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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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Neural Regeneration research 2025年第9期20卷 2655-2666页

作者： Yiyang Qin Wenzhen Zhu Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua Li Xiao-Jiang Li Su Yang Guangdong Key Laboratory of Non-human Primate research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong–HongKong–Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

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 *** 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 *** aggregates alter protein-protein interactions and compromise transcriptional *** 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 *** n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor *** down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor *** 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.

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

Effect of mechanical degradation of laminated elastomeric bearings and shear keys upon seismic behaviors of small-to-medium-span highway bridges in transverse direction

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Earthquake Engineering and Engineering Vibration 2018年第1期17卷 205-220页

作者： Wu Gang Wang Kehai Zhang Panpan Lu Guanya School of Transportation Southeast University Nanjing 210096 China research institute of highway Ministry of Transport Beijing 100088 China

Laminated elastomeric bearings have been widely used for small-to-medium-span highway bridges in China, in which concrete shear keys are set transversely to prohibit large girder displacement. To evaluate bridge seismic responses more accurately, proper analytical models of bearings and shear keys should be developed. Based on a series of cyclic loading experiments and analyses, rational analytical models of laminated elastomeric bearings and shear keys, which can consider mechanical degradation, were developed. The effect of the mechanical degradation was investigated by examining the seismic response of a small-to-medium-span bridge in the transverse direction under a wide range of peak ground accelerations（PGA）. The damage mechanism for small-to-medium-span highway bridges was determined, which can explain the seismic damage investigation during earthquakes in recent years. The experimental results show that the mechanical properties of laminated elastomeric bearings will degrade due to friction sliding, but the degree of decrease is dependent upon the influencing parameters. It can be concluded that the mechanical degradation of laminated elastomeric bearings and shear keys play an important role in the seismic response of bridges. The degradation of mechanical properties of laminated elastomeric bearings and shear keys should be included to evaluate more precise bridge seismic performance.

关键词： bridge engineering mechanical degradation seismic response friction sliding shear keys

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical Neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

Model of desired speed based on vehicle dynamic

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Journal of Beijing institute of Technology 2012年第1期21卷 81-84页

作者：郭伟伟王武宏毛琰熊辉张巍汉 School of Mechanical and Vehicular Engineering Beijing Institute of Technology research institute of highway Ministry of Transport

The desired speed will help the drivers control their driver behavior that could directly influences the traffic safety. This paper presents a basic definition of a driver＇ s desired speed, and analyzes the effects of road geometer parameter, driver behavior and vehicle performance on the desired speed. By setting the familiar horizontal curve as the research environment, the generating process of the desired speed was described. Then, combined with the desired trajectory, the effect of driver＇ s identification of vehicle dynamic on the desired speed was highlighted. Based on the vehicle dynamic theory, a desired speed model that consisted of the desired trajectory, the driver＇s experience and vehicle parameter was established and numerically analyzed.

关键词： traffic safety driver desired speed horizontal curve

Endothelial dysfunction in the kidney transplant population:Current evidence and management strategies

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World Journal of Transplantation 2025年第1期15卷 24-43页

作者： Arun Prabhahar Akshey Batta Juniali Hatwal Vivek Kumar Raja Ramachandran Akash Batta Department of Telemedicine(Internal Medicine and Nephrology) Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Urology and Renal Transplant Neelam HospitalRajpura 140401PunjabIndia Department of Internal Medicine Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Nephrology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Cardiology Dayanand Medical College and HospitalLudhiana 141001PunjabIndia

The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and *** dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)*** kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the *** is also associated with a decline in estimated glomerular filtration *** kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV ***,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft *** in kidney transplant recipients is an underrecognized and poorly studied *** diseases are the leading cause of death among kidney transplant candidates with functioning *** contributes to the pathogenesis of many of the CV *** biomarkers and vasoreactivity tests are available to study endothelial *** an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.

关键词： Endothelial dysfunction Endothelium Cardiovascular disease Kidney transplantation Chronic kidney disease Nitric oxide Flow-mediated dilatation Nitro-glycerine-mediated dilatation Biomarkers

Controversies in fecal incontinence

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World Journal of Gastroenterology 2025年第3期31卷 113-119页

作者： Andreia Albuquerque Satish S C Rao School of Medicine and Biomedical Sciences Fernando Pessoa UniversityGondomar 4420-096PortoPortugal Precancerous Lesions and Early Cancer Management research Group RISE@CI-IPO(Health research Network) Portuguese Oncology Institute of PortoPorto 4200-072Portugal Division of Gastroenterology and Hepatology Department of Internal MedicineAugusta UniversityAugustaGA 30912United States

Fecal incontinence is a common condition that can significantly impact patients’quality of *** anal sphincter injury and anorectal surgeries are common *** ultrasound and anorectal manometry are important diagnostic tools for evaluating *** are various treatment options,including diet,lifestyle modifications,drugs,biofeedback therapy,tibial and sacral nerve neuromodulation therapy,and *** this editorial,we will discuss current controversies and novel approaches to fecal *** for asymptomatic anal sphincter defects after obstetric anal sphincter injury and in patients with inflammatory bowel disease is not generally recommended,but may be helpful in selected *** Garg incontinence score is a new score that includes the assessment of solid,liquid,flatus,mucous,stress and urge fecal *** tests such as translumbosacral anorectal magnetic stimulation and novel therapies such as translumbosacral neuromodulation therapy are promising diagnostic and treatment options,for both fecal incontinence and *** biofeedback therapy can overcome some limitations of the office-based *** muscle-derived cell implantation of the external anal sphincter has been further studied as a possible treatment *** neuromodulation may be useful in scleroderma,congenital fecal incontinence and inflammatory bowel disease but merits further study.

关键词： Fecal incontinence Endoanal ultrasound Anal sphincter defects Biofeedback Neuropathy Sacral neuromodulation

Effect of cholesterol metabolism on hepatolithiasis

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World Journal of Gastroenterology 2025年第1期31卷 157-162页

作者： Lin Zheng Zi-Yu Ye Jun-Ji Ma Department of Gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesNo.215 Heping West RoadShijiazhuang 050000Hebei ProvinceChina

Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after *** metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of ***,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after *** dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating *** article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.

关键词： Hepatolithiasis Cholesterol metabolism High-fat diet 3-hydroxy-3-methylglutaryl-coenzyme A reductase Interlobular bile duct

Record-breaking bifunctional oxygen electrocatalyst accomplished by a data-driven approach for zinc-air batteries

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Journal of Energy Chemistry 2025年第01期 144-145页

作者： Deviprasath Chinnadurai Zhi Wei Seh institute of Materials research and Engineering (IMRE) Agency for Science Technology and Research (A*STAR)

Rechargeable zinc-air batteries(ZABs) have recently drawn great attention in energy research due to their high theoretical capacity,low costs, and inherently safe nature [1–3]. However, the sluggish cathode reactions necessitate the development of bifunctional oxygen electrocatalysts with lower ΔE indicator values. The ΔE indicator is commonly employed to quantitatively evaluate the electrocatalytic activity of a bifunctional oxygen electrocatalyst,representing the overall overpotential from oxygen reduction reaction(ORR) to oxygen evolution reaction(OER).

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