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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

Journal of Integrative Medicine 2024年第1期22卷 72-82页

作者： Jing-shun Meng Yun He Heng-bin Yang Li-ping Zhou Si-yuan Wang Xi-lin Feng Omar Yahya Al-shargi Xiao-min Yu Li-qing Zhu Chang-quan Ling Shanghai University of Traditional Chinese Medicine Shanghai 201203China Oncology Department of Traditional Chinese Medicine Changhai HospitalNaval Medical UniversityShanghai 200433China Faculty of Traditional Chinese Medicine Naval Medical UniversityShanghai 200043China State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology(ministry of Education) School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Yantai Fuheng Biological Technology Co. Ltd.YantaiShandong Province 264006China. Department of Clinical Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

Objective Melittin and its derivatives have been characterized to establish effective gene delivery *** capability of facilitating endosomal release enhances the nanoparticles-based gene ***,little investigation has been conducted to explore its potential application in the context of viral *** Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus *** vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene *** addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 ***,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life *** A total of 76 melittin-related peptides were compiled from existing *** them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 *** p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to ***,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 *** importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 *** The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene *** further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

关键词： Melittin Recombinant adeno-associated virus Capsid engineering Transduction efficiency

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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of Medicine 2024年第2期18卷 357-374页

作者： Haoyu Wang Zhengyuan Wang Zheng Wang Xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying Liang Jiale Wu Huaxin Song qing Qu Jiahui Huang Chunkang Chang Kunwei Shen Xiaosong Chen min Lu Department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132 TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT03295552),decitabine with carboplatin produced an objective response rate(ORR)of 42%in 12 patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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Cubic S/N co-doped TiO_(2) with rich oxygen vacancies from Ti-MOFs for efficient elimination of formaldehyde

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Chinese Chemical Letters 2024年第2期35卷 512-515页

作者： qing Gao Lei Sun Zhihua Wang Jiguang Deng State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical TechnologyBeijing 100029China Beijing Key Laboratory for Green Catalysis and Separation Key Laboratory of Beijing on Regional Air Pollution ControlKey Laboratory of Advanced Functional MaterialsEducation Ministry of ChinaDepartment of Chemical EngineeringBeijing University of TechnologyBeijing 100124China

The cubic S/N co-doped TiO_(2)(TNSx,x is the calcination temperature)photocatalysts with rich oxygen vacancies were obtained by high temperature calcination of sulfur powder and titanium-based MOFs NH_(2)-MIL-125 for the photocatalytic removal of gaseous formaldehyde(a volatile organic compound).Among the obtained catalysts,the presence of oxygen vacancies restricted photogenerated electron and holes recombination.98.00%removal of gaseous formaldehyde in 150 min could be achieved over TNS600 by xenon *** removal efficiency for formaldehyde was well retained for five cycle *** results from PL,TRPL and EIS revealed that TNS600 had the best separation efficiency of photogenerated electrons and holes,and the enhanced charge separation led to a significant increase in photocatalytic *** photocatalytic oxidation mechanism indicated that the ^(•)OH and ^(•)O_(2)−radicals were mainly involved in the efficient elimination of gaseous formaldehyde and were able to mineralize formaldehyde to H_(2)O and CO_(2).

关键词： Metal-organic frameworks Photocatalysis Formaldehyde removal S/N co-doped TiO_(2) Oxygen vacancies

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基于粒度聚类的转炉炼钢氧气消耗量预测

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自动化学报 2024年第1期50卷 132-142页

作者：阳青锋赖旭芝杜胜胡杰陈略峰吴敏中国地质大学(武汉)自动化学院武汉430074 复杂系统先进控制与智能自动化湖北省重点实验室武汉430074 地球探测智能化技术教育部工程研究中心武汉430074

转炉炼钢是钢铁企业的主要耗氧工序,预测转炉炼钢的氧气消耗量对氧气系统合理调度、保证生产安全具有重要意义.考虑到转炉冶炼工况多、钢种数据粒度不统一,提出一种基于粒度聚类的转炉炼钢氧气消耗量预测方法.首先,利用孤立森林异常检... 详细信息

转炉炼钢是钢铁企业的主要耗氧工序,预测转炉炼钢的氧气消耗量对氧气系统合理调度、保证生产安全具有重要意义.考虑到转炉冶炼工况多、钢种数据粒度不统一,提出一种基于粒度聚类的转炉炼钢氧气消耗量预测方法.首先,利用孤立森林异常检测法剔除历史数据库中的异常数据;接着,采用皮尔逊相关性分析和互信息相关系数选取相关影响因子,对不同钢种数据进行信息粒化,实现数据特征提取和维度统一,使用模糊C均值(Fuzzy C-means,FCM)划分工况并建立不同工况下的氧气消耗量预测子模型;最后,利用企业的实际生产数据进行实验,验证所提方法的准确性和有效性.

