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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li qianfeng Zhang Zhiqian Li Long ren Dayi Pan qiyong Gong zhongwei Gu hao Cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Post-synthetic modifications of MOFs by different bolt ligands for controllable release of cargoes

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Chinese Chemical Letters 2024年第10期35卷 404-407页

作者： hao Wang Meng-qi Pan Ya-Fei Wang Chao Chen Jian Xu Yuan-Yuan Gao Chuan-Song qi Wei Li Xian-He Bu College of New Materials and Chemical Engineering Beijing Key Lab of Special Elastomeric Composite MaterialsBeijing Institute of Petrochemical TechnologyBeijing 102617China School of Materials Science and Engineering National Institute for Advanced MaterialsTKL of Metal and Molecule-Based Material ChemistryNankai UniversityTianjin300350China College of Chemical Engineering Inner Mongolia University of TechnologyHohhot 010051China

Post-synthetic modifications(PSM)have drawn great attention as a vigoroso tool to tune or enhance the performance of metal-organic frameworks(MOFs).However,the current PSM method usually have to sacrifice the porosity of MOFs to enrich their functionality,such as pore space partition(PSP)and postsynthetic elimination and insertion(PSE&I),causing a trade-off in this *** address this issue,we herein propose a new PSM strategy of using the size-matching ligands as the bolts to lock MOFs'pores,which could be anchored onto open metal sites(OMSs)after guest loading through a stepwise *** a result,the loaded cargoes undergo a controlled releasing process with respect to different bolt *** proposed strategy provides a promising way to balance the functionality and porosity of MOFs.

关键词： Post-synthetic modifications Metal-organic frameworks Bolting ligand Control release Cargo

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Fast thermal responsive separators toward long-life and safe lithium metal batteries

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Nano Research 2024年第4期17卷 2746-2754页

作者： Pingan Li Zhifang Liu Yitong Peng Shanshan Yang Tao Meng Yunhuan Hu Yingjun Jiang hao Sun qi Li Xianluo Hu State Key Laboratory of Materials Processing and Die and Mould Technology School of Materials Science and EngineeringHuazhong University of Science and TechnologyWuhan 430074China

Lithium metal batteries(LMBs)have been extensively investigated during the past decades because of their ultrahigh energy *** the increasing demand for energy density,however,the safety issue of LMBs has become a significant *** particular,localized areas of increased temperature(namely,hotspots)may be induced and even exacerbated within LMBs by uneven current distribution,internal short circuits,or inadequate heat dissipation,which significantly sacrifices battery safety and cycle ***,we report the rational design and fabrication of a fast thermal responsive separator capable of inhibiting the growth of lithium dendrites and mitigating thermal propagation,thereby reducing the risk of thermal *** as-achieved separator comprises both an electrospun membrane using a phase change material with superior thermal-storage ability and a thermally conductive modification layer of hexagonal boron nitride nanosheets with a fast heat-transfer *** is demonstrated that such a unique integration of heat conduction and heat storage enables the functional separator with attractive abilities to mitigate hotspots and inhibit the growth of lithium dendrites upon the cycling of ***,pouch cells with the thermal-responsive separator,as well as numerical simulations,verify much enhanced safety and cycle life of *** work may offer a new conceptual design of intelligent separators that acts as a functional unit encapsulated within a single cell to boost in-situ thermal management,which will help to develop high-safety and energy-dense LMBs.

关键词： lithium metal batteries separators hotspots safety thermal management

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Multimodal Machine Learning Guides Low Carbon Aeration Strategies in Urban Wastewater Treatment

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Engineering 2024年第5期36卷 51-62页

作者： Hong-Cheng Wang Yu-qi Wang Xu Wang Wan-Xin Yin Ting-Chao Yu Chen-hao Xue Ai-Jie Wang State Key Laboratory of Urban Water Resource and Environment School of Civil and Environmental EngineeringHarbin Institute of Technology(Shenzhen)Shenzhen 518055China Key Laboratory of Drinking Water Safety and Distribution Technology of Zhejiang Province College of Civil Engineering and ArchitectureZhejiang UniversityHangzhou 310058China

