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Design and prototyping of the readout electronics for the transition radiation detector in the high energy cosmic radiation detection facility

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Nuclear Science and Techniques 2024年第4期35卷 189-199页

作者： Jie-Yu Zhu Yang-Zhou Su Hai-Bo Yang Fen-Hua Lu Yan Yang Xi-Wen Liu Ping wei Shu-Cai Wan Hao-Qing xie xian-Qin Li Cong Dai Hui-Jun Hu Hong-Bang Liu Shu-Wen Tang Cheng-Xin zhao Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China

The high energy cosmic-radiation detection(HERD)facility is planned to launch in 2027 and scheduled to be installed on the China Space *** serves as a dark matter particle detector,a cosmic ray instrument,and an observatory for high-energy gamma rays.A transition radiation detector placed on one of its lateral sides serves dual purpose,(ⅰ)calibrating HERD's electromagnetic calorimeter in the TeV energy range,and(ⅱ)serving as an independent detector for high-energy gamma *** this paper,the prototype readout electronics design of the transition radiation detector is demonstrated,which aims to accurately measure the charge of the anodes using the SAMPA application specific integrated circuit *** electronic performance of the prototype system is evaluated in terms of noise,linearity,and *** the presented design,each electronic channel can achieve a dynamic range of 0–100 fC,the RMS noise level not exceeding 0.15 fC,and the integral nonlinearity was<0.2%.To further verify the readout electronic performance,a joint test with the detector was carried out,and the results show that the prototype system can satisfy the requirements of the detector's scientific goals.

关键词： HERD Dark matter particle detection TRD Readout electronics SAMPA Data acquisition Performance test

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1651-1664页

作者： Xiong xie Qiaoshuai Lan Jinyi zhao Sulin Zhang Lu Liu Yumin Zhang wei Xu Maolin Shao Jingjing Peng Shuai Xia Yan Zhu Keke Zhang xianglei Zhang Ruxue Zhang jian Li Wenhao Dai Zhen Ge Shulei Hu Changyue Yu Jiang Wang Dakota Ma Mingyue Zheng Haitao Yang Gengfu Xiao Zihe Rao Lu Lu Leike Zhang Fang Bai Yao zhao Shibo Jiang Hong Liu Drug Discovery and Design Center State Key Laboratory of Drug ResearchCAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China School of Chinese Materia Medica Nanjing University of Chinese Medicine138 Xian Lin RoadJiangsu 210023 NanjingChina School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China National Clinical Research Center for Infectious Disease Shenzhen Third People's HospitalShenzhen 518112China

Respiratory disease caused by coronavirus infection remains a global health *** several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be ***-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging *** L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune ***,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and *** X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of *** showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various *** mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral ***,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in *** addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse *** 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute *** together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with anti

关键词： calpain overcome entrance

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy:A Multicenter Double-Blind Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第3期30卷 195-202页

作者： HUANG Hao-yue LIN Yu-ping wei Hua FU Yu ZHOU Yue-hong FANG zhao-hui QIU Xiao-tang WANG Mei LI Qing-bo LI Shan-shan WANG Shi-dong DAI Fang LIU Zhen-jie zhao Ling WEN Jian-xuan WU Li-yan ZENG Hui-yan ZHANG Jin-ming LU Qi-yun HE Liu SONG wei SUN Lu LUO Lu-lu HE Jia-li xie Wen-wen LIANG Qing-shun HUANG Yuan ZHU Sheng-ling LONG Jie-er GAO Zhi-juan WEN Ze-huai LI Chun-ji OUYANG Wen-wei LI Geng WU Ming-hui LI An-xiang HUANG Jin-zhu Sanjoy K Paul TANG xian-yu FAN Guan-jie Department of Endocrinology Guangdong Provincial Hospital of Chinese MedicineGuangzhou510120China The Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou510120China Department of Endocrinology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China Guangdong Provincial Academy of Chinese Medical Sciences Guangzhou510120China Department of Endocrinology The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Department of Endocrinology Liuyang Hospital of Chinese MedicineChangsha410000China Department of Endocrinology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230000China Department of Endocrinology Hainan Provincial Hospital of Traditional Chinese MedicineHaikou570100China Department of Endocrinology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang110000China Department of Geriatric Luoyang No.1 Hospital of Traditional Chinese MedicineLuoyangHenan Province471000China Department of Endocrinology The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Department of Endocrinology Beijing University of Chinese Medicine Affiliated Dongzhimen HospitalBeijing100000China Department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Melbourne EpiCentre The University of Melbourne and Melbourne HealthMelbourne3013Australia

