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ZIF-90-loaded DNAzyme-responsive PROTAC for the self-powered degradation of NF-κB

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Science China Chemistry 2024年

作者： Min Hou Liang Sun Tianyu Ren Mingda Li Chao Hu Rong Liu Shuang Gu Mingyan Jiang Jianhui Jiang Jianjun He College of Physics and Chemistry Hunan First Normal University hunan provincial key laboratory of animal models and molecular medicine College of Biomedical Sciences College of Chemistry and Chemical Engineering Hunan University Xiangtan Central Hospital

Transcription factors(TFs) play vital roles in regulating gene expressions. Dysregulated or mutated TFs are implicated in a wide array of diseases, highlighting their potential as drug targets. However, TFs are considered undruggable by conventional inhibitor-based modalities. The recently emerged proteolysis targeting chimeras(PROTACs) have exhibited great potential in tackling TFs. In particular, DNA-ligand chimeras that arm E3 ligase-recruiting ligands to TF-binding double-strand DNA represent a promising strategy for the targeted proteolysis of TFs. Here, we report a DNAzyme-inducible PROTAC(DzTAC)that selectively degrades NF-κB in a zinc ion-dependent manner. We further applied zinc-imidazolate metal–organic framework-90(ZIF-90) to encapsulate DzTAC(ZIF-90@DzTAC), facilitating its delivery into cancer cells while self-supplying Zn2+via adenosine triphosphate(ATP)-triggered ZIF-90 dissociation. Moreover, ZIF-90@DzTAC can enhance the treatment efficacy of doxorubicin-based chemotherapy in tumor-bearing mice. The developed DzTAC provides specific modulation over TF activity and opens an avenue for more functional nucleic acid-based control over targeted protein degradation.

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Bombyx mori nucleopolyhedrovirus induces BmFABP1 downregulation to promote viral proliferation

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Insect Science 2023年第6期30卷 1595-1606页

作者： Xiong Wang Guangyu Ma Feifei Ren Mian Muhammad Awais Jingchen Sun College of animal Science Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular BreedingSouth China Agricultural UniversityGuangzhouChina

Fatty acid binding proteins (FABPs) play an important role as endogenous cytoprotectants. However, studies on FABPs in invertebrates are scarce. Previously, we discovered Bombyx mori fatty acid binding protein 1 (BmFABP1) through co-immunoprecipitation. Here, we cloned and identified BmFABP1 from BmN cells. The results of immunofluorescence indicated that BmFABP1 was localized in the cytoplasm. The tissue expression profile of silkworms showed that BmFABP1 was expressed in all tissues except hemocytes. The expression level of BmFABP1 gradually decreases in BmN cells and B. mori larvae after infection with B. mori nucleopolyhedrovirus (BmNPV). Upregulation of BmFABP1 expression through overexpression or WY14643 treatment significantly inhibited the replication of BmNPV, while downregulation of BmFABP1 expression by RNA interference promoted the replication of BmNPV. The same results were obtained in experiments on silkworm larvae. These results suggest that BmNPV induces BmFABP1 downregulation to promote its proliferation and that BmFABP1 has a potential anti-BmNPV role. This is the first report on the antiviral effect of BmFABP1 in silkworms and provides new insights into the study of the FABP protein family. Also, it is important to study BmNPV resistance in silkworms to breed transgenic silkworms with BmNPV resistance.

关键词： antiviral BmFABP1 BmNPV Bombyx mori

Lipo-nutritional quality of pork:The lipid composition,regulation,and molecular mechanisms of fatty acid deposition

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animal Nutrition 2023年第2期13卷 373-385页

作者： Wuzhou Yi Qixin Huang Yizhen Wang Tizhong Shan College of animal Sciences Zhejiang UniversityHangzhouChina The key laboratory of molecular animal Nutrition Ministry of EducationHangzhouChina Zhejiang provincial laboratory of Feed and animal Nutrition HangzhouChina

