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| 1 | 晚期非小细胞肺癌免疫检查点抑制剂新型生物标志物:血液PD-L1动态检测显示文摘背景免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)具有良好疗效已成为恶性肿瘤治疗领域备受瞩目的翘楚。然而,仅有小部分患者获得长期临床获益。如何选择生物标志物来筛查ICIs治疗优势人群仍是一大热点。方法收集51例晚期恶性肿瘤患者的肿瘤组织和配对血样本,进行PD-L1表达的相关性分析。40例晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者接受ICIs治疗,2个月时检测血液PD-L1(bloodPD-L1,bPD-L1)表达的动态变化,包括PD-L1 mRNA、外泌体PD-L1(exosomalPD-L1,exoPD-L1)蛋白和可溶性PD-L1(solublePD-L1,sPD-L1)。应用R软件计算最佳截断值,用于预测最佳客观缓解(best objective response,b OR)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。结果51例不同恶性肿瘤患者中,组织PD-L1(tissuePD-L1,tPD-L1)表达阳性患者的PD-L1mRNA表达水平显著升高。40例接受ICIs治疗的晚期NSCLC患者中,bPD-L1 mRNA上调≥2.04的患者b OR、PFS和OS更佳;21例接受ICIs治疗的晚期NSCLC患者中,exoPD-L1上调≥1.86的患者临床获益更大。sPD-L1动态变化与ICIs疗效无显著相关性。PD-L1 mRNA和exoPD-L1联合检测更有利于预测ICIs治疗疗效。结论bPD-L1表达与tPD-L1表达存在正相关;晚期NSCLC患者ICIs治疗初期PD-L1 mRNA和(或)exoPD-L1表达升高,可作为评估临床获益的新型生物标志物。 | Qiao YANG Mingjing CHEN Jiaoyang GU Kai NIU Xianlan ZHAO Linpeng ZHENG Zihan XU Yongxin YU Feng LI Lingxin MENG Zhengtang CHEN Wenlei ZHUO Luping ZHANG Jianguo SUN 杨峤(译) 孙建国(译) | 2021 | 中国肺癌杂志2021，24，12： | 10 |
| 2 | CRISPR-Cas9-mediated genome editing in one blastomere of two-cell embryos reveals a novel Tet3 function in regulating neocortical development显示文摘学习必要基因的早功能是在发展生物学的一个重要、挑战性的问题。这里,我们为很快在二房间的阶段胚胎的一个分裂球导致 CRISPR-Cas9-mediated 变化建立了一个方法,称为的 2 房间 embryo-CRISPR-Cas9 注射(2CC ) ,学习在里面必需品的 vivo 功能(或未知) 在创始人的基因妄想的鼠标。由注射指向兴趣的基因进的 Cre mRNA 和 CRISPR-Cas9 荧光灯记者老鼠, 2CC 方法能在不同发展阶段跟踪野类型、变异的房间,为变异的房间的 phenotypic 分析的出现内部控制。用这个方法,我们在在发展中的鼠标调整有刺激性、禁止的 synaptic 传播识别了必要基因 Tet3 的新奇函数服的外皮。由产生妄想的变异的老鼠, 2CC 方法允许在多重纸巾和房间的基因功能的快速的屏蔽录入妄想的老鼠创始人,显著地扩展基因工具的当前的一套设备。 | Wang, Lingbo Li, Min-Yin Qu, Chao Miao, Wan-Ying Yin, Qi Liao, Jiaoyang Cao, Hua-Teng Huang, Min Wang, Kai Zuo, Erwei Peng, Guangdun Zhang, Shu-Xin Chen, Guodong Li, Qing Tang, Ke Yu, Qian Li, Zhoujie Wong, Catherine C. L. Xu, Guoliang Jing, Naihe Yu, Xiang Li, Jinsong | 2017 | Cell Research2017，27，6： | 5 |
| 3 | Rapid generation of ACE2 humanized inbred mouse model for COVID-19 with tetraploid complementation显示文摘Although monkeys and pigs can be infected with SARS-Co V-2,they generally have a long growth cycle and a large size that is difficult to handle in large quantities.However,the readily available rats and mice are not susceptible to SARSCo V-2 because of differences in ACE2(angiotensin-converting enzyme 2),the receptor mediating cell entry of SARSCo V-2[1].Thus,the key to establishing a mouse model of COVID-19 is to make the mice express human ACE2 protein,and therefore become SARS-Co V-2 susceptible.Recently reported COVID-19 mouse models using a random insertion transgene approach[2,3]or adenoviral approach to express h ACE2[4],lack the tissue-specificity of h ACE2 expression and might not replicate COVID-19 precisely,limiting their applications in certain studies. | Feng-Liang Liu Kaixin Wu Jiaoyang Sun Zilei Duan Xiongzhi Quan Junqi Kuang Shilong Chu Wei Pang Han Gao Ling Xu Ying-Chang Li Hai-Lin Zhang Xue-Hui ang Rong-Hua Luo Xiao-Li Feng Hans RScholer Xinwen Chen Duanqing Pei Guangming Wu Yong-Tang Zheng Jiekai Chen | 2021 | National Science Review2021，8，2： | 3 |
| 4 | Generation of purple-violet chrysanthemums via anthocyanin B-ring hydroxylation and glucosylation introduced from Osteospermum hybrid F3'5'H and Clitoria ternatea A3'5'GT显示文摘Chrysanthemums possess no metabolic pathway to synthesize delphinidin because of the lack of endogenous F3'5'H gene encoding the key enzyme in its biosynthetic pathway;therefore,there are no blue or blue-purple chrysanthemums occurring naturally.Currently,the introduction of exogenous F3'5'H into chrysanthemums is an efficient method for breeding bluish chrysanthemums.In this study,we explored the effects of the introduction of mutant CmF3'H(generated via site-directed mutagenesis,T485S,CmF3'Hm)and exogenous Osteospermum hybrid F3'5'H(OhF3'5'H)genes combined with Clitoria ternatea A3'5'GT(CtA3'5'GT)on delphinidin synthesis in chrysanthemum.Among the F3'5'H transgenic lines,those overexpressing endogenous CmF3'Hm could not generate blue flower color,although red color was changed to light pink due to CtA3'5'GT function.Meanwhile,OhF3'5'H introduction promoted the accumulation of delphinidin and its derivatives in chrysanthemum,changing the flower color from red-purple to purple-violet.These results indicate the applicability of exogenous OhF3'5'H and CtA3'5'GT transformation for promoting delphinidin synthesis during the molecular breeding of violet/blue chrysanthemums. | Xiaoying Han Yuting Luo Jiaoyang Lin Huiying Wu Hao Sun Lijie Zhou Sumei Chen Zhiyong Guan Weimin Fang Fei Zhang Fadi Chen Jiafu Jiang | 2021 | Ornamental Plant Research2021，1，1： | 3 |
| 5 | In vitro expansion of human sperm through nuclear transfer显示文摘Dear Editor,Mammalian haploid embryonic stem cells(haESCs)represent an ideal tool for genetic analysis due to the presence of only one set of genetic materials.HaESCs fall into two readily distinguishable groups based on their genome origins:parthenogenetic haESCs(PG-haESCs)that are derived from oocyte-originated parthenogenetic embryos and androgenetic haESCs(AG-haESCs)that are produced through sperm nuclear transfer.Both PG-and AGhaESCs are feasible for delineating genome function at cellular level in vitro.Importantly,AG-haESCs can be used as a sperm replacement and applied to deciphering gene function at organismal level when combined with CRISPR-Cas9 technology.1 However,while PG-haESCs have been generated from both rodent and primates,2-5 AG-haESCs can only be obtained in rodent to date. | Xiaoyu Merlin Zhang Keliang Wu Yuxuan Zheng Han Zhao Junpeng Gao Zhenzhen Hou Meiling Zhang Jiaoyang Liao Jingye Zhang Yuan Gao Yuanyuan Li Lin Li Fuchou Tang Zi-Jiang Chen Jinsong Li | 2020 | Cell Research2020，30，4： | 3 |
| 6 | Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development显示文摘Primary germ layers have the potential to form all tissues in the mature organism,and their formation during gastrulation requires precise epigenetic modulation of both proximal and distal regulatory elements.Previous studies indicated that spatial and temporal patterns of gene expression in the gastrula predispose individual regions to distinct cell fates.However,the underlying epigenetic mechanisms remain largely unexplored.Here,we profile the spatiotemporal landscape of the epigenome and transcriptome of the mouse gastrula.We reveal the asynchronous dynamics of proximal chromatin states during germ layer formation as well as unique gastrula-specific epigenomic features of regulatory elements,which have strong usage turnover dynamics and clear germ layerspecific signatures.Importantly,we also find that enhancers around organogenetic genes,which are weakly expressed at the gastrulation stage,are frequently pre-marked by histone H3 lysine 27 acetylation(H3K27ac)in the gastrula.By using the transgenic mice and genome editing system,we demonstrate that a pre-marked enhancer,which is located in the intron of a brain-specific gene 25W009E07Rik,exhibits specific enhancer activity in the ectoderm and future brain tissue,and also executes important function during mouse neural differentiation.Taken together,our study provides the comprehensive epigenetic information for embryonic patterning during mouse gastrulation,demonstrates the importance of gastrula pre-marked enhancers in regulating the correct development of the mouse embryo,and thus broadens the current understanding of mammalian embryonic development and related diseases. | Xianfa Yang Boqiang Hu Jiaoyang Liao Yunbo Qiao Yingying Chen Yun Qian Su Feng Fang Yu Ji Dong Yu Hou He Xu Ran Wang Guangdun Peng Jinsong Li Fucnou Tang Naihe Jing | 2019 | Cell Research2019，29，11： | 1 |
| 7 | Modifications of soy protein isolates using combined extrusion pre-treatment and controlled enzymatic hydrolysis for improved emulsifying properties显示文摘 | CHEN Lin CHEN Jianshe REN Jiaoyang | 2011 | Food Hydrocolloids2011，25，5： | 1 |
