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Orally administered BZL-s RNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice

Science China(Life Sciences) 2023年第7期66卷 1589-1599页

作者： Dandan Zhao yuhao qin Jiaqi Liu Kegong Tang Shuaiyao Lu Zirui Liu Yexuan Lin Cong Zhang Fengming Huang Jiahui Chang Chang Li Mingyao Tian Yiming Ma Xiaoyun Li Congzhao Zhou Xiao Li Xiaozhong Peng Ningyi Jin Chengyu Jiang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of BiochemistryPeking Union Medical CollegeBeijing 100005China Institute of Medical Biology Chinese Academy of Medical SciencesKunming 650031China Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences University of Science and Technology of ChinaHefei 230027China Changchun Veterinary Research Institute Chinese Academy of Agricultural SciencesChangchun 130122China

The global COVID-19 pandemic emerged at the end of December 2019.Acute respiratory distress syndrome(ARDS)and acute lung injury(ALI)are common lethal outcomes of bacterial lipopolysaccharide(LPS),avian influenza virus,and SARS-Co V-2.Toll-like receptor 4(TLR4)is a key target in the pathological pathway of ARDS and ALI.Previous studies have reported that herbal small RNAs(s RNAs)are a functional medical component.BZL-s RNA-20(Accession number:B59471456;Family ID:F2201.Q001979.B11)is a potent inhibitor of Toll-like receptor 4(TLR4)and pro-inflammatory cytokines.Furthermore,BZLs RNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid(LTA)and polyinosinic-polycytidylic acid(poly(I:C)).We found that BZL-s RNA-20 rescued the viability of cells infected with avian influenza H5N1,SARS-Co V-2,and several of its variants of concern(VOCs).Acute lung injury induced by LPS and SARS-Co V-2 in mice was significantly ameliorated by the oral medical decoctosome mimic(bencaosome;sphinganine(d22:0)+BZL-s RNA-20).Our findings suggest that BZLs RNA-20 could be a pan-anti-ARDS/ALI drug.

关键词： oligonucleotide drug herbal medicine ARDS/ALI SARS-CoV-2

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A comprehensive analysis of the Bencao(herbal)small RNA Atlas reveals novel RNA therapeutics for treating human diseases

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Science China(Life Sciences) 2023年第10期66卷 2380-2398页

作者： Yinghao Cao Yexuan Lin Na Sun Xinyi Du Yixin Dong Song Mei Xingyu Deng Xiaobei Li Shaoting Guo Kegong Tang Jiaqi Liu Xiangyu Qiao Dandan Zhao yuhao qin Cong Zhang Tianyi Xin Xiaohu Shi Congzhao Zhou Tao Dong De-an Guo Benedikt MKessler Dong Xu Jingyuan Song Fengming Huang Xiaoyue Wang Chengyu Jiang State Key Laboratory of Common Mechanism Research for Major Diseases Department of BiochemistryInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Key Laboratory of Chinese Medicine Resources Conservation State Administration of Traditional Chinese Medicine of ChinaEngineering Research Center of Chinese Medicine Resource of Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China Department of Traditional Chinese Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100005China Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences University of Science and Technology of ChinaHefei 230027China MRC Human Immunology Unit MRC Weatherall Institute of Molecular MedicineRadcliffe Department of MedicineUniversity of OxfordOxford OX37FZUK Chinese Academy of Medical Sciences(CAMS) CAMS Oxford Institute(COI)Nuffield Department of MedicineUniversity of OxfordOxfordOX37FZUK Shanghai Research Center for Modernization of Traditional Chinese Medicine National Engineering Laboratory for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Target Discovery Institute Centre for Medicines DiscoveryNuffield Department of MedicineUniversity of OxfordOxfordOX37FZUK Department of Electrical Engineering and Computer Science and Christopher S.Bond Life Sciences CenterUniversity of MissouriColumbia MO 65211USA

