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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology
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作者 Yiyang Qin Wenzhen Zhu +6 位作者 Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua Li Xiao-Jiang Li Su Yang 《Neural Regeneration Research》 SCIE CAS 2025年第9期2655-2666,共12页
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r... Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy. 展开更多
关键词 androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model NEURODEGENERATION neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor
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Functions of nuclear factor Y in nervous system development,function and health
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作者 Pedro Moreira Roger Pocock 《Neural Regeneration Research》 SCIE CAS 2025年第10期2887-2894,共8页
Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 y... Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently regeneration.However,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive.In this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression. 展开更多
关键词 axon guidance CCAAT boxes neuronal degeneration neuronal differentiation neuronal regeneration nuclear factor Y complex transcription factor transcriptional regulation
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Risk factors for congenital nasolacrimal duct obstruction in children under two years of age
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作者 Rozhin Kasiri Gholamreza Khataminia +2 位作者 Ali Kasiri Mohammad Sadegh Mirdehghan Mohammad Armin Kasiri 《国际眼科杂志》 CAS 2025年第1期17-23,共7页
·AIM:To identify various risk factors that may play a significant role in the development of congenital nasolacrimal duct obstruction(CNLDO).·METHODS:This observational case-control study included a case gro... ·AIM:To identify various risk factors that may play a significant role in the development of congenital nasolacrimal duct obstruction(CNLDO).·METHODS:This observational case-control study included a case group of 122 children less than two years of age with CNLDO who underwent probing and irrigation treatment at the ophthalmology department of Imam Khomeini Hospital in Ahvaz,Iran,from June 2022 to June2024.A control group of 122 age-matched children without CNLDO was also included for comparison.Data was collected from the children's medical records.·RESULTS:The study found a significant correlation between the occurrence of CNLDO and several maternal factors,such as preeclampsia,the use of levothyroxine,hypothyroidism,having more than three pregnancies(gravidity>3),natural pregnancy,and gestational diabetes mellitus.Additionally,in children,factors,such as oxygen therapy,anemia,reflux,jaundice,and a family history of CNLDO in first-degree relatives were associated with CNLDO,and maternal preeclampsia and hypothyroidism were found to significantly increase the risk of developing CNLDO in children.·CONCLUSION:Given that CNLDO affects both premature and full-term children,the present findings may potentially facilitate the early identification of children and infants at risk of nasolacrimal duct obstruction,thereby preventing the onset of chronic dacryocystitis. 展开更多
关键词 risk factors CONGENITAL nasolacrimal DUCT OBSTRUCTION CHILDREN
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The effects of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents:a meta-analysis
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作者 Xueyun Shao Longfei He Yangyang Liu 《Neural Regeneration Research》 SCIE CAS 2025年第5期1513-1520,共8页
Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase bra... Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408). 展开更多
关键词 adolescents brain-derived neurotrophic factor CHILDREN EXERCISE META-ANALYSIS randomized controlled trials
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Association between autoimmune gastritis and gastric polyps:Clinical characteristics and risk factors
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作者 Jing-Zheng Jin Xiao Liang +4 位作者 Shu-Peng Liu Rui-Lan Wang Qing-Wei Zhang Yu-Feng Shen Xiao-Bo Li 《World Journal of Gastrointestinal Oncology》 SCIE 2025年第1期73-87,共15页
BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double c... BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double center retrospective study included 530 patients diagnosed with AIG from July 2019 to July 2023.We collected clinical,biochemical,serological,and demographic data were of each patient.Logistic regression analyses,both multivariate and univariate,were conducted to pinpoint independent risk factors for GPs in patients with AIG patients.Receiver operating characteristic curves were utilized to establish the optimal cutoff values,sensitivity,and specificity of these risk factors for predicting GPs in patients with AIG.RESULTS Patients with GPs had a higher median age than those without GPs[61(52.25-69)years vs 58(47-66)years,P=0.006].The gastrin-17 levels were significantly elevated in patients with GPs compared with those without GPs[91.9(34.2-138.9)pmol/mL vs 60.9(12.6-98.4)pmol/mL,P<0.001].Additionally,the positive rate of parietal cell antibody(PCA)antibody was higher in these patients than in those without GPs(88.6%vs 73.6%,P<0.001).Multivariate and univariate analyses revealed that PCA positivity[odds ratio(OR)=2.003,P=0.017],pepsinogen II(OR=1.053,P=0.015),and enterochromaffin like cells hyperplasia(OR=3.116,P<0.001)were significant risk factors for GPs,while pepsinogen I was identified as a protective factor.CONCLUSION PCA positivity and enterochromaffin like cells hyperplasia are significant risk factor for the development of GPs in patients with AIG.Elevated gastrin-17 levels may also play a role in this process.These findings suggest potential targets for further research and therapeutic intervention in managing GPs in patients with AIG. 展开更多
关键词 Autoimmune gastritis Gastric polyps Neuroendocrine tumor Risk factors NOMOGRAM
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Social function scores and influencing factors in patients with residual depressive symptoms
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作者 Zong-Ling Liao Xiao-Li Pu +1 位作者 Zhi-Yi Zheng Jie Luo 《World Journal of Psychiatry》 SCIE 2025年第1期117-127,共11页
BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affectin... BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety. 展开更多
关键词 DEPRESSIVE Residual symptoms Social function Influence factors
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Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia
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作者 Danielle Fernezelian Philippe Rondeau +1 位作者 Laura Gence Nicolas Diotel 《Neural Regeneration Research》 SCIE CAS 2025年第10期2938-2954,共17页
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact... After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury. 展开更多
关键词 ANGIOGENESIS cerebral damage inflammation NEUROGENESIS stab wound TELENCEPHALON vascular endothelial growth factor ZEBRAFISH
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Brain-derived neurotrophic factor alterations and cognitive decline in schizophrenia:Implications for early intervention
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作者 Uchenna E Okpete Haewon Byeon 《World Journal of Psychiatry》 SCIE 2025年第1期189-193,共5页
This manuscript explores the recent study by Cui et al which assessed the interplay between inflammatory cytokines and brain-derived neurotrophic factor(BDNF)levels in first-episode schizophrenia patients.The study re... This manuscript explores the recent study by Cui et al which assessed the interplay between inflammatory cytokines and brain-derived neurotrophic factor(BDNF)levels in first-episode schizophrenia patients.The study revealed that higher levels of interleukin-6 and tumor necrosis factor-αcorrelated with reduced BDNF levels and poorer cognitive performance.Schizophrenia is a severe psy-chiatric disorder impacting approximately 1%of the global population,charac-terized by positive symptoms(hallucinations and delusions),negative symptoms(diminished motivation and cognitive impairments)and disorganized thoughts and behaviors.Emerging research highlights the role of BDNF as a potential biomarker for early diagnosis and therapeutic targeting.The findings from Cui et al’s study suggest that targeting neuroinflammation and enhancing BDNF levels may improve cognitive outcomes.Effective treatment approaches involve a com-bination of pharmacological and non-pharmacological interventions tailored to individual patient needs.Hence,monitoring cognitive and neuroinflammatory markers is essential for improving patient outcomes and quality of life.Conse-quently,this manuscript highlights the need for an integrated approach to schizo-phrenia management,considering both clinical symptoms and underlying neuro-biological changes. 展开更多
关键词 SCHIZOPHRENIA Cognitive impairment Neuroinflammatory markers Brain-derived neurotrophic factor INTERLEUKIN Personalized treatment
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Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats
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作者 Ping Zhang Ying Zhu +7 位作者 Pu Chen Tong Zhou Zhe-Yi Han Jun Xiao Jian-Feng Ma Wen Ma Peng Zang Ying Chen 《World Journal of Gastroenterology》 SCIE CAS 2025年第1期93-109,共17页
BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p... BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats. 展开更多
关键词 Simulated microgravity RAT Intestinal flora Gastrointestinal motility Stem cell factor/c-kit signaling pathway
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Burden of mental disorders and risk factors in the Western Pacific region from 1990 to 2021
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作者 Ya-Xin Xu Xiao-Xuan Niu +8 位作者 Wen-Chang Jia Jing Wen Xue-Lin Cheng Yan Han Ming-Hui Peng Jing Zhou Yao Liu Sun-Fang Jiang Xiao-Pan Li 《World Journal of Psychiatry》 SCIE 2025年第1期93-105,共13页
BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD i... BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging challenges.METHODS We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to 2021.Statistical methods included age-standardisation and uncertainty analysis to address variations in population structure and data completeness.RESULTS Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age groups.Depressive and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum disorders.Australia,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the lowest.Additionally,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk factors.CONCLUSION This study highlights the significant burden of MD in the WPR,with variations by age,gender,and nation.The coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response. 展开更多
关键词 Mental disorders Western pacific region Global Burden of Disease Risk factors Disability-adjusted life years
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Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy
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作者 Samuel Abokyi Dennis Yan-yin Tse 《Neural Regeneration Research》 SCIE CAS 2025年第2期366-377,共12页
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu... Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects. 展开更多
关键词 age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma NEUROMODULATION PHAGOCYTOSIS photoreceptor outer segment degradation retinal aging transcription factor EB
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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination
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作者 Josep Tomàs Víctor Cilleros-Mañé +7 位作者 Laia Just-Borràs Marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal Marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza 《Neural Regeneration Research》 SCIE CAS 2025年第2期394-401,共8页
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el... During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases. 展开更多
关键词 acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB
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The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease
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作者 Shengyang Zhou Ting Li +8 位作者 Wei Zhang Jian Wu Hui Hong Wei Quan Xinyu Qiao Chun Cui Chenmeng Qiao Weijiang Zhao Yanqin Shen 《Neural Regeneration Research》 SCIE CAS 2025年第8期2361-2372,共12页
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report... Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease. 展开更多
关键词 cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease NEUROINFLAMMATION Parkinson’s disease RU521 STING type I interferon
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Epithelial-mesenchymal transition- activating transcription factors- multifunctional regulators in cancer 被引量:27
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作者 Minal Garg 《World Journal of Stem Cells》 SCIE CAS 2013年第4期188-195,共8页
The process of epithelial to mesenchymal transition(EMT), first noted during embryogenesis, has also been reported in tumor formation and leads to the development of metastatic growth. It is a naturally occurring proc... The process of epithelial to mesenchymal transition(EMT), first noted during embryogenesis, has also been reported in tumor formation and leads to the development of metastatic growth. It is a naturally occurring process that drives the transformation of adhesive,non-mobile epithelial like cells into mobile cells with a mesenchymal phenotype that have ability to migrate to distant anatomical sites. Activating complex network of embryonic signaling pathways, including Wnt, Notch,hedgehog and transforming growth factor-β pathways,lead to the upregulation of EMT activating transcription factors, crucial for normal tissue development and maintenance. However, deregulation of tightly regulated pathways affecting the process of EMT has been recently investigated in various human cancers. Given the critical role of EMT in metastatic tumor formation,better understanding of the mechanistic regulation provides new opportunities for the development of potential therapeutic targets of clinical importance. 展开更多
关键词 Epithelial-to-mesenchymal transition METASTATIC growth EMBRYONIC signaling pathways Transcription factors CANCER
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Intelligent Recognition Using Ultralight Multifunctional Nano‑Layered Carbon Aerogel Sensors with Human‑Like Tactile Perception 被引量:4
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作者 Huiqi Zhao Yizheng Zhang +8 位作者 Lei Han Weiqi Qian Jiabin Wang Heting Wu Jingchen Li Yuan Dai Zhengyou Zhang Chris RBowen Ya Yang 《Nano-Micro Letters》 SCIE EI CAS CSCD 2024年第1期172-186,共15页
