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Development of pharmacological immunoregulatory anticancer therapeutics:current mechanistic studies and clinical opportunities

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2477-2526页

作者： Nanhao yin Xintong Li Xuanwei Zhang Shaolong xue Yu Cao Gabriele Niedermann You Lu Jianxin xue Division of Thoracic Tumor Multimodality Treatment Cancer Center&State Key Laboratory of Biotherapyand The National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Department of Gynecology and Obstetrics West China Second University HospitalSichuan UniversityNo.20Section 3South Renmin RoadChengdu 610041 SichuanPR China Department of Emergency Medicine Laboratory of Emergency MedicineWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Institute of Disaster Medicine&Institute of Emergency Medicine Sichuan UniversityNo.17Gaopeng AvenueChengdu 610041 SichuanPR China Department of Radiation Oncology Medical Center—University of FreiburgFaculty of MedicineUniversity of FreiburgGerman Cancer Consortium(DKTK)Partner Site DKTK-FreiburgRobert-Koch-Strasse 379106 FreiburgGermany Laboratory of Clinical Cell Therapy West China HospitalSichuan UniversityNo.2222Xinchuan RoadChengdu 610041 SichuanPR China

Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still *** to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable ***,comprehending the larger picture is *** this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint *** with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including LAG-3,TIM-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T *** by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical ***-generation agents also include immune epigenetic drugs and cytokine-based *** therapies,cancer vaccines,and oncolytic viruses are not covered in this *** comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.

关键词： clinical immuno landscape

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Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1599-1605页

作者： Yan-Xia Wu Shuo yin Shan-Shan Song Xiang Liu Yu-Xuan Deng xue-jing Lu Eye School of Chengdu University of Traditional Chinese Medicine Chengdu 610075Sichuan ProvinceChina Ineye Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610084Sichuan ProvinceChina School of Chinese Classics Chengdu University of Traditional Chinese MedicineChengdu 610075Sichuan ProvinceChina Key Laboratory of Sichuan Province Ophthalmopathy Prevention&Cure and Visual Function Protection with Traditional Chinese Medicine Chengdu 610075Sichuan ProvinceChina Retinal Image Technology and Chronic Vascular Disease Prevention&Control and Collaborative Innovation Center Chengdu 610075Sichuan ProvinceChina

AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in ***:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for *** 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were ***:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model ***-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model ***-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the ***:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model.

关键词： retinal ischemia-reperfusion Lycium barbarum glycopeptide pretreatment anti-inflammatory antioxidative rat

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The First Initial Boundary Value Problem for Parabolic Hessian Equations on Riemannian Manifolds

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Communications in Mathematical Research 2013年第4期29卷 305-319页

作者： Ren Chang-yu yin jing-xue School of Mathematics Jilin University

For a class of elliptic Hessian operators, one type of corresponding parabolic Hessian equations is studied on Riemannian manifolds. uniqueness of the admissible solution to the first initial boundary the equations ar... 详细信息

关键词： Hessian operator fully nonlinear Riemannian manifold

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Effects of weaning on intestinal longitudinal muscle-myenteric plexus function in piglets

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Science China(Life Sciences) 2024年第2期67卷 379-390页

作者： jing Li Fenfen Liu Kaibin Mo Hengjia Ni Yulong yin Key Laboratory of Agro-Ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessHunan Research Center of Livestock and Poultry SciencesSouth Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of AgricultureInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China University of Chinese Academy of Sciences Beijing 100008China Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642China

Weaning piglets usually suffer from severe diarrhea(commonly known as postweaning diarrhea,PWD)along with intestinal motility *** peristalsis is mainly regulated by the longitudinal muscle-myenteric plexus(LM-MP).To understand the relationship between intestinal LM-MP function and the development of PWD,we compared the intestinal electrical activity,and the transcriptional profile of the LM-MP between 21-day-old piglets(just weaned,n=7)and 24-day-old piglets(suffered the most severe weaning stress,n=7).The results showed that 24-day-old piglets exhibited different degrees of diarrhea.A significant increase in the slow-wave frequency in the ileum and colon was observed in 24-day-old piglets,while c-kit expression in the intestinal LM-MPs was significantly decreased,indicating that PWD caused by elevated slow-wave frequency may be associated with loss of *** real-time quantitative PCR(RT-q PCR)and enzyme-linked immunosorbent assay(ELISA)showed that intestinal LM-MPs in 24-day-old piglets may undergo inflammation and oxidative *** increases in 8-hydroxy-2′-deoxyguanosine and decreases in thioredoxin suggest that weaning may lead to DNA damage in the LM-MP of 24-day-old *** addition,activating transcription factor 3 was significantly upregulated,indicating nerve damage in the LM-MP of 24-day-old *** transcriptomic results showed that most of the differentially expressed genes in the ileal LM-MP after weaning were downregulated and closely related to the cell cycle *** RT-q PCR analysis showed that the relative expression of p21 was upregulated,while the expression of cyclin A2,cyclin B1,and proliferating cell nuclear antigen was downregulated in the ileal and colonic LM-MP of 24-day-old piglets,suggesting that weaning may inhibit cell proliferation and cause G1/S cell cycle arrest in ileal and colonic *** conclusion,weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP,impairing i

