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Mimotope peptide modified pompon mum-like magnetic microparticles for precise recognition,capture and biotransformation analysis of rituximab in biological fluids

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1317-1328页

作者： jiawen yang Aixuan Zhou Minyi Li Qiaoxian He Jingwei Zhou Jacques Crommen Wentao Wang Zhengjin Jiang Qiqin Wang Institute of Pharmaceutical Analysis College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China Laboratory for the Analysis of Medicines Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium SCIEX Shanghai 200050China

Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.

关键词： Therapeutic monoclonal antibody Mimotope peptide Precise recognition Peptide-based biomaterials Biotransformation Patient serum

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Unravelling the genetic basis for skeletal muscle mitochondrial DNA copy number variations in pigs

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Science China(Life Sciences) 2024年第1期67卷 211-214页

作者： jiawen yang Leilei Cui Yifeng Zhang Ziqi Ling Zhou Zhang Yizhong Huang Junwu Ma Shijun Xiao Bin yang Lusheng Huang National Key Laboratory for Swine Genetic Improvement and Germplasm Innovation Jiangxi Agricultural UniversityNanchang 330045China School of Life Sciences Nanchang UniversityNanchang 330047China

Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modifications.Mitochondrial DNA copy number(mtDNA-CN)is an indicator of mitochondrial biogenesis and has been associated with several diseases,such as cardiovascular disease,depression,chronic kidney disease and aging in humans(Clyde,2022).

关键词： metabolism cardiovascular diseases

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Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones

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Journal of Animal Science and Biotechnology 2024年第2期15卷 578-599页

作者： Min Liu Jia Zhang Yunyan Zhou Shuqi Xiong Mengqing Zhou Lin Wu Qin Liu Zhe Chen Hui Jiang jiawen yang Yuxin Liu Yaxiang Wang Congying Chen Lusheng Huang National Key Laboratory of Swine Genetic Improvement and Germplasm Innovation Jiangxi Agricultural UniversityNanchang 330045China

Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective st

关键词： Estrus return Fecal metabolome Gut microbiota Metagenomics Sex steroid hormones Sow

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Fundamental and practical approaches for single-cell ATAC-seq analysis

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aBIOTECH 2022年第3期3卷 212-223页

作者： Peiyu Shi Yage Nie jiawen yang Weixing Zhang Zhongjie Tang Jin Xu State Key Laboratory of Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou510275China Zhongshan School of Medicine Sun Yat-Sen UniversityGuangzhou510275China

Assays for transposase-accessible chromatin through high-throughput sequencing(ATAC-seq)are effective tools in the study of genome-wide chromatin accessibility landscapes.With the rapid development of single-cell technology,open chromatin regions that play essential roles in epigenetic regulation have been measured at the single-cell level using single-cell ATAC-seq approaches.The application of scATAC-seq has become as popular as that of scRNA-seq.However,owing to the nature of scATAC-seq data,which are sparse and noisy,processing the data requires different methodologies and empirical experience.This review presents a practical guide for processing scATAC-seq data,from quality evaluation to downstream analysis,for various applications.In addition to the epigenomic profiling from scATAC-seq,we also discuss recent studies in which the function of non-coding variants has been investigated based on cell type-specific cis-regulatory elements and how to use the by-product genetic information obtained from scATAC-seq to infer single-cell copy number variants and trace cell lineage.We anticipate that this review will assist researchers in designing and implementing scATAC-seq assays to facilitate research in diverse fields.