Cross-kingdom herbal mi RNA was first reported in 2012.Using a modified herbal extraction protocol,we obtained 73,677,287sequences by RNA-seq from 245 traditional Chinese Medicine(TCM),of which 20,758,257 were unique sequences.We constructed a Bencao(herbal)small RNA(s RNA)Atlas(http://***),annotated the sequences by sequence-based clustering,and created a nomenclature system for Bencao s RNAs.The profiles of 21,757 mi RNAs in the Atlas were highly consistent with those of plant mi RNAs in mi RBase.Using software tools,our results demonstrated that all human genes might be regulated by s RNAs from the Bencao s RNA Atlas,part of the predicted human target genes were experimentally validated,suggesting that Bencao s RNAs might be one of the main bioactive components of herbal medicines.We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions.Moreover,the decoctosome,a lipo-nano particle consisting of 0.5%–2.5%of the decoction,demonstrated potent medical effects.We propose a Bencao(herbal)Index,including small-molecule compounds(SM),protein peptides(P),nucleic acid(N),non-nucleic and non-proteinogenic large-molecule compounds(LM)and elements from Mendeleev's periodic table(E),to quantitatively measure the medical effects of botanic medicine.The Bencao s RNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine,and may provide potential remedies for the theory and practice of one medicine.

关键词： small RNA herbal decoction cross-kingdom regulation traditional Chinese medicine RNA oligonucleotide drug RNA therapeutics Bencao small RNA Atlas

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人原代瘢痕疙瘩成纤维细胞系的建立及鉴定

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中华整形外科杂志 2024年第5期40卷 545-554页

作者：徐梦丽王其飞王静宜陆语豪秦泽莲北京大学第三医院成形外科北京100191

目的尝试构建永生化的人瘢痕疙瘩成纤维细胞(KFbs)系,并对其功能进行鉴定。方法标本取自1例2019年11月在北京大学第三医院行耳垂瘢痕疙瘩手术切除的32岁女性患者。将获得的瘢痕疙瘩去除皮下脂肪和表皮,应用组织贴壁法进行分离和培养,获... 详细信息

目的尝试构建永生化的人瘢痕疙瘩成纤维细胞(KFbs)系,并对其功能进行鉴定。方法标本取自1例2019年11月在北京大学第三医院行耳垂瘢痕疙瘩手术切除的32岁女性患者。将获得的瘢痕疙瘩去除皮下脂肪和表皮,应用组织贴壁法进行分离和培养,获得原代KFbs,以胰蛋白酶消化法进行传代培养;用SV40慢病毒感染原代KFbs,经过嘌呤霉素筛选纯化、传代扩增,获得永生化的人KFb系。对原代KFbs及其细胞系进行染色体核型分析、短串联重复序列(STR)和性别基因检测,来鉴定细胞系身份;采用CCK-8法检测原代KFbs和细胞系增殖能力,并分别用实时定量PCR(qRT-PCR)和蛋白质印迹法检测其特定基因(PGK1、ENO1、LDHA、GLUT1、TGF-β1、COL1、COL3、FN)的mRNA和蛋白表达水平。原代KFbs与细胞系间相关数据比较采用t检验,P0.05)。结论成功建立了永生化的人KFbs系,其形态、表征和功能未发生明显改变,且其增殖速度较原代细胞增快。

关键词：瘢痕疙瘩成纤维细胞永生化细胞系染色体核型鉴定基因

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单核苷酸多态性(SNP)及其在作物中的研究与应用

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分子植物育种 2024年第9期22卷 2987-2995页

作者：甘斌田宇豪熊兴耀胡新喜秦玉芝湖南农业大学园艺学院园艺作物种质创新与品种选育教育部工程研究中心长沙410128 中国农业科学院深圳农业基因组研究所深圳518120

单核苷酸多态性(SNP)主要是指在基因组水平上由单个核苷酸的变异所引起的DNA序列多态性。因密度高、遗传稳定性好、易实现分析的自动化等特点,SNP作为一类遗传标记在作物遗传学分析中广泛应用。SNP通过直接影响生物内部相关基因的表达,... 详细信息

