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co.regulation of circadian clock genes and microRNAs in bone metabolism

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2022年第7期23卷 529-546页

作者： Tingting LI Shihua ZHANG Yuxuan YANG Lingli ZHANG Yu yuan Jun ZOU School of Exercise and Health Guangzhou Sport UniversityGuangzhou510500China School of Kinesiology Shanghai University of SportShanghai200438China co.lege of Graduate Education Shandong Sport UniversityJinan250102China

Mammalian bone is co.stantly metabolized from the embryonic stage,and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation,mediated by osteoclasts and *** is widely reco.nized that circadian clock genes can regulate bone *** recent years,the regulation of bone metabolism by non-co.ing RNAs has beco.e a hotspot of *** can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism,including circadian clock ***,research in this field has been co.ducted only in recent years and the mechanisms involved are not yet well *** studies have focused on how to target circadian clock genes to treat some diseases,such as autoimmune diseases,but few have focused on the co.regulation of circadian clock genes and microRNAs in bone metabolic ***,in this paper we review the progress of research on the co.regulation of bone metabolism by circadian clock genes and microRNAs,aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.

关键词： Circadian rhythm Circadian clock gene MicroRNAs Bone metabolism

Improving Plant Genome Editing with High-Fidelity xCas9 and Non-canonical PAM-Targeting Cas9-NG

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Molecular Plant 2019年第7期12卷 1027-1036页

作者： Zhaohui Zhong Simon Sretenovic Qiurong Ren Lijia Yang Yu Bao Caiyan Qi Mingzhu yuan yao He Shishi Liu Xiaopei Liu Jiaheng Wang Lan Huang Yan Wang Dibin Baby David Wang Tao Zhang Yiping Qi Yong Zhang Department of biotechnology School of Life Sciences and Technology Center for Informational Biology University of 曰ectronic Science and Technology of China Room 216 Main Building No. 4 Section 2 North Jianshe Road Chengdu 610054 China Department of Plant Science and Landscape Architecture University of Maryland College Park MD 20742 USA Jiangsu Key Laboratory of Crop Genetics and Physiology Co-Innovation Center for Modern Production Technology of Grain Crops Key Laboratory of Plant Functional Genomics of the Ministry of Education Yangzhou University Yangzhou 225009 China Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China Yangzhou University Yangzhou 225009 China Indian Institute of Science Education and Research Timpati Andhra Pradesh 517507 India Seven Lakes High School Katy TX 77494 USA Institute for Bioscience and biotechnology Research University of Maryland Rockville MD 20850 USA

Two recently engineered SpCas9 variants, namely xCas9 and Cas9-NG, show promising potential in improving targeting specificity and broadening the targeting range. In this study, we evaluated these Cas9 variants in the model and crop plant, rice. We first tested xCas9-3.7, the most effective xCas9 variant in mammalian cells, for targeted mutagenesis at 16 possible NGN PAM (protospacer adjacent motif) co.binations in duplicates. xCas9 exhibited nearly equivalent editing efficiency to wild-type Cas9 (Cas9-WT) at most canonical NGG PAM sites tested, whereas it showed limited activity at non-canonical NGH (H = A, C, T) PAM sites. High editing efficiency of xCas9 at NGG PAMs was further demonstrated with C to T base editing by both rAPOBECI and PmCDAI cytidine deaminases. With mismatched sgRNAs, we found that xCas9 had improved targeting specificity over the Cas9-WT. Furthermore, we tested two Cas9-NG variants, Cas9-NGv1 and Cas9-NG, for targeting NGN PAMs. Both Cas9-NG variants showed higher editing efficiency at most non-canonical NG PAM sites tested, and enabled much more efficient editing than xCas9 at AT-rich PAM sites such as GAT, GAA, and CAA. Nevertheless, we found that Cas9-NG variants showed significant reduced activity at the canonical NGG PAM sites. In stable transgenic rice lines, we demonstrated that Cas9-NG had much higher editing efficiency than Cas9-NGv1 and xCas9 at NG PAM sites. To expand the base-editing sco.e, we developed an efficient C to T base-editing system by making fusion of Cas9-NG nickase (D10A version), PmCDAI, and UGI. Taken together, our work benchmarked xCas9 as a high-fidelity nuclease for targeting canonical NGG PAMs and Cas9-NG as a preferred variant for targeting relaxed PAMs for plant genome editing.

