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Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing

Signal Transduction and Targeted Therapy 2022年第4期7卷 1258-1270页

作者： Ziwen Zheng Guo li Chong Cui Fang wang Xiaohan wang Zhijiao Xu Huiping Guo Yuxin chen Honghai Tang Daqi wang Mingqian Huang Zheng-Yi chen Xingxu Huang Huawei li Geng-lin li Xiaoxiang Hu Yilai Shu ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing Medicine(Fudan University) Shanghai 200032China State Key Laboratory of Agrobiotechnology China Agricultural UniversityBeijing 100193China College of Biological Sciences China Agricultural UniversityBeijing 100193China School of life Science and Technology Southeast UniversityNanjing 210096China Department of Otolaryngology-Head and Neck Surgery Graduate Program in Speech and Hearing Bioscience and Technology and Program in NeuroscienceHarvard Medical SchoolBostonMA 02115USA Eaton-Peabody Laboratory Massachusetts Eye and Ear InfirmaryBostonMA 02114USA School of life Science and Technology ShanghaiTech UniversityShanghai 200031China CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan UniversityShanghai 200031China

CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene ***,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in *** first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(***)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole ***,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction ***,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 ***,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.

关键词： CRISPR/Cas editing hearing

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STING and TLR9 agonists synergistically enhance the immunogenicity of SARS-CoV-2 subunit vaccine

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Nano Research 2023年第12期16卷 13322-13334页

作者： Yang li Ziwei chen Xinyi Lu Jiufeng Sun Mengyu Guo Huige Zhou Ru Bai Yuliang Zhao chunying chen Yaling wang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 100190China University of chinese academy of Sciences Beijing 100049China The GBA National Institute for Nanotechnology Innovation Guangzhou 510700China Guangdong Provincial Institute of Public Health Guangdong Provincial Center for Disease Control and PreventionGuangzhou 511430China Research Unit of Nanoscience and Technology Chinese Academy of Medical SciencesBeijing 100049China

Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 *** this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and *** system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was *** immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various *** titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant *** conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.

关键词： dual-adjuvant system synergistic immune activation antigen dosage reducing variants neutralizing

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乳腺癌机会性筛查规范路径专家共识

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中国肿瘤 2024年第1期33卷 6-18页

作者：徐志坚刘炬陈万青赵方辉王靖李静黄佳琴赵晓嵬毕晓峰孙萍赵玉达张凯王年昌国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院《健康体检与管理》杂志编委会中华医学会健康管理学分会中华预防医学会肿瘤防控专业委员会国家健康体检与管理专业医疗质控中心北京医学会健康管理学分会中国医师协会医师健康管理与医师健康保险专业委员会国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院北京100021

乳腺癌是中国城市女性发病率最高的恶性肿瘤。研究证实通过群体性筛查能够提高乳腺癌的早期诊断率,从而降低乳腺癌的死亡率。机会性筛查与群体性筛查有一定的区别。乳腺癌机会性筛查是医生推荐给主动进行筛查的非肿瘤就诊患者或体检人... 详细信息

乳腺癌是中国城市女性发病率最高的恶性肿瘤。研究证实通过群体性筛查能够提高乳腺癌的早期诊断率,从而降低乳腺癌的死亡率。机会性筛查与群体性筛查有一定的区别。乳腺癌机会性筛查是医生推荐给主动进行筛查的非肿瘤就诊患者或体检人员进行的乳腺癌相关筛查。为了推进乳腺癌机会性筛查的路径规范化,根据受检人员乳腺癌高危因素的不同,组织多学科专家针对筛查方案、筛查设备、人员要求、筛查流程、异常结果处理流程以及后续的预警提醒流程等关键环节进行归纳与整理,以期达到规范乳腺癌机会性筛查的方法和流程,提高乳腺癌早诊率的目的。

关键词：乳腺癌机会性筛查危险因素规范路径专家共识

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Phylogenetic analyses of some genera in Oedipodidae （Orthoptera： Acridoidea） based on 16S mitochondrial partial gene sequences

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Insect Science 2008年第5期15卷 471-476页

作者： Xiang-chu Yin Xin-Jiang li Wen-Qiang wang Hong Yin cheng-Quan Cao Bao-Hua Ye Zhan Yin College of life Sciences Hebei University Baoding Hebei Province Northwest Plateau Institute of Biology Chinese Academy of Sciences Xining College of life Sciences Yan'an University Yan'an Shaanxi Province College of Plant Protection Shandong Agricultural University Taian Shandong Province China

