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Genetic association analysis-based networks and classification of human UCP1 polymorphisms

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Genes & Diseases 2024年第3期11卷 63-65页

作者： Donghai Li State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityJiangsu 210023China

Uncoupling protein 1(UCP1,also known as thermogenin or SLC25A7)plays an important role in the uncoupling of oxidative phosphorylation and adaptive non-shivering thermogenesis(NST).The genomic location for UCP1 is chromosome 4 q31.1:140,555,770--140,568,961(GRCh38/hg38)and its size is 13,192 bases split into 6 *** dbSNP,3650 short genetic variations of human UCP1 are *** this study,UCP1 serves as an example to construct polymorphism-trait networks and enable a func-tional classification.

关键词： classification. UCP1 networks

Inhibition mechanisms of CRISPR-Cas9 by AcrI IA25.1 and AcrI IA32

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Science China life sciences 2024年

作者： Jianlin Zheng Yuwei Zhu Tengjin Huang Wenbo Gao Jiale He Zhiwei Huang HIT Center for life sciences School of Life Science and Technology Harbin Institute of Technology Westlake Center for Genome Editing Westlake Laboratory of Life Sciences and Biomedicine School of Life Sciences Westlake University

In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, AcrIIA25.1 and AcrIIA32 have been found to effectively inhibit the activity of SpyCas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by AcrIIA25.1 and AcrIIA32 bound to SpyCas9-sgRNA. Using structural analysis and biochemical experiments, we revealed that AcrIIA25.1 and AcrIIA32 recognize a novel, previously-unidentified anti-CRISPR binding site on SpyCas9. We found that both AcrIIA25.1 and AcrIIA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting SpyCas9 from recognizing protospacer adjacent motif(PAM) and unwinding double-stranded DNA. In addition,they may inhibit nuclease activity by blocking the dynamic conformational changes of the SpyCas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of SpyCas9 activity,and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

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Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression,elucidating the curative mechanism of Danzhi Xiaoyao powder

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Journal of Traditional Chinese Medical sciences 2024年第1期11卷 3-20页

作者： Kunyu Li Leiming You Jianhua Zhen Guangrui Huang Ting Wang Yanan Cai Yunan Zhang Anlong Xu school of life sciences Bejing University of Chinese MedicineBeijing 102488China school of life sciences Sun Yat-Sen UniversityGuangzhou 510006Chin

Objective:To investigate the molecular mechanism and identify potential drugs for subthreshold depression(SD),and elucidate the detalied mechanism of Danzhi Xiaoyao powder(DZXY)in ***:Using RNA-sequencing,we identified differentially expressed genes(DEGs)in leukocytes of SD compared to healthy controls,deciphered their functions and pathways,and identified the hub genes of *** also assessed changes in leukocyte transcription factor activity in patients with SD using the TELis *** Connectivity Map database was retrieved to screen candidate drugs for *** on network pharmacology,we elucidated the"multi-component,multi-target,and multi-pathway"mechanism of DZXY in the treatment of ***:We identified 1080 DEGs(padj<0.05 and|log2(fold change)l≥1&protein coding)in the leukocytes of patients with *** DEGs,including hub genes,were primarily involved in immune and inflammatory response-related *** factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune *** Map analysis identified 28 potential drugs for SD treatment,particularly SB-202190 and *** the"Direct Compounds-Direct Targets-Pathways"network for DZXY and SD revealed the curative mechanisms of DZXY in SD,primarily including inflammatory response,lipid metabolism,immune response,and other ***:These results provide new insights into the characteristics and functional changes of leukocytes in SD,partially illustrate the pathogenesis of SD,and suggest potential drugs for *** curative mechanisms of DZXY in SD are also partially elucidated.

关键词： Subthreshold depression Leukocyte mRNAbiomarker CTRA Transcription factor activity CMap Danzhi Xiaoyaopowder Networkpharmacology

The BEL1-like transcription factor GhBLH5-A05 participates in cotton response to drought stress

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The Crop Journal 2024年第1期12卷 177-187页

作者： Jing-Bo Zhang Yao Wang Shi-Peng Zhang Fan Cheng Yong Zheng Yang Li Xue-Bao Li Hubei Key Laboratory of Genetic Regulation and Integrative Biology School of Life SciencesCentral China Normal UniversityWuhan 430079HubeiChina College of life sciences Xinjiang Normal UniversityUrumqi 830017XinjiangChina

Drought stress impairs crop growth and ***1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought *** we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought *** of GhBLH5-A05 in cotton was induced by drought *** of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought ***5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these ***5-A05 interacted with the KNOX transcription factor ***-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and *** conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.

关键词： Cotton(Gossypium hirsutum) BEL1-like transcription factor Drought stress Transcriptional regulation Drought tolerance

Gibberellin promotes cambium reestablishment during secondary vascular tissue regeneration after girdling in an auxin-dependent manner in Populus

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Journal of Integrative Plant Biology 2024年第1期66卷 86-102页

作者： Yufei Zhang Lingyan Wang Yuexin Wu Donghui Wang Xin‐Qiang He State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China

Secondary vascular tissue(SVT)development and regeneration are regulated by *** this study,we used an in vitro SVT regeneration system to demonstrate that gibberellin(GA)treatment significantly promotes auxin-induced cambium *** GA content by overexpressing or knocking down ent-kaurene synthase(KS)affected secondary growth and SVT regeneration in *** poplar DELLA gene GIBBERELLIC ACID INSENSITIVE(PtoGAI)is expressed in a specific pattern during secondary growth and cambium regeneration after *** of PtoGAI disrupted poplar growth and inhibited cambium regeneration,and the inhibition of cambium regeneration could be partially restored by GA *** analysis of the PtaDR5:GUS transgenic plants,the localization of PIN-FORMED 1(PIN1)and the expression of auxin-related genes found that an additional GA treatment could enhance the auxin response as well as the expression of PIN1,which mediates auxin transport during SVT *** together,these findings suggest that GA promotes cambium regeneration by stimulating auxin signal transduction.