Objective:To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction(TW)in treating patients with diabetic peripheral neuropathy(DPN).Methods:It is a multicenter double-blinded randomized controlled *** with DPN were recruited between November 18,2016 and May 30,2018 from 8 hospitals in *** patients received basic treatments for glycemic *** received foot baths with TW herbal granules either 66.9 g(intervention group)or 6.69 g(control group)for 30 min once a day for 2 weeks and followed by a 2-week rest,as a therapeutic *** the Toronto Clinical Scoring System total score(TCSS-TS)6 points,the patients received a total of 3 therapeutic courses(for 12 weeks)and were followed up for 12 *** primary outcome was change in TCSS-TS score at 12 and 24 *** outcomes included changes in bilateral motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of the median and common peroneal *** was also ***:Totally 632 patients were enrolled,and 317 and 315 were randomized to the intervention and control groups,*** the 12-week intervention,patients in both groups showed significant declines in TCSSTS scores,and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment(P0.05),and no serious adverse event was related with ***:Treatment of TW foot baths was safe and significantly benefitted patients with DPN.A low dose of TW appeared to be more effective than a high dose.(Registry *** CTR-IOR-16009331)

关键词： diabetic peripheral neuropathy herbal medicine foot baths Chinese medicine randomized controlled trial Tangbi Waixi Decoction

Two stages power generation test of the hot dry rock exploration and production demonstration project in the Gonghe Basin,northeastern Qinghai-Tibet plateau,China

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China Geology 2024年第3期7卷 409-421页

作者： Er-yong Zhang Dong-guang Wen Gui-ling Wang xian-peng Jin Lin-you Zhang Hai-dong Wu Wen-shi Wang Cheng-ming Ye wei Weng Kuan Li Jin-sheng Wu xian-chun Tang Chong-yuan Zhang Qing-da Feng Sheng Lian Li-sha Hu Gui-lin Zhu Xing-long xie Bin Wu Dan Wang Xue Niu zhao-xuan Niu Dong-lin Liu Hui Zhang Wen-hao Xu Shu-qing Yao Li Yang Center for Hydrogeology and Environmental Geology Survey China Geological SurveyMinistry of Natural ResourcesTianjin 300304China Institute of Hydrogeology and Environmental Geology Chinese Academy of Geological SciencesChina Geological SurveyShijiazhuang 050061China Institute of Exploration Techniques Chinese Academy of Geological SciencesChina Geological SurveyLangfang 065000China Institute of Exploration Engineering China Geological SurveyMinistry of Natural ResourcesBeijing 100083China Institute of Exploration Technology Chinese Academy of Geological SciencesChengdu 611734China Chinese Academy of Geological Sciences China Geological SurveyBeijing 100037China Institute of Geomechanics Chinese Academy of Geological SciencesChina Geological SurveyBeijing 100081China Geoscience Documentation Center China Geological SurveyMinistry of Natural ResourcesBeijing 100083China

The Hot Dry Rock(HDR)is considered as a clean and renewable energy,poised to significantly contribute to the global energy decarbonization *** HDR projects worldwide have accumulated valuable experience in efficient drilling and completion,reservoir construction,and fracture *** 2019,China Geological Survey(CGS)initiated a demonstration project of HDR exploration and production in the Gonghe Basin,aiming to overcome the setbacks faced by HDR *** the ensuing four years,the Gonghe HDR project achieved the first power generation in 2021,followed by the second power generation test in *** establishing the primary well group in the initial phase,two directional wells and one branch well were *** progress was made in successfully constructing the targeted reservoir,realizing inter-well connectivity,power generation and grid connection,implementing of the real-time micro-seismic monitoring.A closed-loop technical validation of the HDR exploration and production was ***,many technical challenges remain in the process of HDR industrialization,such as reservoir fracture network characterization,efficient drilling and completion,multiple fracturing treatment,continuous injection and production,as well as mitigation of induced seismicity and numerical simulation technology.