Basedonthe 16S mitochondrial partial gene sequences of 29 genera, containing 26 from Oedipodidae and one each from Tanaoceridae, Pyrgomorphidae and Tetrigidae （as outgroups）, the homologus sequences were compared and phylogenetic analyses were performed. A phylogenetic tree was inferred by neighbor-joining （N J）. The results of sequences compared show that：（i） in a total of 574 bp of Oedipodidae, the number of substituted nucleotides was 265 bp and the average percentages ofT, C, A and G were 38.3%, 11.4%, 31.8% and 18.5%, respectively, and the content of A＋T （70.1%） was distinctly richer than that of C＋G （29.9%）; and （ii） the average nucleotide divergence of 16S rDNA sequences among genera of Oedipodidae were 9.0%, among families of Acridoidea were 17.0%, and between superfamilies （Tetrigoidea and Acridoidea） were 23.9%, respectively. The phylogenetic tree indicated：（i） the Oedipodidae was a monophyletic group, which suggested that the taxonomic status of this family was confirmed; （ii） the genus Heteropternis separated from the other Oedipodids first and had another unique sound-producing structure in morphology, which is the type-genus of subfamily Heteropterninae; and （iii） the relative intergeneric relationship within the same continent was closer than that of different continents, and between the Eurasian genera and the African genera, was closer than that between Eurasians and Americans.

关键词： Oedipodidae Acridoidea Orthoptera 16S rDNA phylogenetic analyses

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Role of nanoparticles in achieving macroscale superlubricity of graphene/nano-SiO_(2) particle composites

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Friction 2022年第9期10卷 1305-1316页

作者： Panpan li li JI Hongxuan li Lei chen Xiaohong liU Huidi ZHOU Jianmin chen Key Laboratory of Science and Technology on Wear and Protection of Materials Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China

Recent studies have reported that adding nanoparticles to graphene enables macroscale superlubricity to be *** study focuses on the role of nanoparticles in achieving ***,because graphene nanoscrolls can be formed with nanoparticles as seeds under shear force,the applied load(or shear force)is adjusted to manipulate the formation of graphene nanoscrolls and to reveal the relationship between graphene-nanoscroll formation and superlubricating ***,the load-carrying role of spherical nano-SiO_(2)particles during the friction process is verified by comparison with an elaborately designed fullerene that possesses a hollow-structured graphene *** indicate that the incorporated nano-SiO_(2)particles have two roles in promoting the formation of graphene nanoscrolls and exhibiting load-carrying capacity to support macroscale forces for achieving macroscale ***,macroscale superlubricity(friction coefficient:0.006–0.008)can be achieved under a properly tuned applied load(2.0 N)using a simple material system in which a graphene/nano-SiO_(2)particle composite coating slides against a steel counterpart ball without a decorated diamond-like carbon *** approach described in this study could be of significance in engineering.

关键词： nano-SiO_(2)particles graphene macroscale superlubricity lubrication mechanism

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Post-collisional ore-bearing adakitic porphyries from Gangdese porphyry copper belt,southern Tibet:Melting of thickened juvenile arc lower crust

Post-collisional ore-bearing adakitic porphyries from Gangde...

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中国科学院地质与地球物理研究所第11届（2011年度）学术年会

作者： Jin-Xiang li~*,Ke-Zhang Qin~*,Guang-Ming li~*,Bo Xiao,Lei chen,Jun-Xing Zhao Key Laboratory of Mineral Resources,Institute of Geology and Geophysics,chinese academy of Sciences,P.O.Box 9825,beijing 100029,china

Porphyry Cu-Mo deposits,related to the Miocene adakitic porphyries from the Gangdese porphyry copper belt in the southern Tibet,formed in a post-collisional ***,we present the new zircon U-Pb ages,whole-rock chemical,and Sr-Nd and zircon Hf isotopic data for the ore-bearing adakitic porphyries from Gangdese porphyry copper ***-ICP-MS zircon dating for six samples yielded ages ranging from 19 Ma to 14 Ma,indicating they formed in the *** ore-bearing adalatic porphyries show SiO of 61.47-71.67%,KO of 3.29-4.74%,and high Sr content(394-1106 ppm),high Sr/Y ratios(63-158),and low Y(6.12-10.3 ppm) and heavy rare earth element contents(***=0.52-0.91 ppm).They show steep fractionated REE and flat HREE patterns,and strong enrichment in large ion lithophile elements(Cs,Rb,Ba,Th,and U) and depletion of high field strength elements(Nb),with positive Sr and negative Ti *** are no linear variations of Ba,La,Sr/Y,Dy/Yb, (Sr/Sr),andεNd(t) with increasing SiO *** with the zircon positiveεHf(t) values,and wide range of(Sr/Sr)(0.70559 to 0.70908) and ofεNd(t)(-6.8 to 0) values for all the adakitic samples,they were likely derived from the melting of garnet-bearing amphibolite in the juvenile arc mafic lower ***, the adalatic porphyries with low Th/Nb ratios have lower initial Sr/Sr,and higherεNd(t) andεHf(t) values, and those with high Th/Nb show higher initial Sr/Sr,and lowerεNd(t) andεHf(t) *** indicates that the juvenile arc lower crust is derived from the melting of the mantle wedge that was metasomatized by slab fluid or sediment melt during the Neotethyan ocean ***,the juvenile arc lower crust possibly inherited the arc magma characteristics of abundant in F,CI,and Cu and high oxidation state,which contributed to the porphyry Cu-Mo deposits in the Gangdese porphyry copper belt.

