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Establishment of a humanized ST6GAL1 mouse model for influenza research

Animal Models and Experimental Medicine 2024年第3期7卷 337-346页

作者： Lyu Chao Han Feng Gao Qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang National key laboratory of Intelligent Tracking and Forecasting for Infectious diseases Chinese Center for Disease Control and PreventionBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina NHC key laboratory of Biosafety National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Zhejiang provincial key laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing ***:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of *** manipulated embryos were transferred into the oviducts of pseudopregnant female *** offspring were identified using *** exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for *** of the humanized gene was tested by performing immunohistochemical(IHC)*** and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were ***:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT *** mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection *** IHC results revealed that hST6GAL1 was expressed in the lungs of humanized ***,the hematologic and biochemical parameters of the positive mice were within the normal ***:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

关键词： hST6GAL1 humanized mice influenza animal model

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Efficacy and safety of Chinese herbal medicine as adjunctive therapy in sepsis patients with bloodstream infection:a propensity-matched analysis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 197-204页

作者： ZHOU Xianshi ZHONG Minlin XI Xiaotu LI Jun TANG Guanghua the Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou 510120China Emergency Department Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Guangdong provincial key laboratory of Research on Emergency in TCM Guangzhou 510120China Guangzhou key laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious diseases Guangzhou 510120China Administration Department the First Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China

OBJECTIVE:To investigate the efficacy and safety of Chinese herbal medicine in treating sepsis patients with bloodstream ***:A 6-year retrospective study was carried out at a university hospital in *** sepsis patients with bloodstream infection were *** primary outcome was 28-day mortality after *** score method was used to adjust for possible confounding.28-day mortality was estimated by KaplanMeier analysis and compared using the log-rank *** regression analysis was carried out to identify factors impacting in-hospital mortality ***:Following the application of the propensity score method,a total of 176 patients were *** all-cause 28-day mortality in the control group and Chinese herbal medicine group was 21.6%and 14.8%,***-Meier survival analysis showed that Chinese herbal medicine was associated with a lower hazard ratio(HR)in all-cause 28-day death compared with the control group[HR=0.44,95%CI(0.22,0.90),P0.05).Blood-activating and stasis-eliminating herb administration was associated with reduced inhospital mortality among sepsis patients with bloodstream infection[HR=0.54,95%CI(0.34,0.94),Pdiseases as long as no contraindications ***,further studies are needed to validate our results.

关键词： bacteremia medicine Chinese traditional herbal medicine sepsis propensity-matched analysis

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Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein(RNP)to inhibit herpes simplex virus1 infection in vitro and in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1362-1379页

作者： Yuanda Wan Liren Li Ruilin Chen Jiajia Han Qiyun Lei Zhipeng Chen Xiaodong Tang Wenyu Wu Shuwen Liu Xingang Yao NMPA key laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center of Clinical Pharmacy Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China key laboratory of Infectious diseases Research in South China(Southern Medical University) Ministry of EducationGuangzhou 510515China

Extracellular vesicles(EVs)have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins(RNPs),owing to their ability to minimize off-target effects and immune ***,enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within *** response,we employed the Fc/Spa interaction system,in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV ***,the B domain of the Spa protein was fused to the C domain of cargos such as Cre or *** to the robust interaction between Fc and Spa,this method enriched nearly twice the amount of cargo within the *** loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in ***,following neuron-targeting peptide RVG modification,the in vivo dosage in neural tissues substantially increased,contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target *** findings establish a robust platform for efficient EV-based SpCas9 delivery,offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

关键词： Extracellular vesicles CRISPR/Cas9 Ribonucleoproteins PTGFRN Fc/Spa HSV1 Neuron-targeting Delivery

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CHD4-induced up-regulation of ERα activity contributes to breast cancer progression

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Genes & diseases 2024年第3期11卷 132-135页

作者： Aman Sattout Xiaomin Yu Zhuo Sun Yanan Li Yulin Li Shujing Li Wei Huo Huijian Wu School of Bioengineering&key laboratory of Protein Modification and Disease Liaoning ProvinceDalian University of TechnologyDalianLiaoning 116024China Department of Oncology Central Hospital Affiliated with Dalian University of TechnologyDalianLiaoning 116089China

