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Cellular & molecular Immunology 2020年第2期17卷 123-132页

作者： Yifan Zhan Nancy Wang Ajithkumar Vasanthakumar Yuxia Zhang michael Chopin Stephen L.Nutt Axel Kallies andrew m.lew The Walter&Eliza Hall Institute of medical Research ParkvilleVIC 3052Australia Department of medical Biology University of MelbourneParkvilleVIC 3010Australia Guangzhou Institute of Paediatrics Guangzhou Women and Children’s Medical CentreGuangzhou Medical University510623 GuangzhouGuangdongChina Department of microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneParkvilleVIC 3010Australia

A wide array of chemokine receptors,including CCR2,are known to control Treg ***,we report that CCR2 regulates Tregs beyond *** found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg *** a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type(WT)and CCR2−/−***,CCR2 deficiency resulted in profound loss of CD25 ^(hi) FoxP3^(+) Tregs in secondary lymphoid organs as well as in peripheral ***2−/−Treg cells were also functionally inferior to WT ***,these changes to Treg cells did not depend on CCR2+monocytes/moDCs(the cells where CCR2 receptors are most abundant).Rather,we demonstrated that CCR2 was required for TLR-stimulated,but not TCR-or IL-2-stimulated,CD25 upregulation on Treg ***,we propose that CCR2 signaling can increase the fitness of FoxP3^(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.

关键词： CCR2 CD25 organs

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1205-1215页

作者： Xiaoyan Liu Zhe Li Shuai Liu Jing Sun Zhanghua Chen min Jiang Qingling Zhang Yinghua Wei Xin Wang Yi-You Huang Yinyi Shi Yanhui Xu Huifang Xian Fan Bai Changxing Ou Bei Xiong andrew m.lew Jun Cui Rongli Fang Hui Huang Jincun Zhao Xuechuan Hong Yuxia Zhang Fuling Zhou Hai-Bin Luo Department of Hematology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Dawu County People’s Hospital Xiaogan 432826China State Key Laboratory of Respiratory Diseases National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Guangzhou Institute of Pediatrics Guangzhou Women and Children’s Medical CenterState Key Laboratory of Respiratory DiseasesGuangzhou Medical UniversityGuangzhou 510623China Biomedical Pioneering Innovation Center(BIOPIC) School of Life SciencesPeking UniversityBeijing 100871China Department of Infectious Disease and Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Center for Innovative marine Drug Screening&Evaluation(QNLm) School of Medicine and PharmacyOcean University of ChinaQingdao 266100China Walter and Eliza Hall Institute of medical Research and Department of microbiology&Immunology University of MelbourneParkvilleVic 3052Australia School of Life Sciences Sun Yat-sen UniversityGuangzhou 510006China Cardiovascular Department The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China State Key Laboratory of Virology College of ScienceInnovation Center for Traditional Tibetan Medicine Modernization and Quality ControlMedical CollegeTibet UniversityLhasa 850000China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery(mOE) Hubei Province Engineering and Technology Research Center for Fluorinated PharmaceuticalsWuhan University School of Pharmaceutical SciencesWuhan 430071China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan *** antivirals with safe clinical profile are urgently needed to improve the overall *** an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease *** virtual screening of a *** approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in *** a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(Pmphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control *** particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.

关键词： Dipyridamole SARS-CoV-2 COVID-19 Treatment D-dimer Severe cases

CIS controls the functional polarization of Gm-CSF-derived macrophages

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Cellular & molecular Immunology 2023年第1期20卷 65-79页

作者： Shengbo Zhang Jai Rautela Naiara G.Bediaga Tatiana B.Kolesnik Yue You Junli Nie Laura F.Dagley Justin Bedo Hanqing Wang Li Sun Robyn Sutherland Elliot Surgenor Nadia Iannarella Rhys Allan Fernando Souza-Fonseca-Guimaraes Yi Xie Qike Wang Yuxia Zhang Yuekang Xu Stephen L.Nutt andrew m.lew Nicholas D.Huntington Sandra E.Nicholson michaël Chopin Yifan Zhan Walter and Eliza Hall Institute of medical Research ParkvilleVICAustralia Department of medical Biology University of MelbourneParkvilleVICAustralia Department of Biochemistry and molecular Biology Biomedicine Discovery InstituteMonash UniversityClaytonVICAustralia oNKo-Innate Pty Ltd Moonee PondsVICAustralia Department of Computing and Information Systems University of MelbourneParkvilleVICAustralia Department of Respiratory medicine Guangzhou Institute of PediatricsGuangzhou Women and Children’s Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical UniversityGuangzhouGuangdongChina College of Biological Science Anhui Normal UniversityHefeiChina University of Queensland Diamantina Institute University of QueenslandTranslational Research InstituteBrisbaneQLDAustralia Program in Cardiovascular and metabolic Disorders Duke-NUS Medical SchoolDukeSingapore Drug Discovery Shanghai Huaota BiopharmShanghaiChina

