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Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1742-1758页

作者： Renming Fan Ruizhuo Lin Shuo Zhang Aohua Deng Yongrui Hai Junyan Zhuang Yang Liu Maosheng Cheng Gaofei Wei Institute of Medical research Northwestern Polytechnical UniversityXi'an 710072China research&development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationSchool of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

关键词： Anti-tumor drug Prodrug Platinum Chemo-immunotherapy Mitochondrial membrane modeling STING Pyroptosis mtDNA

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Optical responses of metallic plasmonic arrays under the localized excitation

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Nano research 2024年第3期17卷 1571-1577页

作者： Sen Yan Hao Ma Yi-Fan Bao Maofeng Cao Chuan Liu Kaifeng Zhang Xiaowei Wu Jianbo He Xiang Wang Bin Ren State Key Laboratory of Physical Chemistry of Solid Surfaces Department of ChemistryCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005China research&development Group HitachiLtd.Yokohama 244-0817KanagawaJapan department of Electronic Science and Engineering Kyoto UniversityKyoto 615-8510Japan

The metallic plasmonic array that can support both propagating surface plasmon polaritons(PSPPs)and localized surface plasmon resonance(LSPR)possesses rich optical properties and remarkable optical performance,making it a powerful platform for applications in photonics,chemistry,and materials.For practical applications,the excitation spot is usually smaller than the area of metal arrays.It is thus imperative to address“how many array units are enough?”towards a rational design of plasmonic nanostructures.Herein,we employed focused ion beam(FIB)to precisely fabricate a series of plasmonic array structures with increased unit number.By utilizing photoluminescence(PL)and surface-enhanced Raman spectroscopy(SERS),we found that the array units outside the excitation spot still have a significant impact on the optical response within the spot.Combined with the numerical simulation,we found that the boundary of the finite array leads to the loss of PSPP outside the excitation point,which subsequently affects the coupling of PSPP and LSPR in the excitation spot,leading to variations in PL and SERS intensity.Based on the findings,we further tuned the LSPR mode of the metal arrays by electrodeposition to obtain strong near-field enhancement without any influence on the PSPP mode.This work advances the understanding of near-field and far-field optical behavior in finite-size array structures and provides guidance for designing highly-efficient photonic devices.

关键词： plasmonic periodic array finite-size effects dark field scattering surface-enhanced Raman spectroscopy(SERS)

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New frontiers in ectopic pancreatic tissue management

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1215-1217页

作者： Serghei Covantsev department of Clinical research and development Botkin HospitalMoscow 125284Russia

The pancreatic development variations are relatively frequent but are often overlooked in clinical practice.This is due to the fact that they do not present with a distinct clinical picture and are usually asymptomatic.It also refers to the ectopic pancreatic tissue in the stomach.This anomaly can be diagnosed in any part of the digestive system,but it is mostly seen in the upper gastrointestinal tract,especially in the stomach,duodenum and jejunum.The management of this condition has evolved due to the development of minimally invasive procedures.

关键词： Ectopic pancreatic tissue Stomach Endoscopy Laparoscopy Pancreas Anomalies

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Comprehensive evaluations of heat transfer performance with conjugate heat dissipation effect in high-speed rotating free-disk modeling of aero-engines

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Fundamental research 2024年第3期4卷 611-623页

作者： Aqiang Lin Gaowen Liu Ran Chang Yan Chen Qing Feng School of Power and Energy Northwestern Polytechnical UniversityXi'an 710129China Shaanxi Key Laboratory of Thermal Science in Aero-engine System Northwestern Polytechnical UniversityXi'an 710072China research&development Institute of Northwester

Thermal boundary conditions of the turbine disk cavity system are of great importance in the design of secondary air systems in aero-engines.This study aims to investigate the complex heat transfer mechanisms of a rotating turbine disk under high-speed conditions.A high-speed rotating free-disk model with Dorfman empirical solutions is developed to evaluate the heat transfer performance considering various factors.Specifically,the influence of compressibility,variable properties,and heat dissipation is determined using theoretical and numerical analyses.In particular,a novel combined solution method is proposed to simplify the complex heat transfer problem.The results indicate that the heat transfer performance of a free disk is primarily influenced by the rotating Mach number,rotating Reynolds number,Rossby number,and wall temperature ratio.The heat transfer temperature and Nusselt number of the free disk are strongly correlated with the rotating Mach number and rotating Reynolds number.Analysis reveals that heat dissipation is a critical factor affecting the accurate evaluation of the heat transfer performance of the turbine disk.Thus,the combined solution method can serve as a reference for future investigations of flow and heat transfer in high-speed rotating turbine disk cavity systems in aero-engines.

