Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the a...Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the associated economic burden.Consequently,there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer.Natural products(NPs)play a crucial role in the identification and development of anticancer therapeutics.This study identified ustusolate E(UE)and its analog 11α-hydroxy-ustusolate E(HUE)from strain Aspergillus calidoustus TJ403-EL05,and examined their antitumor activities and mechanisms of action.The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS(human gastric cancer cells)and 786-O(human renal clear cell carcinoma cells),induced irreversible DNA damage,blocked the cell cycle at the G_(2)/M phase,and further induced apoptosis in tumor cells.To the best of the authors’knowledge,this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms.The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.展开更多
Extreme ozone pollution events(EOPEs)are associated with synoptic weather patterns(SWPs)and pose severe health and ecological risks.However,a systematic investigation of themeteorological causes,transport pathways,and...Extreme ozone pollution events(EOPEs)are associated with synoptic weather patterns(SWPs)and pose severe health and ecological risks.However,a systematic investigation of themeteorological causes,transport pathways,and source contributions to historical EOPEs is still lacking.In this paper,the K-means clustering method is applied to identify six dominant SWPs during the warm season in the Yangtze River Delta(YRD)region from 2016 to 2022.It provides an integrated analysis of the meteorological factors affecting ozone pollution in Hefei under different SWPs.Using the WRF-FLEXPART model,the transport pathways(TPPs)and geographical sources of the near-surface air masses in Hefei during EOPEs are investigated.The results reveal that Hefei experienced the highest ozone concentration(134.77±42.82μg/m^(3)),exceedance frequency(46 days(23.23%)),and proportion of EOPEs(21 instances,47.7%)under the control of peripheral subsidence of typhoon(Type 5).Regional southeast winds correlated with the ozone pollution in Hefei.During EOPEs,a high boundary layer height,solar radiation,and temperature;lowhumidity and cloud cover;and pronounced subsidence airflow occurred over Hefei and the broader YRD region.The East-South(E_S)patterns exhibited the highest frequency(28 instances,65.11%).Regarding the TPPs and geographical sources of the near-surface air masses during historical EOPEs.The YRD was the main source for land-originating air masses under E_S patterns(50.28%),with Hefei,southern Anhui,southern Jiangsu,and northern Zhejiang being key contributors.These findings can help improve ozone pollution early warning and control mechanisms at urban and regional scales.展开更多
Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure.Therefore,it is necessary to find an efficient and environme...Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure.Therefore,it is necessary to find an efficient and environmentally friendly method to remove minocycline from the environment.This study screened and isolated a minocycline degrading strain DM13 from the activated sludge for municipal sewage pipeline,and optimized the biodegradation of minocycline by DM13 under various environmental conditions.The maximum biodegradation efficiency of 50 mg/L minocycline reached 93%at 72 h with the temperature of 30℃,the initial pH of 7.0,and the inoculation rate of 3%.Two potential biotransformation pathways were proposed,including deamination,demethylation,and decarbonylation.The acute toxicity assessment showed that the biotransformation products of minocycline had lower toxicity than the parent compound.In addition,the first-generation tetracycline antibiotics could be removed,suggesting that strain DM13 has the potential for application in treating antibiotic wastewater.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
The electrochemical reduction of carbon dioxide(CO_(2))into value-added chemicals and fuels has been extensively studied as a promising strategy for mitigating environmental issues and achieving sustainable energy con...The electrochemical reduction of carbon dioxide(CO_(2))into value-added chemicals and fuels has been extensively studied as a promising strategy for mitigating environmental issues and achieving sustainable energy conversion.Substantial efforts have been made to improve the understanding of CO_(2)reduction reaction(CO_(2)RR)mechanisms by computational and spectroscopic studies.An in-depth understanding of CO_(2)RR mechanism can provide the guidance and criteria for designing high-efficiency catalysts,and hence,steering CO_(2)RR to desired products.This review systematically discusses the formation mechanisms and reaction pathways of various CO_(2)RR products,including C_(1)products(CO,HCOOH,and CH_(4)),C_(2)products(C_(2)H_(4),C_(2)H_(5)OH,and CH_(3)COOH),and C_(3+)products(C_(3)H_(6),C_(3)H_(7)OH,and others).The reaction pathways are elucidated by analyzing the adsorption behavior,energy barriers,and intermediate coupling steps involved in the generation of each product.Particular emphasis is placed on the key intermediates,such as^(*)OCHO,^(*)COOH,^(*)CO,^(*)OCCOH,and^(*)CCO,which play crucial roles in determining the product selectivity.The effects of catalyst composition,morphology,and electronic structure on the adsorption and activation of these intermediates are also discussed.Moreover,advanced characterization techniques,including in-situ spectroscopy and isotopic labeling experiments,are highlighted for their contributions to unraveling the reaction mechanisms.The review aims to provide critical insights to reveal the activity-determining para meters and underlying CO_(2)RR mechanisms,which will guide the rational design of next-generation electrocatalysts for selective CO^(2)RR towards high-value products.展开更多
Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a d...Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.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
