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
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
Climate change is one of the most pressing global challenges and spares no nation.Bhutan,as the only carbon negative country in the world,is no exception and being in the Himalayas–a region warming faster than the gl...Climate change is one of the most pressing global challenges and spares no nation.Bhutan,as the only carbon negative country in the world,is no exception and being in the Himalayas–a region warming faster than the global average–further intensifies climate risks.This study explores how Bhutan navigates climate change through the perspectives of 41 policy influencers,including politicians,civil servants,and leaders from nongovernment organisations and the media.The findings are compared with scientific literature from the broader Himalayan region to identify shared vulnerabilities(e.g.,glacial lake outburst floods,water scarcity,and agricultural disruptions)and governance challenges(e.g.,financial constraints,geopolitical pressures,and gaps in policy implementation).The study reveals that Bhutan,like its Himalayan neighbours,prioritizes adaptation over mitigation due to immediate climate threats,despite its carbonnegative status.However,Bhutan faces unique pressures in upholding its dual commitments—maintaining 60%forest cover and carbon neutrality—amid competing development needs.While its Gross National Happiness(GNH)framework provides a holistic governance model,the analysis uncovers systemic barriers,including limited financing,transboundary climate risks,and uneven policy execution,which mirror regional struggles.The paper contributes to climate governance discourse by highlighting the risks of symbolic environmental pledges without robust implementation mechanisms,particularly for vulnerable mountain nations.It calls for integrated policies that bridge mitigation and adaptation,stronger regional cooperation,and equitable climate financing.The findings are relevant for policymakers in the Himalayas and international stakeholders advocating context-specific,justiceoriented climate strategies.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
This study evaluates the stabilizing effect of lignin, extracted from Eucalyptus globulus, on an energetic composite of nitrated cellulose carbamate (NCC) plasticized with diethylene glycol dinitrate (DEGDN), compared...This study evaluates the stabilizing effect of lignin, extracted from Eucalyptus globulus, on an energetic composite of nitrated cellulose carbamate (NCC) plasticized with diethylene glycol dinitrate (DEGDN), compared to conventional stabilizers 2-nitrodiphenylamine (2-NDPA) and 1,3-dimethyl-1,3-diphenylurea (C-II). FTIR analysis confirms lignin's capacity to scavenge nitroxyl radicals formed during thermolysis of nitrocarbamate and nitrate ester bonds, thereby inhibiting decomposition. Moreover, the incorporation of C-II, 2-NDPA, and lignin significantly raised the peak temperature of the main thermolysis, as confirmed by DSC and TGA, indicating a progressive stability enhancement in the order: NCC/DEGDN < NCC/DEGDN/C-II < NCC/DEGDN/lignin < NCC/DEGDN/2-NDPA. Additionally, the effect of each stabilizer on the decomposition pathway was characterized by TGA-FTIR. The findings show that stabilizer type significantly affects the intensity of gaseous products released during decomposition without altering their nature. Notably, NH2 groups formed during NCC degradation play a key role in nitrogen conversion, particularly by reducing toxic NO emissions.展开更多
The overgeneralization of fear is associated with psychiatric disorders and cognitive decline.Recent studies have shown that engram cells in the dorsal dentate gyrus are integrated into functionally heterogeneous ense...The overgeneralization of fear is associated with psychiatric disorders and cognitive decline.Recent studies have shown that engram cells in the dorsal dentate gyrus are integrated into functionally heterogeneous ensembles that are involved in contextual fear memory generalization and discrimination.However,the intracellular signals that promote fear generalization remain to be fully elucidated.In this study,we labeled and manipulated the c-Fos+and Npas4+ensembles in the dorsal dentate gyrus that are activated by contextual fear conditioning using a robust activity marking system.The results showed that increasing the excitability of Fos-dependent robust activity marking by overexpressing NaChBac or decreasing the excitability of Npas4-dependent robust activity marking by overexpressing Kir2.1 promoted fear memory generalization.Furthermore,CRISPR-mediated downregulation of the autophagy-related Atg5 or Atg7 genes in dorsal dentate gyrus neurons inhibited activation of c-Fos,but not Npas4.Knockdown of Atg5 or Atg7 in the Fos-dependent robust activity marking or Npas4-dependent robust activity marking ensemble led to an increase in neuronal excitability and a decrease in spine density in both ensembles.However,Atg7 knockdown in the Fos-dependent robust activity marking ensemble promoted memory generalization,while knockdown of Atg5 or Atg7 in the Npas4-dependent robust activity marking ensemble increased anxiety levels.These results contribute to our understanding of how the varying plasticity of memory engrams is involved in regulating fear memory generalization and anxiety.