for regulatory service products,and a combination of government and market strategies is essential for cultural service products.展开更多
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
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
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
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
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
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
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
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
基金supported by the Major Program of the National Natural Science Foundation of China(41790453)the Natural Science Foundation of Jilin Province(20170101001JC)+1 种基金the National Natural Science Foundation of China(41472304)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2016ZX05026-004-001)。
文摘Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),but has received little attention.The pathway system and controlling factors of CO_(2)distribution in the Bohai Sea are analyzed using data on fault styles and information on the mantle and lithosphere.The relation between volcanic rocks and the distribution of mantle CO_(2)is reassessed using age data for CO_(2)accumulations.The distribution of mantle CO_(2)is controlled by uplift of the asthenosphere and upper mantle,magma conduits in the mantle and fault systems in the crust.Uplifted regions of the asthenosphere are accumulation areas for CO_(2).The area with uplift of the Moho exhibits accumulation of mantle CO_(2)at depth.CO_(2)was mainly derived from vertical migration through the upper mantle and lower crust.The fault style in the upper crust controls the distance of horizontal migration and the locations of CO_(2)concentrations.The distribution of mantle CO_(2)and volcanic rocks are not the same,but both probably followed the same pathways sometimes.Mantle CO_(2)in the Bohai Sea is concentrated in the Bozhong sag and the surrounding area,particularly in a trap that formed before 5.1 Ma and is connected to crustal faults(the Bozhang faults)and lithospheric faults(the Tanlu faults).
文摘In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Cretaceous Yaojia Formation is the main hydrocarbon-bearing layer in the Fulaerji Oilfield. The hydrocarbon source of the oilfield is the Qijia-Gulong Sag which is about 80 km away from the Fulaerji Oilfield. The transport layer of long-distance hydrocarbon migration is the overlapped sandstone complex which fills the incised valley. The incised valley developed during the depositional period from the late Qingshankou Formation to the early Yaojia Formation of Cretaceous （SQqna-SQy0 was about 70 km long and 20 km wide, and extended in the NW-SE direction. The overlapped filling of the incised valley mainly occurred in the expanding system tract of the third-order sequence SQy23 （ESTy23）. Towards the basin, incised valley filling deposits overlapped on the delta developed in the early period, and towards the basin margin, incised valley filling deposits were covered by the shore-shallow lacustrine sandy beach bar developed in the maximum flooding period. All of the delta, the incised valley filling and the shore-shallow sandy beach bar are sandstone-rich, and have high porosity and permeability, and can form an effective hydrocarbon migration and accumulation system. Deltaic sand bodies collected and pumped hydrocarbon from the active source, incised valley filling depositional system completed the long-distance hydrocarbon migration, and lithological traps of shore-shallow lacustrine sandy beach bar accumulated hydrocarbon. The incised valley filling sequences are multi-cycle： an integrated shortterm filling cycle was developed on the erosion surface, and the sequences upward were mud-gravel stone, medium-fine sandstone containing terrigenous gravels and muddy pebbles with cross bedding, silty mudstone with ripple bedding, and mudstone. The incised valley filling deposits are characterized by a strong heterogeneity and the main hydrocarbon migration pathway is the medium-fine sandstone interval.
基金supported by the National Natural Science Foundation of China(No.42377415)the Natural Science Foundation of Sichuan Province(No.2023NSFSC0811),Sichuan Science and Technology Program(Nos.2021JDTD0013 and 2021YFQ0066)+1 种基金the Science and Technology Major Project of Xizhang Autonomous Region of China(No.XZ202201ZD0004G06)the Everest Scientific Research Program(No.80000-2023ZF11405).
文摘The large-scale exploitation of vanadium(Ⅴ) bearing minerals has led to a massive accumulation of Ⅴ tailings, of which Ⅴ pollution poses severe ecological risks. Although the mechanisms of Ⅴ stress to the microbial community have been reported, the influential pathways in a multi-medium-containing system, for example, the soil-tailings-groundwater system,are unknown. The dynamic redox conditions and substance exchange within the system exhibited complex Ⅴ stress on the local microbial communities. In this study, the influence pathways of Ⅴ stress to the microbial community in the soil-tailings-groundwater system were first investigated. High Ⅴ contents were observed in groundwater(139.2 ± 0.15 μg/L) and soil(98.0–323.8 ± 0.02 mg/kg), respectively. Distinct microbial composition was observed for soil and groundwater, where soil showed the highest level of diversity and richness. Firmicutes, Proteobacteria, Actinobacteria, and Acidobacteria were dominant in soil and groundwater with a sum relative abundance of around 80 %. Based on redundancy analysis and structural equation models, Ⅴ was one of the vital driving factors affecting microbial communities. Groundwater microbial communities were influenced by Ⅴ via Cr, dissolved oxygen, and total nitrogen, while Fe, Mn, and total phosphorus were the key mediators for Ⅴ to affect soil microbial communities. Ⅴ affected the microbial community via metabolic pathways related to carbonaceous matter, which was involved in the establishment of survival strategies for metal stress. This study provides novel insights into the influence pathways of Ⅴ on the microorganisms in tailings reservoir for pollution bioremediation.
