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Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance

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Chinese Journal of Natural medicines 2024年第4期22卷 341-355页

作者： WANG Hao GENG Xiaolong AI Fangbin YU Zhilun ZHANG Yan ZHANG Beibei LV Cheng GAO Ruiyang YUE Bei DOU Wei The MOE key laboratory of Standardization of Chinese medicines Shanghai Key Laboratory of Compound Chinese Medicinesand the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaSchool of Traditional Chinese Materia MedicaShanghai University of Traditional Chinese Medicine(SHUTCM)Shanghai 201203China

Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective ***,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains *** study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase ***,nuciferine significantly reduced the migration and invasion capabilities of MH7A *** therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory *** also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA *** results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

关键词： Rheumatoid arthritis Collagen-induced arthritis Fibroblast-like synoviocyte Immune imbalance Nuciferine

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New insights into developmental biology of Eimeria tenella revealed by comparative analysis of mRNA N6-methyladenosine modification between unsporulated oocysts and sporulated oocysts

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Journal of Integrative Agriculture 2024年第1期23卷 239-250页

作者： Qing Liu Bingjin Mu Yijing Meng Linmei Yu Zirui Wang Tao Jia Wenbin Zheng Wenwei Gao Shichen Xie Xingquan Zhu laboratory of Parasitic Diseases College of Veterinary MedicineShanxi Agricultural UniversityTaigu 030801China Research Center for Parasites&Vectors College of Veterinary MedicineHunan Agricultural UniversityChangsha 410128China

Evidence showed that N6-methyladenosine(m^(6)A)modification plays a pivotal role in influencing RNA fate and is strongly associated with cell growth and developmental processes in many ***,no information regarding m^(6)A modification in Eimeria tenella is currently *** the present study,we surveyed the transcriptome-wide prevalence of m^(6)A in sporulated oocysts and unsporulated oocysts of *** RNA immunoprecipitation sequencing(MeRIP-seq)analysis showed that m^(6)A modification was most abundant in the coding sequences,followed by stop *** were 3,903 hypermethylated and 3,178 hypomethylated mRNAs in sporulated oocysts compared with unsporulated *** joint analysis suggested that m^(6)A modification of the majority of genes was positively correlated with mRNA *** mRNA relative expression and m^(6)A level of the selected genes were confirmed by quantitative reverse transcription PCR(RT-qPCR)and *** and KEGG analysis indicated that differentially m^(6)A methylated genes(DMMGs)with significant differences in mRNA expression were closely related to processes such as regulation of gene expression,epigenetic,microtubule,autophagy-other and TOR ***,a total of 96 DMMGs without significant differences in mRNA expression showed significant differences at protein *** and pathway enrichment analysis of the 96 genes showed that RNA methylation may be involved in cell biosynthesis and metabolism of *** firstly present a map of RNA m^(6)A modification in ***,which provides significant insights into developmental biology of ***.

关键词： Eimeria tenella m^(6)A RNA methylation MeRIP-seq RNA-seq proteomic analysis

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Prenatal cadmium exposure impairs neural tube closure via inducing excessive apoptosis in neuroepithelium

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Journal of Environmental Sciences 2024年第4期138卷 572-584页

作者： Shiyong Zhu Xuenan Li Xueyan Dai Jinlong Li College of Veterinary medicine Northeast Agricultural UniversityHarbin 150030China key laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbin 150030China Heilongjiang key laboratory for laboratory Animals and Comparative medicine Northeast Agricultural UniversityHarbin 150030China

Birth defects have become a public health *** hazardous environmental factors exposure to embryos could increase the risk of birth ***,a toxic environmental factor,can cross the placental barrier during *** woman may be subjected to cadmium before taking precautionary protective ***,the link between birth defects and cadmium remains *** exposure can induce excessive apoptosis in neuroepithelium during embryonic development *** exposure activated the p53 via enhancing the adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK)and reactive oxygen species'(ROS)*** cadmium decreases the level of Paired box 3(Pax3)and murine double minute 2(Mdm2),disrupting the process of p53 *** p53 accumulation induced excessive apoptosis in neuroepithelium during embryonic development *** apoptosis led to the failure of neural tube *** study emphasizes that environmental materials may increase the health risk for *** caused the failure of neural tube closure during early embryotic *** women may be exposed by cadmium before taking precautionary protective actions,because of cadmium concentration-containing foods and environmental tobacco *** suggests that prenatal cadmium exposure is a threatening risk factor for birth defects.