关键词： weaning piglets diarrhea longitudinal muscle-myenteric plexus

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Progress of semitransparent emerging photovoltaics for building integrated applications

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Green Energy & Environment 2024年第6期9卷 992-1015页

作者： Zhisheng Zhou Zhangyu Yuan Zhipeng yin Qifan xue Ning Li Fei Huang State Key Laboratory of Luminescent Materials and Devices School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou510640China Pazhou Lab Guangzhou510320China

With the rapid development of emerging photovoltaics technology in recent years,the application of building-integrated photovoltaics(BIPVs)has attracted the research interest of photovoltaic *** meet the practical application requirements of BIPVs,in addition to the evaluation indicator of power conversion efficiency(PCE),other key performance indicators such as heat-insulating ability,average visible light transmittance(AVT),color properties,and integrability are equally *** traditional Si-based photovoltaic technology is typically limited by its opaque properties for application scenarios where transparency is *** emerging PV technologies,such as organic and perovskite photovoltaics are promising candidates for BIPV applications,owing to their advantages such as high PCE,high AVT,and tunable *** present,the PCE of semitransparent perovskite solar cells(ST-PSCs)has attained 14%with AVT of 22–25%;for semitransparent organic solar cells(ST-OSCs),the PCE reached 13%with AVT of almost 40%.In this review article,we summarize recent advances in material selection,optical engineering,and device architecture design for high-performance semitransparent emerging PV devices,and discuss the application of optical modeling,as well as the challenges of commercializing these semitransparent solar cells for building-integrated applications.

关键词： Building integrated photovoltaics Emerging photovoltaics Semitransparent solar cells Perovskite solar cells Organic solar cells

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Assessment of Wet Season Precipitation in the Central United States by the Regional Climate Simulation of the WRFG Member in NARCCAP and Its Relationship with Large-Scale Circulation Biases

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Advances in Atmospheric Sciences 2024年第4期41卷 619-638页

作者： Yating ZHAO Ming xue jing JIANG Xiao-Ming HU Anning HUANG School of Atmospheric Sciences Nanjing UniversityNanjing 210023China Center for Analysis and Prediction of Storms and School of Meteorology The University of OklahomaNorman 73072U.S.A

Assessment of past-climate simulations of regional climate models(RCMs)is important for understanding the reliability of RCMs when used to project future regional ***,we assess the performance and discuss possible causes of biases in a WRF-based RCM with a grid spacing of 50 km,named WRFG,from the North American Regional Climate Change Assessment Program(NARCCAP)in simulating wet season precipitation over the Central United States for a period when observational data are *** RCM reproduces key features of the precipitation distribution characteristics during late spring to early summer,although it tends to underestimate the magnitude of *** dry bias is partially due to the model’s lack of skill in simulating nocturnal precipitation related to the lack of eastward propagating convective systems in the *** in reproducing large-scale circulation and environmental conditions is another contributing *** too weak simulated pressure gradient between the Rocky Mountains and the Gulf of Mexico results in weaker southerly winds in between,leading to a reduction of warm moist air transport from the Gulf to the Central Great *** simulated low-level horizontal convergence fields are less favorable for upward motion than in the NARR and hence,for the development of moist convection as ***,a careful examination of an RCM’s deficiencies and the identification of the source of errors are important when using the RCM to project precipitation changes in future climate scenarios.

关键词： NARCCAP Central United States precipitation low-level jet large-scale environment diurnal variation

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Corporate Credit Ratings Based on Hierarchical Heterogeneous Graph Neural Networks

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Machine Intelligence Research 2024年第2期21卷 257-271页

作者： Bo-jing Feng Xi Cheng Hao-Nan Xu Wen-Fang xue Center for Research on Intelligent Perception and Computing National Laboratory of Pattern RecognitionInstitute of AutomationChinese Academy of SciencesBeijing 100190China

order to help investors understand the credit status of target corporations and reduce investment risks,the corporate credit rating model has become an important evaluation tool in the financial *** models are based on statistical learning,machine learning and deep learning especially graph neural networks(GNNs).However,we found that only few models take the hierarchy,heterogeneity or unlabeled data into account in the actual corporate credit rating ***,we propose a novel framework named hierarchical heterogeneous graph neural networks(HHGNN),which can fully model the hierarchy of corporate features and the heterogeneity of relationships between *** addition,we design an adversarial learning block to make full use of the rich unlabeled samples in the financial *** experiments conducted on the public-listed corporate rating dataset prove that HHGNN achieves SOTA compared to the baseline methods.