单核苷酸多态性(SNP)主要是指在基因组水平上由单个核苷酸的变异所引起的DNA序列多态性。因密度高、遗传稳定性好、易实现分析的自动化等特点,SNP作为一类遗传标记在作物遗传学分析中广泛应用。SNP通过直接影响生物内部相关基因的表达,以及蛋白结构的变化导致遗传变异的发生,在研究生物形态或性状变化以及适应性进化上具有根本性的优势。本研究综述了第三代分子标记技术—单核苷酸多态性(SNP)在植物基因图谱的开发、植物遗传多样性与亲缘关系研究、基因定位和分子标记辅助选择等方面的研究与应用进展。

关键词：作物单核苷酸多态性遗传标记

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高温下基质湿度对马铃薯种薯组织结构和苗期生长生理的影响

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江西农业大学学报 2024年第3期46卷 625-637页

作者：雷紫芊田宇豪张幸媛尹燕熊兴耀秦玉芝湖南农业大学园艺学院/湖南省马铃薯工程技术研究中心/蔬菜生物学湖南省重点实验室湖南长沙410128 中国农业科学院深圳农业基因组研究所广东深圳440307

【目的】探究在高温下不同栽培湿度、种薯状态对马铃薯的种薯活力、萌发与成苗情况的影响。【方法】选择马铃薯品种“兴佳2号”为供试材料,在高温(30℃)胁迫下,以30%、60%、80%3种不同栽培的基质湿度模拟干旱、正常、高湿情况,以及“健... 详细信息

【目的】探究在高温下不同栽培湿度、种薯状态对马铃薯的种薯活力、萌发与成苗情况的影响。【方法】选择马铃薯品种“兴佳2号”为供试材料,在高温(30℃)胁迫下,以30%、60%、80%3种不同栽培的基质湿度模拟干旱、正常、高湿情况,以及“健康整薯”、“局部受损整薯”和“切薯”3种种薯状态进行播种。在播种后萌芽期分析不同处理种薯细胞活力和组织结构的动态变化,苗期对各处理植株生长与生理状态进行综合评价。【结果】萌发期种薯生命活动旺盛,其体内的可溶性糖与可溶性蛋白含量、SOD活性与呼吸强度均有不同程度提高,而丙二醛含量与种薯硬度降低;种薯损伤程度越大,高温下块茎细胞空腔的形成、维管束解体越快,其中切薯从心髓部开始变化,损伤程度最大,变化速度也是最快,损伤薯则是从维管束最开始变化,再同时向上顶芽和向下心髓部扩散,向下扩散速度更快,损伤严重,而整薯开始是芽点变黑,输导组织逐渐破损,损伤程度相对最轻,种薯的完整性较好;高温下基质湿度越大种薯出苗越快,但基质湿度越大出苗速率越快,但出苗率和成苗率越低;同一湿度下不同种薯状态比较,整薯出苗慢但整齐,而损伤薯和切薯出苗相对较快但出苗率和成苗率低。【结论】高温高湿复合胁迫对马铃薯种薯的影响大于单一高温胁迫,在高温逆境下种薯块出现裂纹,后细胞壁破裂,细胞膜收缩,形成空腔,影响出苗率和成苗率,所以在马铃薯秋作中应该播种前2~3 d灌水,忌高温天气播种后大水漫灌,避免高温天气下大雨前播种,选择萌发期小整薯播种,可以快速出苗并获得高成苗率,确保秋作马铃薯稳产。该研究解析了秋播马铃薯种薯的组织细胞学和生理变化,为通过运用有效农艺措施减少秋作种薯烂薯,促进农民增收提供理论参考。

关键词：马铃薯高温基质湿度种薯组织结构生长生理

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Herbal decoctosome is a novel form of medicine

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Science China(Life Sciences) 2019年第3期62卷 333-348页

作者： Xiaoyun Li Zhu Liang Jianchao Du Zhiqing Wang Song Mei Zhiqing Li Yan Zhao DANDan Zhao Yiming Ma Jun Ye Jiantao Xu Yu Zhao Jiahui Chang yuhao qin Lanlan Yu Chenxuan Wang Chengyu Jiang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Department of Biochemistry Peking Union Medical College Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Department of Biophysics and Structural Biology Peking Union Medical College

