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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 | The molecular determinants governing the immunogenicity of Japanese encephalitis live attenuated vaccines显示文摘In the course of isolating the attenuated Japanese encephalitis vaccine SA14-14-2,two attenuated strains SA14-9-7 and SA14-5-3 were also obtained that elicited low antibody responses in humans(o10%and 62%,respectively)and exerted much weaker immune protection in animal challenge experiments.However,the reason for these differences remains unknown.In order to understand why SA14-14-2 is superior to SA14-9-7 and SA14-5-3,we employed a reverse genetics method to identify the key mutations in the virus genome that determine the immunogenicity of live attenuated Japanese encephalitis viruses.We first sequenced the full genomic sequences of SA14-9-7 and SA14-5-3 and found mutations that changed four amino-acid base pairs when compared to the envelope gene of SA14-14-2.We mutated the genome of SA14-14-2 to generate these mutations both singly(E-177,E-264,E-279 and E-315)and in combination(E-177/264,E-279/315 and E-177/264/279/315)and tested these mutants along with parental strains SA14-14-2,SA14-9-7 and SA14-5-3 for their immunogenicity in vivo.When mice were immunized with SA14-9-7 and SA14-5-3,lower levels of neutralizing antibodies were generated compared with the immune response to SA14-14-2.Furthermore,SA14-5-3 was more immunogenic than SA14-9-7,which replicated the results previously seen in humans.Point mutations E-177,E-264,E-279 and E-315 diminished the immunogenicity of SA14-14-2 with E-264 and E-315,contributing the most to this phenotype.The mutant rJEV(E-177/E-264/E-279/E-315)containing all four point mutations exhibited the lowest immunogenicity with a seroconversion rate of 0 at an inoculation dose of 103 PFU(plaque-forming unit).We have identified the key amino acids in the envelope protein that account for the superior immunogenicity of SA14-14-2. | Yuhua Li Yin Fu Xinyu Liu Huiqiang Yang Yongxin Yu Lili Jia Xuguang Li Aaron Farnsworth Junzhi Wang | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 3 |
| 3 | Partial anhysteretic remanent magnetization (pARM) of synthetic single-and multidomain magnetites and its paleoenvironmental significance显示文摘In order to isolate magnetic signals carried by single-domain (SD) ferrimagnetic (FM) minerals from multi-domain (MD) FM minerals, we developed a few pa- rameters using partial anhysteretic remanent magnetization (pARM). Because MD fraction contains only soft (easy to be demagnetized) coercivity spectrum, pARM(>20 mT) was sensitive in eliminating MD contributions. Ratio of pARM(5 mT, 10 mT)/pARM(0, 5 mT) is useful in quantifying a rela- tive abundance of mass ratio between SD and MD fractions. These new proxies can quickly characterize the details of grain size distribution of magnetic minerals in paleoclimatic and paleomagnetic studies. | LIU Qingsong YU Yongjae PAN Yongxin ZHU Rixiang ZHAO Xixi | 2005 | Chinese Science Bulletin2005，50，20： | 3 |
| 4 | Effect of acupuncture plus conventional treatment on brain activity in ischemic stroke patients: a regional homogeneity analysis显示文摘OBJECTIVE: To determine differences in cerebral activity evoked by acupuncture and conventional stroke treatment, and identify the treatment targets.METHODS: In total, 21 patients were randomly divided into two groups. Group A(11 patients) received both acupuncture and conventional treatment, while group B(10 patients) received conventional treatment only. Resting-state functional magnetic resonance imaging(f MRI) was performed on each participant before and after treatment. Regional homogeneity analysis was performed to investigate the potential mechanism of acupuncture treatment by comparing differences in cerebral activity between treatments.RESULTS: Group A showed higher Re Ho in the frontal lobe(BA6, BA46), supra-marginal gyrus(BA40),middle temporal gyrus(BA21), cerebellum, and insula. Group B showed higher Re Ho in the frontal lobe(BA6) and parietal lobe(BA3, BA7).CONCLUSION: Acupuncture and conventional treatment triggered relatively different clinical efficacy and brain responses. Acupuncture treatment more significantly improved the symptoms of stroke patients. More marked changes in sensory,emotional, and motor areas(including the frontal lobe, middle temporal gyrus, cerebellum, and insula) might reflect the specific acupuncture mechanism. | Wu Ping Zeng Fang Li Yongxin Li Ji Qiu Lihua Qin Wei Luo Lu Yin Canxin Xiong Yan Bai Yu Wang Dan Zhou Yumei Liang Fanrong | 2017 | Journal of Traditional Chinese Medicine2017，37，5： | 3 |