关键词： auxin cambium gibberellin Populus secondary vascular tissue regeneration

Chemical Synthesis of a Key Precursor Relevant to the Tetrasaccharide Repeating Unit from Treponema medium ATCC 700293

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Chinese Journal of Chemistry 2024年第14期42卷 1615-1622页

作者： Wenbin Sun Guangzong Tian Meiru Ding Chunjun Qin Xiaopeng Zou Jing Hu Jian Yin Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of Biotechnology&School of Life Sciences and Health EngineeringJiangnan UniversityLihu Avenue 1800WuxiJiangsu214122 China Wuxi school of Medicine Jiangnan UniversityLihu Avenue 1800WuxiJiangsu214122 China

Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denticola and Treponema medium).Although different from conventional lipopolysaccharides,the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine ***,we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L-ornithine(L-Orn)and D-aspartic acid(D-Asp)*** efficiency of non-reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and ***[3+1]glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group,thereby improving the efficiency of synthesizing the target *** L-Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and ***,the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional-group modifications have provided valuable insights for synthesizing other complex bacterial glycans.

关键词： Glycosylation Total synthesis Treponema medium ATCC 700293 Tetrasaccharide precursor Protecting group Oligosaccharides Regioselectivity Neighboring-group effects

Comparative proteomics reveals the response and adaptation mechanisms of white Hypsizygus marmoreus against the biological stress caused by Penicillium

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Food Science and Human Wellness 2024年第3期13卷 1645-1661页

作者： Xiuqing Yang Sizhu Li Xiaohang Li Chenxiao Zhang Meijie Liu Lizhong Guo Lin Liu Hao Yu Shandong Provincial Key Laboratory of Applied Mycology School of Life SciencesQingdao Agricultural UniversityQingdao 266109China

White Hypsizygus marmoreus is a popular edible *** mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and *** could compete for limited space and nutrients through rapid growth and produce a variety of harmful gases,such as benzene,aldehydes,phenols,etc.,to inhibit the growth of *** mycelium.A series of changes occurred in *** proteome after contamination when detected by the label-free tandem mass spectrometry(MS/MS)*** proteins with up-regulated expression worked together to participate in some processes,such as the non-toxic transformation of harmful gases,glutathione metabolism,histone modification,nucleotide excision repair,clearing misfolded proteins,and synthesizing glutamine,which were mainly used in response to biological *** proteins with down-regulated expression are mainly related to the processes of ribosome function,protein processing,spliceosome,carbon metabolism,glycolysis,and *** reduction in the function of these proteins affected the production of the cell components,which might be an adjustment to adapt to growth *** study further enhanced the understanding of the biological stress response and the growth restriction adaptation mechanisms in edible *** also provided a theoretical basis for protein function exploration and edible mushroom food safety research.

关键词： Hypsizygus marmoreus Penicillium Proteomics Biological stress response Adaptation

Evolution and conservation genetics of pangolins

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Integrative Zoology 2024年第3期19卷 426-441页

作者： Tongtong GU Jingyang HU Li YU State Key Laboratory for Conservation and Utilization of Bio-Resource in Yunnan School of Life SciencesYunnan UniversityKunmingChina

Pangolins(Pholidota,Manidae)are classified as an evolutionarily distinct and globally endangered mammal due to their unique morphology(nail-like scales and a myrmecophagous diet)and being the victim of heavy poaching and worldwide *** such,pangolins serve as a textbook example for studying the special phenotypic evolutionary adaptations and conservation genetics of an endangered *** years have demonstrated significant advancements in the fields of molecular genetics and genomics,which have translated to a series of important research achievements and breakthroughs concerning the evolution and conservation genetics of *** review comprehensively presents the hitherto advances in phylogeny,adaptive evolution,conservation genetics,and conservation genomics that are related to pangolins,which will provide an ample understanding of their diversity,molecular adaptation mechanisms,and evolutionary *** addition,we highlight the priority of investigating species/population diversity among pangolins and suggest several avenues of research that are highly relevant for future pangolin conservation.

关键词： adaptive evolution conservation genetics conservation genomics pangolins phylogeny

Targeting autophagy by polyphenols to prevent glycative stress-toxicity in the brain

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Neural Regeneration Research 2024年第5期19卷 941-942页

作者： Alejandro Ponce-Mora Eloy Bejarano Department of Biomedical sciences School of Health Sciences and Veterinary SchoolUniversidad Cardenal Herrera-CEUCEU UniversitiesValenciaSpain

Glycative stress-a pathological hub in brain dysfunction:The nervous system is an intricate network that requires precise and complex *** recent years,growing evidence highlights the detrimental impact of glycative stress on brain homeostasis,which disables a network of vital processes,necessary for optimal function(Gómez et al.,2021).

关键词： homeostasis stress