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TcPO_(2)changes are more pronounced than SpO_(2)changes during simulated altitude changes in a hypobaric oxygen chamber:a nonrandomized controlled trial

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Emergency and Critical Care Medicine 2024年第3期4卷 105-110页

作者： Yang Li Liang Chen Ziyu Fu Zhiwei Wang Shijun sun Xiaorong luan Dedong Ma Tianliang Hu School of Nursing and Rehabilitation Shandong UniversityJinanShandongChina Department of Emergency and Critical Care Medicine Qilu Hospital of Shandong UniversityJinanShandongChina Department of Pulmonary and Critical Care Medicine Qilu Hospital of Shandong UniversityJinanShandongChina Emergency Management Center of State Grid Shandong Electric Power Company JinanShandongChina School of Nursing and Rehabilitation Cheeloo College of MedicineUniversity of ShandongDepartment of Infection ControlQilu Hospital of Shandong UniversityJinanShandongChina School of Mechanical Engineering Shandong UniversityKey Laboratory of the Ministry of Education for Efficient and Clean Machinery ManufacturingNational Experimental Teaching Demonstration Center for Mechanical EngineeringJinanShandongChina

Background:Hypoxia is a significant risk factor of ***,no studies have used transcutaneous tissue partial pressure of oxygen(TcPO_(2))and partial pressure of carbon dioxide(TcPCO_(2))monitors to measure the respective partial pressures in healthy *** saturation(SpO_(2))is often used for traditional monitoring of vital *** study investigated the changes in TcPO_(2)and SpO_(2)values during rapid changes in *** trial was registered at ***(registration ***06076057).Methods:Healthy adult volunteers were instructed to sit vertically in a hypobaric oxygen chamber,which ascended from 0 m to 2500 m at a uniform speed within 10 *** Danish Radiometer TCM4 was used to measure TcPO_(2)and TcPCO_(2)with the ventral side of the upper arm as the measurement *** Shenzhen Kerokan P0D-1 W pulse oximeter was used to measure heart rate and SpO_(2),with values recorded once every 500 ***:Altogether,49 healthy volunteers were recruited between March 2023 and August *** increasing altitude,TcPO_(2)and SpO_(2)decreased significantly(P500 m,statistical significance was identified between TcPO_(2)in both sexes(P<0.05).Statistical significance in TcPCO_(2)and heart rate was observed at the different elevations(P<0.05).Conclusion:In acutely changing low-pressure hypoxic environments,TcPO_(2)changed more dramatically than SpO_(2).

关键词： Altitude change Low-pressure oxygen chamber Transcutaneous oxygen saturation Transcutaneous partial pressure of oxygen

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浅谈染色质高级结构与基因转录的远程调控

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中国细胞生物学学报 2014年第11期36卷 1460-1469页

作者：孙鸾孙玉洁江苏省人类功能基因组学重点实验室南京医科大学基础医学院细胞生物学系南京210029

精确的基因表达调控是细胞分化、个体发育和细胞维持正常生命活动的必要条件,转录调控是真核细胞基因表达调控最关键的环节,其神秘和精深吸引着无数科学家为之奋斗不已。染色质构象捕获及其衍生技术的建立和2003年启动的"DNA元件百科全... 详细信息

精确的基因表达调控是细胞分化、个体发育和细胞维持正常生命活动的必要条件,转录调控是真核细胞基因表达调控最关键的环节,其神秘和精深吸引着无数科学家为之奋斗不已。染色质构象捕获及其衍生技术的建立和2003年启动的"DNA元件百科全书"计划,将人们对基因转录调控的认识从二维层面推向三维空间。基因组中分布着众多调控元件,它们与所调控的靶基因间可相距几万甚至几十万个核苷酸,可以与靶基因位于相同或不同的染色体上。依据染色质环模型,调控元件可通过染色质环高级结构,与靶基因在空间上充分接近并相互作用,发挥其调控功能。同一个调控元件可以调控不同的靶基因,而相同的基因亦可能受不同调控元件的调节,由此细胞在染色质高级结构层面形成了一个复杂的调节基因转录活性的三维网络。该文分别从基因远程调控现象的发现、研究方法、相关机制及面临的挑战等方面作一简要综述。

关键词：基因转录远距离调控染色质高级结构

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Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 795-807页

作者： Yongchun Pan Xiaowei luan Fei Zeng Xuyuan Wang Shurong Qin Qianglan Lu Guanzhong He Yanfeng Gao Xiaolian sun Xin Han Bangshun He Yujun Song Department of Laboratory Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China State Key Laboratory of Natural Medicines Key Laboratory of Drug Quality Control and PharmacovigilanceDepartment of Pharmaceutical AnalysisChina Pharmaceutical UniversityNanjing 211198China School of Medicine&Holistic Integrative Medicine Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene ***,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor ***,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer *** this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are *** intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as *** the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target *** tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation ***,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

关键词： CRISPRdelivery Enzymeencapsulation Logic gate Hybridmaterial Hypoxia Gene editing Precise nanomedicine Multimodal therapy

