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| 1 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
| 2 | Music/voice separation based on the multi-repeating structure of Mel cepstrum coefficient显示文摘For the poor adaptability of the original repeating pattern,an improved music separation method of multi-repeating structure of Mel cepstrum coefficient(MFCC) is proposed.Firstly,the MFCC coefficient matrix(39-dimensional data) of the music signal was extracted.Then the cosine characteristic was applied to the count of similarity matrix of MFCC,and the fragments with consistent similarity are putted together.Next different repeating patterns are built for different groups.Thereby the spectrums of the background music and vocal were separated combined with ideal binary masking(IBM),and the corresponding time domain signals were obtained by inverse Fourier transform.Fnally,the improved method was tested on the music database of different types and length,and the separation results were compared with repeating method of Rafii and the non-negative matrix factorization based on flexible framework method of Ozerov.The experimental results showed that the separation performance of improved method was improved about 3 dB,and the performance of music with melody changed larger was significantly improved.Experiments verified that the improved method was an effective music separation algorithm and more stability. | ZHANG Tianqi XU Xin WU Wangjun LIU Yu | 2015 | Chinese Journal of Acoustics2015，34，4： | 4 |
| 3 | Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β_(2)-AR/MACC1 axis显示文摘Background:Depression is a common,easily ignored,accompanied disease of gastric cancer(GC)patients and is often observed with elevated plasma catecholamine levels.Depression frequently promotes GC progression and leads to poor clinical outcomes;however,the molecular mechanisms underlying depression-induced GC progression remain poorly understood.We aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression-associated catecholamines on GC.Methods:Depression states of GC patients were graded using the Patient Health Questionnaire-9,and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass spectrometry.Migrative and invasive GC cells were examined using transwell assays,and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild stress.Mouse depression-like behaviors were assessed through sucrose preference,forced swimming,and tail suspension tests.Characteristics of the neuroendocrine phenotype were observed via RT-PCR,Western blotting,flow cytometry,and transmission electron microscopy.Results:Fifty-one GC patients(age:53.61±1.79 years;cancer duration:3.71±0.33 months;depression duration:2.37±0.38 months;male-to-female ratio:1.55:1)were enrolled in the study.Depression grade was significantly higher in GC patients showing higher plasma levels of catecholamines(epinephrine:P=0.018;noradrenaline:P=0.009),higher oncogene metastasis-associated in colon cancer-1(MACC1)level(P=0.018),and metastasis(P<0.001).Further,depression-associated catecholamine specifically bound to the beta-2 adrenergic receptor(β_(2)-AR)and upregulated MACC1 expression,and thus promoting neuroendocrine phenotypic transformation through direct binding betweenMACC1 and synaptophysin.Eventually,the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in vivo.However,β_(2)-AR antagonist ICI-118,551 or MACC1 silencing effectively blocked the catecholamineinduced neuroendocrine phenotypic transformation and eliminated depressionenhanced GC migration and invasion.Moreover,β_(2)-AR blocking or MACC1 silencing prevented GC metastasis attributed to a neuroendocrine phenotype in a depression mouse model.Conclusions:Catecholamine-induced neuroendocrine phenotypes of GC cells led to depression-accelerated GC invasion and metastasis via the β_(2)-AR/MACC1 axis,while β_(2)-AR antagonist or MACC1 silencing could reverse it,showing promising potential therapeutic strategies for improving the outcome of GC patients with comorbid depression. | Changqie Pan Jianhua Wu Siting Zheng Huiying Sun Yisheng Fang Zhenhua Huang Min Shi Li Liang Jianping Bin Yulin Liao Jinzhang Chen Wangjun Liao | 2021 | Cancer Communications2021，41，10： | 4 |
| 4 | Metastasis‐associated in colon cancer‐1 upregulation predicts a poor prognosis of gastric cancer, and promotes tumor cell proliferation and invasion显示文摘 | Lin Wang Yajun Wu Li Lin Pengmin Liu Hui Huang Wenjun Liao Dayong Zheng Qiang Zuo Li Sun Na Huang Min Shi Yulin Liao Wangjun Liao | 2013 | Cancer2013，，6： | 1 |
| 5 | Identification of four SNPs and association analysis with meat quality traits in the porcine Pitx2c gene显示文摘The association of the porcine Pitx2c gene with meat quality traits was investigated in the present study.A total of eight single nucleotide polymorphisms (SNPs) were found.Allele frequencies of four SNPs were further detected in four commercial breeds and eight Chinese indigenous breeds.Single SNP and meat quality associations were analyzed in a Yorkshire×Meishan F 2 population.The SNPs c.474C>T (P<0.01) and c.636C>T (P<0.05) showed a significant association with meat color (MCV1).The SNPs c.37G>A and c.47G>A were significantly associated with drip loss rate (DLR),water holding capacity (WHC) and meat color value (MCV1) consistently (P<0.05).Linkage disequilibrium (LD) analysis revealed that the adjacent SNPs were in LD.Two major haplotypes were identified,and association analysis between haplotype combinations and meat quality indicated that the presence of two copies of haplotype 1-CCGG-may improve meat quality. | WU WangJun ZUO Bo REN ZhuQing HAPSARI A.A.R LEI MingGang XU DeQuan LI FengE XIONG YuanZhu | 2011 | Science China(Life Sciences)2011，54，5： | 1 |
