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| 1 | In vitro testicular organogenesis from human fetal gonads produces fertilization-competent spermatids显示文摘Unlike most organs that mature during the fetal period,the male reproductive system reaches maturity only at puberty with the commencement of spermatogenesis.Robust modelling of human testicular organogenesis in vitro would facilitate research into mechanisms of and factors affecting human spermatogenic failure and male fertility preservation in prepubertal tumor patients.Here,we report successful recapitulation of human testicular organogenesis in vitro from fetal gonadal ridge.Our model displayed the formation of mature seminiferous epithelium and self-renewing spermatogonia.Remarkably,in vitro-derived haploid spermatids have undergone meiotic recombination,and showed increased genetic diversity as indicated by genetic analysis.Moreover,these spermatids were able to fertilize oocytes and support subsequent blastocyst formation.The in vitro testicular organogenesis system described here will play an important role in elucidating the regulation of human testis development and maintaining male fertility in prepubertal cancer patients. | Yan Yuan Laihua Li Qing Cheng Feiyang Diao Qiao Zeng Xiaoyu Yang Yibo Wu Hao Zhang Mingqian Huang Junqing Chen Quan Zhou Yunfei Zhu Rong Hua Jianyu Tian Xin Wang Zuomin Zhou Jie Hao Jinjin Yu Dong Hua Jiayin Liu Xuejiang Guo Qi Zhou Jiahao Sha | 2020 | Cell Research2020，30，3： | 6 |
| 2 | Hair cell overexpression of islet 1 reduces age-relatedand noise- induced hearing loss显示文摘 | Mingqian Huang Albena Kantardzhieva Deborah Scheffer | 2013 | The Journal of Neuroscience2013，33，15： | 1 |
| 3 | Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing显示文摘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 expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We 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(AAV-PHP.eB)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 transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,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. | 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 | 2022 | Signal Transduction and Targeted Therapy2022，7，4： | 1 |
| 4 | Shoulder adhesive capsulitis in cancer patients undergoing positron emission tomography-computed tomography and the association with shoulder pain显示文摘BACKGROUND Adhesive capsulitis is a relatively common condition that can develop in cancer patients during treatment.Positron emission tomography-computed tomography(PET-CT)is routinely performed as a follow-up study in cancer patients after therapy.Being aware of PET-CT findings to suggest shoulder adhesive capsulitis may help to alert clinicians for the diagnosis of unsuspected shoulder capsulitis.AIM To assess the association of shoulder adhesive capsulitis with cancer/therapy type and symptoms in cancer patients undergoing PET-CT.METHODS Our prospective study received Institutional Review Board approval.Written informed consent was obtained from all patients,who answered a questionnaire regarding shoulder pain/stiffness at the time of PET-CT study,between March 2015 and April 2019.Patients with advanced glenohumeral arthrosis,metastatic disease or other mass in the shoulder,or shoulder arthroplasty were excluded.Patterns of shoulder capsule 18F-fluorodeoxyglucose(FDG)uptake were noted.Standard Uptake Value(SUV)max and SUVmean values were measured at rotator interval(RI)and deltoid muscle in bilateral shoulders.Normalized SUV(SUV of RI/SUV of deltoid muscle)was also calculated.We assessed if SUV values are different between symptomatic and asymptomatic patients in both shoulders.Covariates were age,gender,and therapy type(surgery,chemotherapy,radiation).Wilcoxon rank sum tests were used to compare unadjusted marginal differences for age,SUV measurements between symptomatic and asymptomatic patients.Multiple linear regression models were used to examine the relationship between right or left shoulder SUV measurements and symptom status,after adjusting for covariates.Statistical significance level was set at P<0.05.RESULTS Of 252 patients initially enrolled for the study(mean age 66 years,67 symptomatic),shoulder PET-CT data were obtained in 200 patients(52 were excluded due to exclusion criteria above).The most common cancer types were lymphoma(n=61),lung(n=54)and breast(n=53).No significant difference was noted between symptomatic and asymptomatic patients in terms of age,gender,proportion of patients who had surgical therapy and radiation therapy.A proportion of patients who received chemotherapy was higher in patients who were asymptomatic in the right shoulder compared to those symptomatic in the right shoulder(65%vs 48%,P=0.012).No such difference was seen for the left shoulder.In both shoulders,SUVmax and SUVmean were higher in symptomatic shoulders than asymptomatic shoulders(Left SUVmax 2.0 vs 1.6,SUVmean 1.6 vs 1.3,both P<0.002;Right SUVmax 2.2 vs 1.8,SUVmean 1.8 vs 1.5,both P<0.01).For lung cancer patients,bilateral RI SUVmax and SUVmean values were higher in symptomatic shoulders than asymptomatic shoulders.For other cancer patients,symptomatic patients had higher left RI SUVmax/mean than asymptomatic patients after adjustment.CONCLUSION In symptomatic patients metabolic activities in RI were higher than asymptomatic patients.Adhesive capsulitis should be considered in cancer patients with shoulder symptoms and positive FDG uptake in RI. | Daichi Hayashi Elaine Gould Robert Shroyer Eric van Staalduinen Jie Yang Musa Mufti Mingqian Huang | 2021 | World Journal of Radiology2021，13，10： | 0 |
| 5 | Genomic,transcriptomic,and epigenomic analysis of a medicinal snake,Bungarus multicinctus,to provides insights into the origin of Elapidae neurotoxins显示文摘The many-banded krait,Bungarus multicinctus,has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia.Characterization of its venoms classified chief phyla of modern animal neurotoxins.However,the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome.Here,we present the 1.58 Gbp genome of B.multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp.Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications.The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins(3FTxs)from membrane tethering before the Colubroidea divergence.Subsequent expansion and mutations diversified and recruited these 3FTxs.After the cobra/krait divergence,the modern unit-B ofβ-bungarotoxin emerged with an extra cysteine residue.A subsequent point substitution in unit-A enabled theβ-bungarotoxin covalent linkage.The B.multicinctus gene expression,chromatin topological organization,and histone modification characteristics were featured by transcriptome,proteome,chromatin conformation capture sequencing,and ChIP-seq.The results highlighted that venom production was under a sophisticated regulation.Our findings provide new insights into snake neurotoxin research,meanwhile will facilitate antivenom development,toxin-driven drug discovery and the quality control of JinQianBaiHuaShe. | Jiang Xu Shuai Guo Xianmei Yin Mingqian Li He Su Xuejiao Liao Qiushi Li Liang Le Shiyu Chen Baosheng Liao Haoyu Hu Juan Lei Yingjie Zhu Xiaohui Qiu Lu Luo Jun Chen Ruiyang Cheng Zhenzhan Chang Han Zhang Nicholas Chieh Wu Yiming Guo Dianyun Hou Jin Pei Jihai Gao Yan Hua Zhihai Huang Shilin Chen | 2023 | Acta Pharmaceutica Sinica B2023，13，5： | 0 |
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