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Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib Sensitivity in Hepatocellular Carcinoma Cells

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Current Medical Science 2024年第4期44卷 789-798页

作者： Chai-ming ZENG bin SHAO Yan-ping CHEN gui-sheng DING Department of Geriatric Medicine Shengli Clinical Medical College of Fujian Medical UniversityFujian Key Laboratory of Geriatrics DiseasesFujian Provincial Center for GeriatricsFujian Provincial HospitalFuzhou350001China Department of Rehabilitation Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou350001China Department of Gynecology Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou350001China Department of Ultrasonography Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou350001China

Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular *** further elucidate the impact of MFN2,this study aimed to investigate its significance on hepatocellular carcinoma(HCC)cell function and its potential role in mediating *** This study investigated the effects of silencing and overexpressing MFN2 on the survival,proliferation,invasion and migration abilities,and sorafenib resistance of MHCC97-L HCC *** experiments were conducted using XAV939(aβ-catenin inhibitor)and HLY78(aβ-catenin activator)to further validate these *** Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells,enhanced their invasion and migration capacities,increased the IC50 of sorafenib,reduced the percentage of TUNEL-positive cells,and decreased the expression of proapoptotic ***,silencing MFN2 markedly induced the nuclear translocation ofβ-catenin,increasedβ-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin ***,overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned *** results confirmed that silencing MFN2 activated theβ-catenin/epithelial-mesenchymal transition(EMT)pathway and reduced the sensitivity of cells to sorafenib,which could be reversed by XAV939 ***,overexpression of MFN2 inhibited theβ-catenin/EMT pathway and increased the sensitivity of cells to sorafenib,which could be altered by *** Low expression of MFN2 in HCC cells promotes the nuclear translocation ofβ-catenin,thereby activating the EMT pathway and mediating resistance to sorafenib.

关键词： mitofusin-2 epithelial-mesenchymal transition sorafenib resistance apoptosis hepatocellular carcinoma

Synthesis of Planar-chiral[2.2]Paracyclophane-Based Oxazole-Pyrimidine Ligands and Application in Nickel-Catalyzed 1,2-Reduction ofα,β-Unsaturated Ketones

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chinese Journal of Chemistry 2024年第7期42卷 705-710页

作者： Juan Wang Qing-Xian Xie Xiang Li Chang-bin Yu Yong-gui Zhou School of Chemistry Dalian University of Technology2 Linggong RoadDalianLiaoning 116024China State Key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianLiaoning 116023China

The planar-chiral ligands have been widely applied as a class of unique and significant ligands in asymmetric *** them,chiral[2.2]paracycyclophane has emerged as a privileged type of planar-chiral framework and has been utilized as an important toolbox due to their structural ***,we design and synthesize[2.2]paracyclophane-derived oxazole-pyrimidine ligands(abberviated as PYMCOX).These N,N-ligands with stable properties,rigid structure and large steric hindrance performed successfully in nickel-catalyzed asymmetric 1,2-reduction ofα,β-unsaturated ketones,affording the chiral allylic alcohols with up to 99%yield and 99%***,this reduction reaction could be conducted on gram-scale without loss of activity and enantioselectivity,and the chiral ligand could be conveniently recovered with high yield.

关键词： Oxazole-pyrimidine ligands Planar chirality Nickel Hydroboration Asymmetric synthesis

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity scorematched analysis

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1537-1547页

作者： Ji-Ming Tang Shu-Jie Huang Qi-bin Chen Han-Sheng Wu gui-bin Qiao Department of Thoracic Surgery Guangdong Provincial People’s HospitalGuangzhou 510080Guangdong ProvinceChina Department of Thoracic Surgery The First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma(ESCC)patients remained *** To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront *** In this retrospective,propensity score-matched study,we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October *** who underwent neoadjuvant therapy were *** collected pa-tients’clinicopathological features and information regarding lymph nodes,in-cluding the total number of resected lymph nodes(NRLN),and pathologically diagnosed positive lymph nodes(RPLN).SPSS and R software were used for statistical *** Among the included 1042 patients,two cohorts:≤21(n=664)and>21 NRLN(n=378)were *** final prognostic model included four variables:T stage,N,venous thrombus,and the number of removed lymph *** them,NRLN>21 was determined as an independent prognosticator after surgery for esophageal cancer(hazards regression=0.66,95%confidence interval:0.50-0.87,P=0.004).A nomogram was created based on the regression coefficients of the variables in the final *** the training cohort,the predictive model dis-played an uncorrected five-year overall survival C-index of 0.659,with a bootstrap-corrected C-index of *** the subgroup analysis,adjuvant chemotherapy was beneficial in the subgroup with NRLN>21 and RPLN≤0.16 and NRLN≤21 and RPLN>*** NRLN>21 was an independent prognostic factor after ESCC *** combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