关键词： Power generation Hot dry rock(HDR) Enhanced geothermal system(EGS) Genesis mechanism Gonghe Basin Directional drilling Reservoir construction Circulation test Induced seismicity Clean energy exploration engineering

Study of the response of 10B-doped MCP to wide-energy range neutrons from eV to MeV

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Nuclear Science and Techniques 2024年第8期35卷 132-141页

作者： Qiang Li Li‑Jiao Wang xiang‑Biao Qiu Jing‑Wen Li wei Xu Tao Li Ze‑Bin Lin Chang‑Jun Ning Yong‑Hao Chen Rui‑Rui Fan Kang Sun Jing‑Yu Tang Rong Zhang Han‑Tao Jing Bo Mei Qi An Hao‑Fan Bai Jiang‑Bo Bai Jie Bao Ping Cao Qi‑Ping Chen Zhen Chen Zeng‑Qi Cui An‑Chuan Fan Chang‑Qing Feng Fan‑Zhen Feng Ke‑Qing Gao Min‑Hao Gu Chang‑Cai Han Zi‑Jie Han Guo‑Zhu He Yong‑Cheng He Yang Hong Yi‑wei Hu Han‑Xiong Huang wei‑Hua Jia Hao‑Yu Jiang wei Jiang Zhi‑Jie Jiang Zheng‑Yao Jin Ling Kang Bo Li Chao Li Gong Li Jia‑Wen Li Xiao Li Yang Li Jie Liu Rong Liu Shu‑Bin Liu Guang‑Yuan Luan Bin‑Bin Qi Jie Ren Zhi‑Zhou Ren Xi‑Chao Ruan zhao‑Hui Song Zhi‑Xin Tan Sheng‑Da Tang Peng‑Cheng Wang zhao‑Hui Wang Zhong‑wei Wen Xiao‑Guang Wu Xuan Wu Li‑Kun xie Yi‑wei Yang Han Yi Yong‑Ji Yu Guo‑Hui Zhang Lin‑Hao Zhang Mo‑Han Zhang Qi‑wei Zhang xian‑Peng Zhang Yu‑Liang Zhang Yue Zhang Zhi‑Yong Zhang Mao‑Yuan zhao Lu‑Ping Zhou Zhi‑Hao Zhou Ke‑Jun Zhu Institute of High Energy Physics Chinese Academy of Sciences(CAS)Beijing 100049China Spallation Neutron Source Science Center Dongguan 523803China State Key Laboratory of Particle Detection and Electronics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Dongguan Songshan Lake Future School Dongguan 523808China North Night Vision Science&Technology(Nanjing)Research Institute Co.Ltd. Nanjing 211106China Sino‑French Institute of Nuclear Engineering and Technology Sun Yat-sen UniversityZhuhai 519082China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China Institute of Nuclear Physics and Chemistry China Academy of Engineering PhysicsMianyang 621900China Key Laboratory of Nuclear Data China Institute of Atomic EnergyBeijing 102413China USTC Archaeometry Lab University of Science and Technology of ChinaHefei 230026China Northwest Institute of Nuclear Technology Xi’an 710024China University of Chinese Academy of Sciences Beijing 100049China

Neutron-sensitive microchannel plates(nMCPs)have applications in neutron detection,including energy spectrum measurements,neutron-induced cross sections,and neutron imaging.10B-doped MCPs(B-MCPs)have attracted significant attention owing to their potential for exhibiting a high neutron detection efficiency over a large neutron energy *** spatial and temporal resolutions are useful for neutron energy-resolved ***,their practical applications still face many technical *** this study,a B-MCP with 10 mol%10B was tested for its response to wide-energy neutrons from eV to MeV at the Back-n white neutron source at the China Spallation Neutron *** neutron detection efficiency was calibrated at 1 eV,which is approximately 300 times that of an ordinary MCP and indicates the success of 10 B *** factors that caused the reduction in the detection efficiency were simulated and *** neutron energy spectrum obtained using B-MCP was compared with that obtained by other measurement methods,and showed very good consistency for neutron energies below tens of *** response is more complicated at higher neutron energy,at which point the elastic and nonelastic reactions of all nuclides of B-MCP gradually become *** is beneficial for the detection of neutrons,as it compensates for the detection efficiency of B-MCP for high-energy neutrons.

