Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially...Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB’s goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.展开更多
Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligen...Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligence.Among its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and research.In this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical Cases.The authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and albumin.In addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+group.However,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.展开更多
Breast cancer is the leading cause of cancer-related mortality in women globally,with its incidence continuing to rise,particularly in low-and middle-income countries,presenting a significant public health challenge w...Breast cancer is the leading cause of cancer-related mortality in women globally,with its incidence continuing to rise,particularly in low-and middle-income countries,presenting a significant public health challenge worldwide[1].According to data from the Institute for Health Metrics and Evaluation(IHME)and the World Health Organization(WHO),the gap in access to healthcare services between high-and low-income countries contributes to delayed detection,increased incidence of advanced-stage disease,and,consequently,higher mortality rates(up to 50%higher compared to high-income countries)[1,2].This translates into inequalities in access to screening and early diagnosis methods,which exacerbate the burden of this disease in low-resource settings where infrastructure,funding,and access to trained professionals are limited[3].展开更多
Background:Stretching has wide appeal,but there seems to exist some mismatch between its purported applications and what the evidence shows.There is compelling evidence for some stretching applications,but for others,...Background:Stretching has wide appeal,but there seems to exist some mismatch between its purported applications and what the evidence shows.There is compelling evidence for some stretching applications,but for others,the evidence seems heterogeneous or unsupportive.The discrepancies even affect some systematic reviews,possibly due to heterogeneous eligibility criteria and search strategies.This consensus paper seeks to unify the divergent findings on stretching and its implications for both athletic performance and clinical practices by delivering evidence-based recommendations.Methods:A panel of 20 experts with a blend of practical experience and scholarly knowledge was assembled.The panel meticulously reviewed existing systematic reviews,defined key terminologies(e.g.,consensus definitions for different stretching modes),and crafted guidelines using a Delphi consensus approach(minimum required agreement:80%).The analysis focused on 8 topics,including stretching's acute and chronic(long-term)effects on range of motion,strength performance,muscle hypertrophy,stiffness,injury prevention,muscle recovery,posture correction,and cardiovascular health.Results:There was consensus that chronic and acute stretching(a)improves range of motion(although alternatives exist)and(b)reduces muscle stiffness(which may not always be desirable);the panel also agreed that chronic stretching(c)may promote vascular health,but more research is warranted.In contrast,consensus was found that stretch training does not(a)contribute substantively to muscle growth,(b)serve as an allencompassing injury prevention strategy,(c)improve posture,or(d)acutely enhance post-exercise recovery.Conclusion:These recommendations provide guidance for athletes and practitioners,highlighting research gaps that should be addressed to more comprehensively understand the full scope of stretching effects.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
Objectives This study aimed to analyse the benefits of a gamified clinical supervision strategy during hospital-based training,particularly regarding the development of critical and reflective thinking among undergrad...Objectives This study aimed to analyse the benefits of a gamified clinical supervision strategy during hospital-based training,particularly regarding the development of critical and reflective thinking among undergraduate nursing students.Methods From April to July 2023,second-year nursing students who undertaking a nine-week clinical placement in a cardiology ward in northern Portugal were selected.Following a two-week diagnostic phase,students participated in a six-week gamified supervision programme comprising weekly 60-min sessions:infection-control decision-making;technical-procedural reasoning;guided emotional and ethical reflection;and clinical reasoning quiz on cardiology topics.Students completed weekly Structured Reflection Guide entries;supervisors recorded structured field notes after each session;and,after the intervention,students answered a post-intervention questionnaire and participated in focus groups.Qualitative data(reflections,field notes,open-ended questionnaire items,and focus-group transcripts)were analyzed using Bardin’s content analysis;quantitative questionnaire items were summarized descriptively.Results All seven students completed the six gamified sessions and submitted weekly reflection entries.Five students(71.4%)completed the questionnaire.Across data sources,students reported that gamified activities supported knowledge consolidation,teamwork,and clinical reasoning.Questionnaire data showed that all respondents(n=5,100%)strongly agreed that gamification enhanced their learning and should be maintained in clinical training.Reflections and focus groups revealed recurring themes related to emotional expression,sense of belonging,and difficulties using structured reflection tools,particularly in terms of comprehension and timing.Conclusion The gamified supervision strategy integrated into clinical training provided structured opportunities for practical engagement,collaborative work,and guided reflection.These findings suggest that gamification may support the development of reflective and critical-thinking processes in authentic clinical environments.展开更多