关键词：转炉炼钢氧气消耗预测信息粒化工况识别

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The association and underlying mechanism of the digit ratio(2D:4D)in hypospadias

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Asian Journal of Andrology 2024年第4期26卷 356-365页

作者： Yu Ding Zu-Quan Chen Wen-Feng Pan Hao-Jie Chen min Wu Yi-qing Lyu Hua Xie Yi-Chen Huang Zhong-Zhong Chen Fang Chen Department of Urology Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Urogenital Development Research Center Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Clinical Research Center for Hypospadias Pediatric CollegeShanghai Jiao Tong University School of MedicineShanghai 200062China.

The second-to-fourth digit(2D:4D)ratio is thought to be associated with prenatal androgen ***,the relationship between the 2D:4D ratio and hypospadias is poorly understood,and its molecular mechanism is not *** this study,by analyzing the hand digit length of 142 boys with hypospadias(23 distal,68 middle,and 51 proximal)and 196 controls enrolled in Shanghai Children’s Hospital(Shanghai,China)from December 2020 to December 2021,we found that the 2D:4D ratio was significantly increased in boys with hypospadias(Pduring pregnancy can impair the growth and development of *** mechanistic explorations revealed that during the androgen-sensitive window,the downregulation of the androgen receptor(AR)caused by low testosterone levels,as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a(Wnt5a),Wnt5b,Smad family member 2(Smad2),and Smad3;mitochondrial function-related genes in cartilage such as AMP-activated protein kinase(AMPK)and nuclear respiratory factor 1(Nrf-1);and vascular development-related genes such as myosin light chain(MLC),notch receptor 3(Notch3),and sphingosine kinase 1(Sphk1),are responsible for the limitation of 4D growth,which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral *** study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

关键词： androgen receptor digit ratio(2D:4D) endochondral ossification hypospadias testosterone level

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Hybrid model for BOF oxygen blowing time prediction based on oxygen balance mechanism and deep neural network

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International Journal of minerals,Metallurgy and Materials 2024年第1期31卷 106-117页

作者： Xin Shao qing Liu Zicheng Xin Jiangshan Zhang Tao Zhou Shaoshuai Li State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China Engineering Research Center of MES Technology for Iron&Steel Production Ministry of EducationBeijing 100083China Laiwu Iron and Steel Group Yinshan Section Steel Co. Ltd.Jinan 271104China

The amount of oxygen blown into the converter is one of the key parameters for the control of the converter blowing process,which directly affects the tap-to-tap time of converter. In this study, a hybrid model based on oxygen balance mechanism (OBM) and deep neural network (DNN) was established for predicting oxygen blowing time in converter. A three-step method was utilized in the hybrid model. First, the oxygen consumption volume was predicted by the OBM model and DNN model, respectively. Second, a more accurate oxygen consumption volume was obtained by integrating the OBM model and DNN model. Finally, the converter oxygen blowing time was calculated according to the oxygen consumption volume and the oxygen supply intensity of each heat. The proposed hybrid model was verified using the actual data collected from an integrated steel plant in China, and compared with multiple linear regression model, OBM model, and neural network model including extreme learning machine, back propagation neural network, and DNN. The test results indicate that the hybrid model with a network structure of 3 hidden layer layers, 32-16-8 neurons per hidden layer, and 0.1 learning rate has the best prediction accuracy and stronger generalization ability compared with other models. The predicted hit ratio of oxygen consumption volume within the error±300 m^(3)is 96.67%;determination coefficient (R^(2)) and root mean square error (RMSE) are0.6984 and 150.03 m^(3), respectively. The oxygen blow time prediction hit ratio within the error±0.6 min is 89.50%;R2and RMSE are0.9486 and 0.3592 min, respectively. As a result, the proposed model can effectively predict the oxygen consumption volume and oxygen blowing time in the converter.

关键词： basic oxygen furnace oxygen consumption oxygen blowing time oxygen balance mechanism deep neural network hybrid model

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Iodine Nutrition, Thyroid-stimulating Hormone, and Related Factors of Postpartum Women from three Different Areas in China: A Cross-sectional Survey

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Biomedical and Environmental Sciences 2024年第3期37卷 254-265页

作者： SHAN Xiao Yun ZOU Yan HUANG Li Chun JIANG Shan ZHOU Wei Wen QIN Qiu Lan LIU Chang qing LUO Xiao Yan LU Jia Xi MAO De Qian LI min YANG Zhen Yu YANG Li Chen Key Laboratory of Trace Element Nutrition of National Health Committee National Institute for Nutrition and HealthChinese Center for Disease Control and PreventionBeijing 100050China Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards School of Public HealthHengyang Medical SchoolUniversity of South ChinaHengyang 241001HunanChina Zhejiang Provincial Center for Disease Prevention and Control Hangzhou 310051ZhejiangChina Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention Nanning 530028GuangxiChina Hebei Provincial Center for Disease Control and Prevention Shijiazhuang 050021HebeiChina

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are *** study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum *** A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this *** urinary iodine concentration(UIC),TSH,VA,and VD were *** The median UIC of total and lactating participants were 142.00µg/L and 139.95µg/L,*** median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44μg/mL,and 24.04 ng/mL,*** differences in the UIC were found between lactating and non-lactating *** and TSH levels were significantly different among the three *** rural UIC was higher than the urban *** mothers had a higher UIC and a higher prevalence of excessive *** UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient *** adjustment,no linear correlation was observed between UIC and VA/*** interaction was found between vitamins A/D and UIC on TSH *** The mothers in the present study had no iodine ***,area type,BMI,and VD may be related to the iodine status or TSH levels.

