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TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways

Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 195-209页

作者： Yan Zhang zhen-zhen Wang An-Qi Han ming-Ya Yang Li-Xin Zhu Fa-ming Pan Yong Wang Department of General Surgery The Second Hospital of Anhui Medical UniversityHefei 230601China Department of General Surgery The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefei 230032China The Key Laboratory of Major Autoimmune Diseases Anhui Medical UniversityHefei 230032China

Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.

关键词： TuBG1 Hepatocellular carcinoma Apoptosis Cell cycling Immunomodulators

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Locally and globally uniform approximations for ruin probabilities of a nonstandard bidimensional risk model with subexponential claims

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Applied Mathematics(A Journal of chinese Universities) 2024年第1期39卷 98-113页

作者： LIU Zai-ming GENG Bing-zhen WANG Shi-jie School of Mathematics and Statistics Central South UniversityChangsha 410083China School of Big Data and Statistics Anhui UniversityHefei 230601China

Consider a nonstandard continuous-time bidimensional risk model with constant force of interest,in which the two classes of claims with subexponential distributions satisfy a general dependence structure and each pair of the claim-inter-arrival times is arbitrarily dependent.Under some mild conditions,we achieve a locally uniform approximation of the finite-time ruin probability for all time horizon within a finite interval.If we further assume that each pair of the claim-inter-arrival times is negative quadrant dependent and the two classes of claims are consistently-varying-tailed,it shows that the above obtained approximation is also globally uniform for all time horizon within an infinite interval.

关键词： bidimensional risk model asymptotic formula subexponential distribution consistently varying tail ruin probability

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Thermodynamic geometry of the RN-Ad S black hole and non-local observables

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Communications in Theoretical Physics 2024年第2期76卷 137-144页

作者： Chao Wang Bin Wu zhen-ming Xu Wen-Li Yang Institute of Physics Shaanxi University of TechnologyHanzhong 723000China School of Physics Northwest UniversityXi'an 710127China Institute of Modern Physics Northwest UniversityXi'an 710127China Shaanxi Key Laboratory for Theoretical Physics Frontiers Xi'an 710127China Peng Huanwu Center for Fundamental Theory Xi'an 710127China

This paper studies the thermodynamic geometry of the Reissner–Nordstr?m-anti-de Sitter(RN-AdS)black hole via detection of the non-local observables in the dual field theory,including the entanglement entropy and equal-time two-point correlation function.With the dimensional analysis,we construct the principle of corresponding states of black hole thermodynamics.As a result,our findings can be applied to black holes with different Ad S backgrounds.In this sense,the probe of the thermodynamic geometry of the RN-Ad S black hole though the non-local observables in dual field theory has been confirmed numerically.

关键词： black hole thermodynamic thermodynamic geometry phase transition non-local observables

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A data-driven approach to RUL prediction of tools

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Advances in Manufacturing 2024年第1期12卷 6-18页

作者： Wei Li Liang-chi Zhang Chu-Han Wu Yan Wang zhen-Xiang Cui Chao Niu Department of Mechanical Engineering University College LondonLondonWC1E 7JEUK Shenzhen Key Laboratory of Cross-Scale Manufacturing Mechanics Southern University of Science and TechnologyShenzhen518055GuangdongPeople’s Republic of China SUSTech Institute for Manufacturing Innovation Southern University of Science and TechnologyShenzhen518055GuangdongPeople’s Republic of China Department of Mechanics and Aerospace Engineering Southern University of Science and TechnologyShenzhen518055GuangdongPeople’s Republic of China School of Mechanical and Manufacturing Engineering The University of New South WalesKensingtonNSW2052Australia Baoshan Iron&Steel Co. Ltd.Shanghai200941People’s Republic of China

An effective and reliable prediction of the remaining useful life(RUL)of a tool is important to a metal forming process because it can significantly reduce unexpected maintenance,avoid machine shutdowns and increase system stability.This study proposes a new data-driven approach to the RUL prediction for metal forming processes under multiple contact sliding conditions.The data-driven approach took advantage of bidirectional long short-term memory(BLSTM)and convolutional neural networks(CNN).A pre-trained lightweight CNN-based network,WearNet,was re-trained to classify the wear states of workpiece surfaces with a high accuracy,then the classification results were passed into a BLSTM-based regression model as inputs for RUL estimation.The experimental results demonstrated that this approach was able to predict the RUL values with a small error(below 5%)and a low root mean square error(RMSE)(around 1.5),which was more superior and robust than the other state-of-the-art methods.