Pork is one of the main meats consumed by people,and its nutritional value is closely related to human *** lipid deposition and composition of pork not only affect the sensory quality but also determine the nutritional quality of *** lipids in pork include triglycerides(TAG)and a small amount of cholesterol and *** are the main lipids in skeletal muscle fat,which is divided into intermuscular fat and intramuscular fat(IMF).In addition to TAG,IMF also contains phospholipids,which are important factors affecting pork *** are three types of fatty acids in TAG:saturated fatty acids(SFA),monounsaturated fatty acids(MUFA),and polyunsaturated fatty acids(PUFA).PUFA,such as n-3 PUFA,have a beneficial effect on health,including the regulation of whole-body energy metabolism and protection against cardiovascular ***,regulating lipid deposition,especially the fatty acid composition,in pork is important for improving the nutritional quality for hu-man ***,several strategies,such as breeding,environmental control,and the nutritional regulation of lipid composition and deposition in pork,have been *** recently,faecal trans-plantation,molecular design breeding and non-coding RNA have been studied and proven useful for regulating lipid deposition in *** this review,we mainly summarized and discussed the research findings to date on the lipid composition and regulation mechanisms of fatty acid deposition and provide new insights into efficient means of improving the lipid composition and lipo-nutritional quality of pork.

关键词： Fatty acid composition Intramuscular fat Dietary factor Gut microbiota Non-coding RNA

Cellular and Transcriptional Dynamics during Brown Adipose Tissue Regeneration under Acute Injury

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Research 2024年第3期2023卷 345-357页

作者： Wenjing You Ziye Xu Wentao Chen Xin Yang Shiqi Liu Liyi Wang Yuang Tu Yanbing Zhou Teresa G.Valencak Yizhen Wang Shihuan Kuang Tizhong Shan College of animal Sciences Zhejiang UniversityHangzhouChina The key laboratory of molecular animal Nutrition Ministry of EducationHangzhouChina Zhejiang provincial laboratory of Feed and animal Nutrition HangzhouChina Department of laboratory medicine the First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina Department of animal Sciences Purdue UniversityWest LafayetteINUSA.

Brown adipose tissue(BAT)is the major site of non-shivering thermogenesis and crucial for systemic *** chronic cold exposures and high-fat diet challenges,BAT undergoes robust remodeling to adapt to physiological ***,whether and how BAT regenerates after acute injuries are poorly ***,we established a novel BAT injury and regeneration model(BAT-IR)in mice and performed single-cell RNA sequencing(scRNA-seq)and bulk RNA-seq to determine cellular and transcriptomic dynamics during *** further defined distinct fibro-adipogenic and myeloid progenitor populations contributing to BAT *** trajectory and gene expression analyses uncovered the involvement of MAPK,Wnt,and Hedgehog(Hh)signaling pathways in BAT *** confirmed the role of Hh signaling in BAT development through Myf5Cre-mediated conditional knockout(cKO)of the Sufu gene to activate Hh signaling in BAT and muscle *** BAT-IR model therefore provides a paradigm to identify conserved cellular and molecular mechanisms underlying BAT development and remodeling.

关键词： injuries involvement acute

Long non-coding RNA FPFSC promotes immature porcine Sertoli cell growth through modulating the miR-326/EHMT2 axis

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Journal of Integrative Agriculture 2024年第11期23卷 3830-3842页

作者： Dan Chu Bin Chen Bo Weng Saina Yan Yanfei Yin Xiangwei Tang Maoliang Ran hunan provincial key laboratory for Genetic Improvement of Domestic animal College of Animal Science and TechnologyHunan Agricultural UniversityChangsha 410128China Xiangxi Vocational and Technical College for Nationalities Xiangxi 416007China

