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Neoantigen cancer vaccines:a new star on the horizon

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Cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling li Jian You liping Hong Weijiang liu Peng Guo Xishan Hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Tianjin Medical University Cancer Institute&Hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer *** of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal *** neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint *** made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of ***,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents *** review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor *** findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

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法源理论视角下的清代刑事法律渊源

山东师范大学学报(社会科学版) 2024年第4期69卷 84-96页

作者：李栋武汉大学法学院

由于没有受到法源理论的指导，既有清代刑事法律渊源研究不仅无法统一各种法律渊源的分类和内容，也无法很好地指明各种法律渊源之间的相互关系。法源理论视角下，清代刑事法律渊源问题研究应在法的适用立场下进行，去寻找那些为案件审... 详细信息

由于没有受到法源理论的指导，既有清代刑事法律渊源研究不仅无法统一各种法律渊源的分类和内容，也无法很好地指明各种法律渊源之间的相互关系。法源理论视角下，清代刑事法律渊源问题研究应在法的适用立场下进行，去寻找那些为案件审判能够提供规范性依据的那些法的创制(规范)行为或事实，并弄清楚裁判依据范围有多大，不同法律渊源适用的层级或顺序为何。法源理论下，法律渊源分为效力渊源和认知渊源。清代刑事法律渊源中属于效力渊源的有律文和例文，属于认知渊源的有刑部通行、司法成案和秋审中的“实体性”规范以及被比附加减的律例。

关键词：法源理论清代刑事法律渊源效力渊源认知渊源

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Deep learning for drug-drug interaction prediction:A comprehensive review

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Quantitative Biology 2024年第1期12卷 30-52页

作者： Xinyue li Zhankun Xiong Wen Zhang Shichao liu College of Informatics Huazhong Agricultural UniversityWuhanChina

The prediction of drug-drug interactions(DDIs)is a crucial task for drug safety research,and identifying potential DDIs helps us to explore the mechanism behind combinatorial *** wet chemical experiments for DDI are cumbersome and time-consuming,and are too small in scale,limiting the efficiency of DDI ***,it is particularly crucial to develop improved computational methods for detecting drug *** the development of deep learning,several computational models based on deep learning have been proposed for DDI *** this review,we summarized the high-quality DDI prediction methods based on deep learning in recent years,and divided them into four categories:neural network-based methods,graph neural network-based methods,knowledge graph-based methods,and multimodal-based ***,we discuss the challenges of existing methods and future potential *** review reveals that deep learning can significantly improve DDI prediction performance compared to traditional machine *** learning models can scale to large-scale datasets and accept multiple data types as input,thus making DDI predictions more efficient and accurate.

关键词： deep learning drug-drug interactions graph neural network knowledge graph multimodal deep learning neural network

Martensite decomposition under thermal-mechanical coupling conditions to fabricate an ultrafine-grained Ti6Al4Mo4Zr1W0.2Si alloy

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Journal of Materials Science & Technology 2024年第1期168卷 157-168页

作者： Taoyu Zhou Jiuxu Yang Nan li Hao Sun Bohua Zhang Zibo Zhao Qingjiang Wang Shi-changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China

The fabrication of ultrafine-grained microstructures(grain size below 1μm)in titanium alloys is beneficial for improving their mechanical properties at room temperature and medium tempera-tures(400-550°C).However,a long-standing challenge involves the low-cost manufacturing of bulk ultrafine-grained titanium *** this work,we developed a facile strategy through martensite de-composition at thermal-mechanical coupling conditions,to fabricate an equiaxed microstructure in a Ti6Al4Mo4Zr1W0.2Si model alloy with an averageαgrain size of 315±62 *** formation of the ultrafine-grained microstructure was because the lattice strain stored in the martensitic initial mi-crostructure enhanced the nucleation rate of dynamic recrystallization,meanwhile,the pinning role of martensite decomposition productsβand(Ti,Zr)_(5)Si_(3)phases suppressed grain coarsening at high *** to conventional(α+β)alloys,the tensile strength of this alloy improved by 20%-30%at both room temperature and 550°C,without decreasing its *** situ SEM observations revealed that the ultrafine-grained microstructure would not only suppress dislocation motions but also contribute to the homogenous deformation in the matrix of the material,therefore,it resulted in higher mechanical *** research results may be of great significance to the development of next-generation aviation titanium alloys.

