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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA centre for Experimental Medicine and rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom centre for Experimental Medicine&rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR activation.Mechanistically,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling.In Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative phosphorylation.Conversely,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity.The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression.We found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA explants.Similar to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient animals.Consistently,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by Syntenin-1.In conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Unveiling protein corona composition:predicting with resampling embedding and machine learning

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Regenerative Biomaterials 2024年第1期3卷 27-33页

作者： Rong Liao Yan Zhuang Xiangfeng Li Ke Chen Xingming Wang Cong Feng Guangfu Yin Xiangdong Zhu Jiangli Lin Xingdong Zhang College of Biomedical Engineering National Engineering Research Centre for BiomaterialsSichuan UniversityChengdu610065China

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration.When nanoparticles(NPs)enter the living system,they quickly interact with proteins in the body fluid,forming the protein corona(PC).The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs.However,achieving accurate predictions remains a significant challenge.Although several machine learning(ML)models like Random Forest(RF)have been used for PC prediction,they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution.In this study,resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data.Various ML models were evaluated,and RF model was finally used for prediction,and good correlation coefficient(R^(2))and root-mean-square deviation(RMSE)values were obtained.Our ablation experiments demonstrated that the proposed method achieved an R^(2) of 0.68,indicating an improvement of approximately 10%,and an RMSE of 0.90,representing a reduction of approximately 10%.Furthermore,through the verification of label-free quantification of four NPs:hydroxyapatite(HA),titanium dioxide(TiO_(2)),silicon dioxide(SiO_(2))and silver(Ag),and we achieved a prediction performance with an R^(2) value>0.70 using Random Oversampling.Additionally,the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration,PDI and surface modification.

关键词： nanoparticles protein corona machine learming resampling technique feature analysis

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Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1077-1097页

作者： Lindokuhle Cindy Nene Heidi Abrahamse Laser research centre Faculty of Health SciencesUniversity of JohannesburgDoornfontein 2028South Africa

Cancer remains one of the diseases with the highest incidence and mortality globally.Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development of resistance for some,including chemotherapy,radiation,and surgery.Sono-photodynamic combinatorial therapy(SPDT)has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic approach.SPDT combines the mechanism of action of sonodynamic therapy(SDT),which uses ultrasound,and photodynamic therapy(PDT),which uses light,to activate a sensitizer and initiate cancer eradication.The use of phthalocyanines(Pcs)as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and PDT.This review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.

关键词： Sonodynamic therapy Photodynamic therapy Combinatorial therapy Phthalocyanines Sensitizer Cancer

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Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor Carlos Spuch José Antonio Lamas Lucas C.González-Matías Federico Mallo Biomedical research centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical research centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migrai

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

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Evaluation of soil loss severity and ecological restoration approach for sustainable agriculture in the Hindu Kush, Karakoram and Himalaya region

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Journal of Mountain Science 2024年第5期21卷 1509-1521页

作者： Arshad ASHRAF Imran AHMAD Climate Energy and Water Research InstituteNational Agricultural Research Centre(NARC)Islamabad 44000Pakistan

Soil erosion has resulted in removal of the topsoils containing fine soil particles and plant nutrients, causing decrease in soil fertility in the Hindu Kush, Karakoram and Himalaya(HKH) region. The existing production of cereal crop grains has been reduced to one third of the potential crop grains production owing to land degradation and poor farming practices. It is necessary to assess risk of soil loss and identify appropriate controlling measures to address issues of low agriculture productivity and water insecurity in the region. In the present study, severity of soil loss was predicted using Revised Universal Loss Equation(RUSLE) and ecological measures were identified for sustainable mountain agriculture in the HKH region of Upper Indus Basin, Pakistan. Overall 62.6% area was found to have very low risk of soil loss, i.e., 100 t/(ha·yr) in about 6.8% and 7.4% areas respectively. The mean rate of soil loss was about 41.9 t/(ha·yr) in the Hindu Kush, 31.1 t/(ha·yr) in the Himalayas, 18.8 t/(ha·yr) in the Karakoram and overall 29.7 t/(ha·yr) in the three HKH ranges. As such no considerable measures have been adopted by the communities for restoration of the degraded areas except raising fruit/farm trees and supporting limited social forestry for their livelihoods. The slopes cleared for cultivation and susceptible to erosion may be stabilized through sowing/planting of multi-purpose plant species and formation of proper bench terraces. The conservation of forest ecosystem and pastures at higher elevations would help in reducing overland water flow, risk of flash flood hazard and minimizing sediment loads in the downstream. It is essential to adopt site-specific resource conservation techniques and restore possible ecosystem health for sustainable agriculture and economic development in the region in future.