Hexafluoropropylene oxide(HFPO)is a crucial fluorinated chemical mainly synthesized from hexafluoropropylene(HFP)through the oxidation of oxygen.However,the reaction network and kinetic characteristics are not fully u...Hexafluoropropylene oxide(HFPO)is a crucial fluorinated chemical mainly synthesized from hexafluoropropylene(HFP)through the oxidation of oxygen.However,the reaction network and kinetic characteristics are not fully understood yet,resulting in a lack of theoretical basis for synthesis process improvement.Here,the free radical reaction mechanism and complete reaction network involved in the noncatalytic oxidation of HFP to synthesize HFPO was explored by density functional theory.Transition state theory was employed to calculate the intrinsic reaction rate constants for elementary reactions.Based on theoretical reaction rate ratios,reaction pathways were selected,and a simplified reaction network was derived.It was found that byproducts were formed owing to the decomposition of HFPO and subsequent reactions with excessive oxygen while oxygen tended to participate more in the main reaction under oxygen-deficient conditions.The variations in reaction pathways occurring at different HFP/oxygen molar ratios was well elucidated by comparing with experimental data.This research establishes a robust theoretical foundation for optimizing and regulating the synthesis of HFPO.展开更多
Introduction: Foreign bodies (FB) in the lower airways (LAs) constitute a potentially life-threatening emergency requiring immediate management. The objective of our study was to describe the patient pathway and manag...Introduction: Foreign bodies (FB) in the lower airways (LAs) constitute a potentially life-threatening emergency requiring immediate management. The objective of our study was to describe the patient pathway and management of foreign bodies in the lower airways. Methodology: This was a descriptive study with retrospective data collection conducted over a 6-year period (January 1, 2014, to December 31, 2019) in the ENT and Head and Neck Surgery Department of Donka National Hospital. Results: We observed a prevalence of 1.79%. The average age was 5.71 years, with a sex ratio of 1.2. However, 82.61% of the cases originated from rural areas. We noted that 78.83% of patients were referred after visiting 1 to 2 healthcare facilities (75.36%). The consultation delay was 3 days. Penetration syndrome was present in 98.56% of cases. The foreign body incidents occurred during play in 54.84% and during meals in 29.09% of cases. Radiographs were performed in 93.9% of cases. Endoscopy was used for both diagnostic and therapeutic purposes in all patients. The foreign bodies were located in the trachea (37.68%), larynx (26.08%), and bronchi (21.73%). Non-organic foreign bodies were predominant (52.17%). Postoperative outcomes were uncomplicated in 95.98% of cases, and the lethality rate was 2.85%. Conclusion: The pathway of patients with foreign bodies in the airways remains unpredictable in our context due to parental hesitations. Early management reduces morbidity and mortality rates.展开更多
As universities in Kazakhstan continue to address the challenges that come with developing English-medium instruction(EMI)programs,university Science,Technology,Engineering,and Mathematics(STEM)teachers need to develo...As universities in Kazakhstan continue to address the challenges that come with developing English-medium instruction(EMI)programs,university Science,Technology,Engineering,and Mathematics(STEM)teachers need to develop capacities to teach in English,while their English teacher counterparts need to develop content-specific pedagogical knowledge.Content and Language Integrated Learning(CLIL)pedagogies,defined as the integration of both language and content curricular goals,have emerged as a vehicle to facilitate this development for both types of teachers.However,what it means to be a CLIL teacher may vary considerably as teachers leverage their professional knowledge and personal experiences.We,therefore,explore teachers’conceptions of CLIL and how their disciplinary,linguistic,and pedagogical backgrounds enable or burden them to forge a“CLIL teacher”identity.This qualitative study illustrates the salient points of the journeys taken by two university teachers,one a specialist in oil and gas,the other an English teacher and teacher educator.Drawing on extended one-on-one interviews,we present two teachers’experiences through a series of CLIL-informed workshops.Using a multidisciplinary analytical framework,we map the ways in which the two teacher participants negotiate their identities in relation to CLIL.The findings highlight the importance of understanding teacher experiences,particularly their language learning backgrounds,attitudes toward supporting student learning,and relationships with their colleagues as they work to adapt to teaching English and STEM subjects in university EMI contexts.展开更多
Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular a...Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular and cellular disturbances,including reduced nitric oxide bioavailability,persistent low-grade inflammation,oxidative stress,endothelial dysfunction,altered mineral metabolism,genetic predispositions,and uremic toxin accumulation.As current pharmacological treatments provide only partial risk reduction,complementary approaches are imperative.Exercise training,both aerobic and resistance,has emerged as a potent non-pharmacological intervention targeting these underlying molecular pathways.Regular exercise can enhance nitric oxide signaling,improve antioxidant defenses,attenuate inflammation,facilitate endothelial repair via endothelial progenitor cells,and stabilize muscle metabolism.Additionally,accumulating evidence points to a genetic dimension in CKD susceptibility and progression.Variants in genes such as APOL1,PKD1,PKD2,UMOD,and COL4A3–5 shape disease onset and severity,and may modulate response to interventions.Exercise may help buffer these genetic risks by inducing epigenetic changes,improving mitochondrial function,and optimizing crosstalk between muscle,adipose tissue,and the vasculature.This review synthesizes how exercise training can ameliorate key molecular mediators in CKD,emphasizing the interplay with genetic and epigenetic factors.We integrate evidence from clinical and experimental studies,discussing how personalized exercise prescriptions,informed by patients’genetic backgrounds and nutritional strategies(such as adequate protein intake),could enhance outcomes.Although large-scale trials linking molecular adaptations to long-term endpoints are needed,current knowledge strongly supports incorporating exercise as a cornerstone in CKD management to counteract pervasive molecular derangements and leverage genetic insights for individualized care.展开更多