关键词： Adakitic Juvenile arc lower crust Hf isotope Porphyry copper deposit Gangdese

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TECHNIQUE OF RAISING OIL RECOVERY BYPOLYMER FLOODING - A CASE STUDY OFTHE 52+3 FORMATION IN GUDONG OIL FIELD

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Scientia Geologica Sinica 1999年第4期 583-590页

作者： Don Zhilin, Tian Ji, Zhao Wei and chen Buoping(Gudong Petroleum Production factory of Shengli Petroleum AdministratveBareau, Dongying, Shandong257000)li Renwei(Institute of Geology chinese academy of Sciences. beijing 100029)

The polymer flooding of the 52+3 Formation in Gudong oil field is the first large scale commercialextending test area Because of the Problems such as: intensive injection and recovery in the Process ofwater drive, varied characteristics of reservoir properties, large serious channel, the high and unevenformation Pressure, uneven injection-production of boundary well, it resulted in low efficiency inreducing water and enhancing oil in the early time of polymer injection. In view of the Problem existed inpolymer injection area and the remaining oil distribution, the paper mainly introduced the matchingtechniques and better method of polymer flooding, and gave a brief evaluation of polymer flood. It is ofpractical and guiding significance to the same type of reservoir and production block.

关键词： TECHNIQUE OF RAISING OIL RECOVERY BYPOLYMER FLOODING In FORMATION IN GUDONG OIL FIELD A CASE STUDY OFTHE 5

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小粒野生稻基因渗入系桂恢1561的有利基因鉴定和育种利用

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中国稻米 2024年第5期30卷 76-83页

作者：齐金岗李孝琼刘开强陈颖王小姣赵丽冰郭嗣斌广西壮族自治区农业科学院水稻研究所/广西水稻遗传育种重点实验室/广西水稻优质化育种研究人才小高地南宁530007

挖掘野生稻有利基因对栽培稻进行遗传改良是当前水稻育种研究的热点。利用远缘杂交技术获得了小粒野生稻基因渗入系桂恢1561,通过农艺性状考查、配合力测定和稻飞虱抗性鉴定,确认桂恢1561粒大(32.2 g)、穗长(28.3 cm)、优质、兼抗褐飞虱... 详细信息

挖掘野生稻有利基因对栽培稻进行遗传改良是当前水稻育种研究的热点。利用远缘杂交技术获得了小粒野生稻基因渗入系桂恢1561,通过农艺性状考查、配合力测定和稻飞虱抗性鉴定,确认桂恢1561粒大(32.2 g)、穗长(28.3 cm)、优质、兼抗褐飞虱(抗级2.5)和白背飞虱(抗级2.9)、配合力好,具有较高的育种价值。利用桂1025/桂恢1561构建的重组自交系和近等基因系对来自于桂恢1561的有利基因进行遗传定位,对PL9、GS12、Bph31(t)和Wbph9(t)等4个主效基因进行连锁分子标记开发;利用分子标记辅助育种技术将桂恢1561有利基因导入多个骨干亲本,创制出9个新的优质、多抗恢复系;进一步以桂恢1561及其衍生系作为恢复系选育出11个优势杂交稻组合,其中,华浙优1561和旱优711已通过广西农作物品种审定委员会审定。

关键词：小粒野生稻基因渗入系桂恢1561 育种基因鉴定

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不同来源人血清白蛋白对血管内皮细胞生物学效应的影响研究

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临床输血与检验 2024年第5期26卷 577-587页