关键词： Remaining useful life(RUL) Bidirectional long short-term memory(BLSTM) Data-driven approach Metal forming

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The ornithine-urea cycle involves fumaric acid biosynthesis in Aureobasidium pullulans var.aubasidani,a green and eco-friendly process for fumaric acid production

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Synthetic and Systems Biotechnology 2023年第1期8卷 33-45页

作者： Xin Wei Miao Zhang Guang-Yuan Wang Guang-Lei Liu zhen-ming chi Zhe chi College of Marine Life Sciences Ocean University of ChinaYushan RoadNo.5QingdaoChina Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology266003China College of Life Science Shandong Province Key Laboratory of Applied MycologyQingdao Agricultural UniversityQingdao266109China

The current petroleum chemical methods for fumaric acid production can cause heavy pollution and global warming.In this study,the engineered strains of A.pullulans var.aubasidani were found to be suitable for green fumaric acid producer.Removal and complementation of the relevant genes showed only the ornithine-urea cycle(OUC)was involved in high level fumarate biosynthesis which was controlled by the Ca^(2+)signaling pathway.Removal of both the GOX gene encoding glucose oxidase and the PKS1 gene encoding the polyketide synthase for 3,5-dihydroxydecanoic acid biosynthesis and overexpression of the PYC gene encoding pyruvate carboxylase made the strain e-PYC produce 88.1±4.3 g/L of fumarate at flask level and 93.9±0.8 g/L of fumarate during the fed-batch fermentation.As a yeast-like fungal strain,it was very easy to cultivate A.pullulans var.aubasidani DH177 and their mutants in the bioreactor and to edit its genomic DNAs to enhance fumarate production.It was found that 2 mol of CO_(2) could be fixed during a maximal theoretical yield of 2 mol of fumarate per mole of glucose consumed in the OUC.Therefore,the OUC-mediated fumarate biosynthesis pathway in A.pullulans var.aubasidani was a green and eco-friendly process for the global sustainable development and carbon neutrality.

关键词： Fumaric acid A.pullulans var.aubasidani Ornithine-urea cycle Ca^(2+)signaling pathway

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Doping engineering of iron oxide nanoparticles towards high performance and biocompatible T_(1)-weighted MRI contrast agents

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Rare Metals 2024年第1期43卷 298-308页

作者： Xue Xu Ping-Li Dong Yu-Yun Chai Run Yang zhen-Hui Ma chi-Chong Lu Department of Chemistry College of Chemistry and Materials EngineeringBeijing Technology and Business UniversityBeijing 100048China Department of Physics Beijing Technology and Business UniversityBeijing 100048China

Extremely small-sized iron oxide nanoparticles(IONPs) are of great interest in magnetic resonance imaging(MRI) due to their biosafety as an alternative to clinical gadolinium(Ⅲ) complexes-based contrast agents.Especially when the particle size is less than 10 nm,it has strong diffusion ability and deep penetration distance in tumor tissue.Substitution doping can significantly enhance the T_(1)contrast effect of nanoparticles by regulating the surface exposed atoms.However,the nucleation and growth processes of multi-component synthesis systems are complex and difficult to be accurately controlled,leading to great challenges in the synthesis of ultra-small-sized nanoparticles with different components and sizes.Here,extremely smallsized superparamagnetic gadolinium-doped iron oxide nanoparticles(GdIONPs,Gd_(x)Fe_(3-x)O_(4) NPs) with adjustable doping amount and controllable size in the range of 3.5-7.5 nm were synthesized by thermal decomposition.Then,as-synthesized GdIONPs were surface modified with a highly water-soluble and biocompatible carboxyl-polyethylene glycol-phosphoric acid ligand with high binding affinity.Gd_(0.65)Fe_(2.35)O_(4) NPs exhibited very high r_(1) relaxivity of 10.6 mmol^(-1)·L·s^(-1) in terms of all metal concentrations and 49.0 mmol^(-1)·L·s^(-1) in terms of gadolinium alone,respectively,3 and 14 times higher than clinical T_(1) contrast agents(Gd-DTPA).GdIONPs can continuously obtain high resolution images of blood vessels,and can be used as an efficient and multifunctional contrast agent for MR T_(1)imaging.This stable and efficient doping strategy provides an easy and effective method to individually optimize the magnetic properties of complex oxides and their relaxation effects for a variety of biomedical applications.