| 8 | Clinical phenotype features and genetic etiologies of 38 children with progressive myoclonic epilepsy显示文摘Background:Progressive myoclonic epilepsy(PME)is a group of neurodegenerative diseases with genetic heterogeneity and phenotypic similarities,and many cases remain unknown of the genetic causes.This study is aim to summarize the clinical features and study the genetic causes of PME patients.Methods:Sanger sequencing of the target gene,Next Generation Sequencing(NGS)panels of epilepsy,trio-based Whole Exome Sequencing(WES)and detection of cytosine-adenine-guanine(CAG)repeat number were used to investigate the genetic causes of PME patients.Results:Thirty-eight children with PME whose seizure onset age ranged from 3 months to 12 years were collected from February 2012 to November 2019 in three hospitals in Beijing,China.The seizure types included myoclonic seizures(n=38),focal seizures(n=19),generalized tonic-clonie seizure(GTCS)(n=13),absence seizures(n=4),atonic seizures(n=3),epileptic spasms(n=2)and tonic seizures(n=1).Twenty-seven cases were sporadic and 11 had family members affected.Established PME-related genes were identified in 30 out of 38(78.9%)patients who had either recessively inherited or de novo heterozygous mutations.Among these 30 cases,there were 12 cases(31.6%)of neuronal ceroid lipofuscinoses(the causing gene contains TPP1,PPT1,CLN5,CLN6 and MFSD8),two cases of sialidosis(the causing gene is NEU1),two cases of neuronopathic Gaucher disease(the causing gene is GBA),one case of spinal muscular atrophy-progressive myoclonic epilepsy(the causing gene is ASAH1),four cases of KCNC1 mutation-related PME,four cases of KCTD7 mutation-related PME,two cases of TBC1D24 mutation-related PME,one case of GOSR2 related PME,and two of dentatorubral-pallidoluysian atrophy(the causing gene is ATN1).In total,13 PME genes were identified in our cohort.The etiology was not clear in eight patients.Conclusion:PME is a group of clinically and genetically heterogeneous diseases.Genetic diagnosis was clear in 78.9%of PME patients.Various of genetic testing methods could increase the rate of genetic diagnosis.Neuronal ceroid lipofuscinoses(NCL)is the most common etiology of PME in children.Nearly one third PME children were diagnosed with NCL.GOSR2 related PME was in our cohort in Asia for the first time. | Jing Zhang Ying Yang Xueyang Niu Jiaoyang Chen Wei Sun Changhong Ding Lifang Dai Liping Zhang Qi Zeng Yi Chen Xiaojuan Tian Xiaoling Yang Taoyun Ji Zhixian Yang Yanling Yang Yuwu Jiang Yuehua Zhang | 2020 | Acta Epileptologica2020，2，1： | 0 |
| 9 | Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma显示文摘More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM. | Yan Zhang Baoyuan Zhang Yongyun Li Yuting Dai Jiaoyang Li Donghe Li Zhizhou Xia Jianming Zhang Ping Liu Ming Chen Bo Jiao Ruibao Ren | 2022 | Frontiers of Medicine2022，16，5： | 0 |
| 10 | Preliminary Study on the Treatment Efficiency of Pasteurized Lime Thermal Alkaline Hydrolysis for Excess Activated Sludge and Reduction of Tetracycline Resistance Genes显示文摘Thermal alkaline hydrolysis is a common pretreatment method for the utilization of excess activated sludge(EAS).Owing to strict environment laws and need for better energy utilization,new methods were developed in this study to improve the efficiency of pretreatment method.Direct thermal hydrolysis(TH),pasteurized thermal hydrolysis(PTH),and alkaline pasteurized thermal hydrolysis(PTH+CaO and PTH+NaOH)methods were used to treat EAS.Each method was compared and analyzed in terms of dissolution in ammonium nitrogen(NH_(4)^(+)-N)and soluble COD(SCOD)in EAS.Furthermore,the removal of tetracycline resistance genes(TRGs)and class 1 transposon gene intI1 from EAS was investigated.The NH_(4)^(+)-N and SCOD concentrations in EAS treated by PTH were 1.24 and 2.58 times higher than those of TH.However,the removal efficiency of total TRGs and intI1 between the groups was comparable.The SCOD concentration of the PTH+NaOH group was 4.37 times higher than that of the PTH group,and the removal efficiency of total TRGs was increased by 9.52%compared with that by PTH.The NH_(4)^(+)-N and SCOD concentrations of the PTH+CaO group could reach 85.04%and 92.14%of the PTH+NaOH group,but the removal efficiency of total TRGs by PTH+CaO was 19.78%lower than that by PTH+NaOH.Thus,to reduce the financial cost in actual operation,lime(CaO)can be used instead of a strong alkali(NaOH),and pasteurized steam at 70℃ instead of conventional high-temperature heating to treat EAS.This study provides a reference for the development of alkaline hydrolysis under moderate temperatures along with the removal of TRGs in EAS. | Maoxia Chen Qixuan Zhou Jiayue Zhang Jiaoyang Li Wei Zhang Huan Liu | 2023 | Journal of Renewable Materials2023，11，10： | 0 |
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