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Supramolecular complex glycoconjugate vaccine generates self-enhancement effects for carbohydrate antigen delivery

Chinese Chemical Letters 2024年第2期35卷 317-322页

作者： Han Lin Yanchun Li Kun Zhou Dan Li Hangyan Yu Jie Zhao Haofei Hong Zhifang Zhou Zhimeng Wu Key laboratory of Carbohydrate Chemistry & biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

Targeting delivery of tumor-associated carbohydrate antigen(TACA)-based vaccine to antigen-presenting cells(APCs)mediated by endogenous antibodies can improve the immunogenicity of ***,an essential requirement of this approach is to generate high titers of endogenous antibodies in vivo through pre-immunization,which complicates the immunization procedure and may cause side ***,we report a new generation of APC-targeting TACA-based supramolecular complex vaccine,assembled by sialyl Thomsen-nouveau-bovine serum albumin-adamantine(sTn-BSA-Ada)and heptavalent rhamnose(Rha)-modifiedβ-cyclodextrin(β-CD)via host-guest *** complex vaccine retained anti-Rha antibodies recruiting capability and facilitated the APCs uptake of the vaccine via the interaction of the Fc-domain with the Fc receptors on *** demonstrate that direct immunization of complex vaccine elicited anti-Rha and anti-sTn specific immune response synchronously,generating a novel self-enhancement effect that can improve the antigen delivery to APCs in high *** structure-activity relationship(SAR)study proved that complex vaccine 4 with polyethylene glycol 6(PEG 6)linker in host molecule provoked a robust and specific sTn immune response comparable to the pre-immunization *** antisera induced by complex vaccine,either through direct immunization or pre-immunization,exhibited equal potency of cytotoxicity against the sTn expression cancer *** study provides a general platform for TACA-based vaccines with self-enhancement effects without the need for pre-immunization.

关键词： Glycoconjugate vaccine Endogenous antibody APC-targeting Supramolecular complex sTn antigen

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Regulatory RNAs in Bacillus subtilis:A review on regulatory mechanism and applications in synthetic biology

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Synthetic and Systems biotechnology 2024年第2期9卷 223-233页

作者： Anqi Peng Guobin Yin Wenjie Zuo Luyao Zhang Guocheng Du Jian Chen Yang Wang Zhen Kang The Science Center for Future Foods Jiangnan UniversityWuxi214122China The Key laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China The Key laboratory of Industrial biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China

Bacteria exhibit a rich repertoire of RNA molecules that intricately regulate gene expression at multiple hierarchical levels,including small RNAs(sRNAs),riboswitches,and antisense ***,the majority of these regulatory RNAs lack or have limited protein-coding capacity but play pivotal roles in orchestrating gene expression by modulating transcription,post-transcription or translation *** and redesigning these regulatory RNA elements have emerged as pivotal strategies in the domains of metabolic engineering and synthetic *** previous investigations predominantly focused on delineating the roles of regulatory RNA in Gram-negative bacterial models such as Escherichia coli and Salmonella enterica,this review aims to summarize the mechanisms and functionalities of endogenous regulatory RNAs inherent to typical Gram-positive bacteria,notably Bacillus ***,we explore the engineering and practical applications of these regulatory RNA elements in the arena of synthetic biology,employing *** as a foundational chassis.

关键词： Regulatory RNA devices Small RNAs Riboswitches Synthetic biology Bacillus subtilis

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Minimizing endogenous cryptic plasmids to construct antibiotic-free expression systems for Escherichia coli Nissle 1917

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Synthetic and Systems biotechnology 2024年第1期9卷 165-175页

作者： Siyan Zhou Linlin Zhao Wenjie Zuo Yilin Zheng Ping Zhang Yanan Sun Yang Wang Guocheng Du Zhen Kang The Science Center for Future Foods Jiangnan UniversityWuxi214122China The Key laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China The Key laboratory of Industrial biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China

The probiotic bacterium Escherichia coli Nissle 1917(EcN)holds significant promise for use in clinical and biological ***,the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its *** this study,we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and *** non-essential elements were removed to create more stable derivatives pMUT1NR△and pMUT2HBC△.Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinaseⅢand the biosynthesis of *** to traditional antibiotic-dependent expression systems,our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.

