检索结果-南通市图书馆

Infection with SARS-CoV-2 can cause pancreatic impairment

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

signal transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China international Co-operation laboratory on signal transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State Key laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients.Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans.Minor and limited phenotypic and histopathological changes were observed in adult models.Systemic proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio levels.Furthermore,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic dysfunction.In contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

A bHLH transcription factor,CsSPT,regulates high-temperature resistance in cucumber

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Horticultural Plant Journal 2024年第2期10卷 503-514页

作者： Yonggui Liang Chenyu Yang Fangyan Ming Bingwei Yu Zhihua Cheng Yixi Wang Zhengkun Qiu Xiaolan Zhang Bihao Cao Shuangshuang Yan Key laboratory of Biology and Genetic Improvement of Horticultural Crops(South China) Ministry of Agriculture and Rural AffairsGuangdong Vegetable Engineering and Technology Research CenterCollege of HorticultureSouth China Agricultural UniversityGuangzhouGuangdong 510642China State Key Laboratories of Agrobiotechnology Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable CropsMOE Joint Laboratory for International Cooperation in Crop Molecular BreedingChina Agricultural UniversityBeijing 100193China

High-temperature stress threatens the growth and yield of crops. Basic helix-loop-helix(bHLH) transcription factors(TFs) have been shown to play important roles in regulating high-temperature resistance in plants. However, the bHLH TFs responsible for high-temperature tolerance in cucumbers have not been identified. We used transcriptome profiling to screen the high temperature-responsive candidate bHLH TFs in cucumber. Here, we found that the expression of 75 CsbHLH genes was altered under high-temperature stress. The expression of the CsSPT gene was induced by high temperatures in TT(Thermotolerant) cucumber plants. However, the Csspt mutant plants obtained by the CRISPR-Cas9 system showed severe thermosensitive symptoms, including wilted leaves with brown margins and reduced root density and cell activity.The Csspt mutant plants also exhibited elevated H_(2)O_(2) levels and down-regulated photosystem-related genes under normal conditions.Furthermore, there were high relative electrolytic leakage(REC), malondialdehyde(MDA), glutathione(GSH), and superoxide radical(O_(2)^(·-)) levels in the Csspt mutant plants, with decreased Proline content after the high-temperature treatment. Transcriptome analysis showed that the photosystem and chloroplast activities in Csspt mutant plants were extremely disrupted by the high-temperature stress compared with wildtype(WT) plants. Moreover, the plant hormone signal transduction, as well as MAPK and calcium signaling pathways were activated in Csspt mutant plants under high-temperature stress. The HSF and HSP family genes shared the same upregulated expression patterns in Csspt and WT plants under high-temperature conditions. However, most bHLH, NAC, and bZIP family genes were significantly down-regulated by heat in Csspt mutant plants. Thus, these results demonstrated that CsSPT regulated the high-temperature response by recruiting photosynthesis components, signaling pathway molecules, and transcription factors. Our results provide important insights into the heat response m

关键词： Cucumber bHLH CsSPT Photosynthesis High temperature

Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第2期19卷 434-439页

作者： Chenxi Zhao Tiangang Zhou Ming Li Jie Liu Xiaoqing Zhao Yilin Pang Xinjie Liu Jiawei Zhang Lei Ma Wenxiang Li Xue Yao Shiqing Feng Department of Orthopedics Tianjin Medical University General HospitalTianjinChina international Science and Technology cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Orthopedic Research Center of Shandong University Cheeloo College of MedicineDepartment of OrthopedicsQilu Hospital of Shandong UniversityJinanShandong ProvinceChina

Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.

关键词： argatroban astrogliosis JAK/STAT signaling pathway protease-activated receptor-1 spinal cord injury thrombin vimentin

Gut liver brain axis in diseases:the implications for therapeutic interventions

在线全文

学校读者我要写书评

暂无评论

signal transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State Key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin Key laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous systems.In the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment strategies.In this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain axis.Some therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain axis.Besides,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)analogs.Targeting gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related therapies.Targeting liver-brain axis contains epigenetic regulation and Aβmetabolism-related therapies.In the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2024年第4期35卷 292-297页

作者： Yi Cao Xiaojiao Ge Yuanyuan Wei Lulu He Aiguo Wu Juan Li Ningbo Key laboratory of Biomedical Imaging Probe Materials and Technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of Sciences Beijing 100049China Advanced Energy Science and Technology Guangdong laboratory Huizhou 516000China

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

关键词： Neuropeptide-drug conjugate Tumor penetration Calcium deposition Tumor inhibition Triple-negative breast cancer

BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/ Stat3 pathway in mesenchymal stem cells

在线全文

学校读者我要写书评

暂无评论

Genes & Diseases 2024年第3期11卷 468-483页

作者： Jie Zhang Jinhai Jiang Hang Liu Shiyu Wang Kaixin Ke Siyuan Liu Yue Jiang Lu Liu Xiang Gao Baicheng He Yuxi Su Department of Pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Key laboratory of Biochemistry and Molecular Pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China Department of Orthopedics Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China orthopedics Department Children's Hospital of Chongqing Medical UniversityChongqing 400014China China international Science and Technology cooperation Base of Child Development and Critical Disorders Jiangxi Hospital Affiliated Children's Hospital of Chongqing Medical UniversityJiangxi 330000China National Clinical Research Center for Child Health and Disorders China

Bone defects and non-union are prevalent in clinical orthopedy,and the outcomes of current treatments are often suboptimal.Bone tissue engineering offers a promising approach to treating these conditions effectively.Bone morphogenetic protein 9(BMP9)can commit mesenchymal stem cells to osteogenic lineage,and a knowledge of the underlying mechanisms may help advance the field of bone tissue engineering.Leucine-rich repeats con-taining G protein-coupled receptor 4(LGR4),a member of G protein-coupled receptors,is essential for modulating bone development.This study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying mechanisms.Bone marrow stromal cells from BMp9-knockout mice exhibited diminished LGR4 expression,and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal cells.Furthermore,LGR4 expression was increased by BMP9 in C3H10T1/2 cells.LGR4 augmented the benefits of BMP9-induced osteogenic markers and bone formation,whereas LGR4 inhibition restricted these effects.Meanwhile,the BMP9-induced li-pogenic markers were increased by LGR4 inhibition.The protein levels of Raptor and p-Stat3 were elevated by BMP9.Raptor knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by BMP9.LGR4 significantly reversed the blocking ef-fect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic markers.Raptor interacts with p-Stat3,and p-Stat3 activates the LGR4 promoter activity.In conclusion,LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells,and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词： BMP9 LGR4 mTORC1 Osteogenic differentiation Stat3

In situ photoelectric biosensing based on ultranarrowband near-infrared plasmonic hot electron photodetection

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Advanced Photonics 2024年第2期6卷 81-89页

作者： Xianghong Nan Wenduo Lai Jie Peng Haiquan Wang Bojun Chen Huifan He Zekang Mo Zikun Xia Ning Tan Zhong Liu Long Wen Dan Gao Qin Chen Jinan University College of Physics&Optoelectronic EngineeringInstitute of NanophotonicsGuangdong Provincial Key Laboratory of Nanophotonic ManipulationGuangzhouChina Tsinghua University Shenzhen International Graduate SchoolState Key Laboratory of Chemical OncogenomicsShenzhenChina Jinan University College of Life Science and TechnologyGuangzhouChina

Narrowband photodetection is an important measurement technique for material analysis and sensing,for example,nondispersive infrared sensing technique.Both photoactive material engineering and nanophotonic filtering schemes have been explored to realize wavelength-selective photodetection,while most devices have a responsive bandwidth larger than 2%of the operating wavelength,limiting sensing performance.Near-infrared photodetection with a bandwidth of less than 0.2%of the operating wavelength was demonstrated experimentally in Au/Si Schottky nanojunctions.A minimum linewidth of photoelectric response down to 2.6 nm was obtained at a wavelength of 1550 nm by carefully tailing the absorptive and radiative loss in the nanostructures.Multiple functions were achieved on chip with the corrugated Au film,including narrowband resonance,light harvesting for sensing and photodetection,and electrodes for hot electron emission.Benefiting from such a unity integration with in situ photoelectric conversion of the optical sensing signal and the ultranarrowband resonance,self-contained on-chip biosensing via simple intensity interrogation was demonstrated with a limit of detection down to 0.0047%in concentration for glucose solution and 150 ng∕m L for rabbit IgG.Promising potential of this technique is expected for the applications in on-site sensing,spectroscopy,spectral imaging,etc.

关键词： plasmonics hot electron sensor photodetector spectroscopy

Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

在线全文

学校读者我要写书评

暂无评论

signal transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its function.However,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive.In this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent y-secretase.We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in mice.Finaly,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout mice.This data demonstrates that the a-secretase is essential for CNTNAP2 processing and its function.Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

signal transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang Jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang Yuanyu Huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical Research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key laboratory of Antiviral Drug Research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion