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Circadian disturbance induces erectile dysfunction by impairing endothelial function

Asian Journal of Andrology 2024年第2期26卷 205-211页

作者： tao Li Yi-Ting jiang Xin-Zhu Qi Peng Chen Jun-Hao Zhang Fu Luo Jun Qiao jiang Gu Guang-shi Du Qiang Wang Department of Urology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Urology Guizhou Provincial People's HospitalGuiyang 550002China Department of Otorhinolaryngology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Guizhou Institute for Food and Drug Control Guiyang 550004China Department of Reproductive Center Guizhou Provincial People's HospitalGuiyang 550002China Translational Medicine Research Center of Guizhou Medical University Guiyang 550025China

In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.***.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 a.***.and on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for analysis.The maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control group.The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein levels.The production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying degrees.Circadian disturbance impaired endothelial function and contributed to erectile dysfunction.For the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly changed.DD,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 levels.No significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly changed.Moreover,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein levels.The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function.Meanwhile,the core circadian elements were detected in the corpora cavernosa,but these were disrupted.However,which circadian element regulates erectile function and how it works need further analysis.

关键词： circadian disturbance endothelial function erectile function light/dark cycle NO/cGMP

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Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

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Neuroscience Bulletin 2024年第2期40卷 182-200页

作者： Yang Zhu Hao Huang Zhi Chen Yong tao Ling-Yi Liao shi-Hao Gao Yan-jiang Wang Chang-Yue Gao Department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqing 400042China Department of Neurology and Center for Clinical Neuroscience Daping HospitalArmy Medical UniversityChongqing 400042China Department of Special Medicine Daping HospitalArmy Medical UniversityChongqing 400042China

Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

关键词： Intermittent theta burst stimulation Alzheimer’s disease Iron-sulfur cluster assembly 1 Mitochondrial dysfunction Neurodegeneration

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Resilient performance of self-centering hybrid rocking walls with curved interface under pseudo-static loading

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Earthquake Engineering and Engineering Vibration 2024年第1期23卷 65-85页

作者： Su Xing Yan shi Sun Xianglei Wang tao School of Civil Engineering Shenyang Jianzhu UniversityShenyang 110168China PetroChina East China Design Institute Co. Ltd.Qingdao 266000China Qingdao Country Garden Bolin Real Estate Co. Ltd.Qingdao 266100China

Frame and rocking wall(FRW)structures have excellent resilient performance during earthquakes.However,the concrete at interfacial corners of rocking walls(RWs)is easily crushed due to local extreme compression during the rocking process.An innovative RW with a curved interface is proposed to prevent interfacial corners from producing local damage,enhancing its earthquake resilient performance(ERP).The precast wall panel with a curved interface is assembled into an integral self-centering hybrid rocking wall(SCRW)by two post-tensioned unbonded prestressed tendons.Moreover,two ordinary energy dissipation steel rebars and two shear reinforcements are arranged to increase the energy dissipation capacity and lateral resistance.Two SCRW specimens and one monolithic reinforced concrete(RC)shear wall(SW)were tested under pseudo-static loading to compare the ERPs of the proposed SCRW and the SW,focusing on studying the effect of the curved interface on the SCRW.The key resilient performance of rocking effects,failure modes,and hysteretic properties of the SCRW were explored.The results show that nonlinear deformations of the SCRW are concentrated along the interface between the SCRW and the foundation,avoiding damage within the SCRW.The restoring force provided by the prestressed tendons can effectively realize self-centering capacity with small residual deformation,and the resilient performance of the SCRW is better than that of monolithic SW.In addition,the curved interface of the SCRW makes the rocking center change and move inward,partially relieving the stress concentration and crush of concrete.The rocking range of the rocking center is about 41.4%of the width of the SCRW.

关键词： self-centering hybrid rocking wall(SCRW) monolithic shear wall(SW) earthquake resilient performance(ERP) curved interface rocking center

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Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape

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Signal Transduction and Targeted Therapy 2024年第1期9卷 326-337页

作者： You Zhai Yicong Du Guanzhang Li Mingchen Yu Huimin Hu Changqing Pan Di Wang Zhongfang shi Xu Yan Xuesong Li tao jiang Wei Zhang Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingPR China Department of Urology Peking University First HospitalInstitute of UrologyPeking UniversityNational Urological Cancer CenterBeijingPR China Department of Pathophysiology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China China National Clinical Research Center for Neurological Diseases BeijingPR China Center of Brain Tumor Beijing Institute for Brain DisordersBeijingPR China Research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingPR China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingPR China

Chimeric antigen receptor(CAR)T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid tumors.Although instances of rapid tumor remissions have been observed in animal models and clinical trials,tumor relapses occur with multiple therapeutic resistance mechanisms.Furthermore,while the mechanisms underlying the long-term therapeutic resistance are well-known,short-term adaptation remains less understood.However,more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term resistance.In this study,we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells,a reversal of previously documented processes.This mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction,also leading to short-term antigen loss and antigen masking.Such type of intercellular communication is independent of CAR downstream signaling,CAR-T cell condition,target antigen,and tumor cell type.However,it is mainly dependent on antigen density and CAR sensitivity,and is associated with tumor cell cholesterol metabolism.Partial mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR sensitivities.Together,our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

关键词： Together instance depletion

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Intelligent 3D garment system of the human body based on deep spiking neural network

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虚拟现实与智能硬件（中英文） 2024年第1期6卷 43-55页

作者： Minghua jiang Zhangyuan TIAN Chenyu YU Yankang shi Li LIU tao PENG Xinrong HU Feng YU School of Computer and Artificial Intelligence Wuhan Textile UniversityWuhan 430200China Engineering Research Center of Hubei Province for Clothing Information Wuhan 430200China

Background Intelligent garments,a burgeoning class of wearable devices,have extensive applications in domains such as sports training and medical rehabilitation.Nonetheless,existing research in the smart wearables domain predominantly emphasizes sensor functionality and quantity,often skipping crucial aspects related to user experience and interaction.Methods To address this gap,this study introduces a novel real-time 3D interactive system based on intelligent garments.The system utilizes lightweight sensor modules to collect human motion data and introduces a dual-stream fusion network based on pulsed neural units to classify and recognize human movements,thereby achieving real-time interaction between users and sensors.Additionally,the system incorporates 3D human visualization functionality,which visualizes sensor data and recognizes human actions as 3D models in real time,providing accurate and comprehensive visual feedback to help users better understand and analyze the details and features of human motion.This system has significant potential for applications in motion detection,medical monitoring,virtual reality,and other fields.The accurate classification of human actions contributes to the development of personalized training plans and injury prevention strategies.Conclusions This study has substantial implications in the domains of intelligent garments,human motion monitoring,and digital twin visualization.The advancement of this system is expected to propel the progress of wearable technology and foster a deeper comprehension of human motion.

关键词： Intelligent garment system Internet of things Human action recognition Deep learning 3D visualization

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