The estrogen signaling system is a crucial regulator of ***,abnormal activation of estrogen signaling may play a role in breast cancer initiation and *** to this pathway is the interaction between estrogen receptor alpha(ERa)and various co-transcription activators.1 Although numerous studies have investigated ER coregulators,the protein-protein interaction networks of ERa are not fully *** research has shown that high chromodomain helicase DNA-binding 4(CHD4)expression is linked to poor prognosis in various cancers.2,?In this study,we demonstrated that both CHD4 and ERαcontribute to breast cancer progression while providing evidence of the regulatory processes and functional interplay between these two proteins.

关键词： breast cancer ERα

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Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1345-1361页

作者： Honglin Huang Ningxi Li Xiaodan Wei Qingzhi Li Junhan Guo Geng Yang Hong Yang Lulu Cai Yiyao Liu Chunhui Wu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s Hospitaland School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China TCM Regulating Metabolic diseases key laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer ***,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)***“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 ***/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer ***,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune ***,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T *** pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant *** study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

关键词： Biomimetic immunoregulator Spatiotemporal delivery Targeted photothermal therapy Amplified immunogenic cell death Immunosuppressive tumor microenvironment PD-L1 degradation TAMs phenotype reversion Metastasis inhibition

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Bilateral choroidal ganglioneuroma:a comprehensive analysis of vision decline in a 6-year-old boy

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1755-1759页

作者： Yi-Zhe Cheng Li-Mei Sun Min-Er Yuan Lin-Yan Zhang Shu-Ya Ke Xiao-Yan Ding State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina Guangdong provincial Clinical Research Center for Ocular diseases Guangzhou 510060Guangdong ProvinceChina

Dear Editor,We write to present a 6-year-old boy with bilateral choroidal ganglioneuroma(CG)by comprehensive multimodal imaging(MMI)in a duration of 6-year *** our knowledge,this is the first case report with elaborate data to delineate the natural history of visual function and MMI in a boy with rare bilateral CG,confirmed by choroid biopsy.

关键词： comprehensive modal fir

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Expert consensus on difficulty assessment of endodontic therapy

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International Journal of oral Science 2024年第1期16卷 15-25页

作者： Dingming Huang Xiaoyan Wang Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Xinmei Chen Jiyao Li Ling Ye Lei Cheng Xin Xu Tao Hu Hongkun Wu Bin Guo Qin Su Zhi Chen Lihong Qiu Wenxia Chen Xi Wei Zhengwei Huang Jinhua Yu Zhengmei Lin Qi Zhang Deqin Yang Jin Zhao Shuang Pan Jian Yang Jiayuan Wu Yihuai Pan Xiaoli Xie Shuli Deng Xiaojing Huang Lan Zhang Lin Yue Xuedong Zhou State key laboratory of oral diseases&National Center for Stomatology&National Clinical Research Center for oral diseases&Department of Operative Dentistry and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghuaSchool of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina The State key laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&key laboratory of oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhanChina Department of Operative Dentistry&Endodontics School of StomatologyThe Fourth Military Medical UniversityXi’anChina Department of Endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina State key laboratory of oral diseases&National Center for Stomatology&National Clinical Research Center for oral diseases&Department of Preventive Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State key laboratory of oral diseases&National Center for Stomatology&National Clinical Research Center for oral diseases&Department of Geriatric dentistry West China Hospital of Stomatology

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

关键词： anatomy difficulty treatment

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The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of oral Exposure

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Biomedical and Environmental Sciences 2024年第1期37卷 31-41页

作者： HONG Tao SUN Wei DENG Yuan LYU Jian Da JIN Cui Hong BAI Ying Long NA Jun ZHANG Rui GAO Yuan PAN Guo Wei YANG Zuo Sen YAN Ling Jun Research Center for Universal Health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Pain Management Shengjing Hospital of China Medical UniversityShenyang 110004LiaoningChina Department of Toxicology School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Maternal and Child Health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Institute of Preventive Medicine China Medical UniversityShenyang 110122LiaoningChina Institute of Chronic diseases Liaoning Provincial Center for Disease Control and PreventionShenyang 110000LiaoningChina