As a traditional model for inheriting Chinese medicine,apprenticeship education has evolved over millennia into a distinctive talent cultivation system.In the new era characterized by upholding tradition while pursuin...As a traditional model for inheriting Chinese medicine,apprenticeship education has evolved over millennia into a distinctive talent cultivation system.In the new era characterized by upholding tradition while pursuing innovation,apprenticeship education serves not only as the core vehicle for sustaining Chinese medical scholarship but also as the key support for resolving contemporary challenges in cultivating TCM professionals.This paper traces the historical evolution and policy context of apprenticeship education,analyzes its current development status and underlying contradictions,and systematically elucidates its irreplaceable value in dimensions such as academic inheritance,critical thinking cultivation,and cultural continuity.By integrating technological innovation and policy guidance,it outlines development pathways to provide practical references for constructing a modernized TCM education system.展开更多
Background:Neurodegenerative diseases(NDs),including Alzheimer‘s disease,Parkinson‘s disease,and Huntington‘s disease,are complex and challenging due to their intricate pathophysiology and limited treatment options...Background:Neurodegenerative diseases(NDs),including Alzheimer‘s disease,Parkinson‘s disease,and Huntington‘s disease,are complex and challenging due to their intricate pathophysiology and limited treatment options.Methods:This review systematically sourced articles related to neurodegenerative diseases,neurodegeneration,quercetin,and clinical studies from primary medical databases,including Scopus,PubMed,and Web of Science.Results:Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration.Quercetin,a flavonoid abundant in vegetables and fruits,is gaining attention for its antioxidant,anti-inflammatory,and antiapoptotic properties.It regulates signaling pathways such as nuclear factor-κB(NF-κB),sirtuins,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt).These pathways are essential for cellular survival,inflammation regulation,and apoptosis.Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models,indicating promising outcomes.Conclusions:The study explores the potential of incorporating laboratory research into practical medical treatment,focusing on quercetin‘s neuroprotective effects on NDs and its optimal dosage.展开更多
Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities.Axillaridine A(AA)is a newly discovered steroidal alkaloid.However,whether AA could suppress osteoc...Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities.Axillaridine A(AA)is a newly discovered steroidal alkaloid.However,whether AA could suppress osteoclastogenesis and alleviate ovariectomy-induced bone loss in mice remains unknown.In vitro,AA significantly suppressed the receptor activator of nuclear factor-κB(NF-κB)ligand(RANKL)-induced osteoclast differentiation via downregulating the expression of osteoclastogenesis-related marker genes,proteins,and transcriptional regulators,including tartrate-resistant acid phosphatase(TRAP),c-Src,matrix metallopeptidase-9(MMP-9),cathepsin K,nuclear factor of activated T cells,cytoplasmic 1(NFATc1),and c-Fos.This was achieved by blocking RANKL-RANK interaction and inhibiting RANKL-mediated RANK signaling pathways,including NF-κB,AKT,and mitogen-activated protein kinases(MAPKs)in osteoclast precursors.In vivo,AA significantly inhibited the ovariectomized(OVX)-induced body weight gain and blood glucose increase in mice.AA did not adversely affect the histomorphologies,weights,and indices of the kidney and liver in OVX mice.AA effectively ameliorated bone loss in OVX mice by inhibiting osteoclastogenesis.AA significantly inhibited the serum levels of tartrate-resistant acid phosphatase 5b(TRACP-5b)and C-telopeptide of type I collagen(CTX-I).AA significantly inhibited the OVX-induced expression of osteoclastogenesis-related marker genes and proteins in the femur.In summary,AA alleviates ovariectomy-induced bone loss in mice by suppressing osteoclastogenesis via inhibition of RANKL-mediated RANK signaling pathways and could be potentially used for the prevention and treatment of osteoclastrelated diseases such as osteoporosis.展开更多
Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable att...Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.Therefore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.展开更多