Humans can perceive our complex world through multi-sensory fusion.Under limited visual conditions,people can sense a variety of tactile signals to identify objects accurately and rapidly.However,replicating this uniq... Humans can perceive our complex world through multi-sensory fusion.Under limited visual conditions,people can sense a variety of tactile signals to identify objects accurately and rapidly.However,replicating this unique capability in robots remains a significant challenge.Here,we present a new form of ultralight multifunctional tactile nano-layered carbon aerogel sensor that provides pressure,temperature,material recognition and 3D location capabilities,which is combined with multimodal supervised learning algorithms for object recognition.The sensor exhibits human-like pressure(0.04–100 kPa)and temperature(21.5–66.2℃)detection,millisecond response times(11 ms),a pressure sensitivity of 92.22 kPa^(−1)and triboelectric durability of over 6000 cycles.The devised algorithm has universality and can accommodate a range of application scenarios.The tactile system can identify common foods in a kitchen scene with 94.63%accuracy and explore the topographic and geomorphic features of a Mars scene with 100%accuracy.This sensing approach empowers robots with versatile tactile perception to advance future society toward heightened sensing,recognition and intelligence. 展开更多
关键词 multifunctional sensor Tactile perception Multimodal machine learning algorithms Universal tactile system Intelligent object recognition
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Highly Aligned Graphene Aerogels for Multifunctional Composites 被引量:1
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作者 Ying Wu Chao An +4 位作者 Yaru Guo Yangyang Zong Naisheng Jiang Qingbin Zheng Zhong‑Zhen Yu 《Nano-Micro Letters》 SCIE EI CAS CSCD 2024年第6期276-342,共67页
Stemming from the unique in-plane honeycomb lattice structure and the sp^(2)hybridized carbon atoms bonded by exceptionally strong carbon–carbon bonds,graphene exhibits remarkable anisotropic electrical,mechanical,an... Stemming from the unique in-plane honeycomb lattice structure and the sp^(2)hybridized carbon atoms bonded by exceptionally strong carbon–carbon bonds,graphene exhibits remarkable anisotropic electrical,mechanical,and thermal properties.To maximize the utilization of graphene’s in-plane properties,pre-constructed and aligned structures,such as oriented aerogels,films,and fibers,have been designed.The unique combination of aligned structure,high surface area,excellent electrical conductivity,mechanical stability,thermal conductivity,and porous nature of highly aligned graphene aerogels allows for tailored and enhanced performance in specific directions,enabling advancements in diverse fields.This review provides a comprehensive overview of recent advances in highly aligned graphene aerogels and their composites.It highlights the fabrication methods of aligned graphene aerogels and the optimization of alignment which can be estimated both qualitatively and quantitatively.The oriented scaffolds endow graphene aerogels and their composites with anisotropic properties,showing enhanced electrical,mechanical,and thermal properties along the alignment at the sacrifice of the perpendicular direction.This review showcases remarkable properties and applications of aligned graphene aerogels and their composites,such as their suitability for electronics,environmental applications,thermal management,and energy storage.Challenges and potential opportunities are proposed to offer new insights into prospects of this material. 展开更多
关键词 Highly aligned graphene aerogels Quantitative characterization of alignment multifunctional composites Anisotropic properties multifunctional applications
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Enhancing multifunctional photocatalysis with acetate-assisted cesium doping and unlocking the potential of Z-scheme solar water splitting 被引量:1
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作者 Mengmeng Ma Jingzhen Li +6 位作者 Xiaogang Zhu Kong Liu Kaige Huang Guodong Yuan Shizhong Yue Zhijie Wang Shengchun Qu 《Carbon Energy》 SCIE EI CAS CSCD 2024年第3期178-195,共18页
Graphitic carbon nitride(g-C_(3)N_(4))has been extensively doped with alkali metals to enlarge photocatalytic output,in which cesium(Cs)doping is predicted to be the most efficient.Nevertheless,the sluggish diffusion ... Graphitic carbon nitride(g-C_(3)N_(4))has been extensively doped with alkali metals to enlarge photocatalytic output,in which cesium(Cs)doping is predicted to be the most efficient.Nevertheless,the sluggish diffusion and doping kinetics of precursors with high melting points,along with imprecise regulation,have raised the debate on whether Cs doping could make sense.For this matter,we attempt to confirm the positive effects of Cs doping on multifunctional photocatalysis by first using cesium acetate with the character of easy manipulation.The optimized Csdoped g-C_(3)N_(4)(CCN)shows a 41.6-fold increase in visible-light-driven hydrogen