| 5 | The structure differences of Japanese encephalitis virus SA14 and SA14-14-2 E proteins elucidate the virulence attenuation mechanism显示文摘Dear Editor,Japanese encephalitis(JE)is a mosquito-borne acute neurological infectious disease caused by the Japanese encephalitis virus(JEV).Globally,68,000 cases of the disease are estimated each year,with a fatality rate of as high as 30%and with approximately 30%-50%of survivors suffering from severe neurological sequelae(WHO,2015). | Xinyu Liu Xin Zhao Rui Na Lili Li Eberhard Warkentin Jennifer Witt Xu Lu Yongxin Yu Yuquan Wei Guohong Peng Yuhua Li Junzhi Wang | 2019 | Protein & Cell2019，10，2： | 3 |
| 6 | Identification and characterization of loop7 motif and its role in regulating biological function of human APOBEC3G through molecular modeling and biological assay显示文摘Human APOBEC3G(h A3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor(Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the h A3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the h A3G–Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation.Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, h A3G–Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3 G degradation by targeting the putative site around loop7. | Congjie Zhai Ling Ma Zhixin Zhang Jiwei Ding Jing Wang Yongxin Zhang Xiaoyu Li Fei Guo Liyan Yu Jinming Zhou Shan Cen | 2017 | Acta Pharmaceutica Sinica B2017，7，5： | 1 |
| 7 | Genetic Diversity and Distribution of Human Norovirus in China (1999–2011)显示文摘 | Yongxin Yu Shuling Yan Bailin Li Yingjie Pan Yongjie Wang Dimitris Paraskevis | 2014 | BioMed Research International2014，，： | 1 |
| 8 | Inhibition of SNAP-25 phosphorylation at Ser187 is involved in chronic morphine-induced down-regulation of SNARE complex formation显示文摘 | Xu Nanjie Yu Yongxin Zhu Jianmei | 2004 | J Biol Chem2004，279，40： | 1 |
| 9 | Inhibitory effects of polyphenols toward HCV from the mangrove plant Excoecaria agallocha L.显示文摘 | Yongxin Li Shanjiang Yu Dong Liu Peter Proksch Wenhan Lin | 2011 | Bioorganic & Medicinal Chemistry Letters2011，，2： | 1 |
| 10 | Hepatitis B virus in- duces a novel inflammation network involving three inflam- matory factors, IL29, IL-8, and cyclooxygenase 显示文摘 | Yi Yu Rui Gong Yongxin M | 2011 | The Journal of Immunology2011，187，9： | 1 |
| 11 | Growth differentiation factor 6,a repressive target of EZH2,promotes the commitment of human embryonic stem cells to mesenchymal stem cells显示文摘Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs.In this study,an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6(GDF6),which is involved in bone formation,was the most upregulated gene associated with MSCs compared to hESCs.Furthermore,we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population.Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine. | Pend Deng Yongxin Yu Christine Hong Cun-Yu Wang | 2020 | Bone Research2020，8，4： | 1 |
| 12 | Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models显示文摘 | Paul R. Gavine Yongxin Ren Lu Han Jing Lv Shiming Fan Wei Zhang Wen Xu Yuan Jie Liu Tianwei Zhang Haihua Fu Yongjuan Yu Huiying Wang Shirlian Xu Feng Zhou Xinying Su XiaoLu Yin Liang Xie Linfang Wang Weiguo Qing Longxian Jiao Weiguo Su Q. May Wang | 2014 | Molecular Oncology2014，，： | 1 |
| 13 | Chronic pulmonary bacterial infection facilitates breast cancer lung metastasis by recruiting tumor-promoting MHCII^(hi) neutrophils显示文摘Breast cancer can metastasize to various organs,including the lungs.The immune microenvironment of the organs to be metastasized plays a crucial role in the metastasis of breast cancer.Infection with pathogens such as viruses and bacteria can alter the immune status of the lung.However,the effect of chronic inflammation caused by bacteria on the formation of a premetastatic niche within the lung is unclear,and the contribution of specific immune mediators to tumor metastasis also remains largely undetermined.Here,we used a mouse model revealing that chronic pulmonary bacterial infection augmented breast cancer lung metastasis by recruiting a distinct subtype of tumor-infiltrating MHCII^(hi) neutrophils into the lung,which exhibit cancer-promoting properties.Functionally,MHCII^(hi) neutrophils enhanced the lung metastasis of breast cancer in a cell-intrinsic manner.Furthermore,we identified CCL2 from lung tissues as an important environmental signal to recruit and maintain MHCII^(hi) neutrophils.Our findings clearly link bacterial-immune crosstalk to breast cancer lung metastasis and define MHCII^(hi) neutrophils as the principal mediator between chronic infection and tumor metastasis. | Teng Ma Yu Tang Taolin Wang Yang Yang Yige Zhang Ruihuan Wang Yongxin Zhang Yi Li Mingbo Wu Miao Tang Xueli Hu Chaoyu Zou Yuan Ren Huan Liu Qianhua Zhang Heyue Li Min Wu Jing Li Xikun Zhou | 2023 | Signal Transduction and Targeted Therapy2023，8，9： | 0 |
