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Alternative splicing of a carboxyl/choline esterase gene enhances the fenpropathrin tolerance of Tetranychus cinnabarinus

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Insect Science 2023年第5期30卷 1255-1266页

作者： peng wei Xinying zeng Haonan Han yiqing Yang Youjun zhang Lin he Key Laboratory of Entomology and Pest Control Engineering College of Plant ProtectionSouthwest UniversityChongqingChina Academy of Agricultural Sciences Southwest UniversityChongqingChina National Citrus Engineering Research Center Southwest UniversityChongqingChina Department of Plant Protection Institute of Vegetables and FlowersChinese Academy of Agricultural SciencesBeijingChina

Detoxification plays a crucial role in agricultural pests to withstand pesticides,and cytochrome P450s,carboxyl/choline esterases(CCEs),and glutathione-S-transferases are the main proteins responsible for their detoxification *** activity of CCEs can be upregulated,downregulated,or modified by ***,few studies have examined the role of alternative splicing in altering the properties of *** identified 2 variants of TcCCE23 in Tetranychus cinnabarinus:a long version(CCE23-V1)and a short version that is 18 nucleotides shorter than CCE23-V1(CCE23-V2).Whether splicing affects the activity of TcCCE23 remains *** of CCE23-V2 in fenpropathrin-resistant *** revealed that splicing affected the detoxification of fenpropathrin by *** mortality of mites was significantly higher when the expression of CCE23-V2 was knocked down(43.2%±3.3%)via injection of CCE23-dsRNA(double-stranded RNA)compared with the control group injected with green fluorescent protein-dsRNA under fenpropathrin exposure;however,the downregulation of CCE23-V1(61.3%±6.3%)by CCE23-small interfering RNA had no such effect,indicating CCE23-V2 plays a greater role in xenobiotic metabolism than *** tolerance of flies overexpressing CCE23-V2 to fenpropathrin(50%lethal dose[LD_(50)]=19.47μg/g)was significantly higher than that of Gal4/UAS-CCE23-V1 transgenic flies(LD_(50)=13.11μg/g).Molecular docking analysis showed that splicing opened a“gate”that enlarges the substrate binding cavity of CCE23-V2,might enhance the ability of CCE23-V2 to harbor fenpropathrin *** findings suggest that splicing might enhance the detoxifying capability of ***,our data improve the understanding of the diversity and complexity of the mechanisms underlying the regulation of CCEs.

关键词： alternative splicing carboxyl/choline esterase(CCE) detoxification function pyrethroid pests

In vitro and in vivo evaluation of bone morphogenetic protein- 2 （BMP-2） immobilized collagen-coated polyetheretherketone （PEEK）

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Frontiers of Materials Science 2015年第1期9卷 38-50页

作者： Ya-wei DU Li-Nan zhang Xin YE he-Min NIE zeng-Tao HOU Teng-Hui zeng Guo-Ping YAN peng SHANG Center for Translational Medicine Research and Development Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China School of Materials Science and Engineering Wuhan Institute of Technology Wuhan 430073 China Department of Biomedical Engineering College of Biology Hunan University Changsha 410082 China Department of Spine Surgery Shenzhen Second People's Hospital Shenzhen 518035 China

Polyetheretherketone （PEEK） is regarded as one of the most potential candidates of biomaterials in spinal implant applications. However, as a bioinert material, PEEK plays a limited role in osteoconduction and osseointegration. In this study, recombinant human bone morphogenetic protein-2 （rhBMP-2） was immobilized onto the surface of collagen-coated PEEK in order to prepare a multi-functional material. After adsorbed onto the PEEK surface by hydroph（bic interaction, collagen was cross-linked with N-（3-dimethylaminopropyl）-N＇-ethyl carbodiimide hydrochloride （EDC） and N-hydro xysuccinimide （NHS）. EDCINHS system also contributed to the immobilization of rhBMP- 2. Water contact angle tests, XPS and SEM clearly demonstrated the surface changes. ELISA tests quantified the amount of rhBMP-2 immobilized and the release over a period of 30 d. In vitro evaluation proved that the osteogenesis differentiation rate was higher when cells were cultured on modified PEEK discs than on regular ones. In vivo tests were conducted and positive changes of major parameters were presented. This report demonstrates that the rhBMP-2 immobilized method for PEEK modification increase bioactivity in vitro and in vivo, suggesting its practicability in orthopedic and spinal clinical applications.