关键词： Ultrafine-grained Titanium alloy In situ observation Deformation mechanism Thermostability

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1465-1478页

作者： Yu-Xin Zhao Yan Cui Xin-Hong li Wen-Hong Yang Shi-Xiang An Jia-Xian Cui Min-Yu Zhang Jing-Kun Lu Xuan Zhang Xiu-Mei Wang li-li Bao Peng-Wei Zhao Department of Anesthesiology Inner Mongolia Chest HospitalThe Fourth HospitalHohhot 010035Inner Mongolia Autonomous RegionChina College of Humanities and Education Inner Mongolia Medical UniversityHohhot 010059Inner Mongolia Autonomous RegionChina Department of Radiotherapy The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010059Inner Mongolia Autonomous RegionChina School of Basic Medical Science Inner Mongolia Medical UniversityHohhot 010059Inner Mongolia Autonomous RegionChina Department of Medical Oncology The Affiliated Cancer Hospital of Inner Mongolia Medical UniversityHohhot 010050Inner Mongolia Autonomous RegionChina

BACKGROUND Colorectal cancer has a low 5-year survival rate and high ***β-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer *** non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and *** To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 *** CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug *** formation assay was employed to assess the effect of hBD-1 on SW620 cell *** was used to screen potentially biologically significant lncRNAs related to the mTOR ***,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot *** hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to ***-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I ***,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR *** lncRNA TCONS_00014506 was ultimately *** the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein *** hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

关键词： Colon cancer Humanβ-defensin-1 LncRNA Mammalian target of rapamycin Autophagy

Field Study of HPTRM Combined with Vegetation and Anchor to Protect Newly Excavated Expansive Soil Slope

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Journal of Earth Science 2024年第4期35卷 1277-1288页

作者： Yingzi Xu Xuhang liao linqiang Tang lin li College of Civil&Architectural Engineering Guangxi UniversityNanning530004China Guangxi Key Laboratory of Disaster Prevention and Engineering Safety Nanning530004China Guangxi Transport Vocational and Technical College Nanning530004China Department of Civil&Architectural Engineering Tennessee State UniversityTennessee37209NashvilleUSA

Anchor reinforced vegetation system(ARVS)comprises high performance turf reinforcement mats(HPTRM),vegetation and *** is a new attempt to apply the system in expansive soil slope *** goal of this paper was to evaluate the effectiveness of ARVS in protecting newly excavated expansive soil *** field tests on the bare slope,grassed slope and ARVS protective slope were carried out,including natural and artificial *** the test,the soil water content,soil deformation,and anchor axial force were monitored,and then the slope protection mechanism of ARVS was *** was found that ARVS can effectively protect expansive soil slopes compared with bare slopes and grassed *** vegetation and HPTRM form a reinforced turf,and the anchors fix it to the slope surface,thus restraining the expansion *** axial force on the anchor of ARVS includes frictional resistance and tensile force transmitted by HPTRM,which is maximum at the early stage of *** neutral point of the anchor of ARVS moves deeper under atmospheric action,but the vegetation and HPTRM on the slope surface can limit this movement.