关键词： Neutron radiation image 10B-doped MCP Neutron response Wide-energy range neutrons

Nondestructive technique for identifying nuclides using neutron resonance transmission analysis at CSNS Back-n

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Nuclear Science and Techniques 2024年第1期35卷 178-187页

作者： Sheng-Da Tang Yong-Hao Chen Jing-Yu Tang Rui-Rui Fan Qiang Li Gong Li Dong Liu Zheng-Yao Jin Xing-Zhu Cui Tian-xiang Chen Yi-wei Yang Rong Liu Han Yi Yang Li Zhen Yang Qi An Hao-Fan Bai Jiang-Bo Bai Jie Bao Ping Cao Qi-Ping Chen Zhen Chen Zeng-Qi Cui An-Chuan Fan Chang-Qing Feng Fan-Zhen Feng Ke-Qing Gao Min-Hao Gu Chang-Cai Han Zi-Jie Han Guo-Zhu He Yong-Cheng He Yang Hong Yi-wei Hu Han-Xiong Huang wei-Hua Jia Hao-yu Jiang wei Jiang Zhi-jie Jiang Ling Kang Bo Li Chao Li Jia-Wen Li Xiao Li Jie Liu Shu-Bin Liu Guang-Yuan Luan Chang-Jun Ning Bin-Bin Qi Jie Ren Zhi-Zhou Ren Xi-Chao Ruan zhao-Hui Song Kang Sun Zhi-Xin Tan Li-Jiao Wang Peng-Cheng Wang zhao-Hui Wang Zhong-wei Wen Xiao-Guang Wu Xuan Wu Li-Kun xie Yong-Ji Yu Guo-Hui Zhang Lin-Hao Zhang Mo-Han Zhang Qi-wei Zhang xian-Peng Zhang Yu-Liang Zhang Yue Zhang Zhi-Yong Zhang Mao-Yuan zhao Lu-Ping Zhou Zhi-Hao Zhou Ke-Jun Zhu Sino-French Institute of Nuclear Engineering and Technology Sun Yat-sen UniversityZhuhai 519082China Institute of High-Energy Physics Chinese Academy of Sciences(CAS)Beijing 100049China Spallation Neutron Source Science Center Dongguan 523803China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Particle Detection and Electronics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China USTC Archaeometry Laboratory University of Science and Technology of ChinaHefei 230026China Institute of Nuclear Physics and Chemistry China Academy of Engineering PhysicsMianyang 621900China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China Key Laboratory of Nuclear Data China Institute of Atomic EnergyBeijing 102413China Northwest Institute of Nuclear Technology Xi’an 710024China University of Chinese Academy of Sciences Beijing 100049China

Nondestructive and noninvasive neutron assays are essential applications of neutron *** resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental composition of an *** back-streaming neutron line(Back-n)is a newly built time-of-flight facility at the China Spallation Neutron Source(CSNS)that provides neutrons in the eV to 300 MeV range.A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test *** results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at *** study reveals its potential future applications.

关键词： CSNS White neutron beam NRTA Nuclide identification Nondestructive method

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成年期视皮层神经元数量减少降低突触连接

现代生物医学进展 2024年第18期24卷 3401-3406页

作者：蓝志达王兆龙谢先屿赵乐文方伟群上海交通大学基础医学院解剖学与生理学系

目的：探究成年期视皮层神经元数量减少对突触连接的改变，为解析创伤性脑损伤导致的视觉功能障碍提供实验依据。方法：采用立体定位技术，以腺相关病毒（Adeno-associated viruses, AAVs）稀疏感染方式于8周龄C57BL/6小鼠初级视皮层（P... 详细信息