In this study,the design,analysis,manufacturing,and testing of a 3D-printed conformal microstrip array antenna for high-temperature environments is presented.3D printing technology is used to fabricate a curved cerami...In this study,the design,analysis,manufacturing,and testing of a 3D-printed conformal microstrip array antenna for high-temperature environments is presented.3D printing technology is used to fabricate a curved ceramic substrate,and laser sintering and microdroplet spraying processes are used to add the conductive metal on the curved substrate.The problems of gain loss,bandwidth reduction,and frequency shift caused by high temperatures are addressed by using a proper antenna design,with parasitic patches,slots,and metal resonant cavities.The antenna prototype is characterized by the curved substrates and the conductive metals for the power dividers,the patch,and the ground plane;its performance is examined up to a temperature of 600℃in a muffle furnace and compared with the results from the numerical analysis.The results show that the antenna can effectively function at 600℃and even higher temperatures.展开更多
Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune respons...Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.展开更多
Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva a...Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to r...The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.展开更多
Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(...Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(CB[8])as the host and terpyridine lanthanum ions metal complex as the vip,constructed by layer-by-layer self-assembly through supramolecular interaction.Moreover,nanofibers with lanthanide luminescence properties exhibit surprising pH-responsive deformation properties and antibacterial behavior.In the tumor micro-environment,the dramatic reduction in the size of the nanofibers enables specific and hierarchical release of anticancer drugs in tumor cells to exert an advanced therapeutic effect.In addition,the synergistic therapeutic efficacy was achieved by reducing the excess of Gram-positive and Gram-negative bacteria surrounding tumor cells.The novel supramolecular nanofibers with sequential drug release and combined therapeutic mode provide new guidance for the synthesis of drug carrier materials and direction for the promotion of nanomaterial-mediated cancer therapy.展开更多
Numerous sectors,such as education,the IT sector,and corporate organizations,transitioned to virtual meetings after the COVID-19 crisis.Organizations now seek to assess participants’fatigue levels in online meetings ...Numerous sectors,such as education,the IT sector,and corporate organizations,transitioned to virtual meetings after the COVID-19 crisis.Organizations now seek to assess participants’fatigue levels in online meetings to remain competitive.Instructors cannot effectively monitor every individual in a virtual environment,which raises significant concerns about participant fatigue.Our proposed system monitors fatigue,identifying attentive and drowsy individuals throughout the online session.We leverage Dlib’s pre-trained facial landmark detector and focus on the eye landmarks only,offering a more detailed analysis for predicting eye opening and closing of the eyes,rather than focusing on the entire face.We introduce an Eye Polygon Area(EPA)formula,which computes eye activity from Dlib eye landmarks by measuring the polygonal area of the eye opening.Unlike the Eye Aspect Ratio(EAR),which relies on a single distance ratio,EPA adapts to different eye shapes(round,narrow,or wide),providing a more reliable measure for fatigue detection.The VMFD system issues a warning if a participant remains in a fatigued condition for 36 consecutive frames.The proposed technology is tested under multiple scenarios,including low-to high-lighting conditions(50-1400 lux)and both with and without glasses.This study builds an OpenCV application in Python,evaluated using the iBUG 300-W dataset,achieving 97.5%accuracy in detecting active participants.We compare VMFD with conventional methods relying on the EAR and show that the EPA technique performs significantly better.展开更多