关键词： Cryptic plasmids Antibiotic-free Gene expression Plasmid stability E.coli Nissle 1917

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Rational engineering of homospermidine synthase for enhanced catalytic efficiency toward spermidine synthesis

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Synthetic and Systems biotechnology 2024年第3期9卷 549-557页

作者： Wenjing Liu Xiaoxiang Hu Yi Yan Yujie Cai The Key laboratory of Industrial biotechnology Ministry of EducationSchool of BiotechnologyJiangnan University1800 Lihu RoadWuxiJiangsu214122China

Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various *** spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme *** on sequence-structure-function relationships,we engineered the widely studied homospermidine synthase from Blastochloris viridis(BvHSS)and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and *** specific activities of BvHSS and the mutants D361E and E232D+D361E(E232D-D)were 8.72,46.04 and 48.30 U/mg,*** optimal pH for both mutants was 9.0,and the optimal temperature was 50◦*** docking and dynamics simulations revealed that mutating aspartic acid at position 361 to glutamic acid narrowed the substrate binding pocket,promoting stable spermidine ***,mutating glutamic acid at position 232 to aspartic acid enlarged the substrate channel entrance,facilitating substrate entry into the active pocket and enhancing spermidine *** whole-cell catalysis lasting 6 h,D361E and E232D-D synthesized 725.3 and 933.5 mg/L of spermidine,*** study offers a practical approach for single-enzyme catalyzed spermidine synthesis and sheds light on the crucial residues influencing homospermidine synthase catalytic activity in spermidine production.

关键词： Homospermidine synthase Polyamine Site-directed mutagenesis Spermidine Structural analysis

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Design-build-test of recombinant Bacillus subtilis chassis cell by lifespan engineering for robust bioprocesses

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Synthetic and Systems biotechnology 2024年第3期9卷 470-480页

作者： Kexin Ren Qiang Wang Jianghua Chen Hengwei Zhang Zhoule Guo Meijuan Xu Zhiming Rao Xian Zhang Key laboratory of Industrial biotechnology of the Ministry of Education School of BiotechnologyJiangnan UniversityWuxiJiangsu214122China Yixing Institute of Food and biotechnology Co. LtdYixing214200China

Microbial cell factories utilize renewable raw materials for industrial chemical production,providing a promising path for sustainable *** subtilis is widely used in industry for its food safety properties,but challenges remain in the limitations of microbial *** study proposes a novel strategy based on lifespan engineering to design robust *** chassis cells to supplement traditional metabolic modification strategies that can alleviate cell autolysis,tolerate toxic substrates,and get a higher mass transfer *** modified chassis cells could produce high levels of L-glutaminase,and tolerate hydroquinone to produceα-arbutin *** a 5 L bioreactor,the L-glutaminase enzyme activity of the final strain CRE15TG was increased to 2817.4±21.7 U m L^(-1),about 1.98-fold compared with that of the wild ***α-arbutin yield of strain CRE15A was increased to 134.7 g L^(-1),about 1.34-fold compared with that of the *** our knowledge,both of the products in this study performed the highest yields reported so *** chassis modification strategy described in this study can Improve the utilization efficiency of chassis cells,mitigate the possible adverse effects caused by excessive metabolic modification of engineered strains,and provide a new idea for the future design of microbial cell factories.

关键词： Bacillus subtilis Chassis cell Lifespan engineering Robustness Industrial production

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Rational design of a single-component mRNA vaccine against orthopoxvirus and SARS-CoV-2

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Science China(Life Sciences) 2024年第6期67卷 1311-1313页

作者： Yilong Yang Xiaofan Zhao Yu Li Xiaodong Zai Xinyi Wang Yue Zhang Xiaolin Wang Peng Lv Jun Zhang Lihua Hou Junjie Xu Wei Chen laboratory of Advanced biotechnology Beijing Institute of BiotechnologyAcademy of Military Medical SciencesBeijing 100071China

Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to *** the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global *** includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).