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
This paper examines a model that combines vortex generators and leading-edge tubercles for controlling the laminar separation bubble(LSB)over an airfoil at low Reynolds numbers(Re).This new concept of passive flow con...This paper examines a model that combines vortex generators and leading-edge tubercles for controlling the laminar separation bubble(LSB)over an airfoil at low Reynolds numbers(Re).This new concept of passive flow control technique utilizing a tubercle and vortex generator(VG)close to the leading edge was analyzed numerically for a NACA0015 airfoil.In this study,the Shear Stress Transport(SST)turbulence model was employed in the numerical modelling.Numerical modelling was completed using the ANSYS-Fluent 18.2 solver.Analyses were conducted to investigate the flow pattern and understand the underlying LSB control phenomena that enabled the new passive flow control method to provide this significant performance benefit.The findings indicated that the new concept of passive flow control technique suppressed the formation of an LSB at the suction surface of the NACA0015 airfoil,resulting in a higher lift coefficient and improved aerodynamic performance.Improvements in LSB dynamics and aerodynamic performance through the passive flow control method lead to increased energy output and enhanced stability.展开更多
Dementia and Alzheimer's disease (AD) are both age-related conditions that predominantly affect older adults.According to prevalence studies,the burden of these diseases on society is expected to increase in the c...Dementia and Alzheimer's disease (AD) are both age-related conditions that predominantly affect older adults.According to prevalence studies,the burden of these diseases on society is expected to increase in the coming years,particularly in relation to rising longevity and life expectancy.Advances in therapeutic and preventive strategies are needed to help reduce their global burden,which remains among the most significant health challenges in aging populations (Brookmeyer et al.,2007).展开更多
Despite Morocco's reliance on sunflower as an oilseed crop,little is known about its agronomic performance when sown in autumn or early winter.This knowledge gap is critical,as spring-sown varieties have shown dec...Despite Morocco's reliance on sunflower as an oilseed crop,little is known about its agronomic performance when sown in autumn or early winter.This knowledge gap is critical,as spring-sown varieties have shown declining performance in recent years under intensifying climate stress.Therefore,targeted breeding strategies could discover genotypes suitable for autumn or early winter sowing,with cold tolerance as a key selection criterion.Currently,‘Ichraq'is the only autumn-planted sunflower variety officially registered in Morocco,although efforts to release additional tolerant varieties are underway.This study evaluated 31 genotypes(MGB1to MGB31)selected from various environments under autumn planting conditions and conserved in the Moroccan Gene Bank.These genotypes were planted in early winter at a mountainous site known for its pronounced winter cold.Eighteen Morphological,physiological and agronomic parameters including initial vigor,leaf area,seed yield,oil content etc.,were assessed using both univariate and multivariate statistical approaches.Analysis of variance revealed significant genotypic differences across most traits,indicating substantial genetic variation.Notably,seed oil content ranged from 23.28%(MGB26)to 43.88%(MGB5),and seed yield from1400 kg/ha(MGB7)to 5400 kg/ha(MGB8).Principal component analysis(PCA)identified that the first principal component,accounting for over 24%of the total phenotypic variance,exhibits a strong positive loading of yield-related traits and chlorophyll content,while displaying a pronounced negative loading for oil content variables.This opposing gradient indicates a clear trade-off between vegetative productivity and oil accumulation across the evaluated genotypes.Hierarchical cluster analysis resolved the germplasm into two principal clusters with high within-group similarity,each further partitioned into relatively homogeneous subgroups.Notably,several genotypes outperformed the control variety Ichraq,underscoring their potential for autumn or early winter cultivation.Nonetheless,essential multi-environment trials remain to validate their phenotypic stability and to ascertain their value as genetic resources for sunflower breeding programs in Morocco and other Mediterranean agro-ecosystems.展开更多
Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progres...Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progression from H.pylori gastritis cancer via precancerous stages[2].Current antibiotic-based treatment regimens are facing increasingly severe challenges of drug resistance[3].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
While degenerative diseases of the central nervous system are commonly linked to age-related macular degeneration and glaucoma,they have also been infrequently associated with retinitis pigmentosa,a condition defined ...While degenerative diseases of the central nervous system are commonly linked to age-related macular degeneration and glaucoma,they have also been infrequently associated with retinitis pigmentosa,a condition defined by retinal degeneration that can be caused by an isoform of receptor expression enhancing protein 6(REEP6)expressed in rod photoreceptors.In this study,we used REEP6 knockout mice(REEP6^(-/-))and wild-type mice(REEP6^(+/+))to examine neurodegenerative pathology within the visual pathways and neural activity in the primary visual cortex(V1)at three specific time points(1,6,and 10 months)during retinitis pigmentosa progression.Microglial activation was observed in both the retina and the primary visual cortex starting at 1 month of age,but no such activation was detected in the lateral geniculate nucleus at any time point.Not only was increased microglial activation observed at 6 and 10 months within the primary visual cortex of REEP6^(-/-)mice,but also coinciding with elevated levels of phosphorylated Tau expression.At 6 and 10 months of age,primary visual cortex neurons in REEP6^(-/-)mice exhibited reduced responses to grating stimuli and increased spontaneous activity compared with neurons in the primary visual cortex of mice in the control group.Our findings show that retinitis pigmentosa induces neurodegenerative pathology within the visual pathway of mice,particularly in the primary visual cortex,suggesting that ocular disease contributes substantially to central nervous system degeneration.It may provide new clues for the selection of treatment opportunities and the development of therapeutic measures for the subsequent treatment of retinitis pigmentosa or even other retinal degenerative diseases.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Climate change is one of the most pressing global challenges and spares no nation.Bhutan,as the only carbon negative country in the world,is no exception and being in the Himalayas–a region warming faster than the global average–further intensifies climate risks.This study explores how Bhutan navigates climate change through the perspectives of 41 policy influencers,including politicians,civil servants,and leaders from nongovernment organisations and the media.The findings are compared with scientific literature from the broader Himalayan region to identify shared vulnerabilities(e.g.,glacial lake outburst floods,water scarcity,and agricultural disruptions)and governance challenges(e.g.,financial constraints,geopolitical pressures,and gaps in policy implementation).The study reveals that Bhutan,like its Himalayan neighbours,prioritizes adaptation over mitigation due to immediate climate threats,despite its carbonnegative status.However,Bhutan faces unique pressures in upholding its dual commitments—maintaining 60%forest cover and carbon neutrality—amid competing development needs.While its Gross National Happiness(GNH)framework provides a holistic governance model,the analysis uncovers systemic barriers,including limited financing,transboundary climate risks,and uneven policy execution,which mirror regional struggles.The paper contributes to climate governance discourse by highlighting the risks of symbolic environmental pledges without robust implementation mechanisms,particularly for vulnerable mountain nations.It calls for integrated policies that bridge mitigation and adaptation,stronger regional cooperation,and equitable climate financing.The findings are relevant for policymakers in the Himalayas and international stakeholders advocating context-specific,justiceoriented climate strategies.
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.