关键词： polyetheretherketone (PEEK) spinal implantation bone morphogeneticprotein-2 (BMP-2) collagen surface modification

Seasonal Variability of Phytoplankton Community Structure in Relation to Different Nitrogen-Phosphorus Ratios in the Southern Coastal Waters of Zhejiang, China

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Journal of Ocean University of China 2013年第4期12卷 577-588页

作者： HUANG wei ZHU Xuyu CheN Quanzhen he Qing LIAO yibo DU Ping zhang peng zeng Jiangning Laboratory of Marine Ecosystem and Biogeochemistry Second Institute of Oceanography State Oceanic Administration College of Fisheries and Life Science Shanghai Ocean University Zhejiang Mariculture Research Institute

With the rapid development of economy and increase of population in the drainage areas, the nutrient loading has increased dramatically in the Changjiang estuary and adjacent coastal waters. To properly assess the impact of nutrient enrichment on phytoplankton community, seasonal microcosm experiments were conducted during August 2010-July 2011 in the coastal waters of Zhejiang Province. The results of the present study indicated that the chl a concentration, cell abundance, diversity indices, species composition and community succession of the phytoplankton varied significantly with different N/P ratios and seasons. Higher growth was observed in the 64：1 （spring）, 32：1 （summer）, 16：1 （autumn） and 128：1,256：1 （winter） treatments, respectively. The values of Shannon-Wiener index （H） and Pielou evenness index （J） were lower in the 8：1 and 16：1 treatments in autumn test, while H value was higher in the 128：1 and 8：1 treatments in winter test. A definite community succession order from diatoms to dinoflagel lares was observed in the autumn and winter tests, while the diatoms dominated the community throughout the culture in the spring and summer tests.

关键词： phytoplankton community succession nutrient enrichment Shannon-Wiener index Pielou evenness index nitrogen-phosphorus ratio

Corrosion resistance of in-situ growth of nano-sized Mg（OH）2 on micro-arc oxidized magnesium alloy AZ31—Influence of EDTA

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Journal of Materials Science & Technology 2019年第6期35卷 1088-1098页

作者： Chang-Yang Li Xiao-Li Fan rong-Chang zeng Lan-Yue Cui Shuo-Qi Li Fen zhang Qing-Kun he M. Bobby Kannan Hong-wei (George) Jiang Dong-Chu Chen Shao-kang Guan College of Materials Science and Engineering Shandong University of Science and Technology Qingdao 266590 China Biomaterials and Engineering Materials (BEM) Laboratory College of Science Technology and Engineering James Cook University Townsville 4811Australia School of Engineering RMIT University Carlton 3053 VIC Australia School of Materials Science and Energy Engineering Foshan University Foshan 528000 China School of Materials Science and Engineering Zhengzhou University Zhengzhou 450002 China

One of the major obstacles for the clinical use of biodegradable magnesium(Mg)-based materials is their high corrosion rate. Micro-arc oxidation(MAO) coatings on Mg alloys provide mild corrosion protection owing to their porous structure. hence, in this study a dense Mg(OH)2 film was fabricated on MAO-coated Mg alloy AZ31 in an alkaline electrolyte containing ethylenediamine tetraacetic acid disodium(EDTA-2 Na) to reinforce the protection. Surface morphology, chemical composition and growth process of the MAO/Mg(OH)2 hybrid coating were examined using field-emission scanning electron microscopy, energy dispersive X-ray spectrometer, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectrophotometer. Corrosion resistance of the coatings was evaluated via potentiodynamic polarization curves and hydrogen evolution tests. Results manifested that the Mg(OH)2 coating possesses a porous nano-sized structure and completely seals the micro-pores and micro-cracks of the MAO *** intermetallic compound of AlMn phase in the substrate plays a key role in the growth of Mg(OH)2 film. The current density of Mg(OH)2-MAO composite coating decreases three orders of magnitude in comparison with that of bare substrate, indicating excellent corrosion resistance. The Mg(OH)2-MAO composite coating is beneficial to the formation of calcium phosphate corrosion products on the surface of Mg alloy AZ31, demonstrating a great promise for orthopaedic applications.