This study tracked the characteristics of atmospheric wet deposition of the toxic element arsenic(As)at both urban(Guangzhou(GZ))and forested(Dinghushan Natural Reserve(DHS))sites within the Pearl River Delta(PRD)regi...This study tracked the characteristics of atmospheric wet deposition of the toxic element arsenic(As)at both urban(Guangzhou(GZ))and forested(Dinghushan Natural Reserve(DHS))sites within the Pearl River Delta(PRD)region between 2016 and 2019,examining its correlation with rainfall patterns.Additionally,by employing backward trajectory analysis and the potential source contribution function(PSCF)in conjunction with pertinent emission inventories,we pinpointed the main pathways of atmospheric arsenic transport and evaluated the emission contributions from priority source areas.The study revealed that the atmospheric arsenic wet deposition fluxes at the GZ and DHS sites exhibited a trend of increase followed by a decrease over the four-year period.Wet season deposition fluxes were more than triple those of the dry season,with urban site showing a difference of over four times.Notably,wet season As deposition at both sites was predominantly affected by heavy rainfall from marine air masses,constituting 31%of the total deposition.The predominant trajectory directions contributing to arsenic deposition at GZ and DHS were northeast(55%)and south(53%),respectively.The primary source areas for both sites were largely outside the PRD region,with the GZ site having 80%to 95%of its source area in the non-PRD region,compared to 69%to 88%at the DHS site.Furthermore,non-PRD areas contributed approximately 65%to arsenic emissions for both sites,with the industrial sector being the dominant emission source,exceeding 97%of the total emissions.展开更多
Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main ...Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main risk factor.Thus,neuroprotective strategies have gained interest.We performed a bibliometric analysis to determine global publishing trends and relationships among prolific authors,publications,institutions,funding agencies,and journals.We also analyzed author keywords to identify research hotspots in glaucoma neuroprotection.Further,based on keyword analysis,we reviewed most recent literature to understand mechanistic pathways underlying glaucomarelated pathophysiological responses leading to RGC loss.Bibliographic data were sourced from Scopus.Basic bibliographic features were characterized using Scopus’s functions.VOSviewer was used for mapping and visualizing bibliometric networks.The analysis included trends in publications since 2000,the most prolific countries,institutions,authors,and the strength of their linkages.A significant increase in publication output over the past two decades was noted.The United States leads in funding support,research output,and citation links,followed by China and the UK.Among the top 10 most cited authors,three are from Japanese institutions.Keyword analysis shows a focus on molecular targets related to ischemia,excitotoxicity,inflammation,and oxidative stress,with fewer emerging drug candidates and limited clinical trials.Based on the most recent literature,emerging molecular targets underlying these key pathophysiological mechanisms are summarized.In conclusion,while pathophysiology and molecular mechanisms are the current focus,there is not much progress in developing new drug candidates and conducting clinical trials.展开更多
Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to asse...Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.展开更多
Oxidative stress and inflammation are closely interrelated processes that are pivotal to the impaired wound healing associated with diabetes.Chronic hyperglycemia in diabetic patients induces excessive reactive oxygen...Oxidative stress and inflammation are closely interrelated processes that are pivotal to the impaired wound healing associated with diabetes.Chronic hyperglycemia in diabetic patients induces excessive reactive oxygen species(ROS)production,which triggers heightened inflammatory responses.The resulting inflammation exacerbates oxidative damage,delays wound closure,and intensifies tissue injury,thereby creating a detrimental cycle that disrupts normal wound healing.Recent research has increasingly focused on the therapeutic potential of natural products in modulating oxidative stress and inflammation to enhance diabetic wound healing.Natural compounds,such as polyphenols,flavonoids,and terpenoids,have demonstrated significant efficacy in reducing oxidative damage and modulating inflammatory pathways.These bioactive agents exhibit potent antioxidant activity by scavenging ROS and enhancing endogenous antioxidant defenses while concurrently inhibiting the release of proinflammatory cytokines.Additionally,natural therapies have been shown to promote angiogenesis,enhance collagen synthesis,and improve fibroblast function,further facilitating wound repair.This review provides insights into the complex interplay between oxidative stress and inflammation in diabetic wound healing and evaluates the therapeutic potential of natural products as adjunctive treatments.Further clinical investigations are essential to validate the efficacy and safety of these natural interventions for diabetic wound management.展开更多
基金supported by the Program for Changjiang Scholars of the Ministry of Education of the People’s Republic of China (No. T2016088)the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021)+4 种基金the National Key R&D Program of China (No. 2021YFA0910500)the Science and Technology Major Project of Hubei Province (No.2021ACA012)the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005)the Academic Frontier Youth Team of HUST (No. 2017QYTD19)the Fundamental Research Funds for the Central Universities (No.2172019kfy XJJS166)
文摘Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the associated economic burden.Consequently,there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer.Natural products(NPs)play a crucial role in the identification and development of anticancer therapeutics.This study identified ustusolate E(UE)and its analog 11α-hydroxy-ustusolate E(HUE)from strain Aspergillus calidoustus TJ403-EL05,and examined their antitumor activities and mechanisms of action.The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS(human gastric cancer cells)and 786-O(human renal clear cell carcinoma cells),induced irreversible DNA damage,blocked the cell cycle at the G_(2)/M phase,and further induced apoptosis in tumor cells.To the best of the authors’knowledge,this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms.The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
基金supported by the National Natural Science Foundation of China(Nos.U19A2044,42105132,42030609,and 41975037)the National Key Research and Development Programof China(No.2022YFC3700303).