文摘This study evaluates the stabilizing effect of lignin, extracted from Eucalyptus globulus, on an energetic composite of nitrated cellulose carbamate (NCC) plasticized with diethylene glycol dinitrate (DEGDN), compared to conventional stabilizers 2-nitrodiphenylamine (2-NDPA) and 1,3-dimethyl-1,3-diphenylurea (C-II). FTIR analysis confirms lignin's capacity to scavenge nitroxyl radicals formed during thermolysis of nitrocarbamate and nitrate ester bonds, thereby inhibiting decomposition. Moreover, the incorporation of C-II, 2-NDPA, and lignin significantly raised the peak temperature of the main thermolysis, as confirmed by DSC and TGA, indicating a progressive stability enhancement in the order: NCC/DEGDN < NCC/DEGDN/C-II < NCC/DEGDN/lignin < NCC/DEGDN/2-NDPA. Additionally, the effect of each stabilizer on the decomposition pathway was characterized by TGA-FTIR. The findings show that stabilizer type significantly affects the intensity of gaseous products released during decomposition without altering their nature. Notably, NH2 groups formed during NCC degradation play a key role in nitrogen conversion, particularly by reducing toxic NO emissions.
基金the STI2030-Major Projects,Nos.2021ZD0203500(to FW),2021ZD0202100(to XL)the National Natural Science Foundation of China,Nos.32222033(to FW),32330041(to LM)and 82021002(to LM),32171041(to XL)and 32450102(to XL)CAMS Innovation Fund for Medical Sciences,No.2021-I2M-5-009(to LM and XL).
文摘The overgeneralization of fear is associated with psychiatric disorders and cognitive decline.Recent studies have shown that engram cells in the dorsal dentate gyrus are integrated into functionally heterogeneous ensembles that are involved in contextual fear memory generalization and discrimination.However,the intracellular signals that promote fear generalization remain to be fully elucidated.In this study,we labeled and manipulated the c-Fos+and Npas4+ensembles in the dorsal dentate gyrus that are activated by contextual fear conditioning using a robust activity marking system.The results showed that increasing the excitability of Fos-dependent robust activity marking by overexpressing NaChBac or decreasing the excitability of Npas4-dependent robust activity marking by overexpressing Kir2.1 promoted fear memory generalization.Furthermore,CRISPR-mediated downregulation of the autophagy-related Atg5 or Atg7 genes in dorsal dentate gyrus neurons inhibited activation of c-Fos,but not Npas4.Knockdown of Atg5 or Atg7 in the Fos-dependent robust activity marking or Npas4-dependent robust activity marking ensemble led to an increase in neuronal excitability and a decrease in spine density in both ensembles.However,Atg7 knockdown in the Fos-dependent robust activity marking ensemble promoted memory generalization,while knockdown of Atg5 or Atg7 in the Npas4-dependent robust activity marking ensemble increased anxiety levels.These results contribute to our understanding of how the varying plasticity of memory engrams is involved in regulating fear memory generalization and anxiety.
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the Scientific Research Projects Unit of Erciyes University under contract no:FDS-2022-11532 and FOA-2025-14773.
文摘This paper examines a model that combines vortex generators and leading-edge tubercles for controlling the laminar separation bubble(LSB)over an airfoil at low Reynolds numbers(Re).This new concept of passive flow control technique utilizing a tubercle and vortex generator(VG)close to the leading edge was analyzed numerically for a NACA0015 airfoil.In this study,the Shear Stress Transport(SST)turbulence model was employed in the numerical modelling.Numerical modelling was completed using the ANSYS-Fluent 18.2 solver.Analyses were conducted to investigate the flow pattern and understand the underlying LSB control phenomena that enabled the new passive flow control method to provide this significant performance benefit.The findings indicated that the new concept of passive flow control technique suppressed the formation of an LSB at the suction surface of the NACA0015 airfoil,resulting in a higher lift coefficient and improved aerodynamic performance.Improvements in LSB dynamics and aerodynamic performance through the passive flow control method lead to increased energy output and enhanced stability.
文摘Dementia and Alzheimer's disease (AD) are both age-related conditions that predominantly affect older adults.According to prevalence studies,the burden of these diseases on society is expected to increase in the coming years,particularly in relation to rising longevity and life expectancy.Advances in therapeutic and preventive strategies are needed to help reduce their global burden,which remains among the most significant health challenges in aging populations (Brookmeyer et al.,2007).
