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QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

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Signal Transduction and Targeted Therapy 2024年第2期9卷 797-806页

作者： Yan Huang Yunpeng Yang Yuanyuan Zhao Hongyun Zhao Ningning Zhou Yaxiong Zhang Likun Chen Ting Zhou Gang Chen Ting Wu lu lu Shilin Xue Xiaoyan Kang Li Zhang Wenfeng fang Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineNo.651 Dongfeng East RoadGuangzhouGuangdong 510060China Department of Medicine Qilu Pharmaceutical Co.Ltd.JinanChina

First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this *** were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were *** frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)***-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line ***,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.

关键词： bevacizumab chemotherapy phase

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ACTN1 promotes malignant progression in cutaneous squamous cell carcinoma by downregulating the p53 signaling pathway

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中华医学杂志(英文版) 2024年第14期137卷 1759-1761页

作者： Yuan Tao lu Xiaohong Jiang Jiahui Chen Nan Tang Biao He Caifeng Liu Wenbei Wang Jun Ci chao Department of Dermatology Yijishan Hospital the First Affiliated Hospital of Wannan Medical College Wuhu Anhui China

To the Editor: Cutaneous squamous cell carcinoma (CSCC) originates from the keratinocytes of the epidermal layer and (or) its associated appendages, manifesting as a rapidly proliferating, highly destructive malignancy, with almost 20,000 cases occurring in China in 2022. The pathogenesis of CSCC is complex, but recent studies have made significant progress. Our previous research identified eight proteins, including actinin alpha 1 (ACTN1), tenascin C (TNC), fascin actin-bundling protein 1 (FSCN1), serpin family B member 1 (SERPINB1), ras-related protein 31 (RAB31), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), and cluster of differentiation 36 (CD36), which are markedly linked to CSCC invasion and metastasis. Besides, our subsequent assays also revealed the elevated serum level of ACTN1 in CSCC patients, which correlated with tumor cell differentiation, invasion depth, and primary tumor diameter. This underscores the potentially pivotal role of ACTN1 in CSCC pathogenesis. This study aimed to further investigate the role of ACTN1 in the pathogenesis of CSCC.

关键词： CANCER STAT3

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Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang lu Yu Gan Qiao Dalian Qin Betty Yuen-Kwan Law fang Ren Jianming Wu Anguo Wu Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial DNA and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial DNA Crosstalk Therapeutic avenues Neurodegenerative diseases

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Water quality and habitat drive phytoplankton taxonomic and functional group patterns in the Yangtze River

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Ecological Processes 2024年第1期13卷 144-158页

作者： Wenqi Gao fangyuan Xiong Ying lu Wei Xin Haihua Wang Gangpeng Feng Chiping Kong Lei fang Xiaoping Gao Yushun Chen State Key Laboratory of Freshwater Ecology and Biotechnology Institute of Hydrobiology Chinese Academy of Sciences University of Chinese Academy of Sciences Jiangxi Institute for Fisheries Sciences Poyang Lake Fisheries Research Centre of Jiangxi Province East China Sea Fisheries Research Institute Chinese Academy of Fishery Sciences Jiujiang Institute of Agricultural Sciences