关键词： Aero-engine Rotating turbine disk Dimensional analysis Compressibility Heat dissipation Dorfman empirical solution

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Data-Driven Design for Targeted Regulation of Heat Transfer in Carbon/Carbon Composite Structure

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Journal of Thermal Science 2024年第2期33卷 648-657页

作者： XIAO Heye WANG Zelin WANG Hui JI Ritian Unmanned System research Institute Northwestern Polytechnical UniversityXi’an710072China School of Aeronautics Northwestern Polytechnical UniversityXi’an710072China research&development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen518063China MOE Key Laboratory of Thermo-Fluid Science and Engineering School of Energy and Power EngineeringXi’an Jiaotong UniversityXi’an710049China

Targeted regulation of heat transfer in carbon/carbon composite structure is built for cooling electronic device.A three-dimensional data-driven design model coupling genetic algorithm(GA) with self-adaption deep learning for targeted regulation of heat transfer in built structure is proposed.The self-adaption deep learning model predicts the temperature of built structure closer to optimal value in GA model.The distributions of pore and carbon fiber bundles in built structure are optimized by the proposed model.The surface temperature of electronic device in the optimized structures is 19.1%-27.5% lower than that in the initial configurations when the porosity of built structure varies from 3% to 11%.The surface temperature of electronic device increases with an increase in porosity.The built structure with carbon fiber bundles near the surface of electronic device and pore distribution in the middle of structure has a higher heat dissipation capacity compared with that in the initial configuration.Besides,the computation time of the proposed model is less than one tenth compared with that of the traditional genetic algorithm.

关键词： targeted regulation of heat transfer self-adaption deep learning genetic algorithm carbon/carbon composite structure

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To improve robustness of mechanical properties of semi-solid cast A356 alloy using taguchi design method

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China Foundry 2024年第2期21卷 175-184页

作者： Yi-wu Xu Hong-yi Zhan Wei Tong Jin-ping Li Le-peng Zhang De-jiang Li Xiao-qin Zeng School of Materials Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240China China Science Lab General Motors Global Research&DevelopmentShanghai 201206China General Motors(China)Investment Co. Ltd.Shanghai 201206China China International Intellectech Corporation(CIIC) Beijing 100004China

Mechanical properties of semi-solid casting are dependent on multiple processing parameters,and improper processing parameters will not only reduce mean data but also increase variations.The present study investigated the impact of parameters in slurry preparation and heat treatment on the yield strength and ductility of T6 heat-treated A356 Al-Si alloy using rapid slurry forming(RSF)semi-solid casting.The focus was primarily on the robustness of mechanical properties based on Taguchi design method.By analyzing signal-to-noise ratio and minimum value calculated from-3S,the optimum slurry preparation parameters and heat treatment parameters were determined to be no quench,enthalpy exchange material(EEM)temperature of 140℃,EEM-to-melt ratio of 6mass%,stirring time of 18 s,solution heat treated at 520℃ for 2 h,and ageing heat treated at 190℃ for 6 h.In a small batch validation,the-3S yield strength and-3S elongation reach 256.1 MPa and 5.03% respectively,showing a satisfactory robustness.The hardness and microstructure of heat-treated samples with the best and worst properties were characterized to gain insight into the underlying mechanisms affecting the mean value and variations of mechanical properties.

关键词： semi-solid casting taguchi design method signal-to-noise ratio mechanical property microstructure

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Multi‑omics integration identifies regulatory factors underlying bovine subclinical mastitis

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Journal of Animal Science and Biotechnology 2024年第3期15卷 987-1007页

作者： Mengqi Wang Naisu Yang Mario Laterriere David Gagne Faith Omonijo Eveline M.Ibeagha‑Awemu Agriculture and Agri‑Food Canada Sherbrooke Research and Development CentreSherbrookeQCCanada department of Animal Science Universite LavalQuebec CityQCCanada Quebec research and development Centre Agriculture and Agri-Food CanadaQuebec CityQCCanada

Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry.Multi-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease pathogenesis.Therefore,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes.Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis.The abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dMHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEMs),respectively.Next,5 factors presenting the principal variation of differential multi-omics signatures were identified.The important roles of Factor 1(DEG,DEM and DEL)and Factor 2(dMHB and DEM),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed.Each of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical mastitis.Also,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastiti

关键词： Candidate discriminant multi-omics signature Gene Long non-coding RNA Methylation haplotype block MicroRNA Multi-omics integration Natural killer cell mediated cytotoxicity pathway Staphylococcus aureus infection pathway

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Does young feces make the elderly live better? Application of fecal microbiota transplantation in healthy aging

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BIOCELL 2024年第6期48卷 873-887页

作者： YUANYUAN LIAO XINSI LI QIAN LI YIZHONG WANG XIUJUN TAN TING GONG department of Endodontics Stomatological Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences ChongqingChina Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education ChongqingChina department of research&development Zhejiang Charioteer Pharmaceutical Co.Ltd.TaizhouChina department of Implantology Stomatological Hospital of Chongqing Medical UniversityChongqingChina