关键词： Median urinary iodine concentration Thyroid-stimulating hormone Vitamin A Vitamin D Postpartum women

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面向科技文献多维语义组织的混合倒排索引构建方法

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现代情报 2024年第2期44卷 107-114,129页

作者：张敏李唯范青中国科学院武汉文献情报中心湖北武汉430071 武汉软件工程职业学院(武汉开放大学) 湖北武汉430205 华中师范大学国家文化产业研究中心湖北武汉430079 科技大数据湖北省重点实验室湖北武汉430071

[目的/意义]为满足科研人员对科技文献内部细粒度语义信息进行高效查询的迫切需求,前期研究提出了面向科技文献的多维语义索引体系,然而基于HashMap的常见倒排索引会导致查询效率低下。本文旨在通过面向不同维度语义特征建立混合倒排索... 详细信息

[目的/意义]为满足科研人员对科技文献内部细粒度语义信息进行高效查询的迫切需求,前期研究提出了面向科技文献的多维语义索引体系,然而基于HashMap的常见倒排索引会导致查询效率低下。本文旨在通过面向不同维度语义特征建立混合倒排索引,以改进语义查询性能。[方法/过程]本文以Treap、B+树等多种数据结构探索适合不同语义维度的倒排索引构建方法,并将其组合形成多种适用于科技文献多维语义组织的混合倒排索引构建方法,并通过对比实验,在排序查询和布尔查询条件下分析验证不同类型倒排索引构建方法的查询性能。[结果/结论]实验结果表明,组合形成的8种混合倒排索引构建方法中,表2所示的C3(HHHB)被证明在排序查询条件下具有最高的效率,而C4(TTTB)则在布尔查询条件下被证明最为高效。本文的方法能有效解决单一索引结构导致的查询效率问题。

关键词：科技文献语义组织混合倒排索引 HashMap Treap B+树

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Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

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Zoological Research 2024年第1期45卷 79-94页

作者： Ya-Ling Zhu Lei-Lei Meng Jin-Hu Ma Xin Yuan Shu-Wen Chen Xin-Rui Yi Xin-Yu Li Yi Wang Yun-Shu Tang min Xue Mei-Zi Zhu Jin Peng Xue-Jin Lu Jian-Zhen Huang Zi-Chen Song Chong Wu Ke-Zhong Zheng qing-qing Dai Fan Huang Hao-Shu Fang Department of Pathophysiology Anhui Medical UniversityHefeiAnhui 230032China Laboratory Animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Hepatobiliary Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China College of Animal Science and Technology Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain ***,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP ***,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory *** total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD *** on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating *** study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

关键词： Non-alcoholic fatty liver disease C/EBPβ Lipopolysaccharide-binding protein H3K27ac Integrative analysis Enhancer

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Measurement of 2p-3d absorption in a hot molybdenum plasma

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Matter and Radiation at Extremes 2024年第4期9卷 68-79页

作者： Gang Xiong Bo qing Zhiyu Zhang Longfei Jing Yang Zhao minxi Wei Yimeng Yang Lifei Hou Chengwu Huang Tuo Zhu Tianming Song min Lv Yan Zhao Yuxue Zhang Guohong Yang Zeqing Wu Jun Yan Yaming Zou Jiyan Zhang Jiamin Yang Shanghai EBIT Laboratory and Key Laboratory of Nuclear Physics and Ion-Beam Application(MOE)Institute of ModernPhysicsFudan UniversityShanghai 200433China Laser Fusion Research Center China Academy of Engineering PhysicsMianyang 621900China Institute of Applied Physics and Computational Mathematics Beijing 100088China

We present measurements of the 2p-3d transition opacity of a hot molybdenum-scandium sample with nearly half-vacant molybdenum M-shell configurations.A plastic-tamped molybdenum-scandium foil sample is radiatively heated to high temperature in a compact D-shaped gold Hohlraum driven by∼30 kJ laser energy at the SG-100 kJ laser facility.X rays transmitted through the molybdenum and scandium plasmas are diffracted by crystals and finally recorded by image *** electron temperatures in the sample in particular spatial and temporal zones are determined by the K-shell absorption of the scandium plasma.A combination of the IRAD3D view factor code and the MULTI hydrodynamic code is used to simulate the spatial distribution and temporal behavior of the sample temperature and *** inferred temperature in the molybdenum plasma reaches a average of 138±11 eV.A detailed configuration-accounting calculation of the n=2–3 transition absorption of the molybdenum plasma is compared with experimental measurements and quite good agreement is *** present measurements provide an opportunity to test opacity models for complicated M-shell configurations.

关键词： molybdenum absorption configuration

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