关键词： xCas9 Cas9-NG high fidelity non-canonical PAM base editing

Mental Health and Psychosocial function of General Population during the co.ID-19 Epidemic in China

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Mental Health and Psychosocial function of General Populatio...

2020年浙江省医学会精神病学学术大会浙江省医师协会精神科医师分会第十三届年会

作者： Qi Zhou Zhenyu Hu Guolin Bian Haihang Yu Xingxing Li Yin Lu Chang Yu Xianglan Li Qin yao Wenhua Zhou Ti-Fei yuan Dongsheng Zhou Ningbo Kangning Hospital Laboratory of Behavioral Neuroscience Ningbo Addiction Research and Treatment CenterSchool of MedicineNingbo UniversityNingboChina3 Shanghai Key Laboratory of Psychotic DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of Medicine co.innovation Center of Neuroregeneration Nantong University

Objective:To investigate the mental health states of the general public during the co.ID-19 epidemic in ***:This cross-sectional,survey-based study co.lected responses from 2435 subjects from February 23,2020 to March 1,2020,in *** degree of symptoms of insomnia,stress and social function was assessed by the Self-Report Questionnaire-20(SRQ-20),the Athens Insomnia Scale(AIS),the Chinese version of the Perceived Stress Scale(CPSS),*** Mann-Whitney U test and Kruskal-Wallis test,Spearman’s co.relation analysis and multivariate logistic regression analysis were employed to assess factors associated with mental ***:Of all participants,784 were males(32.2%) and 1651 were females(67.8%).The perceived stress(CPSS sco.e) is higher in the male(mean(SD)=27.26(10.09)) than the female(mean(SD)=27.03(8.03)).People under 20 years had the lowest AIS sco.es(mean(SD)=2.85(3.31)) and CPSS sco.es(mean(SD)=26.47(9.48)).Those above60 years old presented the highest sco.e on AIS sco.es(mean(SD)=4.02(4.80)) and CPSS sco.es(mean(SD)=30.09(10.8)).The divorced group presented the highest sco.e on AIS sco.es(mean(SD)=3.57(4.51)) and CPSS sco.es(mean(SD)=27.62(8.93)).The farmer reported the highest sco.e on AIS sco.es(mean(SD)=6.56(7.99)) and the civil servants had the highest sco.e on CPSS sco.es(mean(SD)=30.59(8.54)).Illiterate people had the highest AIS sco.es(mean(SD)=10.67(12.22)) and CPSS sco.es(mean(SD)=31.00(28.48)).Hubei province presented the highest AIS sco.es(mean(SD)=4.63(8.05)) and CPSS sco.es(mean(SD)=32.63(12.27)).Spearman’ s co.relation analysis showed that there were significant co.relations between SRQ-20,AIS and CPSS scales with age,marital status and geographical location.A binary logistic regression analysis showed the risk of insomnia in the general population were independently associated with four variables:age,occupation,marital status and geographical location(p<0.01 or 0.05).The risk of stress in the general popula

关键词： Stress co.ID-19 perceived stress insomnia age

Platelet-derived microvesicles deliver miR-30e and promote VSMC apoptosis after balloon injury

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Medicine in Novel Technology and Devices 2022年第1期13卷 22-30页

作者： Li Zi-Tong Chen yuan-Xiu Bao Han Liu Ji-Ting Zhuang Fei Li Hai-Peng yao Qing-Ping Jiang Zong-Lai Qi Ying-Xin Institute of Mechanobiology&Medical Engineering School of Life Sciences&BiotechnologyShanghai Jiao Tong UniversityShanghai200240China Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical EngineeringBeijing Advanced Innovation Center for Biomedical EngineeringBeihang UniversityBeijing100083China

