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Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice

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Fundamental Research 2024年第4期4卷 820-828页

作者： Xiaqing ma Qi Qi Wenying wang Min Huang Haiyan wang Limin Luo xiaotao Xu Tifei yuan Haibo Shi wei jiang Tao Xu department of Anesthesiology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China department of Anesthesiology Suzhou Hospital of Anhui Medical UniversitySuzhou 234000China department of Anesthesiology Affliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai 200233China

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain *** presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some neural function and *** aim of this study was to explore the role of ANLS in the occurrence and maintenance of *** 7 days consecutive morphine injection,a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4(PDK4),phosphorylated pyruvate dehydrogenase(p-PDH)and accumulation of L-lactate was elevated in the spinal dorsal *** administration of inhibitors of PDK,lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal *** astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in *** this study,we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal *** this process,PDK-p-PDH-lactate axis serves a pivotal role,which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

关键词： Pyruvate dehydrogenase kinase 4 Phosphorylated pyruvate dehydrogenase Astrocyte-neuron lactate shuttle Opioid-induced hyperalgesia Lactate

development of a MWDC prototype of the CSR external-target experiment

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NUCLEAR SCIENCE AND TECHNIQUES 2024年第10期35卷 1-14页

作者： He, Zhou-Bo Qin, Zhi ma, Peng yang, He-Run wei, Xiang-Lun Lu, Chen-Gui Wen, Xiang-Jie Zhang, Xiu-Ling Chen, Tao Li, Zhi-Jie yang, yuan-Sheng Zhan, Mei-Qiang Liu, Can-Wen Li, Meng Qiu, Tian-Li Gong, Yi-wei Huang, Xin-Jie Yin, xiao-Hao He, Zhi-Xuan Zhang, Jun-wei Zou, Hai-Chuan Fu, Sheng-wei Guo, dong Yan, Jun-wei Cao, Zhe deng, Zhi Kong, Jie xiao, Zhi-Gang Hu, Rong-jiang Duan, Li-Min Chinese Acad Sci Inst Modern Phys Lanzhou 730000 Peoples R China Univ Chinese Acad Sci Sch Nucl Sci & Technol Beijing 100049 Peoples R China Tsinghua Univ Dept Phys Beijing 100084 Peoples R China Univ Sci & Technol China Hefei 230026 Peoples R China Sichuan Univ Inst Nucl Sci & Technol Key Lab Radiat Phys & Technol Minist Educ Chengdu 610064 Peoples R China Lanzhou Univ Sch Nucl Sci & Technol Lanzhou 730000 Peoples R China North China Univ Water Resources & Elect Power Zhengzhou 450000 Peoples R China

The cooling storage ring (CSR) external-target experiment (CEE) is a spectrometer used in construction to study the properties of nuclear matter in high-baryon density regions at the Heavy-Ion Research Facility in Lanzhou (HIRFL). This study presents the design, simulation, manufacturing, and testing of a half-size prototype of a multi-wire drift chamber (MWDC) for the CEE. First, the performance of the MWDC connected to homemade electronics was simulated. The results demonstrated that an energy resolution of 18.5% % for 5.9-keV X-rays and a position resolution of 194 mu m for protons can be achieved by the current design. Because the size of the largest MWDC reached 176 cm x 314 cm, a set of 98 cm x 98 cm prototypes was built using the new techniques. The positioning accuracy of the anode wires in this prototype is better than 20 mu m. After optimization, using commercially available electronics, the prototype can achieved an energy resolution of 19.7% % for a Fe-55 X-ray source. The CEE-MWDC detector and electronics were simultaneously tested. An energy resolution of 22% % was achieved for the Fe-55 source; the track residuals were approximately 330 mu m for the cosmic rays. The results demonstrate that the current design and techniques meet the requirements of the CEE-MWDC array.

关键词： CEE MWDC Garfield plus plus Fe-55 source Position resolution DRIFT CHAMBER HIRFL-CSR

Frontiers in high entropy alloys and high entropy functional materials

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Rare Metals 2024年第10期43卷 4639-4776页