目的：探究成年期视皮层神经元数量减少对突触连接的改变，为解析创伤性脑损伤导致的视觉功能障碍提供实验依据。方法：采用立体定位技术，以腺相关病毒（Adeno-associated viruses, AAVs）稀疏感染方式于8周龄C57BL/6小鼠初级视皮层（Primary visual cortex, V1）中表达白喉毒素A片段蛋白（Diphtheria toxin A, DTA），引发神经元凋亡。4周后，通过免疫荧光染色、高尔基染色及共聚焦显微镜成像，分析视皮层第2-4层神经元数量以及幸存锥体神经元的树突棘形态特征。结果：通过注射不同滴度（E+11-13）的DTA表达病毒，成功构建了不同水平（14～85%）的视皮层神经元减少小鼠模型。结果发现低滴度（E+11）DTA表达病毒导致中等程度神经元减少（～18%,P<0.01），模拟了轻度创伤性脑损伤患者的皮层神经元丢失水平（16.5～22.9%），并发现该小鼠锥体神经元的树突棘密度与对照组没有差异，而树突棘成熟比例减少～19%(P<0.0001)。结论：成年期视皮层神经元数量减少损害突触连接，可能导致大脑的视觉功能障碍。

关键词：视皮层神经元神经元数量树突棘

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China:A national multicenter survey of 35,566 individuals

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 113-120页

作者： Meng-Fan Liu Rui-Xia Ma xian-Bao Cao Hua Zhang Shui-Hong Zhou wei-Hong Jiang Yan Jiang Jing-Wu Sun Qin-Tai Yang Xue-Zhong Li Ya-Nan Sun Li Shi Min Wang Xi-Cheng Song Fu-Quan Chen Xiao-Shu Zhang Hong-Quan wei Shao-Qing Yu Dong-Dong Zhu Luo Ba Zhi-wei Cao Xu-Ping Xiao Xin wei Zhi-Hong Lin Feng-Hong Chen Chun-Guang Shan Guang-Ke Wang Jing Ye Shen-Hong Qu Chang-Qing zhao Zhen-Lin Wang Hua-Bin Li Feng Liu Xiao-Bo Cui Sheng-Nan Ye Zheng Liu Yu Xu Xiao Cai wei Huang Ru-Xin Zhang Yu-Lin zhao Guo-Dong Yu Guang-Gang Shi Mei-Ping Lu Yang Shen Yu-Tong zhao Jia-Hong Pei Shao-Bing xie Long-Gang Yu Ye-Hai Liu Shao-wei Gu Yu-Cheng Yang Lei Cheng Jian-Feng liu Graduate School of Beijing University of Chinese Medicine BeijingChina Department of Otorhinolaryngology Head and Neck Surgery China-Japan Friendship HospitalBeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First People's Hospital of YinchuanYinchuanChina Department of Otorhinolaryngology The First People's Hospital of Yunnan ProvinceKunmingChina Department of Otorhinolaryngology The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Otorhinolaryngology Head and Neck Surgery Xiangya Hospital Central South UniversityChangshaChina Department of Otorhinolaryngology Head and Neck Surgery The Affiliated Hospital of Qingdao UniversityQingdaoChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of USTCHefeiChina Department of Otorhinolaryngology Head and Neck Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Otorhinolaryngology Head and Neck Surgery Qilu Hospital of Shandong UniversityJinanChina Department of Otorhinolaryngology Head and Neck Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina Department of Otolaryngology The Second Hospital of Shandong UniversityShandong UniversityJinanChina Department of Otorhinolaryngology Head and Neck Surgery Peking University People's HospitalBeijingChina Department of Otorhinolaryngology Head and Neck Surgery Yantai Yuhuangding HospitalQingdao UniversityYantaiChina Department of Otorhinolaryngology Head and Neck Surgery Xijing HospitalThe Fourth Military Medical UniversityXi'anChina Gansu Provincial Center for Disease Control and Prevention LanzhouChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of China Medical UniversityShenyangChina Department of Otorhinolaryngology Head and Neck Surgery Tongji Hospit

