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Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions

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Animal Models and Experimental Medicine 2024年第4期7卷 584-590页

作者： Jing Xu Jilong Ren Kai Xu Minghui fang Meina Ka Fei Xu Xin Wang Jing Wang Zhiqiang Han Guihai Feng Ying Zhang Tang Hai Wei li zheng Hu State key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina key laboratory of Organ Regeneration and Reconstruction Chinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina key laboratory of Organ Regeneration and Transplantation of the ministry of education The First HospitalJilin UniversityChangchunChina Beijing Farm Animal Research Center Institute of ZoologyChinese Academy of SciencesBeijingChina

Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and *** knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHC II molecule plays critical ***:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions ***:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue ***,the safety of our animals after gene editing was verified by using whole-genome sequencing and *** have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional ***:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHC I and II deletion.

关键词： CD4 T cell genetically edited pig immune rejection major histocompatibility complex II xenotransplantation

Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, Molecular Dynamics Simulation and Experimental Validation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 408-420页

作者： FENG Min-chao LUO fang HUANG liang-jiang li Kai CheN Zu-min li Hui YAO Chun QIN Bai-jun CheN Guo-zhong The First Clinical Medical College Guangxi University of Traditional Chinese MedicineNanning 530000China Guangxi key laboratory of Molecular Biology of Traditional Chinese Medicine and Preventive Medicine Nanning 530000China Graduate School Guangxi University of Traditional Chinese MedicineNanning 530000China Department of Gastroenterology the First Affiliated Hospital of Guangxi University of Traditional Chinese MedicineNanning 530023China

Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics ***, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(Phe expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.

关键词： Rheum palmatum L. Salvia miltiorrhiza Bge. molecular docking simulation network pharmacology acute pancreatitis Th17 cell differentiation

Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty:a prospective,double-blind,pilot,randomised controlled trial

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General Psychiatry 2024年第2期37卷 224-233页

作者： Jie Yang Mingshu Tao Rongguang liu Jiaxing fang Chunyan li Dexian Chen Qi Wei Xingyu Xiong Wenxin Zhao Wen Tan Yuan Han Hongxing Zhang he liu Song Zhang Junli Cao Department of Anesthesiology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsuChina Department of Anesthesiology Hospital of Chengdu University of Traditional Chinese Medicine&Traditional Chinese Medicine Hospital of Sichuan ProvinceChengduSichuanChina NMPA key laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs&Jiangsu Province key laboratory of Anesthesiology&Jiangsu key laboratory of Applied technology of Anesthesia and Analgesia Xuzhou Medical UniversityXuzhouJiangsuChina Department of Anesthesiology Eye&ENT Hospital of Fudan UniversityShanghaiChina Department of Anesthesiology&Clinical Research Center for Anesthesia and Perioperative Medicine&Huzhou key laboratory of Basic Research and Clinical Translation for Neuromodulation The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University||Huzhou Central Hospital||The Affiliated Huzhou HospitalZhejiang University School of Medicine||Affiliated Central Hospital Huzhou UniversityHuzhouZhejiangChina Department of Anesthesiology Renji Hospital School of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative *** This study aimed to investigate the effect of transcranial direct current stimulation(tDCS)on PSD in older patients undergoing lower limb major *** In this prospective,double-blind,pilot,randomised,sham-controlled trial,patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS(a-tDCS)or sham tDCS(s-tDCS).The primary outcomes were the objective sleep measures on postoperative nights(N)1 and *** 116 inpatients were assessed for eligibility,and a total of 92 patients were enrolled;47 received a-tDCS and 45 received *** improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups;the respective comparisons were as follows:the promotion of rapid eye movement(REM)sleep time on N1(64.5(33.5-105.5)vs 19.0(0.0,45.0)min,F=20.10,phe total sleep time on N1(506.0(408.0-561.0)vs 392.0(243.0-483.5)min,F=14.13,phe deep sleep time on N1(130.0(103.3-177.0)vs 42.5(9.8-100.8)min,F=24.4,phe percentages of light sleep and REM sleep on N1 and N2(phe postoperative depression and anxiety scores did not differ significantly between the two *** significant adverse events were *** In older patients undergoing lower limb major arthroplasty,a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep ***,this benefit was temporary and was not maintained over time.