关键词： Corporate credit rating hierarchical relation heterogeneous graph neural networks adversarial learning

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Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443

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Chinese Journal of Integrative Medicine 2024年第3期30卷 213-221页

作者： ZHANG Yue XIAO Yan-wei MA jing-xin WANG Ao-xue Department of Dermatology the Second Hospital of Dalian Medical UniversityDalianLiaoning Province116021China Department of Cell Biology Dalian Medical UniversityDalianLiaoning Province116044China

Objective:To investigate the effect and possible mechanism of hydroxysafflor yellow A(HSYA) on human immortalized keratinocyte cell proliferation and ***:HaCaT cells were treated with *** proliferation was detected by the cell counting kit-8 assay,and cell migration was measured using wound healing assay and Transwell migration *** mRNA and protein expression levels of heparin-binding epidermal growth factor(EGF)-like growth factor(HBEGF),EGF receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),and hypoxia-inducible factor-1α(HIF-1α) were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot,***_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with *** expression of circ_0084443 was detected by ***:HSYA(800 μmol/L) significantly promoted HaCaT cell proliferation and migration(P0.05).Conclusion:HSYA played an accelerative role in HaCaT cell proliferation and migration,which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways,and had a particular inhibitory effect on the keratinocyte negative

关键词： hydroxysafflor yellow A circ_0084443 heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor phosphatidylinositol 3-kinase/protein kinase B

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Chromosome-scale genomes of Quercus sichourensis and Quercus rex provide insights into the evolution and adaptation of Fagaceae

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Journal of Genetics and Genomics 2024年第5期51卷 554-565页

作者： xue Liu Weixiong Zhang Yongting Zhang jing Yang Peng Zeng Zunzhe Tian Weibang Sun jing Cai Shaanxi Key Laboratory of Qinling Ecological Intelligent Monitoring and Protection School of Ecology and EnvironmentNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Yunnan Key Laboratory for Integrative Conservation of Plant Species with Extremely Small Populations Kunming Institute of BotanyChinese Academy of SciencesKunmingYunnan 650201China

The Fagaceae,a plant family with a wide distribution and diverse adaptability,has garnered significant interest as a subject of study in plant speciation and ***,certain Fagaceae species are regarded as highly valuable wood resources due to the exceptional quality of their *** this study,we present two high-quality,chromosome-scale genome sequences for Quercus sichourensis(848.75 Mb)and Quercus rex(883.46 Mb).Comparative genomics analysis reveals that the difference in the number of plant disease resistance genes and the nonsynonymous and synonymous substitution ratio(Ka/Ks)of protein-coding genes among Fagaceae species are related to different environmental ***,most genes related to starch synthesis in the investigated Quercoideae species are located on a single chromosome,as compared to the outgroup species,Fagus ***,resequencing and population analysis of *** and *** reveal that *** has lower genetic diversity and higher deleterious mutations compared to *** high-quality,chromosome-level genomes and the population genomic analysis of the critically endangered *** and *** will provide an invaluable resource as well as insights for future study in these two species,even the genus Quercus,to facilitate their conservation.

关键词： Adaptation Quercus sichourensis Quercusrex Chromosome-scale genome assembly Tandem duplication genes Extremely small populations

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Precisely Control Relationship between Sulfur Vacancy and H Absorption for Boosting Hydrogen Evolution Reaction

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Nano-Micro Letters 2024年第4期16卷 14-24页

作者： jing Jin Xinyao Wang Yang Hu Zhuang Zhang Hongbo Liu Jie yin Pinxian Xi College of Chemistry and Chemical Engineering Frontiers Science Center for Rare IsotopesState Key Laboratory of Applied Organic ChemistryLanzhou UniversityLanzhou 730000People’s Republic of China

Ef fective and robust catalyst is the core of water splitting to produce ***, we report an anionic etching method to tailor the sulfur vacancy(VS) of NiS_(2) to further enhance the electrocatalytic performance for hydrogen evolution reaction(HER). With the VS concentration change from 2.4% to 8.5%, the H* adsorption strength on S sites changed and NiS_(2)-VS 5.9% shows the most optimized H* adsorption for HER with an ultralow onset potential(68 m V) and has long-term stability for 100 h in 1 M KOH media. In situ attenuated-total-reflection Fourier transform infrared spectroscopy(ATR-FTIRS) measurements are usually used to monitor the adsorption of intermediates. The S-H* peak of the Ni S_(2)-VS 5.9% appears at a very low voltage, which is favorable for the HER in alkaline media. Density functional theory calculations also demonstrate the Ni S_(2)-VS 5.9% has the optimal |ΔG^(H*)| of 0.17 e V. This work offers a simple and promising pathway to enhance catalytic activity via precise vacancies strategy.

关键词： Hydrogen evolution reaction S vacancies Nanosheet H Adsorption

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