关键词： Magnesium alloys Micro-arc oxidation Magnesium hydroxide Coatings Biomaterials

Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/β-catenin signaling

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Bone Research 2023年第4期11卷 819-833页

作者： Ri-Xu Liu rong-he Gu Zhi-peng Li Zhi-Quan Hao Qin-Xiao Hu Zhen-Yan Li Xiao-Gang Wang Wang Tang Xiao-he Wang Yu-Kai zeng Zhen-wei Li Qiu Dong Xiao-Feng Zhu Di Chen Ke-wei Zhao rong-Hua zhang Zhen-Gang Zha Huan-Tian zhang Department of Bone and Joint Surgery the First Affiliated Hospital of Jinan UniversityKey Laboratory of Regenerative Medicine of Ministry of EducationJinan UniversityGuangzhou 510630 GuangdongChina Department of Orthopedic and Spine Surgery The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120 GuangdongChina School of Basic Medical Sciences of Guangxi Medical University the Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530022 GuangxiChina Key Laboratory of Big Data-Based Precision Medicine School of Engineering MedicineBeihang University100191 BeijingChina Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization College of PharmacyJinan UniversityGuangzhou 510630 GuangdongChina Research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences518005 ShenzhenChina Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese Medicine510375 GuangzhouChina

Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely *** recently demonstrated that Trim21 plays a crucial role in regulating osteoblast(OB)differentiation in ***,how Trim21 contributes to skeletal degenerative disorders,including osteoporosis,remains ***,human and mouse bone specimens were evaluated,and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis ***,we found that global knockout of the Trim21 gene(KO,Trim2^(1-/-))resulted in higher bone mass compared to that of the control *** further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim21 depletion suppressed osteoclast(OC)formation of RAW264.7 *** addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim21^(-/-)and Ctsk-cre;Trim21^(f/f)mice was largely compromised compared to that of the littermate control ***,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of *** importantly,the loss of Trim21 prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 *** current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

关键词： YAP1 osteoporosis depletion

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

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Protein & Cell 2021年第7期12卷 557-577页

作者： Yu-Kun Xia yi-rong zeng Meng-Li zhang peng Liu Fang Liu Hao zhang Chen-Xi he yi-Ping Sun Jin-Ye zhang Cheng zhang Lei Song Chen Ding Yu-Jie Tang Zhen Yang Chen Yang Pu Wang Kun-Liang Guan Yue Xiong Dan Ye Huashan Hospital Fudan Universityand Molecular and Cell Biology LabInstitutes of Biomedical Sciencesand the Shanghai Key Laboratory of Medical Epigeneticsand the Key Laboratory of Metabolism and MolecularMinistry of EducationShanghai 200032China The International Co-Laboratory of Medical Epigenetics and Metabolism Ministry of Science and TechnologyShanghai 200032China Department of Neurosurgery Huashan HospitalFudan UniversityShanghai 200032China Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Department of PathophysiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Key Laboratory of Synthetic Biology Institute of Plant Physiology and EcologyShanghai 200032China Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200032China State Key Laboratory of Proteomics Beijing Proteome Research CenterBeijing Institute of Radiation MedicineBeijing 102206China National Center for Protein Sciences(The PHOENIX Center Beijing)Beijing 102206China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development School of Life SciencesInstitutes of Biomedical SciencesFudan UniversityShanghai 200032China Department of Pharmacology and Moores Cancer Center University of California San DiegoLa JollaCAUSA Lineberger Comprehensive Cancer Center Department of Biochemistry and BiophysicsUniversity of North CarolinaChapel HillNCUSA Department of General Surgery Huashan HospitalFudan UniversityShanghai 200032China