关键词： vaccine Rational

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OsATL32 ubiquitinates the reactive oxygen species-producing OsRac5-OsRbohB module to suppress rice immunity

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Journal of Integrative Plant Biology 2024年第7期66卷 1459-1480页

作者： Yuqing Yan Hui Wang Yan Bi Jiajing Wang Muhammad Noman Dayong Li Fengming Song National Key laboratory for Rice Biology and Breeding Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Ministry of Agriculture Key laboratory of Molecular Biology of Crop Pathogens and Insect Pests Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Key laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province Institute of BiotechnologyZhejiang UniversityHangzhou 310058China

Ubiquitination-mediated protein degradation is integral to plant immunity,with E3 ubiquitin ligases acting as key factors in this ***,we report the functions of OsATL32,a plasma membrane-localized Arabidopsis Tóxicos En Levadura(ATL)-type E3 ubiquitin ligase,in rice(Oryza sativa)immunity and its associated regulatory *** found that the expression of OsATL32 is downregulated in both compatible and incompatible interactions between rice and the rice blast fungus Magnaporthe *** OsATL32 protein level declines in response to infection by a compatible *** strain or to chitin ***32 negatively regulates rice resistance to blast and bacterial leaf blight diseases,as well as chitin-triggered *** and genetic studies revealed that OsATL32 suppresses pathogen-induced reactive oxygen species(ROS)accumulation by mediating ubiquitination and degradation of the ROS-producing OsRac5–OsRbohB module,which enhances rice immunity against *** protein phosphatase PHOSPHATASE AND TENSIN HOMOLOG enhances rice blast resistance by dephosphorylating OsATL32 and promoting its degradation,preventing its negative effect on rice *** study provides insights into the molecular mechanism by which the E3 ligase OsATL32 targets a ROS-producing module to undermine rice immunity.

关键词： E3 ligase OsATL32 OsRac5-OsRbohB module phosphatase OsPTEN reactive oxygen species rice immunity

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Characterization,expression dynamics,and potential function of OPA1 for regulation of mitochondrial morphology during spermiogenesis in Phascolosoma esculenta

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Journal of Oceanology and Limnology 2024年第1期42卷 187-200页

作者： Xinming GAO Binbin FENG Chen DU Congcong HOU Shan JIN Daojun TANG Junquan ZHU Key laboratory of Applied Marine biotechnology by the Ministry of Education and Key laboratory of Marine biotechnology of Zhejiang Province School of Marine SciencesNingbo UniversityNingbo 315211China College of Ecology Lishui UniversityLishui 323000China

Mitochondria undergo morphological changes during spermatogenesis in some *** mechanism and role of mitochondrial morphology regulation,however,remain somewhat *** this study,we analyzed the molecular characteristics,expression dynamics and subcellular localization of optic atrophy protein 1(OPA1),a mitochondrial fusion and cristae maintenance-related protein,to reveal the possible regulatory mechanisms underlying mitochondrial morphology in Phascolosoma esculenta *** full-length cDNA of the *** opa1 gene(Pe-opa1)is 3743 bp in length and encodes 975 amino *** Pe-OPA1 protein is highly conservative and includes a transmembrane domain,a GTPase domain,two helical bundle domains,and a lipid-interacting *** and protein expression was higher in the coelomic fluid(a site of spermatid development)of male *** and increased first and then decreased from March to ***,their expression during the breeding stage was significantly higher than during the non-breeding stage,suggesting that Pe-OPA1 is involved in *** *** Pe-OPA1 protein was more abundant in components consisting of many spermatids than in components without,indicating that Pe-OPA1 mainly plays a role in the spermatid in coelomic ***,Pe-OPA1 was mainly detected in the spermatid *** experiments showed that the Pe-OPA1 are constitutively expressed and co-localized with mitochondria during spermiogenesis,suggesting its involvement in *** *** results provide evidence for Pe-OPA1's involvement in the regulation of mitochondrial morphology during spermiogenesis.