This study proposes to use the unconfined compressive strength(UCS)and the bender element(BE)tests for determining the strength and the initial small-strain shear modulus of Bangkok soft marine clay improved by cement...This study proposes to use the unconfined compressive strength(UCS)and the bender element(BE)tests for determining the strength and the initial small-strain shear modulus of Bangkok soft marine clay improved by cement and polyester fibers.This study varies the content of admixed cement(1%–20%)and polyester fibers(0–20%),including the curing time(3–28 d)for preparing 360 samples.Moreover,this study uses the Michaelis-Menten kinetics concept to model cement hydration saturation.From the study,it is concluded as follows.The modelled results reveals that at least 10%cement and 1%polyester fiber are recommended to attain the 28-d UCS standards(294 kPa)for highway subgrade materials in Thailand.This also fulfils sustainable construction due to reducing normal-use cement from 20%to 10%.Unfortunately,the addition of polyester fibers into the Bangkok clay with at least 5%cement reduces shear modulus by 1.12–1.32 times.The Abram's relationship between shear modulus and the mixing-water-to-cement ratio is found time-dependent.From the composite theory,the BE detects the polyester fiber zone as a defect in the Bangkok clay(matrix)with 5%–20%cement.So,the 28-d shear modulus in the polyester fiber zone is negative(up to0.034 MPa for 20%fiber),similar to softening phenomenon in concrete cracking(negative stiffness).For the 28-d shear modulus of fiber zone,the optimum cement content is around 2%for the positive influences of polyester fibers.Experimentally,the timedependent normalized UCS for 10%and 20%cement is compatible with other studies,and its development rate increases with the cement content as 0.3017,0.3172 and 0.3204 for 5%,10%and 20%cement,respectively.The 28-d relationship between shear modulus and UCS shows that low-cement soft clay requires high polyester fiber content(5%–20%)to activate UCS improvement.However,the soft clay with enough cement(20%)causes the uniformly distributed UCS improvement.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanoca...Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.展开更多
Origanum elongatum(OE)is an aromatic,medicinal plant endemic to Morocco that is widely used in traditional medicine due to its biological properties.This study aimed to elucidate the chemical composition of the essent...Origanum elongatum(OE)is an aromatic,medicinal plant endemic to Morocco that is widely used in traditional medicine due to its biological properties.This study aimed to elucidate the chemical composition of the essential oil(EO)obtained from O.elongatum(OEEO)at three stages of its life cycle,including vegetative stage(OEEO-VS),flowering stage(OEEO-FS),and post-flowering(OEEO-PFS),as well as to evaluate its biological and antiradical characteristics.The chemical analysis of the essential oil was conducted using gas chromatography-mass spectrometry(GC-MS).The antibacterial activity was evaluated in vitro through distinct methodologies,namely,disc diffusion and microatmosphere assay;subsequently,the minimum inhibitory concentration(MIC)was then determined.The antioxidant potential was also measured by using the DPPH and FRAP assays.The GC-MS revealed the predominant of p-cymene(26.83%_31.45%),γ-terpinene(8.46%_26.95%),thymol(13%_29.54%),and carvacrol(20.25%_37.26%),in all three samples,with notable variations according to the phenological stage of the samples.The EOs extracted at three phenological stages demonstrated notable antibacterial efficacy against all the phytopathogen tested.The MICs for Erwinia amylovora exhibited a range of 6.25 and 250μg/mL.However,for Agrobacterium tumefaciens C58 and Allorhizobium vitis S4,the MICs spanned 125 and 250μg/mL.In the DPPH test,the IC50 values were 168.25±1.14,147.01±0.78,and 132.01±2.06μg/mL for EOs derived from the vegetative,flowering,and post-flowering period,respectively.In the FRAP test,the EC50 values were 164.22±1.04,215.73±1.48,and 184.06±0.95μg/mL for the same stages.The findings offer promising prospects for the phytochemical development,demonstrating how the phenological stage significantly influences the therapeutic and biotechnological potential of O.elongatum.This has the potential to open up new avenues of research in the pharmaceutical,agronomic,and environmental fields.展开更多
Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization.Terminalia chebula Retz.(Fam.Combretaceae),is called the‘King of Medicine??in Tibet and is always listed at the l...Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization.Terminalia chebula Retz.(Fam.Combretaceae),is called the‘King of Medicine??in Tibet and is always listed at the lop of the list of‘Ayurvedic Materia Medica??because of its extraordinary power of healing.The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings.Some of the folklore people used this plant in the treatment of asthma,sore throat,vomiting,hiccough,diarrhea,dysentery,bleeding piles,ulcers,gout,heart and bladder diseases.The plant has been demonstrated to possess multiple pharmacological and medicinal activities,such as antioxidant,antimicrobial,antidiabetic,hepatoprotective,anti-inflammatory,antimutagenic,antiproliferative,radioprotective,cardioprotective,antiarthritic,anticaries,gastrointestinal motility and wound healing activity.But no systematic updated information on the therapeutic effectiveness of Terminalia chebula,a popular herbal remedy in India and South-East Asia has so far been reported.This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz.and some of its isolated compounds,along with their safety evaluation.This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine.展开更多
Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs sur...Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.展开更多
文摘Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB’s goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.
文摘Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligence.Among its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and research.In this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical Cases.The authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and albumin.In addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+group.However,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.
