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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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Exploring the material basis and mechanism of Moringa oleifera in alleviating slow transit constipation based on network pharmacology and animal models

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Food Science and Human Wellness 2024年

作者： Sijin Li Xiaoyu Gao Kaifeng Guo Shuangfeng Liu Weiqian Yang Yan Zhao Jun Sheng Zhongbin Bai Yang Tian College of Food Science and Technology， Yunnan Agricultural University Yunnan Key Laboratory of Precision Nutrition and Personalized Food Manufacturing， Yunnan Agricultural University department of Science and Technology， Yunnan Agricultural University College of veterinary Medicine， Yunnan Agricultural University Engineering research Center of development and Utilization of Food and Drug Homologous Resources， Ministry of Education， Yunnan Agricultural University

Moringa oleifera(M. oleifera) have laxative effects， but their active compositions and mechanisms are not very clear thus far. To this end， we systematically explored the active components and mechanism of M. oleifera leaves in relieving constipation by using the slow transit constipation (STC) mouse model and network pharmacology. The results of animal experiments showed that M. oleifera aqueous extract (MOA) had good laxative activity， and its 70% alcohol soluble part (ASP) also showed significant laxative activity(P < 0.01). Network pharmacological prediction results suggested that L-phenylalanine (Phe) was the key compound of ASP， and it might relieve constipation through tachykinin receptor 1 (TACR1) and three kinds of adrenergic receptors， including alpha-1a (ADRA1A)， alpha-2a (ADRA2A)， and alpha-2b (ADRA2B). Further animal experiment results showed that Phe significantly promoted gastrointestinal motility. Phe may relieve STC by enhancing the release of substance P (SP) and upregulating the mRNA expression of TACR1 in the ileum. Importantly， Phe may also promote intestinal movement by downregulating ADRA2A and ADRA2B and upregulating calmodulin and the mRNA and protein expression of myosin light chain 9 (MYL9) in the ileum， thereby activating the GPCR-MLC signaling pathway. These results lay a foundation for the application of M. oleifera and Phe in constipation.

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KSKV:Key-Strategy for Key-Value Data Collection with Local Differential Privacy

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 3063-3083页

作者： Dan Zhao Yang You Chuanwen Luo Ting Chen Yang Liu Artificial Intelligence development research Center Institute of Scientific and Technical Information of ChinaBeijing100038China Industry development department NSFOCUS Inc.BeijingChina School of Information Science and Technology Beijing Forestry UniversityBeijing100083China School of Computer Science and Engineering University of Electronic Science and Technology of ChinaChengdu610054China Institute of Computing Technology China Academy of Railway Sciences Corporation LimitedBeijing10081China

In recent years,the research field of data collection under local differential privacy(LDP)has expanded its focus fromelementary data types to includemore complex structural data,such as set-value and graph ***,our comprehensive review of existing literature reveals that there needs to be more studies that engage with key-value data *** studies would simultaneously collect the frequencies of keys and the mean of values associated with each ***,the allocation of the privacy budget between the frequencies of keys and the means of values for each key does not yield an optimal utility *** the importance of obtaining accurate key frequencies and mean estimations for key-value data collection,this paper presents a novel framework:the Key-Strategy Framework forKey-ValueDataCollection under ***,theKey-StrategyUnary Encoding(KS-UE)strategy is proposed within non-interactive frameworks for the purpose of privacy budget allocation to achieve precise key frequencies;subsequently,the Key-Strategy Generalized Randomized Response(KS-GRR)strategy is introduced for interactive frameworks to enhance the efficiency of collecting frequent keys through group-anditeration *** strategies are adapted for scenarios in which users possess either a single or multiple key-value ***,we demonstrate that the variance of KS-UE is lower than that of existing *** claims are substantiated through extensive experimental evaluation on real-world datasets,confirming the effectiveness and efficiency of the KS-UE and KS-GRR strategies.

关键词： Key-value local differential privacy frequency estimation mean estimation data perturbation

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Satellite Communications with 5G, B5G, and 6G: Challenges and Prospects

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International Journal of Communications, Network and System Sciences 2024年第3期17卷 31-49页

作者： Mehmet Beyaz research & development department TTG International Ltd. Istanbul T&#252rkiye

Satellite communications, pivotal for global connectivity, are increasingly converging with cutting-edge mobile networks, notably 5G, B5G, and 6G. This amalgamation heralds the promise of universal, high-velocity communication, yet it is not without its challenges. Paramount concerns encompass spectrum allocation, the harmonization of network architectures, and inherent latency issues in satellite transmissions. Potential mitigations, such as dynamic spectrum sharing and the deployment of edge computing, are explored as viable solutions. Looking ahead, the advent of quantum communications within satellite frameworks and the integration of AI spotlight promising research trajectories. These advancements aim to foster a seamless and synergistic coexistence between satellite communications and next-gen mobile networks.