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.
基金Supported by Chongqing Social Science Planning Project(Doctoral Project)"Research Support on the Impact of Policy-based Agricultural Insurance on the Production Behavior of Chinese Farmers"(2020BS39).
文摘This article investigates the development process and current status of policy-based agricultural insurance in Chongqing.Based on recent data-including premium income,compensation amounts,the number of insured households,and insurance penetration,the article analyzes the primary challenges faced in the system's operation and proposes recommendations from two dimensions:institutional optimization and practical interventions.These recommendations include establishing a differentiated participation incentive mechanism,optimizing the composition of insurance products,enhancing risk diversification and reinsurance systems,creating an agricultural disaster risk reserve fund,developing a dynamic fiscal subsidy distribution mechanism based on risk and performance,improving information-sharing platforms,strengthening the rural grassroots power grid infrastructure,and accelerating the adoption of modern technologies in underwriting and claims settlement processes.The findings suggest that the coordinated advancement of institutional optimization and technological empowerment can substantially enhance the inclusiveness,sustainability,and operational efficiency of policy-based agricultural insurance in Chongqing,thereby providing substantial support for agricultural modernization and the Rural Revitalization Strategy.
基金financial support was provided by the National Natural Science Foundation of China(Nos.52476146,52006008,and 52471219)the Guangdong Basic and Applied Basic Research Foundation(2023A1515140059 and 2025A1515011255)+2 种基金the Peking University Third Hospital Haidian transformation project(HDCXZHKC2023210)the National Foreign Expert Individual Human Project(Category H,No.H20240116)the State Key Laboratory of New Ceramic Materials Tsinghua University(No.KFZD202402).
文摘The latent heat thermal energy storage system with solid-liquid phase-change material(SLPCM-LHTES)as energy storage medium provides outstanding advantages such as system simplicity,stable temperature control,and high energy storage density,showing great potential toward addressing the energy storage problems associated with decentralized,intermittent,and unstable renewable energy sources.Notably,effective heat transfer within the SLPCM-LHTES is crucial for extending its application potential.Therefore,a comprehensive understanding of the heat transfer processes in SLPCM-LHTES from a theoretical perspective is necessary.In this review,we propose a three-stage heat transfer pathway in SLPCM-LHTES,including external heating,interfacial heat transfer,and intrinsic phase transition processes.From the perspective of this three-stage pathway,the theoretical basis of heat transfer processes and typical efficiency enhancement strategies in SLPCM-LHTES are summarized.Moreover,an overview of the typical applications of SLPCM-LHTES in various fields,such as building energy efficiency,textiles and garments,and battery thermal management,is presented.Finally,the remaining challenges and possible avenues of research in this burgeoning field will also be discussed.
基金supported by Humanities and Social Sciences research project of Ministry of Education(Grant No.24YJCZH342)the Inventory of ecological products and calculation of Gross ecosystem product(GEP)in Zhangye City(Grant No.E4390901)。
文摘Farmland ecosystems are the primary ecosystem type in inland river basins,providing the biological and material basis for human development and survival.The foundation for monetizing the value of agricultural ecological products and transforming green mountains into gold mountains is the precise assessment of ecosystem products in specific geographic units(VEP)within farmland ecosystems,which elucidates regional agricultural resource endowments and spatial distribution.However,agricultural ecological products face challenges in valuation,trading,and monetization,and research on pathways for their value transformation remains limited.This study uses Zhangye City in inland river basins as an example to construct a catalog of farmland ecosystem ecological products and explores VEP accounting methods based on multi-source data,including statistical,remote sensing,and monitoring data,at the city and county scales,and analyzes differentiated value transformation pathways according to the attributes of various agricultural ecological products.The results show that material supply value ranks highest among the VEP of farmland ecosystems in inland river basins,followed by regulatory services,while recreational agriculture value ranks lowest.The ranking of VEP varies from the ranking of farmland ecosystem area,with available agricultural water being a major constraint on the VEP of farmland ecosystems in inland river basins.Regional climate,geographic position,and transportation are linked to the value of agricultural ecosystem products within material supply products.Precipitation,soil structure,and cropping patterns are linked to the value of agricultural ecosystem products within regulatory services.The local cultural resources and tourism infrastructure are linked to the value of agricultural ecosystem products within cultural services.Regarding the pathways for achieving the value of agricultural ecological products,market-oriented strategies dominate the mainstay of material supply products,government-led mechanisms are pivotal for regulatory service products,and a combination of government and market strategies is essential for cultural service products.
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.
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 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.
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.
