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| 1 | Base editing-mediated splicing correction therapy for spinal muscular atrophy显示文摘Dear Editor,Spinal muscular atrophy(SMA)is a devastating autosomal recessive motor neuron disease.1,2 Infants with more severe forms of type I SMA die before the age of 2 if no intervention is provided.1,2 Spinraza and zolgensma have been approved by the FDA as SMA therapeutics for pediatric patients.1,2 However,as an antisense oligonucleotide(ASO)based therapy,spinraza requires four loading doses,followed by three annual maintenance doses.The patients would be subjected to repeated intrathecal injections in the procedure.Zolgensma is a single-dose gene-replacement therapy for SMA,but unfortunately is unreliable in maintaining a high,stable level of gene expression.These issues have limited the therapeutic effects of the two approved drugs for SMA. | Xiang Lin Haizhu Chen Ying-Qian Lu Shunyan Hong Xinde Hu Yanxia Gao Lu-Lu Lai Jin-Jing Li Zishuai Wang Wenqin Ying Lixiang Ma Ning Wang Erwei Zuo Hui Yang Wan-Jin Chen | 2020 | Cell Research2020，30，6： | 5 |
| 2 | Introduction of a multicenter online database for non-metastatic breast cancer in China显示文摘Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors;and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016). | Yaping Yang Jieqiong Liu Min Peng Fengxi Su Xiaoming Xie Zhenzhen Liu Jundong Wu Wei Wei Dongxian Zhou Weiwen Li Ailing Zhang Guosen Su Weixiong Yang Jishang Chen Dekui Ma Yongguang Cai Kai Chen Liling Zhu Qiang Liu Erwei Song | 2020 | Science China(Life Sciences)2020，63，9： | 4 |
| 3 | High activity of hot electrons from bulk 3D graphene materials for efficient photocatalytic hydrogen production显示文摘为经由切开的水的氢生产的有效光催化剂的设计和合成从理论、实际的观点是很重要的。许多基于金属的半导体在最近的十年为这个目的被探索了。这里,第一次完全基于碳的材料,体积三在尺寸上的 cross-linked graphene (3DG ) ,为氢作为光催化剂被开发了生产。它展出 270 摩尔的显著的氢生产率 ??? 琠? 敧敮慲整挠瑹瑯硯捩稠湩 ? 潩獮愠摮爠慥瑣癩? 硯杹湥猠数楣獥 ? 佒 ? 。 | Yanhong Lu Bo Ma Yang Yang Erwei Huang Zhen Ge Tengfei Zhang Suling Zhang Landong Li Naijia Guan Yanfeng Ma Yongsheng Chen | 2017 | Nano Research2017，10，5： | 3 |
| 4 | Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice显示文摘We here report a genome-editing strategy to correct spinal muscular atrophy(SMA).Rather than directly targeting the pathogenic exonic mutations,our strategy employed Cas9 and guide-sg RNA for the targeted disruption of intronic splicing-regulatory elements.We disrupted intronic splicing silencers(ISSs,including ISS-N1 and ISS+100)of survival motor neuron(SMN)2,a key modifier gene of SMA,to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs.Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration.Furthermore,co-injection of Cas9 mRNA from Streptococcus pyogenes(SpCas9)or Cas9 from Staphylococcus aureus(SaCas9)alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56%and 100%of severe SMA transgenic mice(Smn-/-,SMN2tg/-).The median survival of the resulting mice was extended to>400 days.Collectively,our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. | Jin-Jing Li Xiang Lin Cheng Tang Ying-Qian Lu Xinde Hu Erwei Zuo He Li Wenqin Ying Yidi Sun Lu-Lu Lai Hai-Zhu Chen Xin-Xin Guo Qi-Jie Zhang Shuang Wu Changyang Zhou Xiaowen Shen Qifang Wang Min-Ting Lin Li-Xiang Ma Ning Wang Adrian R.Krainer Linyu Shi Hui Yang Wan-Jin Chen | 2020 | National Science Review2020，7，1： | 1 |
| 5 | Correlativity between blood measures related to blood stasis blocking collaterals and gene expression of angiotensin-converting enzyme of renal cortex in diabetic rats and effect of stasis removing and collaterals dredging显示文摘OBJECTIVE: To investigate the correlativity between the changes of blood measures related to blood stasis blocking collaterals and gene expression levels of angiotensin-converting enzyme(ACE)and ACE2 ofrenal cortex in diabetic rats with stasis blocking collaterals syndrome, as well as the effectof stasis removing and collaterals dredging.METHODS: Male Sprague-Dawley rats were divided randomly into normal control group(C group),high-carbohydrate-fat