During vascular remodeling after intimal injury,circulating platelets are activated by exposed co.lagen and release platelet-derived microvesicles(PMVs),which may co.tribute to the injury-induced apoptosis of vascular smooth muscle cells(VSMCs).However,the mechanisms in this process are still *** a rat balloon injury model,platelet adhesion at the injured site was detected,and promoted medial VSMC apoptosis was revealed with dT-mediated dUTP nick-end labeling(TUNEL)in *** apoptosis was promoted by co.ncubation with PMVs in *** analysis indicated the abound expression of the microRNA-30(miR-30)family in platelets,and the expression of the miR-30 family in platelets and PMVs was co.firmed with *** Pathway Analysis(IPA)software identified transcription factor 2(RUNX2)as a pivotal molecule linking miR-30 and cellular *** vitro,PMVs delivered miR-30e,an important member of the miR-30 family,into VSMCs and increased cell apoptosis.A dual-luciferase assay was adopted to verify the interaction of miR-30e with RUNX2,and fluorescence in situ hybridization(FISH)proved the cytoplasmic localization of miR-30e in *** apoptotic effect on VSMCs was further co.firmed by using miR-30e mimics and RUNX2 ***,RUNX2 siRNA altered the expression of its downstream genes,Tnfrsf11b,Smad6 and Mmp13,which may participate in apoptosis,as suggested by *** results indicated that PMVs play important roles in the interactions between circulating elements and VSMCs by delivering miR-30e to VSMCs and then promoting *** and potential intercellular messages may be novel therapeutic targets for preventing pathological vascular remodeling after intimal injury.

关键词： Platelet-derived microvesicles Vascular smooth muscle cells Apoptosis miR-30e RUNX2 Intimal injury

A novel model of drug cue-induced behaviours in rhesus macaque subjected to chronic ketamine exposure

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General Psychiatry 2023年第1期36卷 76-78页

作者： Meng Qin Jiaoqiong Guan Yichun Huang He Lin Ding Cui Tao yao Chaoyang Tian Mali Wong Zhe Shi Tifei yuan Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina Department of Rehabilitation Medicine Guangzhou First People’s HospitalSchool of MedicineSouth China University of Technology School of MedicineGuangzhouGuangdongChina shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina The Third Research Institute of Ministry of Public Security ShanghaiChina Department of Neurosciences Laboratory for Neuro-and PsychophysiologyKU LeuvenLeuvenBelgium Key Laboratory of Biomedical Engineering of Hainan Province School of Biomedical EngineeringHainan UniversityHaikouHainanChina Psychiatry and Behavioral Sciences SUNY Upstate Medical UniversitySyracuseNew YorkUSA Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province Hunan University of Chinese MedicineChangshaHunanChina co.innovation Center of Neuroregeneration Nantong UniversityNantongJiangsuChina

To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a co.prehensive... 详细信息

关键词： drug behaviour ketamine

Helical Arranged Silica Platelets Prepared by Hvperbranched Polypeptide Block co.olymer Template

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Helical Arranged Silica Platelets Prepared by Hvperbranched ...

The 5th Symposium on Molecular Chirality of Chinese Chemical Society & International Chiral Meeting

作者： yuan yao Shunai Che Deyue yan School of Chemistry and Chemical Engineering Shanghai Jiao Tong University800 Dongchuan RoadShanghai 200240

＜正＞Preparation of chiral inorganic materials under the direction of natural and synthetic templates has attracted intensive interests in recent *** inorganic materials with chiral morphology and/or mesochannels had been synthesized with the aid of amino acid derivatives,polypeptides,DNAs and other molecules in the last decades. Herein we report the formation of helical arranged silica platelets under the

关键词： Helical Silica Polypeptide

Cellulose nanofibril matrix drives the dynamic formation of spheroids

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2023年第10期24卷 922-934页

作者： Yi LU Guo LI Yeqiu LI yuan yao co.lege of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310027China ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 311215China School of Physical Science and Technology ShanghaiTech UniversityShanghai 201210China

Multicellular spheroids,which mimic the natural organ co.nterparts,allow the prospect of drug screening and regenerative ***,their application is hampered by low processing efficiency or limited *** study introduces an efficient method to drive rapid multicellular spheroid formation by a cellulose nanofibril *** matrix enables the facilitated growth of spheroids(within 48 h)through multiple cell assembly into size-co.trollable aggregates with well-organized physiological *** efficiency,dimension,and co.formation of the as-formed spheroids depend on the co.centration of extracellular nanofibrils,the number of assembled cells,and the heterogeneity of cell *** above strategy allows the robust formation mechanism of co.pacted tumoroids and hepatocyte spheroids.

关键词： Cellulose Nanofibril Matrix Self-assembly Spheroid

co.expression of TRAIL and Smac delivered by an E1B-55K deleted onco.ytic adenovirus co.taining a caspase-8 cleavage site (IETD) elicits co.plete elimination of hepatocellular carcinoma xenograft

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Co-expression of TRAIL and Smac delivered by an E1B-55K dele...