关键词： expansive soil slope anchor reinforced vegetation system high performance turf reinforcement mats field test slope protection

Spatiotemporal features and vertical structures of four types of mesoscale eddies in the Kuroshio Extension region

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Acta Oceanologica Sinica 2024年第5期43卷 30-40页

作者： Bowen Sun Shuchang Xu Zhankun Wang Yujie Feng Baofu li School of Geography and Tourism Qufu Normal UniversityRizhao 276800China Faculty of Information Science and Engineering Ocean University of ChinaQingdao 266100China

Except for conventional mesoscale eddies,there are also abundant warm cyclonic eddies(WCEs)and cold anticyclonic eddies(CAEs)in the global *** on the global mesoscale eddy trajectory atlas product,satellite altimetric and remote sensing datasets,and three-dimensional temperature/salinity dataset,spatiotemporal features of WCEs and CAEs are compared with traditional cold cyclonic eddies and warm anticyclonic eddies in the Kuroshio Extension(KE;28°−43°N,140°−170°E)*** of abnormal eddies like radius,amplitude,eddy kinetic energy,and proportion in all eddies behave in significant asymmetry on the north and south sides of the KE *** eddies in the general sense,temporal feature analysis reveals that it is more favorable to the formation and maintenance of WCEs and CAEs in summer and autumn,while winter is the *** spatiotemporal variation of abnormal eddies is likely because the marine environment varying with time and ***,proportion of abnormal eddies increases rapidly in decaying stage during the whole eddy lifespan,resulting in smaller average radius,amplitude,sea surface temperature anomaly and sea surface height anomaly compared to normal *** three-dimensional composite structures for four types of eddies expose that the difference between abnormal and conventional eddies is not just limited to the sea surface,but also exists within the water below the sea *** structures also indicate that the anomalous temperature signal is confined in the water from the sea surface to layers at about 30 m in the KE region.

关键词： mesoscale anomaly Kuroshio

Evaluation and Projection of Extreme High Temperature Indices in Southwestern China Using NEX-GDDP-CMIP6

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Journal of Meteorological Research 2024年第1期38卷 88-107页

作者： Fen ZHANG linxiao WEI Yonghua li Hongyu TANG Tianyu ZHANG Baogang YANG China Meteorological Administration Key Open Laboratory of Transforming Climate Resource to Economy Chongqing Climate CentreChongqing 401147

Based on the recently released NASA Earth Exchange Global Daily Downscaled Projections(NEX-GDDP)Coupled Model Intercomparison Project Phase 6(CMIP6) dataset and the gridded observational daily dataset CN05.1, this study evaluates the performance of 26 CMIP6 models in simulating extreme high temperature(EHT) indices in southwestern China and estimates future changes in the EHT indices under the Shared Socioeconomic Pathways(SSPs) SSP1-2.6, SSP2-4.5, and SSP5-8.5 using 11 optimal CMIP6 models. Five EHT indices are employed:annual maximum value of daily maximum temperature(TXX), high temperature days(T35), warm days(TX90P),heat wave frequency(HWF), and heat wave days(HWD). The main results are as follows.(1) NEX-GDDP-CMIP6 is highly capable of simulating the spatial patterns of TXX and T35 in southwestern China but it presents a weaker ability to simulate the spatial patterns of TX90P, HWF, and HWD.(2) The simulated time series of T35, TX90P, HWF,and HWD in southwestern China exhibit consistent upward trends with the observations. The linear trends of increase in TX90P and HWD are much greater than those of increase in TXX, T35, and HWF.(3) The estimated increases in TXX and T35 in southwestern China are significantly greater in Chongqing and the adjacent areas of Sichuan than in the other regions. Spatial distributions of the increases in TX90P, HWF, and HWD generally show higher values in the west and lower values in the east.(4) In the three different scenarios, the projected future TXX,T35, TX90P, and HWD in southwestern China all display a continuous increase with time and radiative forcing levels, whereas HWF initially increases but then decreases under the SSP5-8.5 scenario. By the end of the 21st century, under the SSP5-8.5 scenario, TXX and T35 are projected to increase by 6.0℃ and 45.0 days, respectively. The duration of individual heat waves is also expected to increase.

关键词： NEX-GDDP-CMIP6 extreme high temperature(EHT) southwestern China evaluation projection