作者：刘卿王宗奎徐俊程露李长清杜晞马莉中国医学科学院输血研究所四川成都610052 上海莱士血液制品股份有限公司上海201401

目的研究不同来源人血清白蛋白(human serum albumin,HSA)对血管内皮细胞生物学效应的影响。方法对体外无血清培养的HUVEC细胞添加不同来源HSA处理,利用CCK-8细胞活性检测试剂盒、Annexin V-FITC细胞凋亡检测试剂盒和细胞周期与细胞凋... 详细信息

目的研究不同来源人血清白蛋白(human serum albumin,HSA)对血管内皮细胞生物学效应的影响。方法对体外无血清培养的HUVEC细胞添加不同来源HSA处理,利用CCK-8细胞活性检测试剂盒、Annexin V-FITC细胞凋亡检测试剂盒和细胞周期与细胞凋亡检测试剂盒,检测不同来源HSA处理后各组细胞增殖活性、细胞凋亡情况和细胞周期分布,并分析比较各组间差异。通过细胞划痕实验和管形成实验分析比较不同来源HSA处理对HUVEC细胞迁移和管形成的影响。结果酵母来源rHSA1对HUVEC细胞增殖活性无影响(P=0.49,q=1.601),其他HSA处理组均显示出显著促进HUVEC细胞增殖的活性,且不同来源HSA处理组间的HUVEC增殖活性存在显著差异(P1,F=10.84)。所有HSA处理组均显示出抑制HUVEC细胞凋亡的作用(P1),不同处理组间活细胞(P=0.07,F=2.415)、凋亡细胞(P=0.2,F=1.624)和坏死细胞(P=0.28,F=1.376)比例均无统计学差异。对比无血清对照组,在HSA处理组中除pHSA2和pHSA6处理组G0/G1期细胞比例显著降低(P1)、S期无明显变化、G2/M期细胞比例明显升高(P1)外,其他HSA处理组各细胞周期比例均无明显改变。在划痕实验中,对比无血清对照组,HSA处理组中pHSA(1)和pHSA(2)处理组经过12 h(P1)、24 h(P1)、36 h(P1,P=0.002)后划痕愈合程度更高,差异具有统计学意义,而rHSA(1)和rHSA(2)处理组较对照组无明显差异。在管形成实验中,对比无血清对照组,HSA处理组中pHSA(1)和pHSA(2)处理组的节点数量(P=0.001、P=0.005)、管状分支(P1)及网状结构(P1)均显著增多,而rHSA(1)和rHSA(2)处理组较对照组无统计学差异。结论不同来源HSA均能够显著抑制无血清条件下血管内皮细胞的凋亡,且对血管内皮细胞的增殖活性、细胞周期、细胞迁移和管形成的影响存在一定差异。

关键词：人血清白蛋白血管内皮细胞增殖凋亡迁移血管生成

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Effects of Shuanghuanglian oral liquids on patients with COVID-19:a randomized,open-label,parallel-controlled,multicenter clinical trial

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Frontiers of Medicine 2021年第5期15卷 704-717页

作者： li Ni Zheng Wen Xiaowen Hu Wei Tang Haisheng wang ling Zhou Lujin Wu Hong wang Chang Xu Xizhen Xu Zhichao Xiao Zongzhe li chene li Yujian liu Jialin Duan chen chen Dan li Runhua Zhang Jinliang li Yongxiang Yi Wei Huang Yanyan chen Jianping Zhao Jianping Zuo Jianping Weng Hualiang Jiang Dao Wen wang Division of Cardiology Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China The First Affiliated Hospital of University of Science and Technology of china Hefei 230026China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Harbin Pharmaceutical Group Co. Ltd.Harbin 150070China The Sixth Hospital of Harbin Harbin 150036China The Second Hospital of Nanjing and the Affiliated Hospital of Nanjing University of chinese Medicine Nanjing 210003China Department of Cardiology Chinese People’s Liberation Army Central War Command General HospitalWuhan 430010China Department of Information Management Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Division of Respiratory Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Shanghai Institute for Advanced Immunochemical Studies and School of life Science and Technology ShanghaiTech UniversityShanghai 201210China

We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by three doses(56 in low dose,61 in middle dose,and 59 in high dose)in addition to standard *** control group was composed of 59 patients who received standard therapy *** with SHL was not associated with a difference from standard care in the time to disease *** with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group(93.4%vs.73.9%,P=0.006).Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia,which was evaluated by density reduction of inflammatory focus from baseline,at day 7(mean difference(95%CI),−46.39(−86.83 to−5.94)HU;P=0.025)and day 14(mean difference(95%CI),−74.21(−133.35 to−15.08)HU;P=0.014).No serious adverse events occurred in the SHL *** study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

关键词： COVID-19 SARS-CoV-2 Shuanghuanglian oral liquid clinical trial

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