Additional sex combs-like 1(ASXL1)interacts with BRCA1-associated protein 1(BAP1)deubiquitinase to oppose the polycomb repressive complex 1(PRC1)-mediated histone H2A *** BAP1 mutations are found in a spectrum of human malignancies,while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor *** all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region,resulting in the production of C-terminally truncated mutant ASXL1 *** ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogen-esis are ***,we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target *** show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells,and lose the ability to interact with FOXK1/*** deletion of the mutant allele eliminates the expression of C-termi-nally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1,thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes,particularly those involved in glucose metabolism,oxygen sensing,and JAK-STAT3 signaling *** addition to FOXK1/K2,we also identify other DNA-bind-ing transcription regulators including transcription factors(TFs)which interact with wild-type ASXL1,but not C-terminally truncated *** results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

关键词： ASXL1 BAP1 FOXK1/K2 leukemia epigenetics

Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-he Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei yi Hao zhang wei-Guo Cao rong Li wei Tang Yan Zhao peng-peng Xu Li Wang wei-Li Zhao Shanghai Institute of hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nuclear Medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71

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Virologica Sinica 2024年第5期39卷 812-820页

作者： rong-rong zhang Meng-Jiao he Chao zhou Yan-peng Xu wei Tang Tian-Shu Cao Zheng-Jian Wang Mei Wu Tao Ming yi-Jiao Huang Meng-Xu Sun Hui Zhao Yong-Qiang Deng Xiao-Feng Li Bin Wang Qing Ye Cheng-Feng Qin State Key Laboratory of Pathogen and Biosecurity AMMSBeijing100071China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Medical College(SHMC)Fudan UniversityShanghai200032China Advaccine Biopharmaceutics(Suzhou)Co.LTD Suzhou215000China

Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global *** the inactivated vaccine being licensed,other vaccine candidates based on advanced technology platforms are under *** this report,we rationally designed and constructed two DNA-launched live attenuated vaccine candidates(pDL-EV71)under the control of specific *** vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious *** importantly,the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR/mice,demonstrating its safety ***,a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice.A single-dose immunization with 10μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal ***,our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.

关键词： Hand,foot and mouth disease(HFMD) Human enterovirus 71(EV71) DNA vaccine DNA-launched vaccine Live attenuated vaccine

A review of surface damage/microstructures and their effects on hydrogen/helium retention in tungsten

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Tungsten 2020年第1期2卷 34-71页

作者： Yong‑Gang Li Qi‑rong Zheng Liu‑Ming wei Chuan‑Guo zhang Zhi zeng Key Laboratory of Materials Physics Institute of Solid State PhysicsChinese Academy of SciencesHefei 230031China Science Island Branch of Graduate School University of Science and Technology of ChinaHefei 230026China

The change in surface damage/microstructures and its effects on the hydrogen(H)isotope/helium(he)dynamic behavior are the key factors for investigating issues of tungsten(W)-based plasma-facing materials(PFMs)in fusion such as surface erosion,H/he retention and tritium(T)*** surface damage/microstructures are introduced in W by high-temperature plasma irradiation and new material design,typically including pre-damage and multi-ion co-deposition induced structures,solute elements and related composites,native defects like dislocations and interfaces,and *** experimental and theoretical researches were performed on H isotope/he retention in complex W-based materials in the past *** this review,we aim to provide an overview of typical surface damage/microstructures and their effects on H/he retention in W,both in the experiment and multiscale *** distribution/state,dynamics evolution,and interaction with defects/microstructures of H/he are generally summarized at different ***,the current difficulties,challenges and future directions are also discussed about H/he retention in complex W-based PFMs.

关键词： Surface damage/microstructures Hydrogen/helium retention Tungsten Plasma-facing materials