文摘Extreme ozone pollution events(EOPEs)are associated with synoptic weather patterns(SWPs)and pose severe health and ecological risks.However,a systematic investigation of themeteorological causes,transport pathways,and source contributions to historical EOPEs is still lacking.In this paper,the K-means clustering method is applied to identify six dominant SWPs during the warm season in the Yangtze River Delta(YRD)region from 2016 to 2022.It provides an integrated analysis of the meteorological factors affecting ozone pollution in Hefei under different SWPs.Using the WRF-FLEXPART model,the transport pathways(TPPs)and geographical sources of the near-surface air masses in Hefei during EOPEs are investigated.The results reveal that Hefei experienced the highest ozone concentration(134.77±42.82μg/m^(3)),exceedance frequency(46 days(23.23%)),and proportion of EOPEs(21 instances,47.7%)under the control of peripheral subsidence of typhoon(Type 5).Regional southeast winds correlated with the ozone pollution in Hefei.During EOPEs,a high boundary layer height,solar radiation,and temperature;lowhumidity and cloud cover;and pronounced subsidence airflow occurred over Hefei and the broader YRD region.The East-South(E_S)patterns exhibited the highest frequency(28 instances,65.11%).Regarding the TPPs and geographical sources of the near-surface air masses during historical EOPEs.The YRD was the main source for land-originating air masses under E_S patterns(50.28%),with Hefei,southern Anhui,southern Jiangsu,and northern Zhejiang being key contributors.These findings can help improve ozone pollution early warning and control mechanisms at urban and regional scales.
基金supported by the Natural Science Basic Research Program of Shaanxi Province(No.2023-JC-JQ-36).
文摘Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure.Therefore,it is necessary to find an efficient and environmentally friendly method to remove minocycline from the environment.This study screened and isolated a minocycline degrading strain DM13 from the activated sludge for municipal sewage pipeline,and optimized the biodegradation of minocycline by DM13 under various environmental conditions.The maximum biodegradation efficiency of 50 mg/L minocycline reached 93%at 72 h with the temperature of 30℃,the initial pH of 7.0,and the inoculation rate of 3%.Two potential biotransformation pathways were proposed,including deamination,demethylation,and decarbonylation.The acute toxicity assessment showed that the biotransformation products of minocycline had lower toxicity than the parent compound.In addition,the first-generation tetracycline antibiotics could be removed,suggesting that strain DM13 has the potential for application in treating antibiotic wastewater.
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financially supported by the National Natural Science Foundation of China(Grants 22225901,21975237 and 51702312)the Fundamental Research Funds for the Central Universities(Grant WK2340000101)+5 种基金the USTC Research Funds of the Double First-Class Initiative(Grant YD2340002007 and YD9990002017)the Open Funds of the State Key Laboratory of Rare Earth Resource Utilization(Grant RERU2022007)the China Postdoctoral Science Foundation(Grants 2023M733371,2024M750006 and 2023T160617)Postdoctoral Fellowship Program(Grade C)of China Postdoctoral Science Foundation(GZC20230008)the Natural Science Foundation Youth Project of Anhui Province(2408085QB065)the Postdoctoral Research Funding Project of Anhui Province(2023B727)。
文摘The electrochemical reduction of carbon dioxide(CO_(2))into value-added chemicals and fuels has been extensively studied as a promising strategy for mitigating environmental issues and achieving sustainable energy conversion.Substantial efforts have been made to improve the understanding of CO_(2)reduction reaction(CO_(2)RR)mechanisms by computational and spectroscopic studies.An in-depth understanding of CO_(2)RR mechanism can provide the guidance and criteria for designing high-efficiency catalysts,and hence,steering CO_(2)RR to desired products.This review systematically discusses the formation mechanisms and reaction pathways of various CO_(2)RR products,including C_(1)products(CO,HCOOH,and CH_(4)),C_(2)products(C_(2)H_(4),C_(2)H_(5)OH,and CH_(3)COOH),and C_(3+)products(C_(3)H_(6),C_(3)H_(7)OH,and others).The reaction pathways are elucidated by analyzing the adsorption behavior,energy barriers,and intermediate coupling steps involved in the generation of each product.Particular emphasis is placed on the key intermediates,such as^(*)OCHO,^(*)COOH,^(*)CO,^(*)OCCOH,and^(*)CCO,which play crucial roles in determining the product selectivity.The effects of catalyst composition,morphology,and electronic structure on the adsorption and activation of these intermediates are also discussed.Moreover,advanced characterization techniques,including in-situ spectroscopy and isotopic labeling experiments,are highlighted for their contributions to unraveling the reaction mechanisms.The review aims to provide critical insights to reveal the activity-determining para meters and underlying CO_(2)RR mechanisms,which will guide the rational design of next-generation electrocatalysts for selective CO^(2)RR towards high-value products.