关键词： Esophageal squamous cell carcinoma Lymphadenectomy Adjuvant chemotherapy Prognosis Nomogram

Application of CFD and FEA Coupling to Predict Structural Dynamic Responses of A Trimaran in Uni-and Bi-Directional Waves

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china Ocean Engineering 2024年第1期38卷 81-92页

作者： LIAO Xi-yu XIA Jin-song CHEN Zhan-yang TANG Qin ZHAO Nan ZHAO Wei-dong gui Hong-bin Marine Design&Research Institute of china Shanghai 200011China Ship Structure Division China Ship Scientific Research CenterWuxi 214082China College of Ocean Engineering Harbin Institute of TechnologyWeihaiWeihai 264209China State Key Laboratory of Structural Analysis Optimization and CAE Software for Industrial EquipmentDalian University of TechnologyDalian 116024China School of Foreign Studies Jiangnan UniversityWuxi 214122China

To predict the wave loads of a flexible trimaran in different wave fields,a one-way interaction numerical simulation method is proposed by integrating the fluid solver(Star-CCM+)and structural solver(Abaqus).Differing from the existing coupled CFD-FEA method for monohull ships in head waves,the presented method equates the mass and stiffness of the whole ship to the hull shell so that any transverse and longitudinal section stress of the hull in oblique waves can be ***,verification study and sensitivity analysis are carried out by comparing the trimaran motions using different mesh sizes and time step *** on the wave elevation of uni-and bi-directional waves is also carried *** a comprehensive analysis on the structural responses of the trimaran in different uni-directional regular wave and bi-directional cross sea conditions is carried out,***,the differences in structural response characteristics of trimaran in different wave fields are *** results show that the present method can reduce the computational burden of the two-way fluid-structure interaction simulations.

关键词： CFD-FEA fluid-structure coupling structural responses trimaran bi-directional cross sea

Root-derived long-distance signals trigger ABA synthesis and enhance drought resistance in Arabidopsis

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Journal of Genetics and Genomics 2024年第7期51卷 749-761页

作者： Qian-Qian Liu Jin-Qiu Xia Jie Wu Yi Han gui-Quan Zhang Ping-Xia Zhao Cheng-bin Xiang Division of Life Sciences and Medicine Division of Molecular&Cell BiophysicsHefei National Science Center for Interdisciplinary Sciences at the MicroscaleUniversity of Science and Technology of ChinaThe Innovation Academy of Seed DesignChinese Academy of SciencesHefeiAnhui 230027China College of Life Sciences Anhui Agricultural UniversityHefeiAnhui 230036China College of Agronomy South China Agricultural UniversityGuangzhouGuangdong 510642China School of Biology and Basic Medical Sciences Soochow UniversitySuzhouJiangsu 215123China

Vascular plants have evolved intricate long-distance signaling mechanisms to cope with environmental stress,with reactive oxygen species(ROS)emerging as pivotal systemic signals in plant stress ***,the exact role of ROS as root-to-shoot signals in the drought response has not been *** this study,we reveal that compared with wild-type plants,ferric reductase defective 3(frd3)mutants exhibit enhanced drought resistance concomitant with elevated NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3(NCED3)transcript levels and abscisic acid(ABA)contents in leaves as well as increased hydrogen peroxide(H_(2)O_(2))levels in roots and *** experiments distinctly illustrate that drought resistance can be conferred by the frd3 rootstock regardless of the scion genotype,indicating that long-distance signals originating from frd3 roots promote an increase in ABA levels in ***,the drought resistance conferred by the frd3 mutant rootstock is weakened by the CAT2-overexpressing scion,suggesting that H_(2)O_(2)may be involved in long-distance ***,the results of comparative transcriptome and proteome analyses support the drought resistance phenotype of the frd3 *** together,our findings substantiate the notion that frd3 root-derived long-distance signals trigger ABA synthesis in leaves and enhance drought resistance,providing new evidence for root-to-shoot long-distance signaling in the drought response of plants.