关键词： Iron oxide nanoparticles Small size Magnetic resonance imaging Substitutional doping Gd dopant

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Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

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Asian Journal of Andrology 2024年第1期26卷 57-66页

作者： Chang-Bo Zhao Wei-Bo Chen Wen-zhen Wang Fang-Xin Gong Cui-Qin Fan Ye Li Tian Lan Wen-Jing Wang ming-zhen Yuan Department of Urology Shandong Provincial HospitalShandong UniversityJinan 250012China Department of Andrology Liaocheng People's HospitalShandong UniversityLiaocheng 252000China Department of Urology The Second Hospital of Shandong UniversityJinan 250012China Department of Physiology School of Basic Medical SciencesShandong UniversityJinan 250012China

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this condition.We,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes.Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group.However,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile function.The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group.The expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED group.Moreover,the cell morphology in the cavernous tissue of the DMED group also changed adversely.NO,-OA treatment significantly reversed all these changes observed in the DMED group.In conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.

关键词： apoptosis diabetic mellitus erectile dysfunction nitro-oleic acid NO/cGMP pathway oxidative stress

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Male reproductive function before and after theadjustment of the COVID-19 prevention policy:amulticenter study in china

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Asian Journal of Andrology 2024年第3期26卷 308-314页

作者： Jian-zheng Li Han Wu Li Wang Yun-Shan Wang Feng Kong Long-Qiao Cao ming Liang Xiong Wang ming-zhen Yuan Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan 250000China Institute of Women Children and Reproductive HealthShandongUniversityJinan 250012China Engineering Laboratory of Urinary Organ and Functional Reconstruction of Shandong Province Jinan 250000China The First People’sHospital of Jining Jining 272000China Department of Reproductive Medicine The Second Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250000China Reproductive Medicine Center Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantai 264000China.

At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in china resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in china,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in china,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.

关键词： COVID-19 multicenter study reproduction SARS-CoV-2 semen analysis

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The evolution,pathogenicity and transmissibility of quadruple reassortant H1N2 swine influenza virus in china:A potential threat to public health

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Virologica Sinica 2024年第2期39卷 205-217页

作者： Xinxin Cui Jinhuan Ma Zifeng Pang Lingzhi chi Cuishan Mai Hanlin Liu ming Liao Hailiang Sun College of Veterinary Medicine South China Agricultural UniversityGuangzhou510642China Key Laboratory of Zoonosis Control and Prevention of Guangdong Province South China Agricultural UniversityGuangzhou510642China National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control South China Agricultural UniversityGuangzhou510642China Shandong Vocational Animal Science and Veterinary College Weifang261061China Institute of Animal Health Guangdong Academy of Agricultural SciencesGuangzhou510640China

Swine are regarded as“intermediate hosts”or“mixing vessels”of influenza viruses,capable of generating strains with pandemic potential.From 2020 to 2021,we conducted surveillance on swine H1N2 influenza(swH1N2)viruses in swine farms located in Guangdong,Yunnan,and Guizhou provinces in southern china,as well as Henan and Shandong provinces in northern china.We systematically analyzed the evolution and pathogenicity of swH1N2 isolates,and characterized their replication and transmission abilities.The isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1(PB2,PB1,PA and NP genes),triple-reassortant swine(NS gene),Eurasian Avian-like(HA and M genes),and recent human H3N2(NA gene)lineages.The NA,PB2,and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017(H3N2).The HA gene of swH1N2 exhibits a high evolutionary rate.The five swH1N2 isolates replicate efficiently in human,canine,and swine cells,as well as in the turbinate,trachea,and lungs of mice.A/swine/Shandong/198/2020 strain efficiently replicates in the respiratory tract of pigs and effectively transmitted among them.Collectively,these current swH1N2 viruses possess zoonotic potential,highlighting the need for strengthened surveillance of swH1N2 viruses.

关键词： Swine influenza virus(SIV) H1N2 Evolution Replication Pathogenicity Zoonotic potential

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Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 372-385页

作者： Jia-Li Chen Lu Guo zhen-Ying Wu Kun He Han Li chi Yang Yun-Wei Han Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Clinical Research Institute The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Plastic Surgery Meguiar's Medical Beauty HospitalChengdu 610000Sichuan ProvinceChina

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,china,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

关键词： Circulating tumor cells Neutrophil–lymphocyte ratio Hepatocellular carcinoma Prognosis Survival Marker

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