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| 1 | 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 |
| 2 | HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5-WDR5-dependent transcriptional program显示文摘Background:Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options.Emerging evidence shows that heat shock factor 1(HSF1)drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target.However,the roles of HSF1 in lymphatic metastasis remain largely unknown.Herein,we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential.Methods:We screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors(HSFs)and heat shock proteins(HSPs),and analyzed its clinical relevance in three cohorts.Functional in vitro and in vivo assays were performed in HSF1-silenced and-regained models.We also used Coimmunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual-luciferase reporter assays to investigate the transcriptional program directed by HSF1.The pharmacological inhibitor of HSF1,KRIBB11,was evaluated in popliteal lymph node metastasis models and patientderived xenograft models of bladder cancer.Results:HSF1 expression was positively associated with lymphatic metastasis status,tumor stage,advanced grade,and poor prognosis of bladder cancer.Importantly,HSF1 enhanced the epithelial-mesenchymal transition(EMT)of cancer cells in primary tumor to initiate metastasis,proliferation of cancer cells in lymph nodes,and macrophages infiltration to facilitate multistep lymphatic metastasis.Mechanistically,HSF1 interacted with protein arginine methyltransferase 5(PRMT5)and jointly induced the monomethylation of histone H3 at arginine 2(H3R2me1)and symmetric dimethylation of histone H3 at arginine 2(H3R2me2s).This recruited the WD repeat domain 5(WDR5)/mixed-lineage leukemia(MLL)complex to increase the trimethylation of histone H3 at lysine 4(H3K4me3);resulting in upregulation of lymphoid enhancer-binding factor 1(LEF1),matrix metallopeptidase 9(MMP9),C-C motif chemokine ligand 20(CCL20),and E2F transcription factor 2(E2F2).Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity.Conclusion:Our findings reveal a novel transcriptional program directed by the HSF1-PRMT5-WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer.Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis. | Ming Huang Wen Dong Ruihui Xie Jilin Wu Qiao Su Wuguo Li Kai Yao Yuelong Chen Qianghua Zhou Qiang Zhang Wenwen Li Liang Cheng Shengmeng Peng Siting Chen Jian Huang Xu Chen Tianxin Lin | 2022 | Cancer Communications2022，42，5： | 2 |
| 3 | Truncated glycoprotein E of varicella-zoster virus is an ideal immunogen for Escherichia coli-based vaccine design显示文摘Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we sought to produce a VZV g E immunogen using an E.coli expression system.We found that the soluble expression and yield of g E protein could be enhanced via C-terminal truncations to the protein,thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing.The lead truncated g E(aa 31–358),hereafter referred to as tg E,was a homogenous monomer in solution and showed excellent antigenicity.Finally,we assessed and compared the immunogenicity of tg E with commercial v Oka LAV and Shingrix vaccine.We found that aluminum-adjuvanted tg E was immunogenic as compared with v Oka LAV.When adjuvanted with AS01B,a two-dose immunization of tg E showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage,especially in terms of the proportion of IFN-γ-expressing CD4^(+)T cells.In conclusion,this method of E.coli-mediate tg E expression offers a cost-effective and scalable strategy to generate an ideal VZV g E immunogen for the development of both varicella and zoster vaccines. | Tingting Chen Jie Sun Sibo Zhang Tingting Li Liqin Liu Wenhui Xue Lizhi Zhou Siting Liang Zhili Yu Qingbing Zheng Hai Yu Tong Cheng Jun Zhang Ying Gu Shaowei Li Ningshao Xia | 2023 | Science China(Life Sciences)2023，66，4： | 1 |
| 4 | 显示文摘 | WANG Y LIANG L SHI J Study on the contamination of heavy metals and their correlations in mollusks collected from coastal sites along the Chinese Bohai Sea | 2005 | Environ Int2005，31，8： | 1 |
| 5 | Grafting Propagation Techniques of Red Sandalwood(Pterocarpus santalinus),a Precious Hongmu Tree Species显示文摘[Objectives] This article aimed to study the grafting propagation techniques of red sandalwood ( Pterocarpus santalinus ), so as to provide technical support for the effective propagation of seedlings of this precious Hongmu species.[Methods] Based on the analysis and comparison of the growth performance of the Hongmu tree species introduced to China, taking 1 to 2-year-old Pterocarpus indicus seedlings as rootstocks and single-bud stems of P. santalinus as scions, grafting was carried out from January to April using three grafting propagation methods, cut grafting propagation, skin grafting propagation and oblique grafting propagation.[Results] The results of several years of experiments show that in early spring, P. santalinus could be propagated well using the grafting propagation methods of skin grafting propagation and oblique grafting propagation, with survival rate over 80%. For rootstocks with young age or thin stems, the joint unions of the oblique grafting propagation healed well, without apparent protrusions, unlike those of skin grafting propagation. The survival rate of oblique grafting propagation that is fast and reliable was higher than that of cut grafting propagation.[Conclusions] It is feasible to use the grafting propagation methods to propagate P. santalinus seedlings. This is a traditional and innovative technology path in the propagation of high-quality seedlings of precious Hongmu trees, and can be promoted and applied in industrial practice. | Xiaonan HUANG Yanming LI Yiqing LI Tingting LIU Siting CHEN Chengxiang XU Yingshan QIU Yesheng LIANG | 2019 | Asian Agricultural Research2019，11，7： | 1 |