Traditionally, herbal medicine is consumed by drinking decoctions produced by boiling herbs with water. The functional components of the decoction are heat stable. Small RNAs(sRNAs) were reported as a new class of functional components in decoctions. However, the mechanisms by which sRNAs survive heat treatment of the decoction and enter cells are unclear.Previous studies showed that plant-derived exosome-like nanoparticles(ELNs), which we call botanosomes, could deliver therapeutic reagents in vivo. Here, we report that heat-stable decoctosomes(ELNs) from decoctions have more therapeutic effects than the decoctions in vitro and demonstrate therapeutic efficacy in vivo. Furthermore, sRNAs, such as HJT-sRNA-m7 and PGY-sRNA-6, in the decoctosome exhibit potent anti-fibrosis and anti-inflammatory effects, respectively. Decoctosome is comprised of lipids, chemical compounds, proteins, and s RNAs. A medical decoctosome mimic is called bencaosome. A single lipid sphinganine(d22:0) identified in the decoctosome was mixed and heated with the synthesized sRNAs to form the simplest bencaosome. This simple bencaosome structure was identified by critical micelle concentration(cmc) assay that sRNAs coassembled with sphinganine(d22:0) to form the lipid layers of vesicles. The heating process facilitates co-assembly of sRNAs and sphinganine(d22:0) until a steady state is reached. The artificially produced sphinganine-HJT-sRNA-m7 and sphinganinePGY-sRNA-6 bencaosomes could ameliorate bleomycin-induced lung fibrosis and poly(I:C)-induced lung inflammation, respectively, following oral administration in mice. Our study not only demonstrates that the herbal decoctosome may represent a combinatory remedy in precision medicine but also provides an effective oral delivery route for nucleic acid therapy.

关键词： decoctosome bencaosome sphinganine

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Large-scale analysis of small RNAs derived from traditional Chinese herbs in human tissues

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Science China(Life Sciences) 2019年第3期62卷 321-332页

作者： Fengming Huang Jianchao Du Zhu Liang Zhichao Xu Jiantao Xu Yan Zhao Yexuan Lin Song Mei Quan He Jindong Zhu Qiang Liu Yanxu Zhang yuhao qin Wei Sun Jingyuan Song Shilin Chen Chengyu Jiang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Department of Biochemistry School of Basic Medicine Peking Union Medical College Tsinghua University Institute of Medicinal Plant Development Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences

Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine(TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis.We extracted small RNAs from decoctions of 10 TCM plants(Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development.

关键词： small RNA herbal decoction cross-kingdom regulation miRNA traditional Chinese medicine gene-targeted therapy

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Carbonized wood with ordered channels decorated by NiCo_(2)O_(4) for lightweight and high-performance microwave absorber

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Journal of Advanced Ceramics 2022年第1期11卷 105-119页

作者： Guangyu qin Xiaoxiao HUANG Xu YAN Yunfei HE yuhao LIU Long XIA Bo ZHONG School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001China Beijing Institute of Radio Measurement Beijing 100854China School of Materials Science and Engineering Harbin Institute of Technology at WeihaiWeihai 264009China

Wood-derived carbon has a 3D porous framework composed of through channels along the growth direction,which is a suitable matrix for preparing electromagnetic wave(EMW)absorbing materials with low cost,light weight,and environmental friendliness.Herein,the carbonized wood decorated by short cone-like NiCo_(2)O_(4)(NiCo_(2)O_(4)@CW)with highly ordered straight-channel architecture was successfully manufactured through a facile calcination procedure.The horizontal arrangement of the through channels of NiCo_(2)O_(4)@CW(H-NiCo_(2)O_(4)@CW)exhibits a strong reflection loss value of-64.0 dB at 10.72 GHz with a thickness of 3.62 mm and a low filling ratio of 26 wt%(with the density of 0.98 g-cnf3),and the effective absorption bandwidth(EAB)is 8.08 GHz(9.92-18.0 GHz)at the thickness of 3.2 mm.The excellent microwave absorption(MA)property was ascribed to the ordered-channel structure with abundant interfaces and defects from NiCo_(2)O_(4)@CW,which could promote the interfacial polarization and dipole polarization.What is more,this advantageous structure increased the multiple reflections and scattering.Finite element analysis(FEA)simulation is carried out to detect the interaction between the prepared material and EMW when the ordered channels are arranged in different directions.This research provides a low-cost,sustainable,and environmentally friendly strategy for using carbonized wood to fabricate microwave absorbers with strong attenuation capabilities and light weight.