Objective:This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in ***:This study was conducted by 45 tertiary Grade-A hospitals in *** and offline questionnaire data were obtained from patients infected with COVID-19 between December 28,2022,and February 21,*** collected information included basic demographics,medical history,smoking and drinking history,vaccination history,changes in olfactory and gustatory functions before and after infection,and other postinfection symptoms,as well as the duration and improvement status of olfactory and gustatory ***:Complete questionnaires were obtained from 35,566 *** overall incidence of olfactory and taste dysfunction was 67.75%.Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste *** received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such *** infection,the average olfactory and taste VAS scores were 8.41 and 8.51,respectively;after infection,they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the *** median duration of dysosmia and dysgeusia was 15 and 12 days,respectively,with 0.5%of patients having symptoms lasting for more than 28 *** overall self-reported improvement rate was 59.16%.Recovery was higher in males,never smokers,those who received two or three vaccine doses,and those that had never experienced dental health issues,or chronic accompanying ***:The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in *** and prognosis are influenced by several factors,including sex,SARS-CoV-2 vaccination,history of head-facial trauma,nasal and oral health status,smoking and drinking history,and the persistence of accompanying symptoms.

关键词： epidemiologic studies incidence olfactory disorders prognosis SARS-CoV-2 taste disorders

Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis

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Bioactive Materials 2022年第11期7卷 406-424页

作者： Jin Wang Si-an xie Ning Li Tao Zhang weijuan Yao Hucheng zhao wei Pang Lili Han Jiayu Liu Jing Zhou Department of Physiology and Pathophysiology School of Basic Medical SciencesHemorheology CenterSchool of Basic Medical SciencesPeking UniversityBeijingPR China Key Laboratory of Molecular Cardiovascular Science Ministry of EducationBeijingPR China National Health Commission Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors ResearchPeking UniversityBeijingPR China Department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityNational Clinical Research Center for Digestive DiseaseBeijing Digestive Disease CenterBeijing Key Laboratory for Precancerous Lesion of Digestive DiseaseBeijingPR China Center for Biomechanics and Bioengineering Key Laboratory of Microgravity(National Microgravity Laboratory)And Beijing Key Laboratory of Engineered Construction and MechanobiologyInstitute of MechanicsChinese Academy of SciencesBeijingPR China School of Engineering Sciences University of Chinese Academy of SciencesBeijingPR China Department of Vascular Surgery Peking University People’s HospitalBeijingPR China Institute of Biomechanics and Medical Engineering School of Aerospace EngineeringTsinghua UniversityBeijingPR China

Vascular smooth muscle cell (vSMC) is highly plastic as its phenotype can change in response to mechanical cues inherent to the extracellular matrix (ECM). VSMC may be activated from its quiescent contractile phenotype to a proinflammatory phenotype, whereby the cell secretes chemotactic and inflammatory cytokines, e.g. MCP1 and IL6, to functionally regulate monocyte and macrophage infiltration during the development of various vascular diseases including arteriosclerosis. Here, by culturing vSMCs on polyacrylamide (PA) substrates with variable elastic moduli, we discovered a role of discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that binds collagens, in mediating the mechanical regulation of vSMC gene expression, phenotype, and proinflammatory responses. We found that ECM stiffness induced DDR1 phosphorylation, oligomerization, and endocytosis to repress the expression of DNA methyltransferase 1 (DNMT1), very likely in a collagen-independent manner. The DDR1-to-DNMT1 signaling was sequentially mediated by the extracellular signal-regulated kinases (ERKs) and p53 pathways. ECM stiffness primed vSMC to a proinflammatory phenotype and this regulation was diminished by DDR1 inhibition. In agreement with the in vitro findings, increased DDR1 phosphorylation was observed in human arterial stiffening. DDR1 inhibition in mouse attenuated the acute injury or adenine diet-induced vascular stiffening and inflammation. Furthermore, mouse vasculature with SMC-specific deletion of Dnmt1 exhibited proinflammatory and stiffening phenotypes. Our study demonstrates a role of SMC DDR1 in perceiving the mechanical microenvironments and down-regulating expression of DNMT1 to result in vascular pathologies and has potential implications for optimization of engineering artificial vascular grafts and vascular networks.

关键词： Matrix stiffness Inflammation DDR1 DNMT1 Mechanotransduction