关键词： Cadmium Neural tube closure Excessive apoptosis p53 Embryogenesis

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Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini

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Chinese Journal of Integrative medicine 2024年第4期30卷 366-378页

作者： ZUO Qian XU Ding-qiao YUE Shi-jun FU Rui-jia TANG Yu-ping key laboratory of Shaanxi Administration of Traditional Chinese medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi'an(712046)China

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor,with active ingredients of bufadienolides and indole *** further research and clinical applications,it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells,promoting apoptosis,inhibiting formation of tumor neovascularization,reversing multidrug resistance,and regulating immune response;it also has the functions of relieving cancer pain and regulating immune *** this paper,the chemical composition,pharmacological effects,clinical applications,and adverse reactions of cinobufacini are ***,the extraction of monomer components of cinobufacini,the relationship between different mechanisms,and the causes of adverse reactions need to be further ***,high-quality clinical studies should be conducted.

关键词： cinobufacini chemical composition Chinese medicine pharmacological effect clinical application adverse effect

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The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

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World Journal of Emergency medicine 2024年第2期15卷 98-104页

作者： Qifang Shi Gen Ba Zhenyu Xia Zhengsheng Mao Hao Sun Jinsong Zhang Institute of Poisoning Nanjing Medical UniversityNanjing 211100China Department of Emergency medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of forensic medicine Nanjing Medical UniversityNanjing 211166China The key laboratory of Modern Toxicology of Ministry of Education Nanjing Medical UniversityNanjing 211166China

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison *** aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis ***:This was a retrospective and descriptive study from an institute of *** registration information and test reports spanning the period from April 1,2020 to March 31,2022,were *** with uncertain exposure histories and who underwent toxicological analysis were *** manifestations and categories of toxics were ***:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

关键词： Acute poisoning Toxic exposure Toxicological analysis Clinical manifestation

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Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

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National Science Review 2024年第4期11卷 70-83页

作者： Huiying Zhao Jinrong Liu Yujin Shao Xiang Feng Binhan Zhao Li Sun Yijun Liu Linghui Zeng Xiao-ming Li Hongbin Yang Shumin Duan Yan-qin Yu Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain medicine Zhejiang University School of Medicine Nanhu Brain-Computer Interface Institute Liangzhu laboratory MOE Frontier Science Center for Brain Science and Brain-Machine Integration State Key Laboratory of Brain-Machine Intelligence Zhejiang University NHC and CAMS key laboratory of Medical Neurobiology Zhejiang University key laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of Medicine Hangzhou City University

The nucleus of Darkschewitsch(ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons(NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot *** and chemogenetic manipulations revealed that NDGABA neurons mediate freezing ***, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray(l PAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part(Gi V). Together,these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from the l PAG to Gi V, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.

关键词： nucleus of Darkschewitsch GABAergic population defensive behavior freezing neural circuitry

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Photocaged activity-based probes for improved monitoring of protein S-sulfenylation in living cells

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Chinese Chemical Letters 2024年第2期35卷 451-454页

作者： Jiahao Zhang Haiyue Peng Zi'an Chen Guorui Li Jing Huang State key laboratory of Chemo/Biosensing and Chemometrics Hunan Provincial Key Laboratory of Animal Models and Molecular MedicineSchool of Biomedical SciencesHunan UniversityChangsha 410082China

Protein S-sulfenylation(protein sulfenic acid),as one of the most significant oxidative post-translational modifications(OxiPTMs),plays a vital role in regulating protein function.A variety of activity-based probes have been developed to profile sulfenic acid in living ***,due to the transient presence and low content of sulfenic acid in living cell,high doses of probes are needed to achieve efficient *** importantly,current probes have no temporal control over sulfenic acid *** overcome these limitations,two caged cysteine sulfenic acid probes DYn-2-ONB and DYn-2-Cou with either an o-nitrobenzyl or coumarin protecting group were developed in this *** probes can be efficiently uncaged via irradiation to produce the active C-nucleophile probe *** assay in living cells demonstrated DYn-2-ONB exhibited better labeling capacity compared with DYn-2,providing it as a powerful tool for improved monitoring of protein S-sulfenylation in living cells.