关键词： Climate change Erodibility Indus basin Land degradation Slope stabilization

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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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Study of plasma parameters of coaxial plasma source using triple Langmuir probe and Faraday cup diagnostics

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Plasma Science and Technology 2024年第4期26卷 94-100页

作者： Sunil KANCHI Rohit SHUKLA Archana SHARMA Pulsed Power and Electromagnetics Division Bhabha Atomic Research CentreVisakhapatnam 531011India Homi Bhabha National Institute Mumbai 400085India Beam Technology Development Group Bhabha Atomic Research CentreMumbai 400085India

Coaxial plasma guns are a type of plasma source that produces plasma which propagates radially and axially controlled by the shape of the ground electrode, which has attracted much interest in several applications. In this work, a 120° opening angle of CPG nozzle is used as a plasma gun configuration that operates at the energy of 150 J. The ionization of polyethylene insulator between the electrodes of the gun produces a cloud of hydrogen and carbon plasma.The triple Langmuir probe and Faraday cup are used to measure plasma density and plasma temperature. These methods are used to measure the on-axis and off-axis plasma divergence of the coaxial plasma gun. The peak values of ion densities measured at a distance of 25 mm on-axis from the plasma gun are(1.6±0.5)×10^(19)m^(-3)and(2.8±0.6)×10^(19)m^(-3)for hydrogen and carbon plasma respectively and the peak temperature is 3.02±0.5 eV. The mean propagation velocity of plasma is calculated using the transit times of plasma at different distances from the plasma gun and is found to be 4.54±0.25 cm/μs and 1.81±0.18 cm/μs for hydrogen and carbon plasma respectively. The Debye radius is obtained from the measured experimental data that satisfies the thin sheath approximation. The shot-to-shot stability of plasma parameters facilitates the use of plasma guns in laboratory experiments. These types of plasma sources can be used in many applications like plasma opening switches, plasma devices, and as plasma sources.

关键词： coaxial plasma source triple Langmuir probe Faraday cup plasma density plasma temperature

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Projecting Spring Consecutive Rainfall Events in the Three Gorges Reservoir Based on Triple-Nested Dynamical Downscaling

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Advances in Atmospheric Sciences 2024年第8期41卷 1539-1558页

作者： Yanxin ZHENG Shuanglin LI Noel KEENLYSIDE Shengping HE Lingling SUO Department of Atmospheric Science CMA-CUG Joint Centre for Severe Weather and Climate and Hydro-geological Hazards China University of Geosciences Geophysical Institute University of Bergen and Bjerknes Centre for Climate Research Institute of Atmospheric Physics and Climate Change research Center Chinese Academy of Sciences Three Gorges National Climatological Observatory Nansen Environmental and Remote Sensing Center and Bjerknes centre for Climate research Nansen-Zhu International research centre Institute of Atmospheric PhysicsChinese Academy of Sciences