2012年浙江省血液病学年会

作者： Shibing Wang yuan Tan Wen Lei Yigang Wang Xiumei Zhou Kangjian Zhang Liang Chu Xinyuan Liu Wenbin Qian Xinyuan Institute of Medicine and biotechnology School of Life Science Zhejiang Sci-Tech University Institute of Hematology The First Affiliated Hospital College of Medicine Zhejiang University Laboratory of Molecular Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences

co.bination target therapy is necessary for cancer treatment because tumors are genetically diverse. In our current study, we generated a novel E1B-55K deleted onco.ytic adenovirus that harbors both TRAIL and Smac genes (ZD55-TRAIL-IETD-Smac). In this vector, a caspase-8 cleavage site (IETD) was introduced between the genes, which allows the production of TRAIL and Smac, respectively, within virusinfected cells after activation of caspase-8. In our system, treatment with ZD55-TRAIL-IETD-Smac produced equal expression of TRAIL and Smac, and resulted in significant cytotoxicity against various cancer cells with stronger efficacy than that of ZD55-TRAIL or ZD55-Smac alone. The expression of these two therapeutic genes in the infected cells was downregulated by a caspase-8 inhibitor (Z-IETD-FMK) and upregulated by 5-FU (a activator of caspase-8), suggesting that cleavage of TRAIL-IETD-Smac fusion protein by activation of caspase-8. In a s.c. xenograft hepatocellular carcinoma (HCC) model, the antitumor effect of ZD55-TRAIL-IETD-Smac was significantly stronger than that of ZD55-TRAIL and ZD55-Smac, respectively. Importantly, intratumoral injection of ZD55-TRAIL-IETD-Smac eliminated all xenograft tumors established from a human HCC cell line Bel-7404, resulting in long-term, tumor-free survival. In co.clusion, our data suggest that onco.ytic adenovirus inco.porating two different therapeutic genes by introduction of the IETD sequence may be attractive candidates for clinical application in treatment of cancer.

关键词： TRAIL Smac co.expression IETD virotherapy genetherapy

Dogs lacking Apolipoprotein E show advanced atherosclerosis leading to apparent clinical co.plications

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Science China(Life Sciences) 2022年第7期65卷 1342-1356页

作者： Hui Zhao Jianping Zhao Di Wu Zhaolin Sun Yang Hua Min Zheng Yumei Liu Qi Yang Xiahe Huang yuan Li Yueshan Piao Yingchun Wang Sin Man Lam Huijuan Xu Guanghou Shui Yongjun Wang Haifeng yao Liangxue Lai Zhuo Du Jidong Mi Enqi Liu Xunming Ji Yong Q.Zhang Key Laboratory of Molecular Developmental Biology and CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute ofGenetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Beijing Sinogene biotechnology co.Ltd Beijing 102200China Xuanwu Hospital Capital Medical UniversityBeijing 100053China TianTan Hospital Capital Medical UniversityBeijing 100070China Beijing Petsguard Animal Hospital Beijing 100192China Laboratory Animal Center Xi’an Jiaotong University Health Science CenterXi’an 710049China

Atherosclerotic cardiovascular disease resulting from dysregulated lipid metabolism is the leading cause of morbidity and mortality *** E(ApoE)plays a critical role in cholesterol *** in lipid-metabolizing proteins including ApoE in multiple model organisms such as mice and rats exhibiting elevated levels of cholesterol have been widely used for dissecting the pathology of atherosclerosis,but few of these animal models exhibit advanced atherosclerotic plaques leading to ischemia-induced clinical symptoms,limiting their use for translational *** we report hypercholesterolemia and severe atherosclerosis characterized by stenosis and occlusion of arteries,together with clinical manifestations of stroke and gangrene,in ApoE knockout dogs generated by CRISPR/Cas9 and cloned by somatic cell nuclear transfer ***,the hypercholesterolemia and atherosclerotic co.plications in F0 mutants are recapitulated in their *** the ApoE-associated atherosclerosis and clinical manifestations in mutant dogs are more similar to that in human patients co.pared with those in other animal models,these mutant dogs will be invaluable in developing and evaluating new therapies,including endovascular procedures,against atherosclerosis and related disorders.

关键词： ApoE atherosclerosis hypercholesterolemia gangrene stroke