As we are facing an aging society,anti-aging strategies have been pursued to reduce the negative impacts of aging and increase the health span of human beings.Gut microbiota has become a key factor in the anti-aging process.Modulation of gut microbiota by fecal microbiota transplantation(FMT)to prevent frailty and unhealthy aging has been a hot topic of research.This narrative review summarizes the beneﬁts of FMT for health span and lifespan,brains,eyes,productive systems,bones,and others.The mechanisms of FMT in improving healthy aging are discussed.The increased beneﬁcial bacteria and decreased pathological bacteria decreased gut permeability and systemic inﬂammation,increased short-chain fatty acid(SCFA)and SCFA-producing bacteria,and other factors are listed as mechanisms of FMT to improve healthy aging.The points that need to be considered to ensure the optimal outcomes of FMT are also discussed,such as recipients’age,sex,genetic background,and gut microbiota after FMT.Although thisﬁeld is still in its infancy,it has shown that FMT has great potential to improve healthy aging.

关键词： Gut microbiota Healthy aging Lifespan Fecal microbiota transplantation Co-housing Short-chain fatty acid Inﬂammaging

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Photocatalytic application of magnesium spinel ferrite in wastewater remediation:A review

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Journal of Magnesium and Alloys 2024年第2期12卷 490-505页

作者： Rohit Jasrotia Nikhil Jaswal Jyoti Prakash Chan Choon Kit Jagpreet Singh Abhishek Kandwal School of Physics and Materials Science Shoolini UniversityBajholSolanH.P.India Himalayan Centre of Excellence in Nanotechnology Shoolini UniversityBajholH.P.India INTI International University Putra NilaiNegeri SembilanMalaysia department of Chemistry University Centre for Research&Development Chandigarh UniversityMohali140413PunjabIndia Shenzhen Institute of Advanced Technology Chinese Academy of SciencesChina

This review paper explores the efficacy of magnesium ferrite-based catalysts in photocatalytic degradation of organic contaminates(antibiotic and dyes).We report the influence of different doping strategies,synthesis methods,and composite materials on the degradation efficiency of these pollutants.Our analysis reveals the versatile and promising nature of magnesium ferrite-based catalysts,offering the valuable insights into their practical application for restoring the environment.Due to the smaller band gap and magnetic nature of magnesium ferrite,it holds the benefit of utilising the broader spectrum of light while also being recoverable.The in-depth analysis of magnesium ferrites'photocatalytic mechanism could lead to the development of cheap and reliable photocatalyst for the wastewater treatment.This concise review offers a thorough summary of the key advancements in this field,highlighting the pivotal role of the magnesium ferrite based photocatalysts in addressing the pressing global issue of organic pollutants in wastewater.

关键词： Magnesium ferrite Wastewater Dyes Antibiotics Photocatalytic degradation

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A perspective review on the biosynthesis of plant-based secondary metabolites and their application as potent drugs

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BIOCELL 2024年第4期48卷 541-557页

作者： JHILAM PRAMANIK AKASH KUMAR SARVESH RUSTAGI MEHAK KATYAL SHEETAL THAKUR JUTISHNA BORA SUMIRA MALIK ANCHAL TREHAN NAYAN TALUKDAR PETR SLAMA department of Food Technology ITM UniversityGwaliorIndia department of Food Technology SRM UniversitySonipatIndia department of Food Technology Uttaranchal UniversityDehradunIndia department of Nutrition and Dietetics Manav Rachna International Institute of Research&Studies(MRIIRS)FaridabadIndia University Centre for research and development UIBTChandigarh UniversityMohaliIndia Amity institute of Biotechnology Amity UniversityJharkhandRanchiIndia department of Biotechnology University Center for Research&Development(UCRD)Chandigarh UniversityMohaliPunjabIndia department of Science Guru Nanak College of Pharmaceutical SciencesDehradunIndia Program of Biotechnology Faculty of ScienceAssam down town UniversityGuwahatiIndia department of Animal Morphology Physiology and GeneticsMendel University in BrnoBrnoCzech Republic

Many phytochemicals and their derived metabolites produced by plants are extensively employed in commercial goods,pharmaceutical products as well as in the environmental and medicalﬁelds.However,these secondary metabolites obtained from plants are in low amounts,and it is difﬁcult to synthesize them at the industrial level.Despite these challenges,they may be utilized for a variety of medicinal products that are either available in the market or are being researched and tested.Secondary metabolites are complex compounds that exhibit chirality.Further,under controlled conditions with elicitors,desired secondary metabolites may be produced from plant cell cultures.This review emphasizes the various aspects of secondary metabolites including their types,synthesis,and applications as medicinal products.The article aims to promote the use of plant secondary metabolites in the management and treatment of various diseases.

关键词： Secondary metabolites Medicinal plant Synthesis Health benefits

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