关键词： Cysteine Sulfenic acid Activity-based probe Photocage Light activation Protein S-sulfenylation

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Diabetic retinopathy identification based on multi-sourcefree domain adaptation

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1193-1204页

作者： Guang-Hua Zhang Guang-Ping Zhuo Zhao-Xia Zhang Bin Sun Wei-Hua Yang Shao-Chong Zhang School of Big Data Intelligent Diagnosis&Treatment Industry Taiyuan UniversityTaiyuan 030032Shanxi ProvinceChina shanxi key laboratory of Intelligent Optimization Computing and Blockchain Technology Taiyuan Normal UniversityTaiyuan 030619Shanxi ProvinceChina shanxi Eye Hospital Taiyuan 030002Shanxi ProvinceChina College of Computer Science and Technology Taiyuan Normal UniversityTaiyuan 030619Shanxi ProvinceChina Shenzhen Eye Institute Shenzhen Eye HospitalJinan UniversityShenzhen 518040Guangdong ProvinceChina

AIM:To address the challenges of data labeling difficulties,data privacy,and necessary large amount of labeled data for deep learning methods in diabetic retinopathy(DR)identification,the aim of this study is to develop a source-free domain adaptation(SFDA)method for efficient and effective DR identification from unlabeled ***:A multi-SFDA method was proposed for DR *** method integrates multiple source models,which are trained from the same source domain,to generate synthetic pseudo labels for the unlabeled target ***,a softmax-consistence minimization term is utilized to minimize the intra-class distances between the source and target domains and maximize the inter-class *** is performed using three color fundus photograph datasets(APTOS2019,DDR,and EyePACS).RESULTS:The proposed model was evaluated and provided promising results with respectively 0.8917 and 0.9795 F1-scores on referable and normal/abnormal DR identification *** demonstrated effective DR identification through minimizing intra-class distances and maximizing inter-class distances between source and target ***:The multi-SFDA method provides an effective approach to overcome the challenges in DR *** method not only addresses difficulties in data labeling and privacy issues,but also reduces the need for large amounts of labeled data required by deep learning methods,making it a practical tool for early detection and preservation of vision in diabetic patients.

关键词： diabetic retinopathy multisource-free domain adaptation pseudo-label generation softmaxconsistence minimization

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Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State key laboratory of Reproductive medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai key laboratory of Reproductive medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State key laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

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Synergistic Brønsted Base/Photoredox-Catalyzed Three-Component Coupling with Malonates to Synthesize δ-Hydroxy Esters and δ-Keto Esters

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Chinese Journal of Chemistry 2024年第9期42卷 957-962页

作者： Ting Li Wei Wang Ming Dong Zhije Zhang Sha Yu Zhengchu Chen Siping Wei Dong Yi Green Pharmaceutical Technology key laboratory of Luzhou City Central Nervous System Drug Key Laboratory of Sichuan ProvinceSchoolof PharmacySouthwestMedicalUniversityLuzhouSichuan 646000China Nuclear medicine and Molecular Imaging key laboratory of Sichuan Province LuzhouSichuan 646000China

Multicomponent alkene 1,2-dicarbofunctionalizations(DCFs)have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C-C double bond in one step for enhancing molecular complexity and *** the best of our knowledge,there is only one report on photoredox-catalyzed three-component DCFs with malonates through the radical−radical cross-coupling,while photoredox-catalyzed radical-polar crossover(RPC)-type DCFs with malonates were still ***,we describe a redox-neutral RPC-type 1,2-dialkylation of styrenes with malonates and aldehydes through the synergistic Brønsted base/photoredox catalysis *** transition-metal-free strategy provides an efficient and clean approach to a broad variety ofδ-hydroxy esters and also features exceptionally mild conditions,wide compatibility of substrate scope and functional groups,and high atomic ***,three-component 1,2-alkylacylation from the same starting materials was achieved in one-pot manner through such RPC-type coupling and subsequent two-electron oxidation process,providing a set ofδ-keto esters of interest in pharmaceutical research.

关键词： Alkene difunctionalization Photoredox catalysis Malonates Radical reactions C-C coupling Synthetic methods Aldehydes Alkylation Multicomponentreactions

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