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Natural variation in maize gene ZmSBR1 confers seedling resistance to Fusarium verticillioides

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The Crop Journal 2024年第3期12卷 836-844页

作者： Yunxia Song Peipei Ma Jingyang Gao Chaopei Dong Zhao Wang Yifan luan Jiafa Chen Doudou sun Pei Jing Xuecai Zhang Weibin Song Zijian Zhou Jianyu Wu College of Agronomy Henan Agricultural UniversityZhengzhou 450002HenanChina College of Life Sciences Henan Agricultural UniversityZhengzhou 450002HenanChina Global Maize Program International Maize and Wheat Improvement Center(CIMMYT)Apdo 6-64106600 MexicoDFMexico National Maize Improvement Center Department of Plant Genetics and BreedingChina Agricultural UniversityBeijing 100193China

Maize seedling blight caused by Fusarium verticillioides is a widely occurring maize disease,but the genetics and mechanisms of resistance are not well *** this study,GWAS performed by MLM and 3VmrMLM identified 40 and 20 QTNs,associated with seedling blight *** methods identified 49 and 36 genes,*** verification of candidate gene ZmSBR1 identified by both methods showed that the resistance of a mutant line to seedling blight decreased by 0.37 grade points after inoculation with ***,compared with the *** length of the stem rot lesion caused by *** increased by 86%in mutant seedlings,and the relative length of the adult plant stalk rot increased by 35%in mutant plants compared to the wild type after inoculation with Fusarium *** analysis showed that expression of defense-related genes after inoculation was down-regulated in the mutant compared to the wild type,synthesis of secondary metabolites associated with resistance was reduced,and the immune response triggered by PAMP decreased,resulting in decreased resistance of mutant maize *** gene association analysis showed that most maize inbred lines carried the susceptible haplotype.A functional PCR marker was *** results demonstrated that ZmSBR1 conferred resistance to multiple Fusarium diseases at the seedling and adult growth stages and had important application value in breeding.

关键词： Seedling blight Stalk rot Multiple disease resistance

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Improving antibody affinity through in vitro mutagenesis in complementarity determining regions

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The Journal of Biomedical Research 2022年第3期36卷 155-166页

作者： Wei Ye Xiaoyu Liu Ruiting He Liming Gou Ming Lu Gang Yang Jiaqi Wen Xufei Wang Fang Liu Sujuan Ma Weifeng Qian Shaochang Jia Tong Ding luan sun Wei Gao Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineKey Laboratory of Human Functional Genomics of Jiangsu ProvinceNational Health Commission Key Laboratory of Antibody TechniquesSchool of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215001China Department of Biotherapy Nanjing Jinling HospitalNanjingJiangsu 210002China.

High-affinity antibodies are widely used in diagnostics and for the treatment of human ***,most antibodies are isolated from semi-synthetic libraries by phage display and do not possess in vivo affinity maturation,which is triggered by antigen *** is therefore necessary to engineer the affinity of these antibodies by way of in vitro *** this study,we optimized the affinity of two human monoclonal antibodies which were isolated by phage display in a previous related *** the 42A1 antibody,which targets the liver cancer antigen glypican-3,the variant T57H in the second complementarity-determining region of the heavy chain(CDR-H2)exhibited a 2.6-fold improvement in affinity,as well as enhanced cell-binding *** the I4A3 antibody to severe acute respiratory syndrome coronavirus 2,beneficial single mutations in CDR-H2 and CDR-H3 were randomly combined to select the best synergistic *** these,the mutation S53P-S98T improved binding affinity(about 3.7 fold)and the neutralizing activity(about 12 fold)compared to the parent *** together,single mutations of key residues in antibody CDRs were enough to increase binding affinity with improved antibody *** mutagenic combination of key residues in different CDRs creates additive ***,this study provides a safe and effective in vitro strategy for optimizing antibody affinity.

关键词： antibody engineering phage display affinity maturation

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The role of SATBl-mediated chromatin loop conformation in regulation of coordinated expression of anti-apoptotic BCL2 and pro-apoptotic NOXA genes

The role of SATBl-mediated chromatin loop conformation in re...

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遗传学与表观遗传学前沿暨第三届中国青年遗传学家论坛

作者： Zongdan Wang Yin Yang Lipei Shao luan sun Nan Yang Xiao Han 孙玉洁 Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Cell Biology Nanjing Medical University