文摘Breast cancer is the leading cause of cancer-related mortality in women globally,with its incidence continuing to rise,particularly in low-and middle-income countries,presenting a significant public health challenge worldwide[1].According to data from the Institute for Health Metrics and Evaluation(IHME)and the World Health Organization(WHO),the gap in access to healthcare services between high-and low-income countries contributes to delayed detection,increased incidence of advanced-stage disease,and,consequently,higher mortality rates(up to 50%higher compared to high-income countries)[1,2].This translates into inequalities in access to screening and early diagnosis methods,which exacerbate the burden of this disease in low-resource settings where infrastructure,funding,and access to trained professionals are limited[3].
文摘Background:Stretching has wide appeal,but there seems to exist some mismatch between its purported applications and what the evidence shows.There is compelling evidence for some stretching applications,but for others,the evidence seems heterogeneous or unsupportive.The discrepancies even affect some systematic reviews,possibly due to heterogeneous eligibility criteria and search strategies.This consensus paper seeks to unify the divergent findings on stretching and its implications for both athletic performance and clinical practices by delivering evidence-based recommendations.Methods:A panel of 20 experts with a blend of practical experience and scholarly knowledge was assembled.The panel meticulously reviewed existing systematic reviews,defined key terminologies(e.g.,consensus definitions for different stretching modes),and crafted guidelines using a Delphi consensus approach(minimum required agreement:80%).The analysis focused on 8 topics,including stretching's acute and chronic(long-term)effects on range of motion,strength performance,muscle hypertrophy,stiffness,injury prevention,muscle recovery,posture correction,and cardiovascular health.Results:There was consensus that chronic and acute stretching(a)improves range of motion(although alternatives exist)and(b)reduces muscle stiffness(which may not always be desirable);the panel also agreed that chronic stretching(c)may promote vascular health,but more research is warranted.In contrast,consensus was found that stretch training does not(a)contribute substantively to muscle growth,(b)serve as an allencompassing injury prevention strategy,(c)improve posture,or(d)acutely enhance post-exercise recovery.Conclusion:These recommendations provide guidance for athletes and practitioners,highlighting research gaps that should be addressed to more comprehensively understand the full scope of stretching effects.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
文摘Objectives This study aimed to analyse the benefits of a gamified clinical supervision strategy during hospital-based training,particularly regarding the development of critical and reflective thinking among undergraduate nursing students.Methods From April to July 2023,second-year nursing students who undertaking a nine-week clinical placement in a cardiology ward in northern Portugal were selected.Following a two-week diagnostic phase,students participated in a six-week gamified supervision programme comprising weekly 60-min sessions:infection-control decision-making;technical-procedural reasoning;guided emotional and ethical reflection;and clinical reasoning quiz on cardiology topics.Students completed weekly Structured Reflection Guide entries;supervisors recorded structured field notes after each session;and,after the intervention,students answered a post-intervention questionnaire and participated in focus groups.Qualitative data(reflections,field notes,open-ended questionnaire items,and focus-group transcripts)were analyzed using Bardin’s content analysis;quantitative questionnaire items were summarized descriptively.Results All seven students completed the six gamified sessions and submitted weekly reflection entries.Five students(71.4%)completed the questionnaire.Across data sources,students reported that gamified activities supported knowledge consolidation,teamwork,and clinical reasoning.Questionnaire data showed that all respondents(n=5,100%)strongly agreed that gamification enhanced their learning and should be maintained in clinical training.Reflections and focus groups revealed recurring themes related to emotional expression,sense of belonging,and difficulties using structured reflection tools,particularly in terms of comprehension and timing.Conclusion The gamified supervision strategy integrated into clinical training provided structured opportunities for practical engagement,collaborative work,and guided reflection.These findings suggest that gamification may support the development of reflective and critical-thinking processes in authentic clinical environments.
基金National Natural Science Foundation of China(No.U2241205)the Natural Science Basic Research Program of Shaanxi(Nos.2022JC-33,2023-GHZD-35,and 2024JC-ZDXM-25)+1 种基金the Fundamental Research Funds for the Central Universitiesthe National 111 Project to provide fund for conducting experiments。
文摘In this study,the design,analysis,manufacturing,and testing of a 3D-printed conformal microstrip array antenna for high-temperature environments is presented.3D printing technology is used to fabricate a curved ceramic substrate,and laser sintering and microdroplet spraying processes are used to add the conductive metal on the curved substrate.The problems of gain loss,bandwidth reduction,and frequency shift caused by high temperatures are addressed by using a proper antenna design,with parasitic patches,slots,and metal resonant cavities.The antenna prototype is characterized by the curved substrates and the conductive metals for the power dividers,the patch,and the ground plane;its performance is examined up to a temperature of 600℃in a muffle furnace and compared with the results from the numerical analysis.The results show that the antenna can effectively function at 600℃and even higher temperatures.