Spring consecutive rainfall events(CREs) are key triggers of geological hazards in the Three Gorges Reservoir area(TGR), China. However, previous projections of CREs based on the direct outputs of global climate models(GCMs) are subject to considerable uncertainties, largely caused by their coarse resolution. This study applies a triple-nested WRF(Weather research and Forecasting) model dynamical downscaling, driven by a GCM, MIROC6(Model for Interdisciplinary research on Climate, version 6), to improve the historical simulation and reduce the uncertainties in the future projection of CREs in the TGR. Results indicate that WRF has better performances in reproducing the observed rainfall in terms of the daily probability distribution, monthly evolution and duration of rainfall events, demonstrating the ability of WRF in simulating CREs. Thus, the triple-nested WRF is applied to project the future changes of CREs under the middle-of-the-road and fossil-fueled development scenarios. It is indicated that light and moderate rainfall and the duration of continuous rainfall spells will decrease in the TGR, leading to a decrease in the frequency of CREs. Meanwhile, the duration, rainfall amount, and intensity of CREs is projected to regional increase in the central-west TGR. These results are inconsistent with the raw projection of MIROC6. Observational diagnosis implies that CREs are mainly contributed by the vertical moisture advection. Such a synoptic contribution is captured well by WRF, which is not the case in MIROC6,indicating larger uncertainties in the CREs projected by MIROC6.

关键词： consecutive rainfall events geological hazards projection Three Gorges Reservoir area triple-nested downscaling

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Wood By-Products as UV Protection:A Consequence Review

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Journal of Renewable Materials 2024年第4期12卷 699-720页

作者： Naglaa Salem El‑Sayed Mohamed Hasanin Samir Kamel Cellulose and Paper Department National Research CentreCairo12622Egypt

In recent decades,the ozone layer has suffered considerable damage,increasing the entry of ultraviolet(UV)light into the atmosphere and reaching the earth’s surface,negatively affecting life.Accordingly,researchers aimed to solve this problem by synthesizing advanced UV-shielding materials.On the other hand,developing an easy and green strategy to prepare functional materials with outstanding properties based on naturally abundant and environmentally friendly raw materials is highly desirable for sustainable development.Because biomass-derived materials are sustainable and biodegradable,they present a promising substitute for petroleum-based polymers.The three main structural constituents of the plant biomass-based materials that are naturally available are cellulose,hemicellulose,and lignin.This review details current developments using wood-based products such as cellulose,hemicellulose,and lignin in UV-shielding applications.It will start with assembling the structure and chemistry of cellulose,hemicellulose,and lignin,followed by their contributions to preparing UV-shielding materials.Finally,it will briefly discuss the different processing methods for the design of UV-shielding materials.The wood by-products offer additional opportunities to use the whole tree harvest.

关键词： UV-shielding wood cellulose lignin hemicellulose sunlight protection

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Potential risk genes for primary Sjogren's syndrome from a meta-analysis by linear regression and random forest classification

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Genes & Diseases 2024年第3期11卷 128-131页

作者： Tomas Cerdo Teresa Torres Moral Maimonides Biomedical research Institute of Cordoba(IMIBIC) Reina Sofia University HospitalUniversity of CordobaCordoba 14004Spain centre for rheumatology research Division of MedicineUniversity College LondonLondon W1T 4JFUK Faculty of Computer Sciences Multimedia and TelecommunicationUniversitat Oberta de CatalunyaBarcelona 08018Spain Dermatology Department Melanoma UnitAugust Pi i Sunyer Biomedical Research Institute(IDIBAPS)and Hospital ClinicBarcelona 08036Spain Center for Networked Biomedical research on Rare Diseases(CIBERER) Carlos II Health InstituteMadrid 28029Spain

Primary Sjogren's syndrome(psS)is one of the most widespread autoimmune diseases with unknown origin,characterized by a lymphocytic infiltrate of the exocrine glands and the production of anti-SSA/Ro and anti-SSB/La antibodies that cause dysfunction and destruction mainly of salivary and lachrymal glands,leading to dry eyes and dry mouth.In the absence of a standardized evidence-based screening tool to decide which patients with dry eye must be referred for study of this pathology.

关键词： Sjogren lymphocytic salivary

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