Background Although phytoplankton are important primary producers in food webs, they are relatively less studied in large rivers compared to other types of systems. To fill this research gap, we studied phytoplankton taxonomic and functional composition and their relationships with water quality, habitat, climate, and land use across 30 river sections in the middle and lower reaches of the Yangtze River during 2017–*** Major observed phytoplankton groups were cyanobacteria, bacillariophyta, and chlorophyta. Phytoplankton total abundance, total biomass, and species richness significantly decreased in the dry season compared to the wet season, with the species and functional composition differing significantly between seasons. Phytoplankton species differences between seasons were mainly contributed by Oscillatoria sp., Pseudanabaena sp., and Melosira granulata. The dfferences in phytoplankton functional groups between seasons were mainly contributed by P（including Closterium sp., Melosira sp.）, Lo（including Merismopedia sp., Peridinium sp., Ceratium sp., and Gymnodinium sp.）, and J（including Pediastrum sp., Tetraedron sp., Crucigenia sp., Scenedesmus sp., and Coelastrum sp.）. The variance partitioning showed that water quality（NO3-N, total suspended solids, turbidity） and habitat（water flow, river bank and river channel conditions） were critical factors in shaping phytoplankton patterns, followed by climate and land *** Results indicated that there was significant seasonal variation of phytoplankton in the Yangtze River, with water quality and habitat primarily driving phytoplankton patterns. Our study contributes to the understanding of natural and anthropogenic factors that drive seasonal successional processes of phytoplankton in the Yangtze River. These findings have important implications for environmental management as well as towards the ecological restoration of large rivers.

关键词： Yangtze River Phytoplankton Functional group Water quality Physical habitat

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An Improved Thermal Conductivity Measurement Scheme for Macroscopic Graphitic Films Using the Laser Flash Method

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Journal of Thermal Science 2024年第4期33卷 1480-1490页

作者： ZHANG Peijuan MING Xin LIU Yingjun WANG Xuelong SHI Hang HAO Yuanyuan lu Jiahao LIU Zheng LAI Haiwen ZHANG Ying GAO Weiwei XU Zhen GAO chao MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringKey Laboratory of Adsorption and Separation Materials&Technologies of Zhejiang ProvinceZhejiang UniversityHangzhou310027China Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuan030032China Special Equipment Safety Supervision and Inspection Institute of Jiangsu Province National Graphene Products Quality Inspection and Testing Center(Jiangsu)Wuxi214174China Hangzhou Gaoxi Technol Co. LtdHangzhou311113China China Academy of Aerospace Aerodynamics Beijing100074China

Achieving efficient thermal management urges to exploit high-thermal-conductivity materials to satisfy the boosted demand of heat *** is critical to adopt standardized characterization protocols to evaluate the intrinsic thermal conductivity of thermal management ***,for the most representative laser flash method,the lack of standard measurement methodology and systematic description on the thermal diffusivity and influencing factors has led to significant deviations and confusion of the thermal conduction performance in the emerging thermal management ***,the measurement error factors of thermal diffusivity by the common laser flash analyzer(LFA)are *** high-thermal-conductivity graphitic film(GF)as a typical case,the key factors are analyzed to guide the measurement protocol of related carbon-based thermal management *** basic principle of the LFA measurement,actual pre-processing conditions,instrument parameters setting,and data analysis are elaborated for accurate ***,the graphene thick films and common isotropic materials are also extended to meet various thermal measurement *** on the existing practical problems,we propose a feasible test flow to achieve a unified and standardized thermal conductivity measurement,which is beneficial to the rapid development of carbon-based thermal management materials.

关键词： thermal management graphitic film laser flash method thermal conductivity thermal diffusivity

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Flavonoid extracts from chrysanthemum with appropriate anthocyanins turn blue when exposed to iron ions

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Horticultural Plant Journal 2024年第3期10卷 837-852页

作者： Yanfei Li Jiaying Wang Chenfei lu Zhongman Wang Chengyan Deng Kang Gao Jingjing Li Zhijun fang Hao Liu Yan Hong Silan Dai Beijing Key Laboratory of Ornamental Plants Germplasm Innovation&Molecular Breeding National Engineering Research Center for FloricultureBeijingLaboratory of Urban and Rural Ecological EnvironmentKey Laboratory for Genetics and Breeding of Forest Trees and Ornamental Plants of Ministry of EducationSchool of Landscape ArchitectureBeijing Forestry UniversityBeijing 100083China Beijing Greenland Maintenance and Management Service Center Beijing 102211China Beijing North Asia Landscape Co. Beijing 102211China