evolution reaction(HER)compared to pure g-C_(3)N_(4) and impressive degradation capability,especially with 77%refractory tetracycline and almost 100%rhodamine B degradedwithin an hour.The penetration ofCs+is demonstrated to be a mode of interlayer doping,and Cs–N bonds(especially with sp^(2) pyridine N in C═N–C),along with robust chemical interaction and electron exchange,are fabricated.This atomic configuration triggers the broadened spectral response,the improved charge migration,and the activated photocatalytic capacity.Furthermore,we evaluate the CCN/cadmium sulfide hybrid as a Z-scheme configuration,promoting the visible HER yield to 9.02 mmol g^(−1) h^(−1),which is the highest ever reported among all CCN systems.This work adds to the rapidly expanding field of manipulation strategies and supports further development of mediating served for photocatalysis. 展开更多
关键词 acetate-assisted cesium doping multifunctionAL PHOTOCATALYSIS Z-scheme
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Spatial variability and driving factors of soil multifunctionality in drylands of China 被引量:1
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作者 ZHANG Shihang CHEN Yusen +5 位作者 LU Yongxing GUO Hao GUO Xing LIU Chaohong ZHOU Xiaobing ZHANG Yuanming 《Regional Sustainability》 2022年第3期223-232,共10页
Drylands are highly vulnerable to climate change and human activities.The drylands of China account for approximately 10.8%of global drylands,and China is the country most severely affected by aridity in Asia.Therefor... Drylands are highly vulnerable to climate change and human activities.The drylands of China account for approximately 10.8%of global drylands,and China is the country most severely affected by aridity in Asia.Therefore,studying the spatial variation characteristics in soil multifunctionality(SMF)and investigating the driving factors are critical for elucidating and managing the functions of dryland ecosystems in China.Based on the environmental factors(mean annual precipitation(MAP),mean annual temperature(MAT),solar radiation(Srad),soil acidity(pH),enhanced vegetation index(EVI),and cation exchange capacity(CEC))and aridity from the“dataset of soil properties for land surface modeling over China”,we used non-linear regression,ordinary least square(OLS)regression,structural equation model(SEM),and other analytical methods to investigate the relationships of SMF with environmental factors across different aridity levels in China.SMF in different dryland regions varied significantly and showed a patchy distribution,with SMF index values ranging from–1.21 to 2.42.Regions with SMF index values from–0.20 to 0.51 accounting for 63.0%of dryland area in China.OLS regression results revealed that environmental factors like MAP,MAT,Srad,pH,EVI,and CEC were significantly related to SMF(P<0.05).MAP and MAT were correlated to SMF at the whole aridity level(P<0.05).SEM results showed that the driving factors of SMF differed depending on the aridity level.Soil pH was the strongest driving factor of SMF when the aridity was less than 0.80(P<0.001).Both soil CEC and EVI had a positive effect on SMF when aridity was greater than 0.80(P<0.01),with soil CEC being the strongest driving factor.The importance ranking revealed that the relative importance contribution of soil pH to SMF was greatest when aridity was less than 0.80(66.9%).When aridity was set to greater than 0.80,the relative importance contributions of CEC and EVI to SMF increased(45.1%and 31.9%,respectively).Our findings indicated that SMF had high spatial heterogeneity in drylands of China.The aridity threshold controlled the impact of environmental factors on SMF. 展开更多
关键词 DRYLANDS Soil multifunctionality (SMF) Aridity Index(AI) Spatial variability Driving factors Aridity level
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Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning 被引量:10
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作者 Ling Wang Deng-Yan Long 《World Journal of Clinical Cases》 SCIE 2024年第7期1235-1242,共8页
BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective pr... BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration. 展开更多
关键词 Intensive care unit-acquired weakness Risk factors Machine learning PREVENTION Strategies
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The roles of macrophage migration inhibitory factor in retinal diseases 被引量:2
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作者 Hongbing Zhang Xianjiao Zhang +3 位作者 Hongsong Li Bing Wang Pei Chen Jiamin Meng 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期309-315,共7页
Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF i... Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma. 展开更多
关键词 diabetic retinopathy GLAUCOMA macrophage migration inhibitory factor migration inhibitory factor receptor optic neuropathy retinal degeneration retinal neovascular uveal melanoma UVEITIS
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