control group(H group) and streptozotocin(STZ)-injecting group. The diabeticrats were induced from rats in the STZ-injecting groupby high-carbohydrate-fat diet combined with STZ intraperitoneal injection, with sustained high-carbohydrate-fat diet fed afterwards, and were further divided into model group(M group)and Chinese medicine of stasis removing and collaterals dredging group(Z group). Rats in the Z group were fed with stasis-removing-and-collaterals-dredging herbal granule suspension intragastrically daily for 16 weeks, while drinking water of corresponding volume was administrated to the rats in other groups. At the end of the 16 th week after successful establishment of models, the ultrastructures of glomeruli in different groups were detected by a transmission electron microscopy; and blood measures related to blood stasis blocking collaterals, including lipid profile and blood viscosity measures, were tested, as well as the relative gene expressions of ACE and ACE2.RESULTS: Changes in ultrastructures of glomeruli in the M group were characterized by lack of clarity in structure and occasional thickening of glomerular basement membrane and extensive fusion in foot processes. The correlation analysis showed that there were positive correlations between lipid profile, blood viscosity, and the ACE mRNA expression levels in the M group(P<0.05), except for cholesterol. And except for triglyceride, the blood measures were in negative correlation with the ACE2 mRNA expression levels in the M group(P<0.05).Compared with the C and H groups, the lipid profile, plasma viscosity and blood viscosity were significantly higher(P<0.01). All the above-mentioned measures were significantly improved in the Z group rats(P<0.05). ACE mRNA expression was significantly higher in the M group thanin the C group(P<0.05). ACE2 mRNA level was significantly lower in the M group than in the C and H groups(P<0.01)and its levelin the Z group was higher than that in the M group(P<0.01).CONCLUSION: Blood measuresrelated to blood stasis blocking collaterals had positive linear correlations with ACE mRNAexpression and negative linear correlations with ACE2 mRNA expression in the M group. Chinese recipe of stasis removing and collaterals dredging could play a renal protecting role for diabetic rats by reducing lipid profile and blood viscosity, down-regulating ACE mRNA expression and up-regulating ACE2 mRNA expression. | Jing Xu Lu Bai Erwei Ma Qian Guo Yuehua Wang Muqing Zhang Zhiqiang Chen | 2014 | Journal of Traditional Chinese Medicine2014，34，5： | 1 |
| 6 | Quantitative characterization of filamentous fungal promoters on a single-cell resolution to discover cryptic natural products显示文摘Characterization of filamentous fungal regulatory elements remains challenging because of time-consuming transformation technologies and limited quantitative methods.Here we established a method for quantitative assessment of filamentous fungal promoters based on flow cytometry detection of the superfolder green fluorescent protein at single-cell resolution.Using this quantitative method,we acquired a library of 93 native promoter elements from Aspergillus nidulans in a high-throughput format.The strengths of identified promoters covered a 37-fold range by flow cytometry.P_(zipA) and P_(sltA)were identified as the strongest promoters,which were 2.9-and 1.5-fold higher than that of the commonly used constitutive promoter P_(gpdA).Thus,we applied P_(zipA)and P_(sltA)to activate the silent nonribosomal peptide synthetase gene Afpes1 from Aspergillus fumigatus in its native host and the heterologous host A.nidulans.The metabolic products of Afpes1 were identified as new cyclic tetrapeptide derivatives,namely,fumiganins A and B.Our method provides an innovative strategy for natural product discovery in fungi. | Peng-Lin Wei Jie Fan Jingwen Yu Zihui Ma Xian Guo Nancy PKeller Erwei Li Chunbo Lou Wen-Bing Yin | 2023 | Science China(Life Sciences)2023，66，4： | 0 |
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