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Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Key Laboratory of Reproduction and Genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

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Thyroid-stimulating hormone-thyroid hormone signaling contributes to circadian regulation through repressing clock2/npas2 in zebrafish

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Journal of Genetics and Genomics 2024年第1期51卷 61-74页

作者： Cheng Ji Yue Ou Wangjianfei Yu Jiaxin Lv Fanmiao Zhang Huashan Li Zeyun Gu Jiayuan Li Zhaomin Zhong Han Wang Center for Circadian Clocks Soochow UniversitySuzhouJiangsu 215123China School of Biology and Basic medical sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215123China

Thyroid-stimulating hormone(TSH)is important for the thyroid gland,development,growth,and *** in TSH production or the thyrotrope cells within the pituitary gland cause congenital hypothyroidism(CH),resulting in growth retardation and neurocognitive *** human TSH is known to display rhythmicity,the molecular mechanisms underlying the circadian regulation of TSH and the effects of TSH-thyroid hormone(TH)signaling on the circadian clock remain *** we show that TSH,thyroxine(T4),triiodothyronine(T3),and tshba display rhythmicity in both larval and adult zebrafish and tshba is regulated directly by the circadian clock via both E′-box and *** tshba^(−/−)mutants manifest congenital hypothyroidism,with the characteristics of low levels of T_(4)and T_(3)and growth *** or overexpression of tshba alters the rhythmicity of locomotor activities and expression of core circadian clock genes and hypothalamic-pituitary-thyroid(HPT)axis-related ***,TSH-TH signaling regulates clock2/npas2 via the thyroid response element(TRE)in its promoter,and transcriptome analysis reveals extensive functions of Tshba in ***,our results demonstrate that zebrafish tshba is a direct target of the circadian clock and in turn plays critical roles in circadian regulation along with other functions.

关键词： Thyroid-stimulating hormone subunitβa (tshba) Thyroid hormone Circadian rhythm TALEN Zebrafish

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Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1693-1710页

作者： Xiong Chen Jinfu Qian Shiqi Liang Jianchang Qian Wu Luo Yujuan Shi Hong Zhu Xiang Hu Gaojun Wu Xiaokun Li Guang Liang Department of Endocrinology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China Department of Wound Repair the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Department of Cardiology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China School of Pharmaceutical sciences Hangzhou Medical CollegeHangzhou 311399China

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs–NFκB signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.

关键词： Diabetic cardiomyopathy Protein tyrosine kinases FGFR1 Cardiomyocytes Inflammatory responses Toll-like receptor4 c-Src NFkB

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Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1

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Chinese Chemical Letters 2024年第5期35卷 201-206页

作者： Yulong Shi Fenbei Chen Mengyuan Wu Xin Zhang Runze Meng Kun Wang Yan Wang Yuheng Mei Qionglu Duan Yinghong Li Rongmei Gao Yuhuan Li Hongbin Deng Jiandong Jiang Yanxiang Wang Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacy Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJining 272000China

Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and *** them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of *** chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against ***,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane ***,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

关键词： Aloperine SARS-CoV-2 TMPRSS2 SR-B1 Synthesis

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HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

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Science Bulletin 2024年第2期69卷 173-178页

作者： Siyuan Jiang Xiaoqi Han Tihui Liu Ying He Zidong Zhao Tongfeng Liu Shuwen Cheng Jihang Zhang Liqiang Duan Yajuan Liu Tianyou Cheng Yong Liu Qinong Ye Shan Gao Zhongda Hospital Medical SchoolAdvanced Institute for Life and HealthSoutheast UniversityNanjing 20096China medical School of Guizhou university Guiyang 550025China Shanxi Academy of Advanced Research and Innovation Taiyuan 030032China Zhongda Hospital School of Life Sciences and TechnologyAdvanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Nanjing university medical School Nanjing 210046China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430072China Department of medical Molecular Biology Beijing Institute of BiotechnologyCollaborative Innovation Center for Cancer MedicineBeijing 100850China

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

关键词： endocytosis cargo uptake

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Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