| 6 | Evolution of tumor microenvironment in colorectal liver metastases under treatment stress显示文摘Dear editor,The tumor microenvironment(TME)heavily impacts disease biology and may influence responses to systemic treatments,and thereby,affects patients’prognosis.In our previous study,we found that immune features could predict prognosis and guide the therapy choices for stage I-III colon cancer[1,2].Increasing evidence shows that therapyinduced TME changes can promote tumor progression,metastasis,and the development of resistance[3,4].However,the TME dynamics in colorectal liver metastases(CRLM)under treatment are still incompletely clear. | Na Huang Dongqiang Zeng Xiaoxiang Rong Chunlin Wang Zhenzhen Wu Jian Guo Yuqi Wang Jin Li Jing Li Jiao Wang Siting Zheng Genjie Huang Jianping Bin Yulin Liao Qian Li Xin Yi Wangjun Liao Min Shi | 2022 | Cancer Communications2022，42，5： | 1 |
| 7 | An ultrapotent pan-β-coronavirus lineage B(β-CoV-B)neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope显示文摘New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design.Here,we identified a receptorbinding domain(RBD)-binding antibody,XG014,which potently neutralizesβ-coronavirus lineage B(β-CoV-B),including SARS-CoV-2,its circulating variants,SARSCoV and bat SARSr-CoV WIV1.Interestingly,antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibodydependent SARS-CoV-2 spike(S)protein-mediated cellcell fusion,suggesting a unique mode of recognition by XG014.Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional“down”conformation,while its family member XG005 directly competes with ACE2 binding and position the RBD“up”.Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo.Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines againstβ-CoV-B and newly emerging SARS-CoV-2 variants of concern. | Zezhong Liu Wei Xu Zhenguo Chen Wangjun Fu Wuqiang Zhan Yidan Gao Jie Zhou Yunjiao Zhou Jianbo Wu Qian Wang Xiang Zhang Aihua Hao Wei Wu Qianqian Zhang Yaming Li Kaiyue Fan Ruihong Chen Qiaochu Jiang Christian TMayer Till Schoofs Youhua Xie Shibo Jiang Yumei Wen Zhenghong Yuan Kang Wang Lu Lu Lei Sun Qiao Wang | 2022 | Protein & Cell2022，13，9： | 1 |
| 8 | Improving the slurrying ability of XiMeng brown coal by medium- to low-temperature thermal treatment显示文摘 | Jiefeng Zhu Jianzhong Liu Wangjun Shen Junhong Wu Ruikun Wang Junhu Zhou Kefa Cen | 2014 | Fuel Processing Technology2014，，： | 1 |
| 9 | Metastasis‐associated in colon cancer‐1 upregulation predicts a poor prognosis of gastric cancer, and promotes tumor cell proliferation and invasion显示文摘 | Lin Wang Yajun Wu Li Lin Pengmin Liu Hui Huang Wenjun Liao Dayong Zheng Qiang Zuo Li Sun Na Huang Min Shi Yulin Liao Wangjun Liao | 2013 | Int J Cancer2013，，6： | 1 |
| 10 | Glutamine metabolic microenvironment drives M2 macrophage polarization tomediate trastuzumab resistance in HER2-positive gastric cancer显示文摘Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit,and there is currently no effective reversal measure.Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves,while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking.This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients.Methods:Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing.Bioinformatics were used to analyze cell subtypes,metabolic pathways,and molecular signaling pathways.Changes in microenvironmental indicators(such as macrophage,angiogenesis,and metabolism)were verified by immunofluorescence(IF)and immunohistochemical(IHC)analyses.Finally,a multi-scale agent-based model(ABM)was constructed.The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM.Results:Based on transcriptome sequencing,molecular biology,and in vivo experiments,we found that the level of glutamine metabolism in trastuzumabresistant HER2-positive cells was increased,and glutaminase 1(GLS1)was significantly overexpressed.Meanwhile,tumor-derived GLS1 microvesicles drove M2macrophage polarization.Furthermore,angiogenesis promoted trastuzumab resistance.IHC showed high glutamine metabolism,M2 macrophage polarization,and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nudemice.Mechanistically,the cell division cycle 42(CDC42)promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B(NF-κB)p65 and drove GLS1microvesicle secretion through IQmotif-containing GTPase-activating protein 1(IQGAP1).Based on the ABM and in vivo experiments,we confirmed that the combination of anti-glutamine metabolism,anti-angiogenesis,and pro-M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2-positive gastric cancer.Conclusions:This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism,M2 macrophage polarization,and pro-angiogenic function of macrophages,leading to acquired trastuzumab resistance in HER2-positive gastric cancer.A combination of anti-glutamine metabolism,anti-angiogenesis,and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance. | Xingbin Hu Zhenfeng Ma Beibei Xu Shulong Li Zhiqi Yao Bishan Liang Jiao Wang Wangjun Liao Li Lin Chunling Wang Siting Zheng Qijing Wu Qiong Huang Le Yu Fenghua Wang Min Shi | 2023 | Cancer Communications2023，43，8： | 0 |
| 11 | Selection and structural bases of potent broadly neutralizing antibodies from 3-dose vaccinees that are highly effective against diverse SARS-CoV-2 variants,including Omicron sublineages显示文摘Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to the lineage B of the genus Betacoronavirus in the Coronaviridae family,is the causative agent of the C0VID19 pandemic,1 which has lasted for over two years,resulting in unprecedented public health and socioeconomic crisis.Several SARS-CoV-2 variants of interest(VOIs)as well as variants of concern(VOCs),including the Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.l),Delta(B.1.617.2)and the most recently identified Omicron sublineages(BA.1,BA.1.1,BA.2 and BA.3),have emerged at different time points over the course of the pandemic,leading to the resurge nee of outbreaks across the world.Among these variants. | Lei Wang Wangjun Fu Linlin Bao Zijing Jia Yuxia Zhang Yunjiao Zhou Wei Wu Jianbo wu Qianqian Zhang Yidan Gao Kang Wang Qiao Wang Chuan Qin Xiangxi Wang | 2022 | Cell Research2022，32，7： | 0 |
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