Sertoli cells are indispensable for guaranteeing normal spermatogenesis and male *** a huge number of long non-coding RNAs(lncRNAs)are identified from developing porcine testicular tissues and have been predicted with crucial regulatory roles in spermatogenesis,their functions and regulatory mechanisms are still in ***,we mainly explored the regulatory and functional roles of lncFPFSC in proliferation and apoptosis of immature porcine Sertoli *** results demonstrated that lncFPFSC was predominantly located in the cytoplasm of immature porcine Sertoli *** overexpression promoted cell cycle progression and cell proliferation,as well as inhibited cell apoptosis,whereas siRNA-induced lncFPFSC knockdown resulted in the opposite ***,lncFPFSC acted as a sponge for *** of miR-326 inhibited cell proliferation and induced cell apoptosis,which further abolished the effects of lncFPFSC *** euchromatic histone-lysine N-methyltransferase 2(EHMT2)gene was directly targeted by miR-326,and its mRNA and protein expressions were both negatively regulated by miR-326 in immature porcine Sertoli ***,siRNA-induced EHMT2 knockdown resulted a similar effect of miR-326 ***,lncFPFSC promoted proliferation and inhibited apoptosis in immature porcine Sertoli cells through modulating the miR-326/EHMT2 *** study expanded our understanding of non-coding RNAs in participating porcine spermatogenesis through deciding the fate of Sertoli cells,and the competing endogenous RNA(ceRNA)network,and provided new molecular markers to treat Sertoli cell disorder inducing male infertility.

关键词： porcine Sertoli cells proliferation apoptosis lncRNA FPFSC miR-326 EHMT2 gene

Enzyme-modulate conformational changes in amphiphile peptide for selectively cell delivery

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Chinese Chemical Letters 2024年第12期35卷 273-276页

作者： Weiyu Chen Zenghui Li Chenguang Zhao Lisha Zha Junfeng Shi Dan Yuan hunan provincial key laboratory of animal models and molecular medicine State Key Laboratory of Chemo/Bio-Sensing and ChemometricsSchool of Biomedical SciencesHunan University Shenzhen Research Institute Hunan University

Achieving selectivity in cell penetrating peptide(CPP) design is crucial to mitigate systemic toxicity and enable precise targeting based on distinct cellular phenotypes. Herein, we designed an amphiphilic peptide, L17Yp, by incorporating phosphorylated tyrosine into natural occurring M-lycotoxin peptide, known for its potent membrane-lytic activity. This strategic modification induced a conformational shift, as confirmed by circular dichroism spectroscopy, transitioning it from its bioactive α-helix conformation to an inactive random coli configuration, effectively shielding its membrane-penetrating capacity. Upon exposure to alkaline phosphatase, L17Yp undergoes enzymatic dephosphorylation, prompting a conformational shift that restores its membrane-transduction capabilities. This unique property hold promises for selective drug delivery. This work introduces an enzymatic approach for targeted perturbation of the cell membrane, offering promising prospects for precise drug delivery applications.

关键词： Enzymatic action Dephosphorylation Conformation shift Cell-penetrating peptide Selective delivery

Identification of an H1N1 subtype of swine influenza virus and serological analysis

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Journal of Integrative Agriculture 2019年第7期18卷 1436-1442页

作者： SUN Fa-chao TAN Min ZHANG Yuan-chao WANG Yu-chao CAO Sheng-liang DING Guo-fei CONG Fang-yuan GUO Li-hong LIU Si-dang XIAO Yi-hong Department of Basic Veterinary medicine College of Animal Science and Veterinary Medicine/Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention/Shandong Provincial Engineering Technology Research Center of Animal Disease Control and PreventionShandong Agricultural University

To investigate the epizootic of swine influenza virus(SIV),60 nasal swabs were collected from a clinical cases of pig farm in Tai’an City,Shandong Province of China in April *** was isolated by inoculating into 10-day-old Special Pathogen Free embryonated eggs and the whole genome was *** H1N1 subtype SIV was isolated and designated as A/swine/Shandong/TA04/2017(H1N1).Phylogenetic analysis showed that apart from the polymerase A(PA) fragment belonging to the 2009 pandemic H1N1 branch,seven genome segments belonged to avian-like H1N1 influenza virus *** cleavage site sequence of the hemagglutinin(HA) protein was PSIQSR↓G,which is a typical molecular biological *** potential N-glycosylation sites(N14,N26,N277,N484 and N543) were found in the HA *** further investigate the epidemiology of SIV in this farm,the 995 serum samples were assessed with EAH1N1 2009 pandemic H1N1 and H3 N2 *** results showed that the total positive rate was 65.43%.The positive rates of single virus infection detected by EAH1N1,2009 pdmH1N1 and H3 N2 for serum HI(Hemagglutination inhibition) were 48.35,30.85 and 7.47%,*** results showed that SIV in Shandong Province has been reassorted in some segments and the SIV-positive rate was high on the SIV outbreak *** data provide evidence of an epizootic of SIV.