关键词： Chromatin accessibility scATAC-seq Data analysis Bioinformatic tools

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Brain structure and structural basis of neurodegenerative diseases

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Biophysics Reports 2022年第3期8卷 170-181页

作者： jiawen yang Sen-Fang Sui Zheng Liu Cryo-electron Microscopy Center Southern University of Science and Technology Department of Biology Southern University of Science and Technology State Key Laboratory of Membrane Biology Beijing Advanced Innovation Center for Structural Biology Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University

The brain is one of the most complex organs in nature. In this organ, multiple neurons, neuron clusters,or multiple brain regions are interconnected to form a complex structural network where various brain functions are completed through interaction. In recent years, multiple tools and techniques have been developed to analyze the composition of different cell types in the brain and to construct the brain atlas on macroscopic, mesoscopic, and microscopic levels. Meanwhile, researchers have found that many neuropsychiatric diseases, such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease,are closely related to abnormal changes of brain structure, which means the investigation in brain structure not only provides a new idea for understanding the pathological mechanism of the diseases,but also provides imaging markers for early diagnosis and potential treatment. This article pays attention to the research of human brain structure, reviews the research progress of human brain structure and the structural mechanism of neurodegenerative diseases, and discusses the problems and prospects in the field.

关键词： Brain atlas Brain ultrastructure Neurodegenerative disease Parkinson’s disease Alzheimer’s disease Huntington’s disease

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Polyhalogenated carbazoles induce hepatic metabolic disorders in mice via alteration in gut microbiota

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Journal of Environmental Sciences 2023年第5期127卷 603-614页

作者： Chenyang Ji Yunkai Luo jiawen yang Yaoyao Dai Jiahui Miao Siqing Yue Meirong Zhao Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province Interdisciplinary Research AcademyZhejiang Shuren UniversityHangzhou 310015China Department of Ultrasound in Medicine The Fourth Affiliated Hospital of Zhejiang University School of MedicalYiwu 322000China Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province College of EnvironmentZhejiang University of TechnologyHangzhou 310014China

Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.

关键词： Polyhalogenated carbazoles Liver Metabolic disorders Gut microbiota

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Construction of a transposase accessible chromatin landscape reveals chromatin state of repeat elements and potential causal variant for complex traits in pigs

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Journal of Animal Science and Biotechnology 2023年第2期14卷 529-545页

作者： Tao Jiang Ziqi Ling Zhimin Zhou Xiaoyun Chen Liqing Chen Sha Liu Yingchun Sun jiawen yang Bin yang Jianzhen Huang Lusheng Huang State Key Laboratory of Pig Genetic Improvement and Production Technology Jiangxi Agricultural UniversityNanchang 330045China

Background:A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits.However,the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs.Results:Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq,and identified 557,273 merged peaks,which greatly expanded the pig regulatory ele-ment repository.We revealed tissue-specific regulatory elements which were associated with tissue-relevant biologi-cal functions.We identified both positive and negative significant correlations between the regulatory elements and gene transcripts,which showed distinct distributions in terms of their strength and distances from corresponding genes.We investigated the presence of transposable elements(TEs)in open chromatin regions across all tissues,these included identifications of porcine endogenous retroviruses(PERVs)exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements.Furthermore,we prior-itized a potential causal variant for polyunsaturated fatty acid in the muscle.Conclusions:Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions,as well as regula-tory variants of loci associated with complex traits in pigs.

关键词： Chromatin accessibility Pig Tissue specific Transcriptome Transposable elements

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Mapping and analysis of a spatiotemporal H3K27ac and gene expression spectrum in pigs

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Science China(Life Sciences) 2022年第8期65卷 1517-1534页

作者： Yaling Zhu Zhimin Zhou Tao Huang Zhen Zhang Wanbo Li Ziqi Ling Tao Jiang jiawen yang Siyu yang Yanyuan Xiao Carole Charlier Michel Georges Bin yang Lusheng Huang State Key Laboratory of Pig Genetic Improvement and Production Technology Jiangxi Agricultural UniversityNanchang 330045China Laboratory Animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefei 230032China Unit of Animal Genomics GIGA-Institute and Faculty of Veterinary MedicineUniversity of Liege4000 LiegeBelgium