基金supported by National Key R&D Program:Key Special Project on Research for the Prevention and Treatment of Common Diseases-2022 Annual Project,Nos.2022YFC2504900,2022YFC2504902(both to ZL).
文摘Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.
文摘Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)the National Natural Science Foundation of China(82471925)。
文摘The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.
基金supported by the National Natural Science Foundation of China(No.82273919)Natural Science Foundation of Heilongjiang Province(No.LH2024H013)China Postdoctoral Science Foundation(No.2022MD723781).
文摘Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(CB[8])as the host and terpyridine lanthanum ions metal complex as the vip,constructed by layer-by-layer self-assembly through supramolecular interaction.Moreover,nanofibers with lanthanide luminescence properties exhibit surprising pH-responsive deformation properties and antibacterial behavior.In the tumor micro-environment,the dramatic reduction in the size of the nanofibers enables specific and hierarchical release of anticancer drugs in tumor cells to exert an advanced therapeutic effect.In addition,the synergistic therapeutic efficacy was achieved by reducing the excess of Gram-positive and Gram-negative bacteria surrounding tumor cells.The novel supramolecular nanofibers with sequential drug release and combined therapeutic mode provide new guidance for the synthesis of drug carrier materials and direction for the promotion of nanomaterial-mediated cancer therapy.
文摘Numerous sectors,such as education,the IT sector,and corporate organizations,transitioned to virtual meetings after the COVID-19 crisis.Organizations now seek to assess participants’fatigue levels in online meetings to remain competitive.Instructors cannot effectively monitor every individual in a virtual environment,which raises significant concerns about participant fatigue.Our proposed system monitors fatigue,identifying attentive and drowsy individuals throughout the online session.We leverage Dlib’s pre-trained facial landmark detector and focus on the eye landmarks only,offering a more detailed analysis for predicting eye opening and closing of the eyes,rather than focusing on the entire face.We introduce an Eye Polygon Area(EPA)formula,which computes eye activity from Dlib eye landmarks by measuring the polygonal area of the eye opening.Unlike the Eye Aspect Ratio(EAR),which relies on a single distance ratio,EPA adapts to different eye shapes(round,narrow,or wide),providing a more reliable measure for fatigue detection.The VMFD system issues a warning if a participant remains in a fatigued condition for 36 consecutive frames.The proposed technology is tested under multiple scenarios,including low-to high-lighting conditions(50-1400 lux)and both with and without glasses.This study builds an OpenCV application in Python,evaluated using the iBUG 300-W dataset,achieving 97.5%accuracy in detecting active participants.We compare VMFD with conventional methods relying on the EAR and show that the EPA technique performs significantly better.
基金allocated by National Science,Research and Innovation Fund(NSRF)King Mongkut's University of Technology North Bangkok(project no.KMUTNB-FF-67-B-44 and KMUTNB-FF-67-B-45)supported by the NSRF through the Program Management Unit for Human Resources&Institutional Development,Research and Innovation(grant no.B40G660036).
文摘This study proposes to use the unconfined compressive strength(UCS)and the bender element(BE)tests for determining the strength and the initial small-strain shear modulus of Bangkok soft marine clay improved by cement and polyester fibers.This study varies the content of admixed cement(1%–20%)and polyester fibers(0–20%),including the curing time(3–28 d)for preparing 360 samples.Moreover,this study uses the Michaelis-Menten kinetics concept to model cement hydration saturation.From the study,it is concluded as follows.The modelled results reveals that at least 10%cement and 1%polyester fiber are recommended to attain the 28-d UCS standards(294 kPa)for highway subgrade materials in Thailand.This also fulfils sustainable construction due to reducing normal-use cement from 20%to 10%.Unfortunately,the addition of polyester fibers into the Bangkok clay with at least 5%cement reduces shear modulus by 1.12–1.32 times.The Abram's relationship between shear modulus and the mixing-water-to-cement ratio is found time-dependent.From the composite theory,the BE detects the polyester fiber zone as a defect in the Bangkok clay(matrix)with 5%–20%cement.So,the 28-d shear modulus in the polyester fiber zone is negative(up to0.034 MPa for 20%fiber),similar to softening phenomenon in concrete cracking(negative stiffness).For the 28-d shear modulus of fiber zone,the optimum cement content is around 2%for the positive influences of polyester fibers.Experimentally,the timedependent normalized UCS for 10%and 20%cement is compatible with other studies,and its development rate increases with the cement content as 0.3017,0.3172 and 0.3204 for 5%,10%and 20%cement,respectively.The 28-d relationship between shear modulus and UCS shows that low-cement soft clay requires high polyester fiber content(5%–20%)to activate UCS improvement.However,the soft clay with enough cement(20%)causes the uniformly distributed UCS improvement.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
基金supported by National Natural Science Foundation of China(82272943)Shanghai Municipal Science and Technology Commission(21Y11913400)Fundamental Research Funds for the Central Universities and National Key Research and Development Program of China(2022YFC2407405).