关键词： sleep stimulation postoperative

Unveiling the existence and ecological hazards of trace organic pollutants in wastewater treatment plant effluents across China

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Eco-Environment & health 2024年第1期3卷 21-29页

作者： Jianchao liu fang Yang Yuanfei Cai Guanghua Lu Yiping li Ming li linhua Fan li Gao key laboratory of Integrated Regulation and Resource Development of Shallow Lakes of ministry of education College of EnvironmentHohai UniversityNanjing 210098China College of Natural Resources and Environment Northwest A&F UniversityYangling 712100China School of Engineering RMIT UniversityMelbourneVIC 3001Australia Institute for Sustainable Industries and liveable Cities Victoria UniversityMelbourneVictoria 8001Australia

The presence of trace organic pollutants in the effluent of wastewater treatment plants(WWTPs)poses considerable risks to aquatic organisms and human health.A large-scale survey of 302 trace organic pollutants in the effluent of 46 Chinese WWTPs was conducted to gain an improved understanding of their occurrence and ecological *** survey data showed that 216 compounds in 11 chemical classes had been detected in *** sum concentrations of the trace contaminants in effluent ranged from 1,392 ng/L to 35,453 ng/L,with the maximum concentration of perfluoroalkyl substances(PFASs)recorded as the highest(30,573 ng/L),which was markedly less than the reported 185,000 ng/L for the 38 American *** concentration of bisphenol analogs(BPs)was up to 4,422 ng/L,significantly higher than those reported in France,Germany,Japan,Korea,and the *** and BPs were the major pollutants,accounting for 59%of the total ***,a total of 119 contaminants were found to have ecological risks(RQ>0.01).Among these,23 contaminants(RQ>1.0)warrant higher attention and should be prioritized for *** study lists valuable information for controlling contaminants with higher priority in WWTP effluent in China.

关键词： Wastewater treatment Effluent Trace organic pollutants Ecological risk assessment

A Generic Strategy to Create Mechanically Interlocked Nanocomposite/Hydrogel Hybrid Electrodes for Epidermal Electronics

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Nano-Micro Letters 2024年第5期16卷 120-133页

作者： Qian Wang Yanyan li Yong lin Yuping Sun Chong Bai Haorun Guo Ting fang Gaohua Hu Yanqing Lu Desheng Kong College of Engineering and Applied Sciences National Laboratory of Solid State Microstructureand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210023People’s Republic of China State key laboratory of Analytical chemistry for life Science and Jiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjing 210023People’s Republic of China College of Chemical Engineering and technology Engineering Research Center of Seawater Utilization Technology of Ministry of EducationState Key Laboratory of Reliability and Intelligence of Electrical EquipmentHebei University of TechnologyTianjin 300130People’s Republic of China key laboratory of Intelligent Optical Sensing and Manipulation Nanjing UniversityNanjing 210093People’s Republic of China

Stretchable electronics are crucial enablers for next-generation wearables intimately integrated into the human *** the primary compliant conductors used in these devices,metallic nanostructure/elastomer composites often struggle to form conformal contact with the textured *** electrodes have been consequently developed based on conductive nanocomposite and soft hydrogels to establish seamless skin-device ***,chemical modifications are typically needed for reliable bonding,which can alter their original *** overcome this limitation,this study presents a facile fabrication approach for mechanically interlocked nanocomposite/hydrogel hybrid *** this physical process,soft microfoams are thermally laminated on silver nanowire nanocomposites as a porous interface,which forms an interpenetrating network with the *** microfoam-enabled bonding strategy is generally compatible with various *** resulting interlocked hybrids have a 28-fold improved interfacial toughness compared to directly stacked *** electrodes achieve firm attachment to the skin and low contact impedance using tissue-adhesive *** have been successfully integrated into an epidermal sleeve to distinguish hand gestures by sensing mus-cle *** nanocomposite/hydrogel hybrids reported here offer a promising platform to combine the benefits of both materials for epidermal devices and systems.

关键词： Stretchable electronics Epidermal electronics Silver nanowire Conductive nanocomposites Hydrogel

Junshanyinzhen tea extract prevents obesity by regulating gut microbiota and metabolic endotoxemia in high-fat diet fed rats

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Food Science and Human Wellness 2024年第4期13卷 2036-2047页

作者： Jian Ouyang Xiuping li Changwei liu Danmin Lu Jie Ouyang fang Zhou Qi liu Jianan Huang Zhonghua liu key laboratory of Tea Science of ministry of education Hunan Agricultural UniversityChangsha 410128China National Research Center of Engineering technology for Utilization of Functional Ingredients from Botanicals Hunan Agricultural UniversityChangsha 410128China Co-Innovation Center of education ministry for Utilization of Botanical Functional Ingredients Hunan Agricultural UniversityChangsha 410128China key laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops Ministry of Agriculture and Rural AffairsHunan Agricultural UniversityChangsha 410128China

Obesity is associated with gut dysbiosis and metabolic *** tea extract(JSTE)reduced fat accumulation and body weight in obese ***,the effects and mechanism of JSTE in preventing obesity were ***,we used different doses of JSTE(75,150 and 300 mg/(kg·day))to evaluate the effect on high-fat diet(HFD)-induced rats under 8 weeks of ***,our results showed that JSTE could significantly reduce body weight gain,blood lipid levels and fat accumulation,improve fatty damage in liver tissue(Phe expression of intestinal tight junction proteins(Plieved metabolic endotoxemia(Phe microbial diversity and the ratio of Firmicutes to Bacteroidetes to normal levels in HFD-fed *** and Erysipelotrichaceae,which are positively related to obesity,were decreased by JSTE intervention(Phese results suggested that JSTE might effectively prevent obesity by modulating gut microbiota dysbiosis,intestinal barrier dysfunction,metabolic endotoxemia and chronic low-grade infl ammation in HFD-induced rats.