作者： Wen-Tao Zhang Wen Huang Fu-Jie Yu Qi Zhao Xin-dong Zhu Tao Feng Yao jiang xiao-Ming Li Xue-Fei Miao He Zhu Si Lan Xue-Qian wang Bao-Long Shen Zhe Jia Feng-Qi Zhang wei wang Qi Liu yang Ren Xun-Li wang xiao-Ya Cui xiao-yang wang Ya-Nan Chen Bing-Bing Fan Meng-Ru Li Qi-Long Gao Jia-Ming Guo Zeng-Bao Jiao Zhi-Min Guo Yu-Ping Zhao Qian Yu Rui Huang Ling-Kun Zhang Yi-Ping Lu Xu-Bo Li Huai-Jun Lin Yan ma wei-Ming yang Zhi-Hua Shen Hai-Yan He Yong-Gang Sun Yong-jiang Huang de-Zhuang wang Qing-Feng Liu Fei-yang wang Hui Liu Hong-Hui Wu Li-Qiang wang yang Lu Nan wang Tian-Li wang wei-Bing Liao Yi-Han wang yuan Wu Yu-Zhen Yin Jie Pan Yi Zhang Qing wang Jian-yang Zhang Tao yang Yasir Sohail Jin-Yu Zhang Hua Ji Qiang Li wei-Di Liu Zhi-Gang Chen Xiong-Jun Liu Wen ma Liang mao Zhen-Duo Wu School of materials Science and Engineering Nanjing University of Science and Technology jiangsu Key Laboratory for Advanced Metallic materials School of Materials Science and Engineering Southeast University department of Physics City University of Hong Kong School of materials Science and Engineering Tianjin University School of Physics and Microelectronics Zhengzhou University department of Mechanical Engineering Research Institute for Advanced Manufacturing The Hong Kong Polytechnic University Center of Electron Microscopy and State Key Laboratory of Silicon materials School of Materials Science and Engineering Zhejiang University Key Laboratory of Solidification Control and Digital Preparation Technology (Liaoning Province) School of Materials Science and Engineering Dalian University of Technology Institute of Advanced Wear & Corrosion Resistance and Functional materials Jinan University School of Mechanics and Civil Engineering China University of Mining and Technology School of Physical Sciences Great Bay University School of materials Science andengineering Harbin Institute of Technology State Key Laboratory of materials-Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University Beijing Advanced Innovation Center for materials Genome Engineering Research Institute for Carbon Neutrality University of Science and Technology Beijing department of Mechanical Engineering The University of Hong Kong School of Computing Macquarie University Key Laboratory of Optoelectronic devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic Engineering Shenzhen University State Key Laboratory for Advanced Metals and materials University of Science and Technology Beijing State Key Laboratory of materials Processing and Die & Mould Technology School of Materials Science and Engineering Huazhong University of Science and Technology Institute of materials Shanghai University department of materials Science and Engineering C

Owing to their exceptional properties, high-entropy alloys(HEAs) and high-entropy materials have emerged as promising research areas and shown diverse applications. Here,the recent advances in the field are comprehensively reviewed,organized into five sections. The first section introduces the background of HEAs, covering their definition, significance,application prospects, basic properties, design principles, and microstructure. The subsequent section focuses on cutting-edge high-entropy structural materials, highlighting developments such as nanostructured alloys, grain boundary engineering,eutectic systems, cryogenic alloys, thin films, micro-nano-lattice structures, additive manufacturing, high entropy metallic glasses, nano-precipitate strengthened alloys, composition modulation, alloy fibers, and refractory systems. In the following section, the emphasis shifts to functional materials, exploring HEAs as catalysts, magneto-caloric materials, corrosion-resistant alloys, radiation-resistant alloys, hydrogen storage systems, and materials for biomedicine. Additionally, the review encompasses functional high-entropy materials outside the realm of alloys, including thermoelectric, quantum dots, nanooxide catalysts, energy storage materials, negative thermal expansion ceramics,and high-entropy wave absorption materials. The paper concludes with an outlook, discussing future directions and potential growth areas in the field. Through this comprehensive review,researchers, engineers, and scientists may gain valuable insights into the recent progress and opportunities for further exploration in the exciting domains of high-entropy alloys and functional materials.

关键词： Cutting-edge structural materials Cutting-edgefunctional materials High entropy alloys

A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang xiao-Li ma Xiang-Ling He wei-Hua Pan xiao-Hong Zhang Sha-Yi jiang Ju Gao Fu Li wei Yao Song Gu wei-Ling Zhang Qiang Zhao Shi-Hao Huang Yong-Jun Fang wei Liu Hui-Zhong Niu Chun-Mei wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen Huang Zhi-Yong Zhong Xi-Ge wang Zhong-Rong Li Liang-Chun yang Ye-Ming Wu Huan-Min wang Xin Sun xiao-Jun yuan department of Pediatric Hematology/Oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical Oncology department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China department of Hematology/Oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China department of Hematology/Oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China department of Hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China department of Hematology/Oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China department of Pediatric Surgery Children's Hospital of Fudan UniversityShanghai 201102China department of General Surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China department of Hematology/Oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China department of Hematology/Oncology Henan Children's HospitalZhengzhou 450018China department of Pediatric General Surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's Hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： wei Ya-ru HOU Yun-long YIN Yu-jie LI Zhen LIU Yi HAN Ning-xin wang Zi-xuan LIU Lu wang xiao-qi HAO yuan-jie ma Kun GU Jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese MedicineShijiazhuang050090China Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center Shijiazhuang050035China Hebei Institute of Integrated Traditional and Western Medicine Shijiazhuang050035China National Key Laboratory for Innovation and Transformation of Luobing Theory Shijiazhuang050035China department of Cardiology Hebei Yiling HospitalShijiazhuang050091China Graduate School Hebei Medical UniversityShijiazhuang050017China

Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in *** A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 *** to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)*** day after modeling,TXL and BNPL were administered by *** injection of LY-294002 was performed twice a week for 4 consecutive *** was used to measure cardiac function in *** staining was used to evaluate the degree of myocardial fibrosis in *** and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,*** protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-Sma),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western *** TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-Sma,thus inhibited the occurrence of EndMT(P0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of *** TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway

Stratigraphic framework and sedimentary evolution during the Cryogenian-Ediacaran transition in northeastern Sichuan Basin,South China

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Petroleum Science 2024年第2期21卷 823-835页

作者： Yi Zhang Hong-wei Kuang Yong-Qing Liu Qiang Shi dong-Ge wang Ke-Ning Qi Yu-Chong wang Da-wei Qiao xiao-Shuai Chen Li-Zhi Wu Meng Tian Long Chen Yi wei Liao-yuan Song Jian Li Zi-Gang Wu Yun-Qian Liu Xuan-Chun Liu An-Qing Chen Zhi-wei Liao Institute of Geology Chinese Academy of Geological SciencesBeijing100037China State Key Laboratory of Coal Mine Disaster Dynamics and Control School of Resources and Safety EngineeringChongqing UniversityChongqing400044China No.205 Geological Team Chongqing Bureau of Geology and Minerals ExplorationChongqing401121China Chongqing Institute of Geological Survey Chongqing401122China Key Laboratory of deep-time Geography and Environment Reconstruction and Applications of Ministry of Natural Resources Chengdu University of TechnologyChengdu610059SichuanChina

The northeastern Sichuan area in the northern yangtze margin has unique Ediacaran geological records,especially the Doushantuo Formation(DST),and become a hot research area in recent ***,the Cryogenian-Ediacaran(C-E)boundary has not been precisely identified,which restricts the in-depth study of geological information during this crucial transitional period and is unfavorable for a systematic and complete understanding of the yangtze Block and even the global paleogeographic *** study conducted stratigraphy,sedimentology,and chronostratigraphy to establish the stratigraphic framework and sedimentary evolution of the C-E transition strata in northeastern *** results showed that the Ediacaran sediments,without the cap dolomite,unconformably overlaid the Cryogenian sediments in the studied *** Member II of the DST,characterized by 50-160 m of red-green sandstone(approximately equivalent to the original Chengkou“Guanyinya Formation”),directly overlaid the Cryogenian sediments and displayed a 623±2.3 ma maximum depositional age from the detrital zircon U-Pb *** stratigraphic correlations indicate that the C-E transition strata in northeastern Sichuan had a consistent lithological association and sedimentary sequence characteristics but differed from the Three ***,the upper Nantuo massive glacial diamictites transition to the icebergs rafted lonestone-bearing mudstones at the top,then change upward to DST barrier coast *** proposed DST of the northeastern Sichuan Basin was divided into three lithostratigraphic members without the regional Member I cap dolomite:(i)Member II purple-red,gray-green sandstone strata,(ii)MemberⅢblack mudstone strata,and(iii)Member IV P-Mn bearing *** the C-E transition,the study area experienced(i)the global deglaciation stage in the terminal marinoan glaciation and(ii)the filling-leveling up stage with clastic rocks in the early ***,the early Ediacaran

关键词： marinoan glaciation Doushantuo formation Cap dolomite deglacial and coastal deposits detrital zircon U-Pb dating

Calculation of the energy dependence of fission fragments yields and kinetic energy distributions for neutron-induced ^(235)U fission

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Chinese Physics C 2024年第8期48卷 159-169页

作者： Ya-Ning Han Zheng wei Yi-Xuan wang dong-Ying Huo Peng-Qi Zhang Ming Li Jun ma Kang Wu Yong-Guang Zheng yuan He Zhi-Yong deng Tian-Zhi jiang Xiang-Lin Zhuo Jin Li Yun Zhang Yu Zhang Jun-Run wang xiao-dong Su Ze-En Yao School of Nuclear Science and Technology Lanzhou UniversityLanzhou 730000China Engineering Research Center for Neutron Application Technology Ministry of EducationLanzhou UniversityLanzhou 730000China MOE Frontiers Science Center for Rare Isotopes Lanzhou UniversityLanzhou 730000China School of mathematics and Statistics Lanzhou UniversityLanzhou 730000China Nuclear Power Institute of China Chengdu 610000China