The cytokine granulocyte-macrophage-colony stimulating factor (Gm-CSF) possesses the capacity to differentiate monocytes into macrophages (mØs) with opposing functions, namely, proinflammatory m1-like mØs and immunosuppressive m2-like mØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of mØs under Gm-CSF signaling remains elusive. Here, we showed that Gm-CSF-induced mØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive m2-like mØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the m1-like polarization program. In vivo, CIS deficiency induced the differentiation of m2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of Gm-CSF in mØ differentiation and uncovers the role of Gm-CSF in controlling allergic inflammation.

关键词： CIS Gm-CSF macrophage m2 m1

Spin-based magnetic random-access memory for high-performance computing

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National Science Review 2024年第3期11卷 20-23页

作者： Kaiming Cai Tianli Jin Wen Siang lew School of Physics Huazhong University of Science and Technology Interuniversity microelectronics Centre(ImEC) School of Physical and mathematical Sciences Nanyang Technological University

memory serves as a critical component in today's electronic systems for data storage and processing. In traditional computer architectures, the logic and memory units are physically separated, due to the performance gap in operational speed and capacity among memories, resulting in the fundamental limitation of the von Neumann computers.

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Elucidating the Degradation Pathways of Human Insulin in the Solid State

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： andrew Fagan Lorraine m.Bateman Joseph P.O'Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of Pharmacy University College Cork Analytical and Biological Chemistry Research Facility (ABCRF) University College Cork School of Chemistry University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as Rybelsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. Solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those observed in solution. While no unfolding was observed to occur, significant deamidation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin Solid state Stability

Electron push-pull effects induced performance promotion in covalent organic polymer thin films-based memristor for neuromorphic application

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Chinese Chemical Letters 2024年第5期35卷 227-231页

作者： Panke Zhou Hong Yu mun Yin Chee Tao Zeng Tianli Jin Hongling Yu Shuo Wu Wen Siang lew Xiong Chen State Key Laboratory of Photocatalysis on Energy and Environment College of ChemistryFuzhou UniversityFuzhou 350116China School of Physical and mathematical Sciences Nanyang Technological UniversitySingapore 637371Singapore Department of materials Science and Engineering National University of SingaporeSingapore 117575Singapore

Covalent organic polymer(COP)thin film-based memristors have generated intensive research interest,but the studies are still in their ***,by controlling the content of hydroxyl groups in the aldehyde monomer,Py-COP thin films with different electronic push-pull effects were fabricated bearing distinct memory performances,where the films were prepared by the solid-liquid interface method on the ITO substrates and further fabricated as memory devices with ITO/Py-COPs/Ag *** Py-COP-1-based memory device only exhibited binary memory behavior with an ON/OFF ratio of 1:10^(1.87).In contrast,the device based on Py-COP-2 demonstrated ternary memory behavior with an ON/OFF ratio of 1:10^(0.6):10^(3.1) and a ternary yield of 55%.The ternary memory mechanism of the ITO/Py-COP-2/Ag memory device is most likely due to the combination of the trapping of charge carriers and conductive ***,the Py-COPs-based devices can successfully emulate the synaptic potentiation/depression behavior,clarifying the programmability of these devices in neuromorphic *** results suggest that the electronic properties of COPs can be precisely tuned at the molecular level,which provides a promising route for designing multi-level memory devices.

关键词： Covalent organic polymers Push-pull effects multi-level memory memristor

Rational Schur Superalgebras

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Algebra Colloquium 2024年第2期31卷 209-220页

作者： andrew Riesen Shun-Jen Cheng Department of mathematical and Statistical Sciences University of Alberta 1132489 Ave NWEdmontonAlbertaCanada 不详

We develop and study the generalization of rational Schur algebras to the super *** to the classical case,this provides a new method for studying rational supermodules of the general linear supergroup GL(m|n).Furthermore,we establish a Schur-Weyl duality result for rational Schur superalgebras and conclude that under certain conditions these objects will be semisimple.