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Animal Models and Experimental Medicine 2024年第3期7卷 195-207页

作者： Maryam Golmohammadi Seyed Arash Aghaei Meibodi Sulieman Ibraheem Shelash Al-Hawary Jitendra Gupta Ibrohim B.Sapaev Mazin A.A.Najm Marim Alwave Mozhgan Nazifi Mohammadreza Rahmani Mohammad Yasin Zamanian Gervason Moriasi School of Medicine Shahid Beheshti University of Medical SciencesTehranIran Department of Business Administration Business SchoolAl al-Bayt UniversityMafraqJordan Institute of Pharmaceutical Research GLA UniversityMathuraIndia Tashkent Institute of Irrigation and Agricultural Mechanization Engineers TashkentUzbekistan New Uzbekistan university TashkentUzbekistan Pharmaceutical Chemistry Department College of PharmacyAl-Ayen UniversityThi-QarIraq medical Technical College Al-Farahidi UniversityBaghdadIraq Department of Neurology Hamadan University of Medical SciencesHamadanIran Physiology-Pharmacology Research Center Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran Department of Physiology and Pharmacology School of MedicineRafsanjan University of Medical SciencesRafsanjanIran Neurophysiology Research Center Hamadan University of Medical SciencesHamadanIran Department of Pharmacology and Toxicology School of PharmacyHamadan University of Medical SciencesHamadanIran Department of medical Biochemistry School of MedicineCollege of Health SciencesMount Kenya UniversityThikaKenya

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and *** damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative *** the disease progresses,the loss of RGCs leads to vision ***,protecting RGCs from damage and promoting their survival are important goals in managing *** this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of *** present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the ***,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed *** was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling *** could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt ***,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

关键词： glaucoma ischemic-reperfusion injury oxidative stress resveratrol retinal ganglion cells

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C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus

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Virologica Sinica 2024年第2期39卷 277-289页

作者： Lei Yu Xinjin Liu Xiaoqin Wei Junrui Ren Xueyun Wang Shuwen Wu Ke Lan State Key Laboratory of Virology Medical Research InstituteCollege of Life SciencesWuhan UniversityWuhan430072China Frontier Science Center for Immunology and Metabolism Wuhan UniversityWuhan430072China Taikang Center for Life and medical sciences Wuhan UniversityWuhan430072China

Influenza A virus(IAV)binds sialic acid receptors on the cell surface to enter the host cells,which is the key step in initiating infection,transmission and *** the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity,and provide new targets for *** the present study,we reported a novel membrane protein,C1QTNF5,which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in *** found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein,and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus(1–103 aa).In addition,we further demonstrated that overexpression of C1QTNF5 promotes IAV entry,while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral ***,C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells,but promotes IAV to attach to these cells,suggesting that C1QTNF5 is an important attachment factor for *** work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.

关键词： C1QTNF5 Influenza A virus Viral entry Hemagglutinin Attachment factor

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Ocular myositis--a diagnostic dilemma

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1171-1172页

作者： Ishita Bajaj Jolly Rohatgi university College of medical sciences New Delhi 110095India

Dear Editor,Orbital myositis is a relatively rare entity but is the next most common cause of extra ocular muscle disease after thyroid associated orbitopathy(TAO)[1-2].It was first described by Gleason in 1903 as an orbital pseudotumour and then renamed in 1930[3].It usually affects young females than *** muscles differ from skeletal muscles by a smaller unit size and higher motor neuron discharge,higher blood flow and volume of mitochondria fractions that allow inflammatory cells to reach and circulate easier,causing inflammation[4].Clinical findings include moderate to severe orbital pain,painful diplopia increased with eye movement,exophthalmos,swollen eyelids,conjunctival hyperemia or chemosis *** enhanced magnetic resonance imaging(CEMRI)is the most sensitive modality which discloses enhancement or thickening of inflamed extraocular muscle.