文摘Despite Morocco's reliance on sunflower as an oilseed crop,little is known about its agronomic performance when sown in autumn or early winter.This knowledge gap is critical,as spring-sown varieties have shown declining performance in recent years under intensifying climate stress.Therefore,targeted breeding strategies could discover genotypes suitable for autumn or early winter sowing,with cold tolerance as a key selection criterion.Currently,‘Ichraq'is the only autumn-planted sunflower variety officially registered in Morocco,although efforts to release additional tolerant varieties are underway.This study evaluated 31 genotypes(MGB1to MGB31)selected from various environments under autumn planting conditions and conserved in the Moroccan Gene Bank.These genotypes were planted in early winter at a mountainous site known for its pronounced winter cold.Eighteen Morphological,physiological and agronomic parameters including initial vigor,leaf area,seed yield,oil content etc.,were assessed using both univariate and multivariate statistical approaches.Analysis of variance revealed significant genotypic differences across most traits,indicating substantial genetic variation.Notably,seed oil content ranged from 23.28%(MGB26)to 43.88%(MGB5),and seed yield from1400 kg/ha(MGB7)to 5400 kg/ha(MGB8).Principal component analysis(PCA)identified that the first principal component,accounting for over 24%of the total phenotypic variance,exhibits a strong positive loading of yield-related traits and chlorophyll content,while displaying a pronounced negative loading for oil content variables.This opposing gradient indicates a clear trade-off between vegetative productivity and oil accumulation across the evaluated genotypes.Hierarchical cluster analysis resolved the germplasm into two principal clusters with high within-group similarity,each further partitioned into relatively homogeneous subgroups.Notably,several genotypes outperformed the control variety Ichraq,underscoring their potential for autumn or early winter cultivation.Nonetheless,essential multi-environment trials remain to validate their phenotypic stability and to ascertain their value as genetic resources for sunflower breeding programs in Morocco and other Mediterranean agro-ecosystems.
基金supported by the National Natural Science Foundation of China(82573571,82470594)National Science and Technology Major Project(2025ZD0545300)+2 种基金Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)Key Project of Heilongjiang Provincial Joint Fund of Natural Science Foundation(ZL2025H017)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13).
文摘Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progression from H.pylori gastritis cancer via precancerous stages[2].Current antibiotic-based treatment regimens are facing increasingly severe challenges of drug resistance[3].
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 STI 2030-Major Projects,No.2022ZD0208503(to DY)the Fund of Chinese Academy of Science(“Xi Bu Zhi Guang”Project)(to YY)the Sichuan Science and Technology Program,No.2023YFS0312(to YY).
文摘While degenerative diseases of the central nervous system are commonly linked to age-related macular degeneration and glaucoma,they have also been infrequently associated with retinitis pigmentosa,a condition defined by retinal degeneration that can be caused by an isoform of receptor expression enhancing protein 6(REEP6)expressed in rod photoreceptors.In this study,we used REEP6 knockout mice(REEP6^(-/-))and wild-type mice(REEP6^(+/+))to examine neurodegenerative pathology within the visual pathways and neural activity in the primary visual cortex(V1)at three specific time points(1,6,and 10 months)during retinitis pigmentosa progression.Microglial activation was observed in both the retina and the primary visual cortex starting at 1 month of age,but no such activation was detected in the lateral geniculate nucleus at any time point.Not only was increased microglial activation observed at 6 and 10 months within the primary visual cortex of REEP6^(-/-)mice,but also coinciding with elevated levels of phosphorylated Tau expression.At 6 and 10 months of age,primary visual cortex neurons in REEP6^(-/-)mice exhibited reduced responses to grating stimuli and increased spontaneous activity compared with neurons in the primary visual cortex of mice in the control group.Our findings show that retinitis pigmentosa induces neurodegenerative pathology within the visual pathway of mice,particularly in the primary visual cortex,suggesting that ocular disease contributes substantially to central nervous system degeneration.It may provide new clues for the selection of treatment opportunities and the development of therapeutic measures for the subsequent treatment of retinitis pigmentosa or even other retinal degenerative diseases.