The potential for reducing greenhouse gas(GHG)emissions and energy consumption in wastewater treatment can be realized through intelligent control,with machine learning(ML)and multimodality emerging as a promising ***,we introduce an ML technique based on multimodal strategies,focusing specifically on intelligent aeration control in wastewater treatment plants(WWTPs).The generalization of the multimodal strategy is demonstrated on eight ML *** results demonstrate that this multimodal strategy significantly enhances model indicators for ML in environmental science and the efficiency of aeration control,exhibiting exceptional performance and *** random forest with visual models achieves the highest accuracy in forecasting aeration quantity in multimodal models,with a mean absolute percentage error of 4.4%and a coefficient of determination of *** testing in a full-scale plant reveals that the multimodal model can reduce operation costs by 19.8%compared to traditional fuzzy control *** potential application of these strategies in critical water science domains is *** foster accessibility and promote widespread adoption,the multimodal ML models are freely available on GitHub,thereby eliminating technical barriers and encouraging the application of artificial intelligence in urban wastewater treatment.

关键词： Wastewater treatment Multimodal machine learning Deep learning Aeration control Interpretable machine learning

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Porous block copolymer films with self-adjustable optical transmittance and passive radiative cooling

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Nano Research 2024年第9期17卷 8472-8478页

作者： Xue Meng Weiming Tang Shuyun Zhuo Jince Zhao Zixuan ren.zhonghe Sun hao Yan tianyi Zhao Ziguang Zhao Mingjie Liu School of Future Technology University of Chinese Academy of SciencesBeijing 100049China Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of EducationSchool of ChemistryBeihang UniversityBeijing 100191China

As an energy-free cooling technique,radiative cooling has garnered significant attention in the field of energy ***,traditional radiative cooling films often possess static optical properties and their inherent opacity limits their applications in building such as ***,there exists a requirement for passive radiative cooling films endowed with adjustable *** we report the porous block copolymer films with self-adjustable optical transmittance and passive radiative *** a result,the film exhibited a high solar reflectance(0.3-2.5μm)of 96.9%and a high infrared emittance(8-13μm)of 97.9%.Outdoor experiments demonstrated that the film surface temperature was 6.6℃lower than ambient temperature,with a cooling power of 104.8 W·m^(-2).In addition,the film’s transmittance can be regulated by altering the polarity of the post-processing solvent,providing an effective approach for regulating indoor light intensity and thermal balance,thereby enhancing the applicability of radiative cooling.

关键词： passive radiative cooling block copolymer porous structure self-adjustable optical transmittance

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Emerging memristors and applications in reservoir computing

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Frontiers of physics 2024年第1期19卷 219-239页

作者： hao Chen Xin-Gui Tang Zhihao Shen Wen-Tao Guo qi-Jun Sun Zhenhua Tang Yan-Ping Jiang School of Physics and Optoelectronic Engineering Guangdong University of TechnologyGuangzhou Higher Education Mega CenterGuangzhou 510006China

Recently, with the emergence of ChatGPT, the field of artificial intelligence has garnered widespread attention from various sectors of society. Reservoir Computing (RC) is a neuromorphic computing algorithm used to analyze time-series data. Unlike traditional artificial neural networks that require the weight values of all nodes in the trained network, RC only needs to train the readout layer. This makes the training process faster and more efficient, and it has been used in various applications, including speech recognition, image classification, and control systems. Its flexibility and efficiency make it a popular choice for processing large amounts of complex data. A recent research trend is to develop physical RC, which utilizes the nonlinear dynamic and short-term memory properties of physical systems (photonic modules, spintronic devices, memristors, etc.) to construct a fixed random neural network structure for processing input data to reduce computing time and energy. In this paper, we introduced the recent development of memristors and demonstrated the remarkable data processing capability of RC systems based on memristors. Not only do they possess excellent data processing ability comparable to digital RC systems, but they also have lower energy consumption and greater robustness. Finally, we discussed the development prospects and challenges faced by memristors-based RC systems.