基金Supported by National Key Research and Development Program Project,No.2017YFC1700601Shaanxi Provincial Key Research and Development Program Project,No.2018SF-350Leading Talents in Scientific and Technological Innovation of the Shaanxi Province Special Support Plan,No.00518。
文摘Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.
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supported by the National Key Research&Development Program of China(2021YFB3803200)the National Natural Science Foundation of China(22288102).
文摘Hexafluoropropylene oxide(HFPO)is a crucial fluorinated chemical mainly synthesized from hexafluoropropylene(HFP)through the oxidation of oxygen.However,the reaction network and kinetic characteristics are not fully understood yet,resulting in a lack of theoretical basis for synthesis process improvement.Here,the free radical reaction mechanism and complete reaction network involved in the noncatalytic oxidation of HFP to synthesize HFPO was explored by density functional theory.Transition state theory was employed to calculate the intrinsic reaction rate constants for elementary reactions.Based on theoretical reaction rate ratios,reaction pathways were selected,and a simplified reaction network was derived.It was found that byproducts were formed owing to the decomposition of HFPO and subsequent reactions with excessive oxygen while oxygen tended to participate more in the main reaction under oxygen-deficient conditions.The variations in reaction pathways occurring at different HFP/oxygen molar ratios was well elucidated by comparing with experimental data.This research establishes a robust theoretical foundation for optimizing and regulating the synthesis of HFPO.
文摘Introduction: Foreign bodies (FB) in the lower airways (LAs) constitute a potentially life-threatening emergency requiring immediate management. The objective of our study was to describe the patient pathway and management of foreign bodies in the lower airways. Methodology: This was a descriptive study with retrospective data collection conducted over a 6-year period (January 1, 2014, to December 31, 2019) in the ENT and Head and Neck Surgery Department of Donka National Hospital. Results: We observed a prevalence of 1.79%. The average age was 5.71 years, with a sex ratio of 1.2. However, 82.61% of the cases originated from rural areas. We noted that 78.83% of patients were referred after visiting 1 to 2 healthcare facilities (75.36%). The consultation delay was 3 days. Penetration syndrome was present in 98.56% of cases. The foreign body incidents occurred during play in 54.84% and during meals in 29.09% of cases. Radiographs were performed in 93.9% of cases. Endoscopy was used for both diagnostic and therapeutic purposes in all patients. The foreign bodies were located in the trachea (37.68%), larynx (26.08%), and bronchi (21.73%). Non-organic foreign bodies were predominant (52.17%). Postoperative outcomes were uncomplicated in 95.98% of cases, and the lethality rate was 2.85%. Conclusion: The pathway of patients with foreign bodies in the airways remains unpredictable in our context due to parental hesitations. Early management reduces morbidity and mortality rates.
基金funding from the U.S.-Kazakhstan University Partnerships program funded by the U.S.Mission to Kazakhstan and administered by American Councils[Award number SKZ100-19-CA-0149].
文摘As universities in Kazakhstan continue to address the challenges that come with developing English-medium instruction(EMI)programs,university Science,Technology,Engineering,and Mathematics(STEM)teachers need to develop capacities to teach in English,while their English teacher counterparts need to develop content-specific pedagogical knowledge.Content and Language Integrated Learning(CLIL)pedagogies,defined as the integration of both language and content curricular goals,have emerged as a vehicle to facilitate this development for both types of teachers.However,what it means to be a CLIL teacher may vary considerably as teachers leverage their professional knowledge and personal experiences.We,therefore,explore teachers’conceptions of CLIL and how their disciplinary,linguistic,and pedagogical backgrounds enable or burden them to forge a“CLIL teacher”identity.This qualitative study illustrates the salient points of the journeys taken by two university teachers,one a specialist in oil and gas,the other an English teacher and teacher educator.Drawing on extended one-on-one interviews,we present two teachers’experiences through a series of CLIL-informed workshops.Using a multidisciplinary analytical framework,we map the ways in which the two teacher participants negotiate their identities in relation to CLIL.The findings highlight the importance of understanding teacher experiences,particularly their language learning backgrounds,attitudes toward supporting student learning,and relationships with their colleagues as they work to adapt to teaching English and STEM subjects in university EMI contexts.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(grant number:NRF-2022R1A2C1092743).