关键词： Junshanyinzhen tea Obesity Gut microbiota Gut barrier function Metabolic endotoxemia

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Molecular crowding electrolytes for stabilizing Zn metal anode in rechargeable aqueous batteries

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Chinese Chemical Letters 2024年第7期35卷 445-451页

作者： li lin Song-lin Tian Zhen-Yu Hu Yu Zhang li-Min Chang Jia-Jun Wang Wan-Qiang liu Qing-Shuang Wang fang Wang School of Materials Science and Engineering Changchun University of Science and TechnologyChangchun 130022China School of life Science and technology Changchun University of Science and TechnologyChangchun 130022China key laboratory of Preparation and Applications of Environmental Friendly Materials of the ministry of education Jilin Normal UniversityChangchun 130103China Zhongshan Institute of Changchun University of Science and technology Zhongshan 528437China

A solid electrolyte interphase(SEI)with a robust mechanical property and a high ionic conductivity is imperative for high-performance zinc metal ***,it is difficult to form such a SEI directly from an *** this work,a molecular crowding effect is based on the introduction of Zn(OTF)_(2)and Zn(ClO_(4))_(2)to 2 mol/L ZnSO_(4)*** and experiments indicate that the Zn(OTF)_(2)and Zn(ClO_(4))_(2)not only create a molecularly crowded electrolyte environment to promote the interaction of Zn^(2+)and OTF^(-),but also participate in the reduction to construct a robust and high ionic-conductive SEI,thus promoting metal zinc deposition to the(002)crystal *** this molecular crowding electrolyte,a high current density of 1 mA/cm^(2)can be obtained by assembling symmetric batteries with Zn as the anode for over 1000 *** in a temperature environment of-10℃,a current density of 1 mA/cm^(2)can be obtained by assembling symmetric batteries with Zn for over 200 ***//Bi_(2)S_(3)/VS4@C cells achieve a CE rate of up to 99.81%over 1000 ***,the utilization of a molecular crowding electrolyte is deemed a highly effective approach to fabricating a sophisticated SEI for a zinc anode.

关键词： Zinc ion batteries Anode Electrolyte Solid electrolyte interphase Molecular crowding effect

Structure-guided isolation of anti-neuroinflammatory sesquiterpene coumarins from Ferula sinkiangensis

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Chinese Journal of Natural Medicines 2024年第7期22卷 643-653页

作者： DANG Wen GUO Tingting ZHOU Di MENG Qingqi fang Mingxia CheN Gang liN Bin HOU Yue li Ning 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 110016China College of life and health Sciences Northeastern UniversityShenyang 110004China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders,inflammation,tumors,various cancers,and alopecia *** primary bioactive constituents,sesquiterpene coumarins,have demonstrated notable therapeutic potential against *** this study,a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of *** compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques,including calculated electronic circular dichroism(ECD).Anti-neuroinflammatory assays revealed that compounds 2,3,and 6 significantly inhibited nitric oxide(NO)production in lipopolysaccharide(LPS)-stimulated BV2 microglial cells,with IC_(50)values ranging from 1.63 to 12.25μmol·L^(−1).

关键词： Ferula sinkiangensis Sesquiterpene coumarins Structure elucidation Anti-neuroinflammatory activity

The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

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Journal of Genetics and Genomics 2024年第7期51卷 735-748页

作者： Tongyu Zhang Yingxi Zhu Xiaochen Wang Danyang Chong Haiquan Wang Dandan Bu Mengfei Zhao Lei fang Chaojun li ministry of education key laboratory of Model Animals for Disease Study Model Animal Research CenterMedical School of Nanjing UniversityNational Resource Center for Mutant MiceNanjingJiangsu 210093China State key laboratory of Reproductive Medicine and Offspring health China International Joint Research Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthGusu SchoolNanjing Medical UniversityNanjingJiangsu 211166China

In mammals,the neonatal heart can regenerate upon injury within a short time after birth,while adults lose this *** reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal ***,we reveal that cardiac metabolic reprogramming could be regulated by altering global protein *** performing 4D label-free proteomics and lysine lactylation(Kla)omics analyses in mouse hearts at postnatal days 1,5,and 7,2297 Kla sites from 980 proteins are identified,among which 1262 Kla sites from 409 proteins are *** clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic *** expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid ***,we verify the Kla levels of several differentially modified proteins,including ACAT1,ACADL,ACADVL,PFKM,PKM,and ***,our study reports a comprehensive Kla map in the neonatal mouse heart,which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

关键词： Lactylation Metabolicrep rogramming Postnatal heart regeneration Cell proliferation