Although some species that accumulate only cyanidin(Cy)in nature can produce blue flowers through iron ions,there has been no evidence of blue chrysanthemums being generated in this *** study revealed that flavonoid extracts from the ray florets of the chrysanthemum cultivar‘Wandai Fengguang’turned blue when exposed to Fe^(3+).Samples that could turn blue were labeled as CB(Cy-determined blue flowers),while samples that did not turn blue were labeled as CN(Cy-determined non-blue flowers).After a series of experiments,a stable screening system was established using flavonoid extracts containing NaAc buffer at pH 5.5 and a total anthocyanin concentration(TAC)of 30 μmol·L^(-1),and the addition of Fe^(3+)from 0 to 0.25 μmol·L^(-1)allowed for the selection of five CB samples from 39 chrysanthemum *** five CB samples exhibited flower color phenotypes that belonged to Cluster-I with redness(a*)values ranging from 29.03 to 45.99,yellowness(b*)values from-11.31 to 3.77,and brightness(L*)values from 29.07 to ***,the ratio of TAC to total luteolin concentration(TLC)was found to be a critical factor for distinguishing between CB and CN *** realize the desired blue hue in the flavonoid extracts with the participation of Fe^(3+),a TAC to TLC ratio of 2.25 and above is ***,the protoplasts and ray florets of CB samples that turned blue with the involvement of Fe^(2+)showed great potential for cultivating blue chrysanthemums through ferric-anthocyanin ***,this study reveals that blue flowers can be cultivated through the increase in the iron ion concentration,combined with the accumulation of Cy.

关键词： Chrysanthemum×morifolium Cyanidin Copigment Ferric-anthocyanin chelate Blue flower

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Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration Research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan lu Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian fang Jun Yu Department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina Clinical Research Center for Neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases HangzhouZhejiang ProvinceChina

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral *** E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and ***,the effect of Spi1 on intracerebral hemorrhage remains *** this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage *** showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained ***,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and *** conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral *** new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

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Mechanism of Ta on the microstructure and properties of Fe-Mn damping alloys

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Tungsten 2024年第4期6卷 767-777页

作者： Gui-Xiang Liu Kun Zhang chao Han Xiao-Lin Shao Jun lu Lin Zhang Xiao-Song Jiang Zi-Xuan Wu Liu Yang The Second Sub-Institute Nuclear Power Institute of China Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials Science and Engineering Southwest Jiao tong University School of Engineering and Materials Science Queen Mary University of London Institute for Applied Materials (IAM-WK) Karlsruhe Institute of Technology (KIT)

Fe-Mn-Co-xTa alloys（x=0,1,2,3 wt.%） were fabricated using spark plasma sintering to explore the influence of Ta content on the microstructure,mechanical properties,and damping characteristics of Fe-17Mn-3Co damping *** micro structural analysis reveals the dominant presence of γ-austenite,ε-martensite,α'-martensite,and Co3Ta precipitates within the *** increments in Ta content exhibit proportional enhancements in hardness,tensile strength,and fracture elongation of the ***,these improvements in mechanical attributes are closely correlated with the generated second-phase *** the Ta content increases,there is a gradual augmentation in the formation of Co3Ta within the ***,the damping property initially experiences an ascent followed by a subsequent decline with rising Ta *** damping behavior finds its origins in multiple mechanisms,including grain boundary damping stemming from reduced grain size,interfacial damping induced by the generated Co3Ta,and dislocation *** is noteworthy that the emergence of the secondary phase wields a dual impact on damping *** the one hand,the proliferation of the second phase fosters increased interfaces for energy *** the other hand,these interfaces give rise to compressive stresses,constraining interface movement and thus impeding damping property enhancement.