| 14 | Molecular modeling of human APOBEC3G to predict the binding modes of the inhibitor compounds IMB26 and IMB35显示文摘APOBEC3G(A3G)is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication.The virally encoded protein Vif binds to A3G and induces its degradation,thereby counteracting the antiviral activity of A3G.Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development.Currently,there is an urgent need for understanding the three dimensional structure of full-length A3G.In this work,we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2(APO2)and the catalytic domain structure of A3G.Two compounds,IMB26 and IMB35,which have been shown to bind to A3G and block degradation by Vif,were docked into the A3G model and the binding modes were generated for further analysis.The results may be used to design or optimize molecules targeting Vif–A3G interaction,and lead to the development of novel anti-HIV drugs. | Zhixin Zhang Congjie Zhai Zeyun Mi Jiwei Ding Yongxin Zhang Xing Shi Xiaoyu Li Liyan Yu Zhuorong Li Jiandong Jiang Jinming Zhou Shan Cen | 2013 | Acta Pharmaceutica Sinica B2013，3，4： | 0 |
| 15 | Replication priority of hepatitis C virus genotype 2a in a Chinese cohort显示文摘HCV genotypes have been documented in clinical practice.The aim of this study was to determine the replication priority of different HCV genotypes in a Chinese HCV positive cohort.Serum samples from 491 apparently healthy Chinese blood donors testing positive for HCV antibodies and naive to antiviral drug therapy were tested.Genotyping analysis showed that genotypes 1b and 2a were predominant and accounted for 77.6%of the HCV infections.Among the genotype groups,individuals infected with genotype 2a had an HCV RNA viral load(108 copies/mL)about 200-fold(lg,2.3)greater than those infected with other genotypes(10^(4)–10^(5)copies/mL)indicating a replication priority of genotype 2a.However,there was no correlation between HCV genotype and antibody response suggesting that the amplification advantage of genotype 2a results from a favorable interaction with the host cellular environment.In conclusion,HCV genotypes 1b and 2a are the predominant genotypes in China and genotype 2a possesses a significant replication priority compared with the other genotypes.This suggests the existence of host cellular factors that may act as drug-targets for entirely clearing HCV infection in the future. | Zhen Yang Yongxin Yu Hongzhong Zhang Guifang Shang Jialiang Gao Jian-Dong Jiang Zonggen Peng | 2014 | Acta Pharmaceutica Sinica B2014，4，4： | 0 |
| 16 | CUL4B orchestrates mesenchymal stem cell commitment by epigenetically repressing KLF4 and C/EBPδ显示文摘Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellular mechanism that regulates MSC commitment remains unclear.Here,we identified Cullin 4B(CUL4B)as a critical regulator of MSC commitment.CUL4B is expressed in bone marrow MSCs(BMSCs)and downregulated with aging in mice and humans.Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation.Moreover,depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy.In addition,CUL4B deficiency in MSCs reduced bone strength.Mechanistically,CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδexpression,respectively.The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription.Collectively,this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs,which has therapeutic implications in osteoporosis. | Ruiqi Yu Hong Han Shuxian Chu Yijun Ding Shiqi Jin Yufeng Wang Wei Jiang Yuting Liu Yongxin Zou Molin Wang Qiao Liu Gongping Sun Baichun Jiang Yaoqin Gong | 2023 | Bone Research2023，11，2： | 0 |
| 17 | Optimization of Supercritical Extraction Process of Laoshan Black Tea by Response Surface Methodology显示文摘[Objectives]Laoshan black tea was subjected to supercritical CO_(2) extraction. [Methods]The extraction conditions of Laoshan black tea were studied by an orthogonal experiment and optimized by response surface methodology. [Results] The optimum extraction conditions of black tea extract by supercritical CO_(2) extraction were as follows: extraction pressure 23.53 MPa, extraction time 1.73 h, and extraction temperature 49.75 ℃, with which the extract yield could reach 5.15% theoretically. [Conclusions] Based on the traditional extraction process, a supercritical extraction method optimized by response surface methodology and a unique extraction process were formed, which enriches the extraction processes and methods of natural raw materials. | Yongxin LIU Zhiguang LIU Zengyu WANG Shuai ZHANG Guofeng YU Jianhong SUN Shoutao CAO Qiulin LIU Xulun WEI Cuishu LENG Fuhua MA Xuegang LI Yinlong WANG Shoujie NIE | 2023 | Agricultural Biotechnology2023，12，1： | 0 |
