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Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

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World Journal of Gastroenterology 2024年第30期30卷 3564-3573页

作者： Ling-Xiao Xu Jia-Jia Yuan Ran Xue jun {1. Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment *** To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic *** This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 201. and june 2022 at Beijing Cancer Hospital and the First Hospital of China Medical *** patients were administered nab-paclitaxel(1.0 mg/m^(2),day 1.and capecitabine(2000 mg/m^(2),twice daily,days 1.7)in 1.-day cycles until experiencing intolerable toxicity or disease *** primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and *** A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were *** response assessment was impeded for one patient due to premature demise from tumor *** the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):1..80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 1..1.months(95%CI:8.3-1..9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41.patients(93.1.%)experienced at least one adverse event(AE),with 1. patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91.),and no treatment-related deaths were *** Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

关键词： Nab-paclitaxel Capecitabine Biliary tract cancer Objective response rate Phase II clinical trial

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Colorectal Cancer Segmentation Algorithm Based on Deep Features from Enhanced CT Images

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Computers, Materials & Continua 2024年第8期80卷 2495-2510页

作者： Shi Qiu Hongbing Lu jun Shu Ting Liang Tao {1. School of Biomedical Engineering Fourth Military Medical UniversityXi’an710119China Department of Radiology Xijing HospitalFourth Military Medical UniversityXi’an710032China Department of Radiology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710061China School of Computer Science and Engineering North Minzu UniversityYinchuan750030China

Colorectal cancer,a malignant lesion of the intestines,significantly affects human health and life,emphasizing the necessity of early detection and *** segmentation of colorectal cancer regions directly impacts subsequent staging,treatment methods,and prognostic *** colonoscopy is an effective method for detecting colorectal cancer,its data collection approach can cause patient *** address this,current research utilizes Computed Tomography(CT)imaging;however,conventional CT images only capture transient states,lacking sufficient representational capability to precisely locate colorectal *** study utilizes enhanced CT images,constructing a deep feature network from the arterial,portal venous,and delay phases to simulate the physician’s diagnostic process and achieve accurate cancer *** innovations include:1.Utilizing portal venous phase CT images to introduce a context-aware multi-scale aggregation module for preliminary shape extraction of colorectal cancer.2)Building an image sequence based on arterial and delay phases,transforming the cancer segmentation issue into an anomaly detection problem,establishing a pixel-pairing strategy,and proposing a colorectal cancer segmentation algorithm using a Siamese *** with 84 clinical cases of colorectal cancer enhanced CT data demonstrated an Area Overlap Measure of 0.90,significantly better than Fully Convolutional Networks(FCNs)at *** research will explore the relationship between conventional and enhanced CT to further reduce segmentation time and improve accuracy.

关键词： Colorectal cancer enhanced CT multi-scale siamese network segmentation

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A First-principles Study on the Adhesion Strength,Interfacial Stability,and Electronic Properties of Mg/Mg_(2)Y Interface

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Acta Metallurgica Sinica(English Letters) 2024年第3期37卷 537-550页

作者： Yunxuan zhou Wen{1. Tian Quan Dong Hailian Wang {1. Tan Xianhua Chen Kaihong Zheng Fusheng Pan College of Materials Science and Engineering National Engineering Research Center for Magnesium AlloysChongqing UniversityChongqing 400044China State Key Laboratory of Mechanical Transmission Chongqing UniversityChongqing 400044China Institute of New Materials Guangdong Academy of SciencesGuangzhou 510650China

The interfacial microstructures and configurations directly affect the comprehensive properties of the composites,but their interfacial adhesion mechanism is complicated to expound by experimental *** this work,based on the stacking sequence of the Mg/Mg_(2)Y interface models,nine different Mg/Mg_(2)Y interface configurations with top site,bridge site,and hollow site(HCP)under Mg1.Mg_(2),and Y terminations were successfully constructed and systematically explored by first-principles *** results showed that the Mg_(2)Y(0001.surface with Y termination is the most stable when the yttrium chemical potential()is less than-1.09 eV;otherwise,Mg_(2)Y(0001.surface with Mg1.termination is the most *** seven-layer Mg(0001.and eleven-layer Mg_(2)Y(0001.slabs are employed to reflect the bulk-like interior ***,the Mg(0001./Mg_(2)Y(0001.with the Y-HCP stacking has the largest interface thermodynamic stability with the value of 2.383 J/m^(2) in all interface configurations owing to its largest work of *** addition,the interfacial energy of Y-HCP stacking is significantly smaller than those of Mg1.HCP when is approximately less than-0.55 eV,showing that it is more *** thermodynamic stability of Mg/Mg_(2)Y with Y-HCP is due to Mg-Y chemical bonds formed between Mg and Y ***,the Mg/Mg_(2)Y interfaces are strong interfaces based on the Griffith fracture theory.