Special AT-rich binding protein 1(SATB1)is a global genomic organizer that integrates higher-order chromatin organization with regulation of gene *** expression of SATB1 has been associated with various *** of apoptosis is one of a hallmark of ***,the intrinsic link between SATB1 and regulation of apoptosis still has to be *** previous study has found that the major break point region(mbr)located within3’-UTR of the BCL2 gene is a regulatory ***1 mediates specific long-range chromosomal interaction between the mbr and BCL-2 promoter to regulate the BCL2 expression during early apoptosis,which highlighted the role of SATB1-mediated chromatin loop conformation in regulation of *** this study we searched new target genes of the mbr within BCL2 family members and investigated the role of SATB1 in regulating coordinated expression of anti-apoptotic BCL2 gene and pro-apoptotic NOXA gene that are 3.4Mb away on Chromosome *** demonstrated that the SATB1 bound site within NOXA gene was specially juxtaposed with both mbr element and BCL2 promoter through SATB1-mediated chromatin-loop conformation in Jurkat cells with chromosome conformation capture(3C)and chromatin immuneprecipitation(ChIP)*** SATB1-mediated BCL2 and NOXA chromatin loop conformation was required for coordinated expression of these two distinct BCL2 family ***-regulation of SATB1 expression induced disassembly of mbr-BCL2 chromatin loop and increased assembly of mbr-NOXA chromatin *** of SATB1 levels resulted in switch between mbr-BCL2 and mbr-NOXA chromatin loops and thus changed expression levels of the genes *** early apoptosis SATB1 coordinated expression of BCL2 and NOXA genes through mediating dynamic change in long-range chromatin *** role of SATB1 was very specific,since transfection with mutant SATB1 resistant to caspase-6 or treatment with caspase-6 inhibitor restored BCL-

关键词： Chromatin loop SATB1 BCL2 NOXA

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Composition,function,and timing:exploring the early‑life gut microbiota in piglets for probiotic interventions

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Journal of Animal Science and Biotechnology 2024年第2期15卷 659-678页

作者： Jianping Quan Cineng Xu Donglin Ruan Yong Ye Yibin Qiu Jie Wu Shenping Zhou Menghao luan Xiang Zhao Yue Chen Danyang Lin Ying sun Jifei Yang Enqin Zheng Gengyuan Cai Zhenfang Wu Jie Yang College of Animal Science and National Engineering Research Center for Breeding Swine Industry South China Agricultural UniversityGuangzhouGuangdongPeople’s Republic of China Guangdong Provincial Key Laboratory of Agro‑Animal Genomics and Molecular Breeding South China Agricultural UniversityGuangzhouGuangdongChina Yunfu Subcenter of Guangdong Laboratory for Lingnan Modern Agriculture YunfuGuangdongChina National Engineering Research Center for Breeding Swine Industry Wens Foodstuff Group Co.Ltd.YunfuGuangdongPeople’s Republic of China

Background The establishment of a robust gut microbiota in piglets during their early developmental stage holds the potential for long-term advantageous ***,the optimal timeframe for introducing probiotics to achieve this outcome remains *** In the context of this investigation,we conducted a longitudinal assessment of the fecal microbiota of 63 piglets at three distinct pre-weaning time ***,we gathered vaginal and fecal samples from 23 *** 16S rRNA gene and metagenomic sequencing methodologies,we conducted a comprehensive analysis of the fluctuation patterns in microbial composition,functional capacity,interaction networks,and colonization resistance within the gut microbiota of *** the piglets progressed in age,discernible modifications in intestinal microbial diversity,composition,and function were observed.A source-tracking analysis unveiled the pivotal role of fecal and vaginal microbiota derived from sows in populating the gut microbiota of neonatal *** D21,the microbial interaction network displayed a more concise and efficient configuration,accompanied by enhanced colonization resistance relative to the other two time ***,we identified three strains of Ruminococcus *** D10 as potential candidates for improving piglets’weight gain during the weaning *** The findings of this study propose that D10 represents the most opportune juncture for the introduction of external probiotic interventions during the early stages of piglet *** investigation augments our comprehension of the microbiota dynamics in early-life of piglets and offers valuable insights for guiding forthcoming probiotic interventions.

关键词： Colonization resistance Intestinal microbiota Piglet Weaning Weight gain

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面向一统的都城规划——再论隋大兴的空间形制建构及其历史意义

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城市规划 2024年第9期48卷 99-110页

作者：栾滨孙晖大连理工大学建筑与艺术学院

隋大兴是在一统全国过程中规划建设的新都城。其营建不仅在于都城空间本身,也包括以都城为核心面向整个疆域的一系列空间建构。本文分析了中国古代“大一统”思想的发展演变以及隋大兴的建设背景,认为隋初围绕大兴城在疆域范围、近畿区... 详细信息

隋大兴是在一统全国过程中规划建设的新都城。其营建不仅在于都城空间本身,也包括以都城为核心面向整个疆域的一系列空间建构。本文分析了中国古代“大一统”思想的发展演变以及隋大兴的建设背景,认为隋初围绕大兴城在疆域范围、近畿区域、都城形态三个层面的一系列空间建构是中国古代“大一统”思想与全国一统进程实际需要相结合的空间政治实践,呼应了当时的军事、政治、经济、文化等需求,丰富和发展了“大一统”理念在都城规划中的表达,提高了都城在国家秩序建构和国家认同形成方面的作用,推动了隋唐“大一统”时代的形成和巩固。

关键词：隋大兴大一统都城形制疆域建构国家秩序

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