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in *** Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after *** was performed to corroborate these *** In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by *** peak time of nanoplastic absorption in blood was *** Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

关键词： Microplastics Nanoplastics IVIS Spectrum small-animal imaging system Tissue distribution Blood

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Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase

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Chinese Journal of Natural Medicines 2024年第6期22卷 486-500页

作者： YANG Yanqiu CHE Yue FANG Mingxia YAO Xiaohu ZHOU Di WANG Feng CHEN Gang LIANG Dong LI Ning HOU Yue key laboratory of Bioresource Research and Development of liaoning Province College of Life and Health SciencesNorth-eastern UniversityShenyang 110000China National Frontiers Science Center for Industrial Intelligence and Systems Optimization Key Laboratory of Data Analytics and Optimization for Smart IndustryMinistry of EducationNortheastern UniversityShenyang 110000China School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning provinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110000China State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and Pharmaceutical SciencesGuangxi Normal UniversityGuilin 541000China

Neuroinflammation,mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3(NLRP3)inflammasome,is a significant contributor to the pathogenesis of neurodegenerative diseases(NDDs).Reynos-in,a natural sesquiterpene lactone(SL),exhibits a broad spectrum of pharmacological effects,suggesting its potential therapeutic ***,the effects and mechanism of reynosin on neuroinflammation remain *** current study explores the effects and mechanisms of reynosin on neuroinflammation using mice and BV-2 microglial cells treated with lipopolysaccharide(LPS).Our findings reveal that reynosin effectively reduces microglial inflammation in vitro,as demonstrated by decreased CD11b expression and lowered interleukin-1 beta(IL-1β)and interleukin-18(IL-18)mRNA and protein ***,in vivo,results showed a re-duction in the number of Iba-1 positive cells and alleviation of morphological alterations,alongside decreased expressions of IL-1βand *** analysis indicates that reynosin inhibits NLRP3 inflammasome activation,evidenced by reduced transcription of NLRP3 and caspase-1,diminished NLRP3 protein expression,inhibited apoptosis-associated speck-like protein containing a CARD(ASC)oli-gomerization,and decreased caspase-1 ***,reynosin curtailed the activation of nicotinamide adenine dinuc-leotide phosphate(NADPH)oxidase,demonstrated by reduced NADP^(+)and NADPH levels,downregulation of gp91^(phox) mRNA,pro-tein expression,suppression of p47^(phox) expression and translocation to the ***,reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in *** collective findings underscore reynosin’s capacity to mitigate mi-croglial inflammation by inhibiting the NLRP3 inflammasome,thus highlighting its potential as a therapeutic agent for managing neuroinflammation.

关键词： Microglia NLRP3 inflammasome Reactive oxygen species NADPH oxidase Neuron Reynosin

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Emerging mechanisms of non-alcoholic steatohepatitis and novel drug therapies

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Chinese Journal of Natural Medicines 2024年第8期22卷 724-745页

作者： CHEN Hao ZHOU Yang HAO Haiping XIONG Jing Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu provincial key laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Non-alcoholic fatty liver disease(NAFLD)has become a leading cause of chronic liver disease *** initiates with simple steatosis(NAFL)and can progress to the more severe condition of non-alcoholic steatohepatitis(NASH).NASH often advances to end-stage liver diseases such as liver fibrosis,cirrhosis,and hepatocellular carcinoma(HCC).Notably,the transition from NASH to end-stage liver diseases is irreversible,and the precise mechanisms driving this progression are not yet fully ***,there is a critical need for the development of effective therapies to arrest or reverse this *** review provides a comprehensive overview of the pathogenesis of NASH,examines the current therapeutic targets and pharmacological treatments,and offers insights for future drug discovery and development strategies for NASH therapy.

关键词： Metabolic dysfunction Drug development Bile acids Liver-gut axis Inflammation Fibrosis

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