关键词： Mg/Mg_(2)Y interface Interface stability Work of adhesion Electronic structure First-principles calculations

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Deformation monitoring of long-span railway bridges based on SBAS-InSAR technology

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Geodesy and Geodynamics 2024年第2期15卷 122-132页

作者： Lv zhou Xinyi Li Yuanjin Pan {1. Ma Cheng Wang Anping Shi Yukai Chen College of Geomatics and Geoinformation Guilin University of TechnologyGuilin 541004China Hubei Luo Jia Laboratory Wuhan 430079China Ecological Spatiotemporal Big Data Perception Service Laboratory Guilin 541004China School of Geodesy and Geomatics Wuhan UniversityWuhan 430079China China Railway Siyuan Survey and Design Group Co. Ltd.Wuhan 430063China

The deformation monitoring of long-span railway bridges is significant to ensure the safety of human life and *** interferometric synthetic aperture radar(In SAR)technology has the advantage of high accuracy in bridge deformation *** study monitored the deformation of the Ganjiang Super Bridge based on the small baseline subsets(SBAS)In SAR technology and Sentinel-1. *** analyzed the deformation results combined with bridge structure,temperature,and riverbed sediment *** results are as follows:(1.The Ganjiang Super Bridge area is stable overall,with deformation rates ranging from-1..6 mm/yr to 1..7 mm/yr(2)The settlement of the Ganjiang Super Bridge deck gradually increases from the bridge tower toward the main span,which conforms to the typical deformation pattern of a cable-stayed bridge.(3)The sediment scouring from the riverbed cause the serious settlement on the bridge’s east side compared with that on the west side.(4)The bridge deformation negatively correlates with temperature,with a faster settlement at a higher temperature and a slow rebound trend at a lower *** study findings can provide scientific data support for the health monitoring of long-span railway bridges.

关键词： SBAS-InSAR Long-span railway bridge Deformation monitoring Bridge structure Time series deformation

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Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： jun {1. Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han Xuetao Cao Institute of Immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against *** cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains *** can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune *** we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell ***-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)***,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon *** in ***,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of *** in *** transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory ***,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against *** study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

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Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 1.C metabolic flux analysis

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Journal of Pharmaceutical Analysis 2024年第2期14卷 244-258页

作者： Baixi Shan Haoyan zhou Congying Guo Xiaolu Liu Mingyu Wu Rao Zhai {1. Chen State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing210009China Department of Pharmacognosy School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing210009China

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-1.C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1.(TGF-β1.-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1. (HIF-1.) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 1.C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.

关键词： Pulmonary fibrosis Tanshinone IIA 1.C-metabolic flux analysis Metabolic reprogramming

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New roles of tumor-derived exosomes in tumor microenvironment

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Chinese Journal of Cancer Research 2024年第2期36卷 151-166页

作者： Shiqian Chen Jinzhe Sun Huan zhou Hongbin Lei Dan Zang {1. Chen Department of Oncology the Second Hospital of Dalian Medical UniversityDalian 116023China Department of Radiotherapy the Second Hospital of Dalian Medical UniversityDalian 116023China

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

关键词： Tumor-derived exosomes tumorigenesis tumor microenvironment diagnosis treatment

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Enhanced thermoelectric performance enabled by compositing ZrO_(2)in n-type SiGe alloy with low thermal conductivity

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Rare Metals 2024年第3期43卷 1167-1176页

作者： Meng-Fei Wang Hua-jun Lai Ji-Sheng Liang jun-Liang Chen Wang-Yang Ding Qi zhou Ying Peng Cheng-Yan Liu Lei Miao Guangxi Key Laboratory for Relativity Astrophysics State Key Laboratory of Featured Metal Materials and Life-Cycle Safety for Composite StructuresSchool of Physical Science and TechnologyGuangxi UniversityNanning530004China Guangxi Academy of Sciences Nanning530007China Key Laboratory of Information Material Engineering Research Center of Electronic Information Materials and DevicesGuilin University of Electronic TechnologyMinistry of EducationGuilin541004China Guangxi Key Laboratory of Precision Navigation Technology and Application School of Information and CommunicationGuilin University of Electronic TechnologyGuilin541004China