文摘Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.
文摘Origanum elongatum(OE)is an aromatic,medicinal plant endemic to Morocco that is widely used in traditional medicine due to its biological properties.This study aimed to elucidate the chemical composition of the essential oil(EO)obtained from O.elongatum(OEEO)at three stages of its life cycle,including vegetative stage(OEEO-VS),flowering stage(OEEO-FS),and post-flowering(OEEO-PFS),as well as to evaluate its biological and antiradical characteristics.The chemical analysis of the essential oil was conducted using gas chromatography-mass spectrometry(GC-MS).The antibacterial activity was evaluated in vitro through distinct methodologies,namely,disc diffusion and microatmosphere assay;subsequently,the minimum inhibitory concentration(MIC)was then determined.The antioxidant potential was also measured by using the DPPH and FRAP assays.The GC-MS revealed the predominant of p-cymene(26.83%_31.45%),γ-terpinene(8.46%_26.95%),thymol(13%_29.54%),and carvacrol(20.25%_37.26%),in all three samples,with notable variations according to the phenological stage of the samples.The EOs extracted at three phenological stages demonstrated notable antibacterial efficacy against all the phytopathogen tested.The MICs for Erwinia amylovora exhibited a range of 6.25 and 250μg/mL.However,for Agrobacterium tumefaciens C58 and Allorhizobium vitis S4,the MICs spanned 125 and 250μg/mL.In the DPPH test,the IC50 values were 168.25±1.14,147.01±0.78,and 132.01±2.06μg/mL for EOs derived from the vegetative,flowering,and post-flowering period,respectively.In the FRAP test,the EC50 values were 164.22±1.04,215.73±1.48,and 184.06±0.95μg/mL for the same stages.The findings offer promising prospects for the phytochemical development,demonstrating how the phenological stage significantly influences the therapeutic and biotechnological potential of O.elongatum.This has the potential to open up new avenues of research in the pharmaceutical,agronomic,and environmental fields.
基金Supported by Indian Statistical Institute,Kolkata,India(GrantNo,Project A/C No.5613)
文摘Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization.Terminalia chebula Retz.(Fam.Combretaceae),is called the‘King of Medicine??in Tibet and is always listed at the lop of the list of‘Ayurvedic Materia Medica??because of its extraordinary power of healing.The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings.Some of the folklore people used this plant in the treatment of asthma,sore throat,vomiting,hiccough,diarrhea,dysentery,bleeding piles,ulcers,gout,heart and bladder diseases.The plant has been demonstrated to possess multiple pharmacological and medicinal activities,such as antioxidant,antimicrobial,antidiabetic,hepatoprotective,anti-inflammatory,antimutagenic,antiproliferative,radioprotective,cardioprotective,antiarthritic,anticaries,gastrointestinal motility and wound healing activity.But no systematic updated information on the therapeutic effectiveness of Terminalia chebula,a popular herbal remedy in India and South-East Asia has so far been reported.This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz.and some of its isolated compounds,along with their safety evaluation.This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine.
基金supported by the National Natural Science Foundation of China,Nos.82473334(to LZ),82401629(to XL)the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region,No.2022CJE09013(to LZ)+4 种基金Mianyang Science and Technology Bureau(Mianyang Science and Technology Program),No.2023ZYDF097(to LZ)NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX001(to LZ)Spinal Cord Diseases Clinical Medical Center of Yunnan Province,No.2024JSKFKT-16(to BG)the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
文摘Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