关键词： microwave absorption(MA) wood-derived carbon ordered-channel architecture light weight finite element analysis(FEA)

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青藏高原地区积雪与雪线高度时空变化研究

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华北水利水电大学学报（自然科学版） 2024年第2期45卷 48-58页

作者：刘小妮莫李娟辛昱昊陈松峰赵雯颉吴金雨鞠琴河海大学中国气象局水文气象重点开放实验室江苏南京210098 河海大学水灾害防御全国重点实验室江苏南京210098 太湖流域水文水资源监测中心江苏无锡214024 浙江省水利水电勘测设计院浙江杭州310002 江苏省水资源服务中心江苏南京210029

积雪对气候变化具有高度敏感性,研究积雪变化对区域水循环及生态环境演变具有重要意义。基于遥感数据和河流水系分布情况,将青藏高原划分为12个子流域,分析了青藏高原及其子流域的积雪深度、积雪覆盖率、雪线高度的时空变化特征。结果表... 详细信息

积雪对气候变化具有高度敏感性,研究积雪变化对区域水循环及生态环境演变具有重要意义。基于遥感数据和河流水系分布情况,将青藏高原划分为12个子流域,分析了青藏高原及其子流域的积雪深度、积雪覆盖率、雪线高度的时空变化特征。结果表明:①1979—2020年青藏高原积雪深度呈明显降低趋势,空间上积雪深度由中心区域向四周递增,阿姆河流域多年平均积雪深度最大,印度河流域的次之。②2000-2015年青藏高原多年平均积雪覆盖率为29.66%,呈平缓的下降趋势,印度河流域的积雪覆盖率最大,高达39.83%,塔里木河的次之。③青藏高原雪线高度的变化范围为[4700,5000]m,夏季的雪线高度整体偏高,在8月达到最大值;各子流域雪线高度由大到小的排序依次为雅鲁藏布江流域、印度河流域、河西流域、恒河流域、长江流域、怒江流域、阿姆河流域、塔里木河流域、柴达木河流域、内河流域、黄河流域、澜沧江流域。研究结果对寒区水资源管理和生态环境可持续发展具有重要意义。

关键词：积雪深度积雪覆盖率雪线高度时空变化青藏高原

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“互联网+智库”的智库协同应急模式研究

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晋图学刊 2024年第2期 32-41页

作者：唐明伟秦宇豪朱翼毛芳芳南京审计大学计算机学院江苏南京211815 江苏省数据工程与知识服务重点实验室江苏南京210023

文章旨在实践解析“多方协同应急”的国家突发事件应急体系战略原则,构建一种联合多个智库,共同应对突发事件的协同应急模式。文章从技术角度剖析“互联网+”跨界融合理念的实现方法,依此创建了“互联网+智库”的智库协同应急模式,从智... 详细信息

文章旨在实践解析“多方协同应急”的国家突发事件应急体系战略原则,构建一种联合多个智库,共同应对突发事件的协同应急模式。文章从技术角度剖析“互联网+”跨界融合理念的实现方法,依此创建了“互联网+智库”的智库协同应急模式,从智库连接、信息协同和智库协同应急决策三个机制设计了该模式的运作方式,并给出了该模式的应用建议。应用该模式,理论上可以联合多个相关智库共同应对突发事件,从而为政府部门的应急工作提供科学有力的支持。

关键词： “互联网+” 智库协同协同应急

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