关键词： ocular muscles inflammation

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Chain Extender-induced Hydrogen Bonding Organization Determines the Morphology and Properties of Thermoplastic Polycarbonate Polyurethane

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Chinese Journal of Polymer Science 2024年第1期42卷 87-96,I0009页

作者： Yi-Lang Qin Ping Zhu Chen-Xi Ouyang Xia Dong Fuwai Hospital Chinese Academyof Medical Sciences&Peking Union Medical College/National Center for Cardiovascular DiseasesBejing 100037China CASKey Laboratoryof Engineering Plastics CAS Research/Education Centerfor Excellence in Molecular SciencesInstitute ofChemistryChinese Academy of SciencesBeijing 100190China university of Chinese Academy of sciences Beijing 100049China

Thermoplastic polycarbonate polyurethanes(PCUs) are multiblock copolymers that have been applied for medical devices for long time. Aliphatic diols are common chain extenders(CE) involved in the composition of the hard segments of PCU. However, limited knowledge was discovered about how the chemical structure of CE affects the hydrogen bonding organization within PCUs and their mechanical *** investigate this problem, a group of PCUs were synthesized respectively by extending the polymer chain with 1,4-butanediol(BDO),aminoethanol(MEA), ethanediol(EO) as three kinds of chain extenders. Tiny differences in the CE chemical structure results in remarkable variations in phase separation, condensed morphologies, thermal and mechanical properties, which are characterized by Fourier transform infrared spectrometer, atomic force microscopy, small-angle X-ray scattering, differential scanning calorimetry, and tensile tests. The microstructural evolution during unilateral deformation and the different mechanism induced by the different CEs was probed and unveil by in situ wide-and small-angle X-ray diffraction. Symmetry of CE can improve the organization of the hydrogen bonding. The coherence strength of the urethane/urea group also plays a key role by comparing the two PCUs with ethanediol and aminoethanol.

关键词： Thermoplastic polycarbonate polyurethane Chain extender Hydrogen bonding Mechanical properties

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Nurses'attitude toward patients'safety climate during COVID-19 pandemic:a cross-sectional study

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Frontiers of Nursing 2024年第1期11卷 39-46页

作者： Asra Nassehi Kobra Ghorbanzadeh Somaye Moayedi Javad Jafari Parvin Mahmoodi Mojtaba Jafari Department of Nursing Bam University of Medical SciencesBamIran Department of Nursing Khalkhal University of Medical SciencesKhalkhalIran Community Nursing Research Center Department of NursingZahedan University of Medical SciencesZahedanIran Clinical Care Research Center Department of NursingNursing and Midwifery SchoolKurdistan University of Medical SciencesSanandajIran

Objective:Patient safety is a fundamental factor in improving the quality of care provided in ***,it is considered a significant parameter by all healthcare organizations around the *** present study was conducted to investigate the attitude of nurses toward the patient safety climate during the Coronavirus Disease 2019(COVID-19)pandemic in the southeast of ***:This is a cross-sectional descriptive *** all the nurses working in one of the hospitals in the southeast of Iran,171 nurses participated in the study through convenience sampling *** survey was conducted between June 1 and July 30,2020.A 2-part questionnaire including demographic information and an assessment of nurses'attitudes toward patients'safety climate was used for data collection in *** content validity of the scale is(0.77)and reliability was re-calculated and confirmed by the present study with Cronbach's alpha(α=0.9).Data were analyzed by SPSS 20(IBM Corporation,Armonk,New York,United States)using descriptive and analytical statistical ***:The mean score of safety climates was 3.2±5.20(out of 5 scores).The results showed that among all dimensions of the safety climate,only the education dimension was statistically significant between males and females(P<0.001).Also,there was a significant relationship between the overall average of the safety climate and its dimensions according to the people's position only in the dimension of supervisors'attitude(P<0.01)and burnout(P<0.01).Additionally,a significant correlation between the education level and the overall score of safety climate(P<0.01),as well as the supervisor's attitude dimension(P<0.01),was ***:The results showed that the safety climate was at a relatively favorable *** the impact of nurses'attitudes on the safety climate of patients,its improvement seems *** is recommended to design training courses and educate nurses in order to promote a p

关键词： COVID-19 Iran nurses patient safety climate

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