The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac-targeted Ch IP-Seq and RNA-Seq in fetal(prenatal days 74–75) and adult(postnatal days 132–150) tissues(brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bama Xiang and European highly selected Large White pigs of both sexes. We identified 101,290 H3K27ac peaks, marking 18,521promoters and 82,769 enhancers, including peaks that were active across all tissues and developmental stages(which could indicate safe harbor locus for exogenous gene insertion) and tissue-and developmental stage-specific peaks(which regulate gene pathways matching tissue-and developmental stage-specific physiological functions). We found that H3K27ac and DNA methylation in the promoter region of the XIST gene may be involved in X chromosome inactivation and demonstrated the utility of the present resource for revealing the regulatory patterns of known causal genes and prioritizing candidate causal variants for complex traits in pigs. In addition, we identified an average of 1,124 super-enhancers per sample and found that they were more likely to show tissue-specific activity than ordinary peaks. We have developed a web browser to improve the accessibility of the results(http://***/pencode/?genome=sus Scr11).

关键词： H3K27ac ChIP-Seq RNA-Seq pig XIST complex traits

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Rational construction of high-active CO_(3)O_(4) electrocatalysts for oxygen evolution reaction

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Nano Research 2023年第1期16卷 624-633页

作者： Tianyun Zhang Shichao Zhao Chuanming Zhu Jing Shi Chao Su jiawen yang Meng Wang Jun Li Junhui Li Pingle Liu Conghui Wang College of Chemical Engineering Xiangtan UniversityXiangtan 411105China State Key Laboratory of Coal Conversion Institute of Coal ChemistryChinese Academy of SciencesTaiyuan 030001China Analytical Instrumentation center Institute of Coal ChemistryChinese Academy of SciencesTaiyuan 030001China

Rational construction of high-efficiency electrocatalysts for oxygen evolution reaction(OER)is critical for renewable-energy technologies,but it is highly challenging to rationally regulate their surface structures to improve the OER performance.Herein,we proposed a“model-etching”strategy to investigate chemical etching of CO_(3)O_(4).The cubic CO_(3)O_(4)nanocrystals enclosed by well-defined facets are synthesized as model crystals,whose uniform surface structures allow us to study the etching mechanism at atomic level.Etching kinetics study together with DFT calculations discloses that{111}facets,the highly active facets for OER,serve as etch-stop facets in the etching reaction and H_(2)SO_(4)molecules play a special role in creating surface Co2^(+),the active center of OER.These results direct us to rationally optimize the surface structures of CO_(3)O_(4) to develop highly active OER electrocatalysts.The favorable performance of overpotential(η)and the Tafel slope decrease even to 268 mV@10 mA·cm−2 and 74 mV·dec−1,respectively.In general,our study shows that chemical etching of model crystals could help us rationally construct high-efficiency electrocatalysts.

关键词： cobalt oxide chemical etching high active facets oxygen evolution reaction surface structure

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交通需求管理的通勤福利效应——以“禁摩限电”为例

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城市规划 2024年第1期48卷 44-54页

作者：彭莹郝柘淞杨家文苏品任湖南大学公共管理学院北京大学城市规划与设计学院

在市民个体层面,“禁摩限电”政策的实施效果尚缺乏定量评估。本研究将交通模式特征和土地利用特征整合到离散选择模型中,模拟计算了“禁摩限电”对市民通勤福利(模式转变和成本变化)的影响。研究发现,实施“禁摩限电”后:(1)超过35%的... 详细信息

在市民个体层面,“禁摩限电”政策的实施效果尚缺乏定量评估。本研究将交通模式特征和土地利用特征整合到离散选择模型中,模拟计算了“禁摩限电”对市民通勤福利(模式转变和成本变化)的影响。研究发现,实施“禁摩限电”后:(1)超过35%的摩托车和电动自行车使用者转向小汽车出行。小汽车分担率由不足30%上升到50%以上;(2)弱势群体的福利损失高于其他群体。单程通勤的时间平均增加6.9min以上,经济成本平均增加0.5元以上。(3)郊区镇居民的单程通勤时间和经济成本分别比其他区域市民多增加20%和0.2元。城市中心周边市民的换乘次数和候车时间增加明显。在我国实施公交优先发展战略,倡导绿色出行的背景下,本研究对于优化相关政策实施具有重要参考价值。

关键词：模式选择出行结构出行成本出行行为

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