关键词： Satellite Communications Spectrum Allocation Edge Computing AI Integration 5G B5G 6G

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A noval iron-capturing nanocomposites against biofilms for disrupting bacterial nutritional balance

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Science China Chemistry 2024年第6期67卷 1760-1761页

作者： Jinying Lin Qihang Ding Yao Sun department of Oral Implantology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool of StomatologyJilin UniversityChangchun130021China department of Chemistry Korea UniversitySeoul02841Korea National Key Laboratory of Green Pesticide International Joint Research Center for Intelligent Biosensor Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhan430079China

Currently,the escalating crisis of bacterial infections and antibiotic resistance poses a significant global public health challenge[1-3].This situation has driven the search for novel antimicrobial ***,a crucial micr... 详细信息

关键词： metabolism resistance balance

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Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

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BIOCELL 2024年第6期48卷 923-934页

作者： BINGJIE LI WENBO CAO JINJING XIAO YIXIAO CHEN QIYING WEI MINGJIN YUE SAIJUN MO department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina Collaborative Innovation Center of Henan Province for Cancer Chemoprevention ZhengzhouChina State Key Laboratory of Esophageal Cancer Prevention and Treatment ZhengzhouChina department of research and development Henan Tianxing Education and Media Company LimitedZhengzhouChina

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,inﬁltrating distant regions devoid of lymphatic or vascular *** often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of *** its clinical signiﬁcance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of speciﬁc and efﬁcacious diagnostic and therapeutic *** the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-speciﬁc expression proﬁles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and *** the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as inﬂuential players in *** involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic *** study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in *** comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

关键词： Perineural invasion Non-coding RNA Diagnose and treatment Cancer Biomarker

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Self-powered UVC detectors based on α-Ga_(2)O_(3) with enchanted speed performance

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Journal of Semiconductors 2024年第8期45卷 74-80页

作者： Aleksei Almaev Alexander Tsymbalov Bogdan Kushnarev Vladimir Nikolaev Alexei Pechnikov Mikhail Scheglov Andrei Chikiryaka Laboratory of Metal Oxide Semiconductors Research and Development Center for Advanced Technologies in MicroelectronicsNational Research Tomsk State UniversityTomsk 634050Russia Fokon LLC Kaluga 248035Russia department of Semiconductor Electronics and Physics of Semiconductors National University of Science and Technology MISISMoscow 119049Russia Perfect Crystals LLC Saint Petersburg 194223Russia

Detectors were developed for detecting irradiation in the short-wavelength ultraviolet(UVC)interval using high-quality single-crystallineα-Ga_(2)O_(3) films with Pt interdigital *** films ofα-Ga_(2)O_(3) were grown on planar sapphire substrates with c-plane orientation using halide vapor phase *** spectral dependencies of the photo to dark current ratio,responsivity,external quantum efficiency and detectivity of the structures were investigated in the wavelength interval of 200−370 *** maximum of photo to dark current ratio,responsivity,external quantum efficiency,and detectivity of the structures were 1.16×10^(4) ***.,30.6 A/W,1.65×10^(4)%,and 6.95×10^(15) Hz^(0.5)·cm/W at a wavelength of 230 nm and an applied voltage of 1 *** high values of photoelectric properties were due to the internal enhancement of the photoresponse associated with strong hole ***α-Ga_(2)O_(3) film-based UVC detectors can function in self-powered operation mode due to the built-in electric field at the Pt/α-Ga_(2)O_(3) *** a wavelength of 254 nm and zero applied voltage,the structures exhibit a responsivity of 0.13 mA/W and an external quantum efficiency of 6.2×10^(−2)%.The UVC detectors based on theα-Ga_(2)O_(3) films demonstrate high-speed performance with a rise time of 18 ms in self-powered mode.