关键词： reservoir computing memristor resistive switching artificial synapse neuromorphic computing

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Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization

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Bone Research 2024年第2期12卷 372-389页

作者： Longqing Wang Wenhao Jiang Siyuan Zhao Dong Xie qing Chen qi Zhao hao Wu Jian Luo Lili Yang Spine Center Department of OrthopaedicsShanghai Changzheng HospitalSecond Affiliated Hospital of Naval Medical UniversityShanghai 200003PR China Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Tongji University School of MedicineShanghaiPR China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiPR China Department of Orthopaedics No.905 Hospital of PLA NavyShanghaiPR China

Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve *** both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPLL process at a single-cell resolution,and validate these findings in clinical *** study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in ***,our study identifies LOXL2 as a key regulator in this *** gain-and loss-of-function studies,we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament *** acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and *** function is not related to the enzymatic activity of ***,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of LOXL2-mediated vascular *** disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone *** findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

关键词： LOXL2 ligament finding

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ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

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Bone Research 2024年第2期12卷 453-468页

作者： Lei Xiong hao-Han Guo Jin-Xiu Pan Xiao ren Daehoon Lee Li Chen Lin Mei Wen-Cheng Xiong Department of Neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Louis Stoke VA Medical Center ClevelandOH 44106USA

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and *** how Wnt/β-catenin signaling is regulated in OBs remain ***6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling ***,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone *** we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone *** knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone *** and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not *** cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

关键词： LRP6 impaired organs

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Typhoon-Induced Ocean Waves and Stokes Drift:A Case Study of Typhoon Mangkhut(2018)

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China Ocean Engineering 2024年第4期38卷 711-724页

作者： WU Zhi-yuan GAO Kai CHEN Jie ZHANG hao-jian DENG Bin JIANG Chang-bo LIU Yi-zhuang LYU Zhao YAN ren School of Hydraulic and Environmental Engineering Changsha University of Science&TechnologyChangsha 410114China Key Laboratory of Water-Sediment Sciences and Water Disaster Prevention of Hunan Province Changsha 410114China State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering Hohai UniversityNanjing 210024China State Key Laboratory of Coastal and Offshore Engineering Dalian University of TechnologyDalian 116024China School of Civil Engineering Hunan University of TechnologyZhuzhou 412007China

Ocean waves and Stokes drift are generated by *** study investigated the characteristics of ocean waves and wave-induced Stokes drift and their effects during Typhoon Mangkhut using European Centre for MediumRange Weather Forecasts(ECMWF)ERA5 datasets and observational *** results revealed that the typhoon generated intense cyclones and huge typhoon waves with a maximum wind speed of 45 m/s,a minimum pressure of955 h Pa,and a maximum significant wave height of 12 *** Stokes drift caused by typhoon waves exceeded 0.6m/s,the Stokes depth scale exceeded 18 m,and the maximum Stokes transport reached 6 m^(2)/*** spatial distribution of 10-m wind speed,typhoon wave height,Stokes drift,Stokes depth,and Stokes transport during the typhoon was highly correlated with the typhoon *** distribution along the typhoon track showed significant zonal asymmetry,with greater intensity on the right side of the typhoon track than on the left *** findings provide important insights into the impact of typhoons on ocean waves and Stokes drift,thus improving our understanding of the interactions between typhoons and the ocean *** study also investigated the contribution of Stokes transport to the total net transport during typhoons using Ekman-Stokes Numbers as a comparative *** results indicated that the ratio of Stokes transport to the total net transport reached up to 50%within the typhoon radius,while it was approximately 30%outside the *** Stokes transport induced by typhoon waves led to divergence in the transport direction,which resulted in upwelling of the lower ocean as a compensation ***,Stokes transport played a crucial role in the vertical mixing of the ocean during *** findings suggested that Stokes transport should be paid more attention to,particularly in high latitude ocean regions,where strong winds can amplify its effects.

关键词： Stokes drift typhoon waves Ekman-Stokes transport vertical mixing Typhoon Mangkhut

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Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2610-2630页

作者： Ze-hao Yu Lei-Ming Zhang Zhi-qi Dai Meng-Na Zhang Si-Ming Zheng Health Science Center The First Affiliated Hospital of Ningbo UniversityNingbo 315000Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina College of Medicine The First Affiliated Hospital of Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic *** To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after *** The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint *** clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival *** Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic *** The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after *** recent years,there has been a similarly optimistic trend in GSRC mortality *** trend in GSRC showed discrepancies based on age and *** operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this *** area under the curve indicated that the performance of the new model outperformed that of the pathological staging *** The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

关键词： Signet ring cell carcinoma Locally advanced gastric cancer Adjuvant chemotherapy Nomogram Epidemiology Overall survival

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