Fission fragments yields and average total kinetic energy are fundamental nuclear data for nuclear energy applications and the study of nuclear *** fission products,such as ^(95)Zr,^(99)Mo,^(140)Ba,^(144)Ce,and ^(147)Nd,serve as burnup monitors,assessing the number of fissions induced by neutrons on ^(235)***,current experimental data for these fission products worldwide are inconsistent,introducing significant uncertainty into related scientific *** this study,we employed the Potential-driving Model to calculate the independent yields of ^(235)U and evaluate its advantages in such ***,we investigated the energy dependence of independent yields to select important ***,we calculated the cumulative yields of ^(95)Zr,^(99)Mo,^(140)Ba,^(144)Ce,and ^(147)Nd,and compared them with existing literature data to explore the energy dependence of fission products for ^(235)*** the lack of fission product yield data above 14.8 MeV,we extended our calculated incident neutron energy to 20 MeV,aiming to support future scientific *** Geant4 physical model does not consider the influence of incident neutron energy on the average total kinetic energy of fission fragments;thus,we introduced the excitation function of the total kinetic energy of fission fragments recommended by madland et al.,which effectively describes the experimental data of the average total kinetic energy of fragments formed in ^(235)U *** this paper,we comprehensively discuss the energy dependence of fission product yields and average total kinetic energy.

关键词： ^(235)U(n f) potential-driving model fission yields kinetic energies energy dependence

Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

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Military Medical Research 2024年第1期11卷 50-79页

作者： Shuai Liu jiang-Ming Yu Yan-Chang Gan xiao-Zhong Qiu Zhe-Chen Gao Huan wang Shi-Xuan Chen yuan Xiong Guo-Hui Liu Si-En Lin Alec McCarthy Johnson V.John Dai-Xu wei Hong-Hao Hou Guangdong Provincial Key Laboratory of Construction and detection in Tissue Engineering the Fifth Affiliated HospitalSchool of Basic Medical ScienceSouthern Medical UniversityGuangzhou 510900China department of Orthopedics Tongren HospitalShanghai Jiao Tong UniversityShanghai 200336China The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033GuangdongChina Engineering Research Center of Clinical Functional materials and Diagnosis&Treatment devices of Zhejiang Province Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325011ZhejiangChina department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China department of Orthopaedics and Traumatology Faculty of Medicinethe Chinese University of Hong KongHong Kong SAR 999077China department of Functional materials Terasaki Institute for Biomedical InnovationLos AngelesCA 90064USA mary&Dick Holland Regenerative Medicine Program College of MedicineUniversity of Nebraska Medical CenterOmahaNE 68130USA Zigong Affiliated Hospital of Southwest Medical University Zigong Psychiatric Research CenterZigong Institute of Brain ScienceZigong 643002SichuanChina Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineDepartment of Life Sciences and MedicineNorthwest UniversityXi’an 710127China

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative *** contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative *** paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future *** highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ***,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE ***,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

关键词： Biomimic Scaffold Biosynthesis Natural biomaterial Tissue engineering

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor

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Science China(Life Sciences) 2024年第7期67卷 1502-1513页

作者： Luo-yuan Xia Xue-Feng wang xiao-Ming Cui Yi-Ming Zhang Zhen-Fei wang En-Tao Li Chang-Fa Fan Ke Song yuan-Guo Li Run-Ze Ye Fang-Xu Li Dai-Yun Zhu Jie Zhang Zhuang-Zhuang Shi Ming-Zhu Zhang Liang-Jing Li Shi-Jing Shen Song Jin Ya-wei Zhang wei-Guang Fu Lin Zhao Wen-Hao wang Tie-Cheng wang You-Chun wang Jia-Fu jiang Yan-Ling Hu Na Jia Yu-wei Gao Wu-Chun Cao Institute of EcoHealth School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China Changchun Veterinary Research Institute Changchun 130122China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijing 102629China National Institutes for Food and Drug Control Beijing 102629China Life Sciences Institute Guangxi Medical UniversityNanning 530020China College of Life Sciences Shandong Normal UniversityJinan 250014China Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical SciencesBeijing 100071China

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to *** we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a malayan pangolin(manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial *** replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 *** intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar *** population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V *** findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

关键词： pangolin SARS-CoV-2-related virus infectivity pathogenicity human cell lines human ACE2 receptor hACE2-transgenic mice