关键词： HVPE gallium oxide solar-blind ultraviolet detector self-powered mode

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A seismic elastic moduli module for the measurements of low-frequency wave dispersion and attenuation of fluid-saturated rocks under different pressures

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Petroleum Science 2024年第1期21卷 162-181页

作者： Yan-Xiao He Shang-Xu Wang Gen-Yang Tang Chao Sun Hong-Bing Li San-Yi Yuan Xian Wei Li-Deng Gan Xiao-Feng Dai Qiang Ge Peng-Peng Wei Hui-Qing Zhang National Key Laboratory of Petroleum Resources and Engineering CNPC Key Lab of Geophysical ExplorationCollege of GeophysicsChina University of Petroleum(Beijing)Beijing102249China School of Resources and Geosciences China University of Mining and TechnologyXuzhou221116JiangsuChina research Institute of Petroleum Exploration and development CNPCBeijing100083China Beijing Vocational College of Labour and Social Security Beijing100029China PetroChina Dagang Oilfield Exploration and development research Institute CNPCTianjin300280China

Knowledge about the seismic elastic modulus dispersion,and associated attenuation,in fluid-saturated rocks is essential for better interpretation of seismic observations taken as part of hydrocarbon identification and time-lapse seismic surveillance of both conventional and unconventional reservoir and overburden performances.A Seismic Elastic Moduli Module has been developed,based on the forced-oscillations method,to experimentally investigate the frequency dependence of Young's modulus and Poisson's ratio,as well as the inferred attenuation,of cylindrical samples under different confining pressure *** with three standard samples showed that the measured elastic moduli were consistent with the published data,indicating that the new apparatus can operate reliably over a wide frequency range of f∈[1-2000,10^(6)]*** Young's modulus and Poisson's ratio of the shale and the tight sandstone samples were measured under axial stress oscillations to assess the frequency-and pressure-dependent *** dry condition,both samples appear to be nearly frequency independent,with weak pressure dependence for the shale and significant pressure dependence for the *** particular,it was found that the tight sandstone with complex pore microstructure exhibited apparent dispersion and attenuation under brine or glycerin saturation conditions,the levels of which were strongly influenced by the increased effective *** addition,the measured Young's moduli results were compared with the theoretical predictions from a scaled poroelastic model with a reasonably good agreement,revealing that the combined fluid flow mechanisms at both mesoscopic and microscopic scales possibly responsible for the measured dispersion.

关键词： Low-frequency measurements Dispersion and attenuation Rock physics Fluid flow

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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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Comparative study between three carbonaceous nanoblades and nanodarts for antimicrobial applications

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Journal of Environmental Sciences 2024年第2期136卷 594-605页

作者： Mohamed S.Selim Ahmed M.Azzam Mohamed A.Shenashen Shimaa A.Higazy Bayaumy B.Mostafa Sherif A.El-Safty National Institute for Materials Science(NIMS) 1-2-1 SengenTsukuba-ShiIbaraki-Ken 305-0047Japan Petroleum Application department Egyptian Petroleum Research InstituteNasr City 11727Egypt department of Environmental research Theodor Bilharz Research InstituteGizaEgypt

The design of nanostructured materials occupies a privileged position in the development and management of affordable and effective technology in the antibacterial ***,we discuss the antimicrobial properties of three carbonaceous nanoblades and nanodarts materials of graphene oxide(GO),reduced graphene oxide(RGO),and single-wall carbon nanotubes(SWCNTs)that have a mechano-bactericidal effect,and the ability to piercing or slicing bacterial *** demonstrate the significance of size,morphology and composition on the antibacterial activity mechanism,the designed nanomaterials have been *** minimum inhibitory concentration(MIC),standard agar well diffusion,and transmission electron microscopy were utilized to evaluate the antibacterial activity of GO,RGO,and *** on the evidence obtained,the three carbonaceous materials exhibit activity against all microbial strains tested by completely encapsulating bacterial cells and causing morphological disruption by degrading the microbial cell membrane in the order of RGO>GO>*** of the external cell wall structure and outer membrane proteins,the synthesized carbonaceous nanomaterials exhibited higher antibacterial activity against Gram-positive bacterial strains than Gram-negative and fungal *** had the lowest MIC values(0.062,0.125,and 0.25 mg/mL against ***,***,and ***,respectively),as well as minimum fungal concentrations(0.5 mg/mL for both *** and ***).At 12 hr,the cell viability values against tested microbial strains were completely *** lysis and death occurred as a result of severe membrane damage caused by microorganisms perched on RGO *** work gives an insight into the design of effective graphene-based antimicrobial materials for water treatment and remediation.

关键词： Antimicrobial properties Nanoblades Mechano-bactericidal effect RGO nanosheets Gram-positive bacteria Cell viability

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