关键词： frd3 Drought resistance Root-to-shoot long-distance signals Reactive oxygen species(ROS) H_(2)O_(2) Iron ABA

Detecting secondary spin with extreme mass ratio inspirals in scalar-tensor theory

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chinese Physics C 2024年第9期48卷 210-224页

作者： Hong Guo Chao Zhang Yunqi Liu Rui-Hong Yue Yun-gui Gong bin Wang Center for Gravitation and Cosmology College of Physical Science and TechnologyYangzhou UniversityYangzhou 225009China Escola de Engenharia de Lorena Universidade de São PauloLorenaSP 12602-810Brazil Shanghai Frontier Research Center for Gravitational Wave Detection Shanghai Jiao Tong UniversitySha nghai 200240 China 4 School of Aeronautics and AstronauticsShanghai Jiao Tong UniversityShanghai 200240China School of Physics Huazhong University of Science and TechnologyWuhan 430074China Department of Physics School of Physical Science and TechnologyNingbo UniversityNingbo 315211China

In this study,we investigate the detectability of the secondary spin in an extreme mass ratio inspiral(EMRI) system within a modified gravity model coupled with a scalar *** central black hole,which reduces to a Kerr one,is circularly spiralled by a scalar-charged spinning secondary body on the equatorial *** analysis reveals that the presence of the scalar field amplifies the secondary spin effect,allowing for a lower limit of the detectability and an improved resolution of the secondary spin when the scalar charge is sufficiently *** findings suggest that secondary spin detection is more feasible when the primary mass is not large,and TianQin is the optimal choice for detection.

关键词： Gravitational wave EMRI secondary spin scalar radiation

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor

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World Journal of Gastroenterology 2024年第8期30卷 863-880页

作者： gui-Ming Deng Hai-bin Song Zhong-Ze Du Ying-Wei Xue Hong-Jiang Song Yuan-Zhou Li Department of Gastrointestinal Surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina Department of Radiology Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of *** immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be *** We performed a retrospective study of patients who were undergoing immuno-therapy for *** the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral *** was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic *** were developed to predict the PFS and OS of patients on the basis of the results of multivariate *** We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had *** with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these ***,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an *** prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,*** The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

关键词： Gastric cancer Sarcopenia Myosteatosis,Immune checkpoint inhibitor Prognostic factor Overall survival Progression-free survival

A new twist to the interplay between superconductivity and Kondo correlation

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Science china(Physics,Mechanics & Astronomy) 2024年第8期67卷 1-2页

作者： gui-Lu Long Department of Physics Tsinghua UniversityBeijing 100084China Beijing Academy of Quantum Information Sciences Beijing 100193China

Recently,Deng et al.[1] found a new twist to the intriguing physics resulting from the interplay between Kondo correlation and *** correlation [2,3] and superconductivity [4,5] are two fundamental phenomena in condens... 详细信息

关键词： Kondo twist

Numerical investigation and modeling of sweep effects on inlet flow field of axial compressor cascades

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chinese Journal of Aeronautics 2024年第2期37卷 296-308页

作者： Jiancheng ZHANG Donghai JIN Xingmin gui School of Energy and Power Engineering Beihang UniversityBeijing 100191China Jiangxi Research Institue of Beihang University Nanchang 330096China

Swept blades are widely utilized in transonic compressors/fans and provide high load,high through-flow,high efficiency,and adequate stall ***,there is limited quantitative research on the mechanism of the effect of swept blades on the flow field,resulting in a lack of direct quantitative guidance for the design and analysis of swept blades in fans/*** better understand this mechanism,this study employs a reduced-dimensional force equilibrium method to analyze more than 1500 swept cascades *** verify that circumferential fluctuation terms are responsible for inducing radial migration in the inlet airflow field of the swept blade,resulting in variations in the incidence angle and consequently leading to changes in the characteristics of the swept ***,a combination of simple functions and machine learning is utilized to model the circumferential fluctuation terms and quantify the sweep *** prediction accuracy of the model is high,with coefficient of determination greater than 0.95 on the test *** the model is applied in a meridional flow analysis program,the calculation accuracy of the program for the incidence angle is improved by 0.4°and 0.6°at the design and off-design conditions respectively,compensating for the program’s original ***,the model can also provide quantitative guidance for the design of swept blades,thereby reducing the number of design iterations and improving design efficiency.

关键词： Turbomachinery Sweep aerodynamics Quasi-3D method Incidence angle Circumferential fluctuation Machine learning