关键词： Damping Fe–Mn–Co Mechanical properties Spark plasma sintering Ta

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Subjective cognitive decline domain improves accuracy of plasma Aβ_(42)/Aβ_(40)for preclinical Alzheimer’s disease diagnosis:The SILCODE study

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Chinese Medical Journal 2024年第9期137卷 1127-1129页

作者： Mingkai Zhang Xiaoni Wang Weina Zhao Yuxia Li chao Ying Jiehui Jiang Yanning Cai Jie lu Ying Han Department of Neurology Xuanwu Hospital of Capital Medical UniversityBeijing 100053China Department of Neurology Sir Run Run Shaw HospitalAffiliated with School of MedicineZhejiang UniversityHangzhouZhejiang 310016China Department of Neurology Hongqi Hospital Affiliated to Mudanjiang Medical UniversityMudanjiangHeilongjiang 157011China Heilongjiang Key Laboratory of Ischemic Stroke Prevention and Treatment MudanjiangHeilongjiang 157011China Department of Neurology Tangshan Central HospitalTangshanHebei 063000China Department of Neurobiology Xuanwu Hospital of Capital Medical UniversityKey Laboratory for Neurodegenerative Diseases of the Ministry of EducationBeijing 100053China Institute for Advanced Communication and Data Science Shanghai UniversityShanghai 200444China Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijing 100053China Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics Beijing 100053China Key Laboratory of Neurodegenerative Diseases Ministry of EducationBeijing 100053China School of Biomedical Engineering Hainan UniversityHaikouHainan 570228China Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijing 100053China National Clinical Research Center for Geriatric Disorders Beijing 100053China Institute of Biomedical Engineering Shenzhen Bay LaboratoryShenzhenGuangdong 518132China

To the Editor:Accumulating evidence has shown that the preclinical stage of Alzheimer’s disease(AD)(i.e.,asymptomatic amyloidosis)lasts for decades before the onset of cognitive symptoms,providing a large window for early *** pathology,the earliest pathological change associated with AD,can be detected in vivo with cerebrospinal fluid(CSF)analysis or positron emission tomography(PET),and its presence is necessary for the diagnosis of preclinical AD(pre-AD).However,both PET scans and CSF analyses are expensive,hampering their use in large-scale ***,blood-based biomarkers are desirable alternatives,as they are cost-effective and not invasive.

关键词： diagnosis clinical Alzheimer

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Tunable near-infrared light emission from layered TiS_(3) nanoribbons

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Frontiers of physics 2024年第4期19卷 103-111页

作者： Junrong Zhang Cheng Chen Yanming Wang Yang lu Honghong Li Xingang Hou Yaning Liang Long fang Du Xiang Kai Zhang Junyong Wang School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaHefei 230026China CAS Key Laboratory of Nanophotonic Materials and Devices&Key Laboratory of Nanodevices and Applications i-LabSuzhou Institute of Nano-Tech and Nano-Bionics(SINANO)Chinese Academy of SciencesSuzhou 215123China Frontier Institute of Chip and System Fudan UniversityShanghai 200438China School of Materials Science and Engineering Shanghai UniversityShanghai 200444China College of Energy&Power Engineering Inner Mongolia University of TechnologyHohhot 010051China

The low-dimensional light source shows promise in photonic integrated *** layered van der Waals material that exhibits luminescence in the near-infrared optical communication waveband is an essential component in on-chip light ***,the tunable near-infrared photoluminescence(PL)of the air-stable layered titanium trisulfide(TiS3)is *** with iodine particles as a transport agent,TiS3 grown by chemical vapor transport using sulfur powder as a transport agent has fewer sulfur vacancies,which increases the luminescence intensity by an order of *** PL emission wavelength can be regulated in the near-infrared regime by thickness *** addition,we observed an interesting anisotropic strain response of PL in layered TiS3 nanoribbon:a blue shift of PL was achieved when the uniaxial tensile strain was applied along the b-axis,while a negligible shift was observed when the strain was applied along the *** work reveals the tunable nearinfrared luminescent properties of TiS3 nanoribbons,suggesting their potential applications as near-infrared light sources in photonic integrated circuits.

关键词： titanium trisulfide near-infrared luminescence S-vacancy tunability strain engineering

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