关键词： SIV H1N1 subtype genetic analysis molecular feature serology

The role of extracellular vesicles in animal reproduction and diseases

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Journal of animal Science and Biotechnology 2022年第6期13卷 1634-1656页

作者： Sangiliyandi Gurunathan Min-Hee Kang Hyuk Song Nam Hyung Kim Jin-Hoi Kim Department of Stem Cell and Regenerative Biotechnology Konkuk UniversitySeoul 05029Korea Guangdong provincial key laboratory of Large animal models for Biomedicine Wuyi UniversityJiangmen 529020China

Extracellular vesicles(EVs)are nanosized membrane-enclosed compartments that serve as messengers in cell-to-cell communication,both in normal physiology and in pathological *** can transfer functional proteins and genetic information to alter the phenotype and function of recipient cells,which undergo different changes that positively affect their structural and functional *** fluids are enriched with several subpopulations of EVs,including exosomes,microvesicles(MVs),and apoptotic bodies carrying several cargoes,such as lipids,proteins,and nucleic *** associated with the reproductive system are actively involved in the regulation of different physiological events,including gamete maturation,fertilization,and embryo and fetal *** can influence follicle development,oocyte maturation,embryo production,and endometrial-conceptus *** loaded with cargoes are used to diagnose various diseases,including pregnancy disorders;however,these are dependent on the type of cell of origin and pathological ***-derived microRNAs(miRNAs)and proteins in the placenta regulate inflammatory responses and trophoblast invasion through intercellular delivery in the placental *** review presents evidence regarding the types of extracellular vesicles,and general aspects of isolation,purification,and characterization of EVs,particularly from various types of ***,we discuss EVs as mediators and messengers in reproductive biology,the effects of EVs on placentation and pregnancy disorders,the role of EVs in animal reproduction,in the male reproductive system,and mother and embryo *** addition,we emphasize the role of microRNAs in embryo implantation and the role of EVs in reproductive and therapeutic ***,we discuss the future perspectives of EVs in reproductive biology.

关键词： Embryos Extracellular vesicles Implantation MicroRNA Pregnancy disorders

Base editors:development and applications in biomedicine

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Frontiers of medicine 2023年第3期17卷 359-387页

作者： Yanhui Liang Fangbing Chen Kepin Wang Liangxue Lai China-New Zealand Joint laboratory on Biomedicine and Health CAS Key Laboratory of Regenerative BiologyGuangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineCentre for Regenerative Medicine and HealthHong Kong Institute of Science and InnovationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Research Unit of Generation of Large animal Disease models Chinese Academy of Medical Sciences(2019RU015)Guangzhou 510530China Sanya Institute of Swine Resource Hainan Provincial Research Centre of Laboratory AnimalsSanya 572000China Guangdong provincial key laboratory of Large animal models for Biomedicine Wuyi UniversityJiangmen 529020China

Base editor(BE)is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase,enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break(DSB)or requiring donor DNA templates in living *** editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems,such as CRISPR/Cas9,as the DSB induced by Cas9 will cause severe damage to the ***,base editors have important applications in the field of biomedicine,including gene function investigation,directed protein evolution,genetic lineage tracing,disease modeling,and gene *** the development of the two main base editors,cytosine base editors(CBEs)and adenine base editors(ABEs),scientists have developed more than 100 optimized base editors with improved editing efficiency,precision,specificity,targeting scope,and capacity to be delivered in vivo,greatly enhancing their application potential in ***,we review the recent development of base editors,summarize their applications in the biomedical field,and discuss future perspectives and challenges for therapeutic applications.

关键词： base editing CBE ABE ADAR DdCBE disease model therapeutic application