| 18 | Ultrasensitive detection of IgE levels based on magnetic nanocapturer linked immunosensor assay for early diagnosis of cancer显示文摘Rapid and accurate detection of immunoglobulin E(Ig E) in serum and reduction of serum dosage are of great significance for clinical detection. Herein, we described a rapid magnetic separation of Ig E from patient serum based on Fe3 O4@Si O2-NTA@026 sdab as the capture probe and multiple horseradish peroxidase(HRP)-labeled antibodies linked gold nanoparticles(Au NPs) as chemiluminescence(CL) signal amplifier for ultrasensitive detection of total Ig E. Results showed that the limit of detection of our immunosensor system in serum samples was 0.03 k U/L, which is lowest in comparison with current methods, and far lower than that of Immuno CAP for Ig E detection(0.1 k U/L). Furthermore, our immunosensor possessed satisfied repeatability and accuracy, as well as good stability. In comparison with the Immuno CAP for the quantitative detection of Ig E, highly consistent results were achieved in 20 serum samples. Specially, this method was also successfully utilized for assessing the Ig E traces in breast cancer patients,which provides a new idea for the diagnosis of early cancer. Therefore, we believe that such versatile immunosensor will offer an alternative method for the on-site monitoring and determination of various Ig E-related diseases. | Yongxin Liu Mengda Cao Zhongxi Huang Changmin Yu Naidi Yang Qiong Wu Liang Shi Wenjie Duan Yi Zhu Jifu Wei Lin Li Wei Huang | 2022 | Chinese Chemical Letters2022，33，4： | 0 |
| 19 | Removal Effect of Nitrifying Bacteria on Ammonia Nitrogen in Water显示文摘[Objectives]To investigate the removal effect of nitrifying bacteria on ammonia nitrogen in water.[Methods]In this experiment,the treated water(referred to as raw water hereinafter)from the Changping Town Qiaoli Water Treatment Project in Dongguan City of Guangdong Province was used as the experimental water body,and the nitrifying bacteria liquid used in the project was taken as the experimental material,to explore the removal effect of the nitrifying bacteria liquid on the ammonia nitrogen in the water body.[Results]Under the condition that other variables remain unchanged,the more the amount of nitrifying bacteria liquid added,the higher the removal efficiency of nitrifying bacteria liquid;under the same conditions,the removal effect of ammonia nitrogen in a stirred water body is better than that in an unstirred water body;the removal effect of ammonia nitrogen in a water body with bio-media/carriers is better than that without bio-media/carriers.[Conclusions]Nitrifying bacteria have a better removal effect on the ammonia nitrogen in the water body. | Jianqiao QIN Yongxin LI Min DAI Dongni YU | 2022 | Asian Agricultural Research2022，14，1： | 0 |
| 20 | Study on Flow Field Simulation at Transmission Towers in Loess Hilly Regions Based on Circular Boundary Constraints显示文摘When using high-voltage transmission lines for energy transmission in loess hilly regions,local extreme wind fields such as turbulence and high-speed cyclones occur from time to time,which can cause many kinds of mechanical and electrical failures,seriously affecting the reliable and stable energy transmission of the power grid.The existing research focuses on the wind field simulation of ideal micro-terrain and actual terrain with mostly single microterrain characteristics.Model boundary constraints and the influence of constrained boundaries are the main problems that need to be solved to accurately model and simulate complex flow fields.In this paper,a flow field simulation method based on circular boundary constraints is carried out.During the study,the influence of the model boundary and the selection conditions of themodeling range are systematically analyzed.It is more suitable to make sure that the air domain is 4 times higher than the height of the hill undulations,in addition to ensuring that there should be a minimum of 400 m between the study region and the boundary.Then,an actual terrain model of a power grid line in Shanxi is established,through the method proposed in this paper,the wind speed at the location of the transmission tower line under different wind directions is analyzed,and it is found that when the incidence direction is 45 degrees north by east the wind speed is the highest.The findings demonstrate that the circular boundary model has the advantage of more easily adjusting the wind incidence direction,in addition to theoretically reducing the errors caused by traditional models in boundary processing.It can accurately obtain the distribution characteristics of the flow field affected by the terrain,and quickly screen out the extreme working conditions that are most harmful to the transmission lines in the actual transmission line for energy transmission in complex loess hilly regions. | Yongxin Liu Huaiwei Cao Puyu Zhao Gang Yang Hua Yu Fuwei He Bo He | 2023 | Energy Engineering2023，120，10： | 0 |
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