关键词： optic atrophy protein 1(OPA1) spermiogenesis Phascolosoma esculenta mitochondrial dynamics spermatid

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RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila

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Marine Life Science & Technology 2024年第2期6卷 183-197页

作者： Huijuan Hao Yinjie Lian Chenhui Ren Sitong Yang Min Zhao Tao Bo Jing Xu Wei Wang Key laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Institute of BiotechnologyShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China Shanxi Key laboratory of biotechnology Taiyuan 030006China

Histone modification and nucleosome assembly play important roles in chromatin-related *** chaperones form different complexes and coordinate histone transportation and *** histone chaperone complexes have been identified in different *** ciliate protozoa(ciliates)have various chromatin structures and different nuclear ***,histone chaperone components and functions of different subunits remain unclear in ***-rahymema thermophila contains a transcriptionally active macronucleus(MAC)and a transcriptionally inactive micronu-cleus(MIC)which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental ***,we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental ***1 knockdown inhibited cellular *** macronuclear morphology became bigger in growing *** abnormal macronuclear structure also occurred in the starvation ***,micronuclear meiosis was disturbed during sexual development,leading to a failure to generate new gametic ***1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental ***1 knockdown affected expression levels of the genes involved in chromatin organization and *** together,RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in ***.

关键词： Gametogenesis Histone chaperone Macronuclear structure RebL1 Tetrahymena thermophilaIntroduction

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Combined proteomic and metabolomic studies on the liver of Amur sturgeon Acipenser schrenckii under titanium dioxide nanoparticle exposure

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Journal of Oceanology and Limnology 2024年第3期42卷 1001-1015页

作者： Zhou ZHOU Ting LIU Jie KONG Zhenxing ZHAO Junquan ZHU Key laboratory of Aquacultural biotechnology Ministry of Educationand Key Laboratory of Marine Biotechnology of Zhejiang ProvinceCollege of Marine SciencesNingbo UniversityNingbo 315000China Guizhou Fisheries Research Institute Guizhou Academy of Agriculture SciencesGuiyang 550000China

Nanomaterials,particularly titanium dioxide nanoparticles(TiO_(2)-NPs),are extensively utilized across various ***,their environmental release has raised concerns regarding their potential ecological and environmental *** reproductive toxicity of TiO_(2)-NPs in fish species has attracted considerable attention,yet conflicting research outcomes have been *** investigated the effects of TiO_(2)-NPs exposure on the liver of juvenile Amur sturgeon Acipenser schrenckii using label-free proteomic and untargeted metabolomic *** experiment included a control group and three groups exposed to different concentrations of TiO_(2)-NPs(low,TL;medium,TM;high,TH).Compared to the control group,9,19,and 25 proteins and 35,73,and 158 metabolites were differentially expressed in the TH,TM,and TL TiO_(2)-NP-exposed groups,*** differentially expressed genes(DEGs)were enriched in the Kyoto Encyclopedia for Genes and Genomes(KEGG)pathways related to glycolysis and ***,among the 126 correlated proteins,the most enriched pathways were associated with endocytosis and protein processing in the endoplasmic ***,syringic acid was significantly downregulated across all three TiO_(2)-NP-exposed *** obtain a comprehensive overview of the TiO_(2)-NP-induced expression changes,a co-regulated network of proteins and metabolites associated with TiO_(2)-NPs exposure was *** to TiO_(2)-NPs led to enrichment and alteration of pathways related to immune responses,including endocytosis,protein processing in the endoplasmic reticulum,and peroxisome proliferator-activated receptor(PPAR)*** conclusion,our findings indicate that exposure to TiO_(2)-NPs might disrupt glucose metabolism and induce immune responses,thus contributing to our understanding of the environmental impacts of nanomaterials and highlighting the need for further research and development of potential mitigation strategies.

关键词： TiO_(2)-nanoparticle exposure proteomics metabolomics glucose metabolism immune response

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