SiGe-based thermoelectric(TE)materials have gained increasing interests due to their low maintenance costs,environmental friendliness and long ***,the intrinsically high thermal conductivity of Si-based materials also results in poor TE *** this investigation,a zirconia(ZrO_(2))composite strategy was applied to an n-type SiGe alloy,tremendously elevating its TE *** mechanical alloying and spark plasma sintering(SPS)processes,the ZrO_(2)induced the formation of nanopores in the SiGe matrix via phosphorus ***,such increase in porosity enhanced the phonon scattering and dramatically suppressed lattice thermal conductivity,from 2.83 to 1.59 W·m^(-1.·K^(-1.at 873 ***,reduced phosphorus doping led to an increase in Seebeck coefficients and a relatively minor decrease in electrical conductivity,The power factor didn't deteriorate significantly,either,as its maximum of~3.43 mW·m^(-1.)K^(-2)was achieved at 873 K with(Si_(0.8)Ge_(0.2))_(0.097)P_(0.03)(ZrO_(2))_(0.003).In short,a peak figure of merit(ZT)of~1.27 at 873 K and an average ZT~0.7 from 323 to 873 K were *** study demonstrates that the electrical and thermal transportation of SiGe material can be synergistically tuned by compositing ZrO_(2),illustrating a novel strategy to optimize the TE properties of bulk materials.

关键词： Thermoelectric SiGe alloy ZrO2 composting P element adsorption nanopores

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Mode division multiplexing reconstructive spectrometer with an all-fiber photonics lantern

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Frontiers of Optoelectronics 2024年第3期17卷 29-38页

作者： junrui Liang jun Ye Xiaoya Ma Yao Lu jun Li Jiangming Xu Zilun Chen Jinyong Leng Zongfu Jiang Pu zhou College of Advanced Disciplinary Studies National University of Defense TechnologyChangsha 410073China Nanhu Laser Laboratory National University of Defense TechnologyChangsha 410073China Hunan Provincial Key Laboratory of High Energy Laser Technology National University of Defense TechnologyChangsha 410073China Space Engineering University Beijing 101416China

This study presents a high-accuracy,all-fber mode division multiplexing(MDM)reconstructive spectrometer(RS).The MDM was achieved by utilizing a custom-designed 3×1.mode-selective photonics lantern to launch distinct spatial modes into the multimode fber(MMF).This facilitated the information transmission by increasing light scattering processes,thereby encoding the optical spectra more comprehensively into speckle *** resolution of 2 pm and the recovery of 2000 spectral channels were *** to methods employing single-mode excitation and two-mode excitation,the three-mode excitation method reduced the recovered error by 88%and 50%respectively.A resolution enhancement approach based on alternating mode modulation was proposed,reaching the MMF limit for the 3 dB bandwidth of the spectral correlation *** proof-of-concept study can be further extended to encompass diverse programmable mode *** is not only succinct and highly efcient but also well-suited for a variety of high-accuracy,high-resolution spectral measurement scenarios.

关键词： High-accuracy Resolution enhancement Reconstructive spectrometer Mode division multiplexing Photonics lantern

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Hapln1.promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF1. trapping

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Journal of Pharmaceutical Analysis 2024年第3期14卷 335-347页

作者： Ding-jun Hao Yue Qin Shi-Jie {1. Bu-Huai Dong jun-Song Yang Peng Zou Li-Ping Wang Yuan-Ting Zhao Department of Spine Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an710054China Department of Anesthesiology Honghui HospitalXi'an Jiaotong UniversityXi'an710054China Department of Cardiovascular Medicine Honghui HospitalXi'an Jiaotong UniversityXi'an710054China State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy West China HospitalSichuan UniversityChengdu610041China

Hyaluronan and proteoglycan link protein 1.Hapln1.supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is *** study aimed to explore the potential regulation of Hapln1.in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial ***-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,*** single-cell RNA sequencing data were retrieved for bioinformatic *** results showed that recombinant human Hapln1.rhHapln1.promotes the proliferation of hiPSC-CMs in a dose-dependent *** a physical binding protein of Hapln1.versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 1.(GDF1.).GDF1.,but not NODAL,was expressed by ***1. expression was unaffected by rhHapln1.***,this molecule was required for rhHapln1.mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and *** mouse Hapln1.rmHapln1.could induce cardiac regeneration in the adult mouse model of myocardial *** addition,rmHapln1.induced hiPSC-CM *** conclusion,Hapln1.can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF1. trapping and subsequent activation of the TGF-β/SMAD2/3 signaling ***1.might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

关键词： Hapln1 Versican GDF1. iPSC-CMs Cardiomyocyte proliferation

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