文摘Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular and cellular disturbances,including reduced nitric oxide bioavailability,persistent low-grade inflammation,oxidative stress,endothelial dysfunction,altered mineral metabolism,genetic predispositions,and uremic toxin accumulation.As current pharmacological treatments provide only partial risk reduction,complementary approaches are imperative.Exercise training,both aerobic and resistance,has emerged as a potent non-pharmacological intervention targeting these underlying molecular pathways.Regular exercise can enhance nitric oxide signaling,improve antioxidant defenses,attenuate inflammation,facilitate endothelial repair via endothelial progenitor cells,and stabilize muscle metabolism.Additionally,accumulating evidence points to a genetic dimension in CKD susceptibility and progression.Variants in genes such as APOL1,PKD1,PKD2,UMOD,and COL4A3–5 shape disease onset and severity,and may modulate response to interventions.Exercise may help buffer these genetic risks by inducing epigenetic changes,improving mitochondrial function,and optimizing crosstalk between muscle,adipose tissue,and the vasculature.This review synthesizes how exercise training can ameliorate key molecular mediators in CKD,emphasizing the interplay with genetic and epigenetic factors.We integrate evidence from clinical and experimental studies,discussing how personalized exercise prescriptions,informed by patients’genetic backgrounds and nutritional strategies(such as adequate protein intake),could enhance outcomes.Although large-scale trials linking molecular adaptations to long-term endpoints are needed,current knowledge strongly supports incorporating exercise as a cornerstone in CKD management to counteract pervasive molecular derangements and leverage genetic insights for individualized care.
文摘As a traditional model for inheriting Chinese medicine,apprenticeship education has evolved over millennia into a distinctive talent cultivation system.In the new era characterized by upholding tradition while pursuing innovation,apprenticeship education serves not only as the core vehicle for sustaining Chinese medical scholarship but also as the key support for resolving contemporary challenges in cultivating TCM professionals.This paper traces the historical evolution and policy context of apprenticeship education,analyzes its current development status and underlying contradictions,and systematically elucidates its irreplaceable value in dimensions such as academic inheritance,critical thinking cultivation,and cultural continuity.By integrating technological innovation and policy guidance,it outlines development pathways to provide practical references for constructing a modernized TCM education system.
基金financially supporting this work through the Large Research Group Project under grant number R.G.P.2/510/45。
文摘Background:Neurodegenerative diseases(NDs),including Alzheimer‘s disease,Parkinson‘s disease,and Huntington‘s disease,are complex and challenging due to their intricate pathophysiology and limited treatment options.Methods:This review systematically sourced articles related to neurodegenerative diseases,neurodegeneration,quercetin,and clinical studies from primary medical databases,including Scopus,PubMed,and Web of Science.Results:Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration.Quercetin,a flavonoid abundant in vegetables and fruits,is gaining attention for its antioxidant,anti-inflammatory,and antiapoptotic properties.It regulates signaling pathways such as nuclear factor-κB(NF-κB),sirtuins,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt).These pathways are essential for cellular survival,inflammation regulation,and apoptosis.Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models,indicating promising outcomes.Conclusions:The study explores the potential of incorporating laboratory research into practical medical treatment,focusing on quercetin‘s neuroprotective effects on NDs and its optimal dosage.
基金supported by the grants from the National Natural Science Foundation of China(82404638)the Xingdian Talent Plan of Yunnan Province(XDYC-QNRC-2023-0427 and XDYC-YLXZ2022-0025)the Natural Science Foundation of Yunnan Province(202101BD070001-034,202101BD070001-049,202201AT070267,and 202201AU070183)。
文摘Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities.Axillaridine A(AA)is a newly discovered steroidal alkaloid.However,whether AA could suppress osteoclastogenesis and alleviate ovariectomy-induced bone loss in mice remains unknown.In vitro,AA significantly suppressed the receptor activator of nuclear factor-κB(NF-κB)ligand(RANKL)-induced osteoclast differentiation via downregulating the expression of osteoclastogenesis-related marker genes,proteins,and transcriptional regulators,including tartrate-resistant acid phosphatase(TRAP),c-Src,matrix metallopeptidase-9(MMP-9),cathepsin K,nuclear factor of activated T cells,cytoplasmic 1(NFATc1),and c-Fos.This was achieved by blocking RANKL-RANK interaction and inhibiting RANKL-mediated RANK signaling pathways,including NF-κB,AKT,and mitogen-activated protein kinases(MAPKs)in osteoclast precursors.In vivo,AA significantly inhibited the ovariectomized(OVX)-induced body weight gain and blood glucose increase in mice.AA did not adversely affect the histomorphologies,weights,and indices of the kidney and liver in OVX mice.AA effectively ameliorated bone loss in OVX mice by inhibiting osteoclastogenesis.AA significantly inhibited the serum levels of tartrate-resistant acid phosphatase 5b(TRACP-5b)and C-telopeptide of type I collagen(CTX-I).AA significantly inhibited the OVX-induced expression of osteoclastogenesis-related marker genes and proteins in the femur.In summary,AA alleviates ovariectomy-induced bone loss in mice by suppressing osteoclastogenesis via inhibition of RANKL-mediated RANK signaling pathways and could be potentially used for the prevention and treatment of osteoclastrelated diseases such as osteoporosis.