| 6 | Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues显示文摘Although the function of tRNAs in the translational process is well established,it remains controversial whether tRNA abundance is tightly associated with translational efficiency(TE)in mammals.Moreover,how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed.Here,we measured both tRNA expression using demethylase-tRNA sequencing(DM-tRNA-seq)and TE of mRNAs using ribosome-tagging sequencing(RiboTag-seq)in the brain,heart,and testis of mice.Remarkable variation in the expression of tRNA isodecoders was observed among different tissues.When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons,we observed an expected reduction in the variation of anticodon expression across all samples,an unexpected smaller variation of anticodon usage bias,and an unexpected larger variation of tRNA isotype expression at amino acid level.Regardless of whether or not they share the same anticodons,the isodecoders encoding the same amino acids are co-expressed across different tissues.Based on the expression of tRNAs and the TE of mRNAs,we find that the tRNA adaptation index(tAI)and TE are significantly correlated in the same tissues but not between tissues;and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues.We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms.This study provides a resource for tRNA and translation studies,as well as novel insights into the dynamics of tRNAs and their roles in translational regulation. | Peng Yu Siting Zhou Yan Gao Yu Liang Wenbing Guo Dan Ohtan Wang Shuaiwen Ding Shuibin Lin Jinkai Wang Yixian Cun | 2023 | Genomics, Proteomics & Bioinformatics2023，21，4： | 1 |
| 7 | Design and Analysis of Wide Speed Regulation of Variable Leakage Flux Reverse Salient-pole Motor显示文摘In this article, a new variable leakage flux reverse salient-pole motor(VLF-RSPM) is raised to widen the speed range. The innovation is to realize both reverse salient-pole characteristics and variable leakage flux characteristics by using a method of adding magnetic bridges and magnetic barriers. Firstly, the evolution of the topological structure and working principle of the motor are introduced. Secondly, based on 2D Finite Element Analysis(FEA), the electromagnetic properties and noise of the motor are analyzed in detail, and the electromagnetic properties are contrasted with that of the conventional V-type synchronous motor(CVTSM). The results show that VLF-RSPM has the advantages of small torque ripple, strong magnetic weakening ability, low noise, high efficiency, and low risk of permanent magnet demagnetization under different conditions. In addition, it is verified that the proposed motor extends the speed range. | Xiping Liu Siting Zhu Dabin Liu Jianwei Liang | 2023 | CES Transactions on Electrical Machines and Systems2023，7，3： | 0 |
| 8 | Investigation of an Intensifying-flux Variable Flux-leakage Interior Permanent Magnet Machine for Wide Speed Range显示文摘In this paper,a novel intensifying-flux variable flux-leakage interior permanent magnet(IFVF-IPM)machine is proposed,in which flux barriers were designed deliberately between the adjacent poles to obtain intensifying-flux effect and variable flux-leakage property.The rotor topology and design principles of the proposed machine are also introduced.Then,a multi-objective optimization method is adopted based on the sensitivity analysis,and some design variables of IFVF-IPM machine with strong sensitivity are selected to optimization progress by using the non-dominated sorting genetic algorithm-Ⅱ(NSGA-Ⅱ).Moreover,the electromagnetic characteristics of conventional IPM machine,conventional IFVF-IPM machine(CIFVF-IPM)and the novel IFVF-IPM machine are compared based on the finite element analysis(FEA)method which includes flux linkage,inductances characteristic,torque-speed envelops and power characteristic,as well as evaluation of the risk of irreversible demagnetization.Finally,the experiment results show that the IFVF-IPM machine has a better performance in flux weakening capability for wide speed range and a lower risk of irreversible demagnetization,which indicates the validity and feasibility of the proposed machine. | Xiping Liu Dabin Liu Siting Zhu Jianwei Liang | 2022 | CES Transactions on Electrical Machines and Systems2022，6，2： | 0 |
| 9 | 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 |
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