基金supported by the National Natural Science Foundation of China(Grant No.:82174222)Shandong Province Natural Science Foundation,China(Grant No.:ZR2021LZY015).
文摘Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.Therefore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.
基金supported by the National Natural Science Foundation of China(Nos.42121004,42275107,and 42077205)the National Key Research and Development Plan(No.2023YFC3706202)+1 种基金the Foundational and Applied Basic Research in Guangzhou in 2023(No.2023A04J0251)the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province(No.2019B121205004)。
文摘This study tracked the characteristics of atmospheric wet deposition of the toxic element arsenic(As)at both urban(Guangzhou(GZ))and forested(Dinghushan Natural Reserve(DHS))sites within the Pearl River Delta(PRD)region between 2016 and 2019,examining its correlation with rainfall patterns.Additionally,by employing backward trajectory analysis and the potential source contribution function(PSCF)in conjunction with pertinent emission inventories,we pinpointed the main pathways of atmospheric arsenic transport and evaluated the emission contributions from priority source areas.The study revealed that the atmospheric arsenic wet deposition fluxes at the GZ and DHS sites exhibited a trend of increase followed by a decrease over the four-year period.Wet season deposition fluxes were more than triple those of the dry season,with urban site showing a difference of over four times.Notably,wet season As deposition at both sites was predominantly affected by heavy rainfall from marine air masses,constituting 31%of the total deposition.The predominant trajectory directions contributing to arsenic deposition at GZ and DHS were northeast(55%)and south(53%),respectively.The primary source areas for both sites were largely outside the PRD region,with the GZ site having 80%to 95%of its source area in the non-PRD region,compared to 69%to 88%at the DHS site.Furthermore,non-PRD areas contributed approximately 65%to arsenic emissions for both sites,with the industrial sector being the dominant emission source,exceeding 97%of the total emissions.
基金Supported by the Ministry of Higher Education(Malaysia)(No.FRGS/1/2023/SKK15/IMU/01/1)International Medical University[No.PHMS I-2023(01)].
文摘Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main risk factor.Thus,neuroprotective strategies have gained interest.We performed a bibliometric analysis to determine global publishing trends and relationships among prolific authors,publications,institutions,funding agencies,and journals.We also analyzed author keywords to identify research hotspots in glaucoma neuroprotection.Further,based on keyword analysis,we reviewed most recent literature to understand mechanistic pathways underlying glaucomarelated pathophysiological responses leading to RGC loss.Bibliographic data were sourced from Scopus.Basic bibliographic features were characterized using Scopus’s functions.VOSviewer was used for mapping and visualizing bibliometric networks.The analysis included trends in publications since 2000,the most prolific countries,institutions,authors,and the strength of their linkages.A significant increase in publication output over the past two decades was noted.The United States leads in funding support,research output,and citation links,followed by China and the UK.Among the top 10 most cited authors,three are from Japanese institutions.Keyword analysis shows a focus on molecular targets related to ischemia,excitotoxicity,inflammation,and oxidative stress,with fewer emerging drug candidates and limited clinical trials.Based on the most recent literature,emerging molecular targets underlying these key pathophysiological mechanisms are summarized.In conclusion,while pathophysiology and molecular mechanisms are the current focus,there is not much progress in developing new drug candidates and conducting clinical trials.
基金supported by the National Natural Science Foundation of China[81701350 and 31671252]the Health Technology Plan of Zhejiang Province[2023RC205].
文摘Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
基金Supported by National Natural Science Foundation of China,No.81973854Scientific Research Programme Project of Hebei Provincial Administration of Traditional Chinese Medicine,No.T2025095+1 种基金the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine‘Tuoxin Project’Fund Scientific Research Topics,No.2023012Key Project of the Huzhou City Science and Technology Plan,No.2023GZ83.
文摘Oxidative stress and inflammation are closely interrelated processes that are pivotal to the impaired wound healing associated with diabetes.Chronic hyperglycemia in diabetic patients induces excessive reactive oxygen species(ROS)production,which triggers heightened inflammatory responses.The resulting inflammation exacerbates oxidative damage,delays wound closure,and intensifies tissue injury,thereby creating a detrimental cycle that disrupts normal wound healing.Recent research has increasingly focused on the therapeutic potential of natural products in modulating oxidative stress and inflammation to enhance diabetic wound healing.Natural compounds,such as polyphenols,flavonoids,and terpenoids,have demonstrated significant efficacy in reducing oxidative damage and modulating inflammatory pathways.These bioactive agents exhibit potent antioxidant activity by scavenging ROS and enhancing endogenous antioxidant defenses while concurrently inhibiting the release of proinflammatory cytokines.Additionally,natural therapies have been shown to promote angiogenesis,enhance collagen synthesis,and improve fibroblast function,further facilitating wound repair.This review provides insights into the complex interplay between oxidative stress and inflammation in diabetic wound healing and evaluates the therapeutic potential of natural products as adjunctive treatments.Further clinical investigations are essential to validate the efficacy and safety of these natural interventions for diabetic wound management.