关键词： Schur algebra supermathematics general linear supergroup

Particle Size Optimization of Thermochemical Salt Hydrates for High Energy Density Thermal Storage

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Energy & Environmental materials 2024年第2期7卷 326-333页

作者： andrew martin Drew Lilley Raνi Prasher Sumanjeet Kaur Energy Technologies Area Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of mechanical Engineering UC BerkeleyBerkeleyCA 94720USA

Thermal energy storage(TES)solutions offer opportunities to reduce energy consumption,greenhouse gas emissions,and ***,they can help reduce the peak load and address the intermittency of renewable energy sources by time shifting the load,which are critical toward zero energy *** materials(TCms)as a class of TES undergo a solid-gas reversible chemical reaction with water vapor to store and release energy with high storage capacities(600 kWh m^(-3))and negligible self-discharge that makes them uniquely suited as compact,stand-alone units for daily or seasonal ***,TCms suffer from instabilities at the material(salt particles)and reactor level(packed beds of salt),resulting in poor multi-cycle efficiency and high-levelized cost of *** this study,a model is developed to predict the pulverization limit or Rcrit of various salt hydrates during thermal *** is critical as it provides design rules to make mechanically stable TCm composites as well as enables the use of more energy-efficient manufacturing process(solid-state mixing)to make the *** model is experimentally validated on multiple TCm salt hydrates with different water content,and effect of Rcrit on hydration and dehydration kinetics is also investigated.

关键词： high energy density hydration kinetics long-term cycling thermal energy storage thermochemical materials

Some mean Convergence Theorems for the maximum of Normed Double Sums of Banach Space Valued Random Elements

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Acta mathematica Sinica,English Series 2024年第7期40卷 1727-1740页

作者： andrew ROSALSKY Le Van THANH Nguyen Thi THUY Department of Statistics University of FloridaGainesvilleFL 32611-8545USA Department of mathematics Vinh UniversityVinhNghe AnViet Nam High School for Gifted Students Vinh UniversityVinhNghe AnViet Nam

In this correspondence,we establish mean convergence theorems for the maximum of normed double sums of Banach space valued random *** of the results pertain to random elements which are *** expand and improve a number of particular cases in the literature on mean convergence of random elements in Banach *** of the main contributions of the paper is to simplify and improve a recent result of Li,Presnell,and Rosalsky[Journal of mathematical Inequalities,16,117–126(2022)].A new maximal inequality for double sums of m-dependent random elements is proved which may be of independent *** sharpness of the results is illustrated by four examples.

关键词： Double sum mean convergence Rademacher type p Banach space Banach space valued random element m-dependent random elements

Carbon dioxide enrichment affected flower numbers transiently and increased successful post-pollination development stably but without altering final acorn production in mature pedunculate oak (Quercus robur L.)

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Journal of Forestry Research 2024年第4期35卷 1-12页

作者： Ryan mcClory Richard H.Ellis martin Lukac Jo Clark Carolina mayoral Kris m.Hart andrew R.G.Plackett A.Rob macKenzie School of Agriculture Policy and DevelopmentUniversity of ReadingAgricultureEarley GateWhiteknights RoadPO Box 237Reading RG66EUUK Faculty of Forestry and Wood Sciences Czech University of Life Sciences PraguePrague 165000Czechia Future Trees Trust Harwell Innovation CentreBuilding 173Curie AvenueHarwellOxford OX110QGUK Birmingham Institute of Forest Research University of BirminghamEdgbastonBirmingham B152TTUK School of Biosciences University of BirminghamEdgbastonBirmingham B152TTUK School of Geography Earth and Environmental SciencesUniversity of BirminghamEdgbastonBirmingham B152TTUK

Acorn production in oak(Quercus spp.)shows considerable inter-annual variation,known as masting,which provides a natural defence against seed predators but a highly-variable supply of acorns for uses such as in commercial tree planting each *** emissions of greenhouse gases have been very widely reported to influence plant growth and seed or fruit size and quantity via the‘fertilisation effect’that leads to enhanced *** examine if acorn production in mature woodland communities will be affected by further increase in CO_(2),the contents of litter traps from a Free Air Carbon Enrichment(FACE)experiment in deciduous woodland in central England were analysed for numbers of flowers and acorns of pedunculate oak(Quercus robur L.)at different stages of development and their predation levels under ambient and elevated CO_(2) ***-annual variation in acorn numbers was considerable and cyclical between 2015 and 2021,with the greatest numbers of mature acorns in 2015,2017 and 2020 but almost none in *** numbers of flowers,enlarged cups,immature acorns,empty acorn cups,and galls in the litter traps also varied amongst years;comparatively high numbers of enlarged cups were recorded in 2018,suggesting *** at this site is a fruit maturation masting species(i.e.,the extent of abortion of pollinated flowers during acorn development affects mature acorn numbers greatly).Raising the atmospheric CO_(2) concentration by 150μL L^(−1),from early 2017,increased the numbers of immature acorns,and all acorn evidence(empty cups+immature acorns+mature acorns)detected in the litter traps compared to ambient controls by 2021,but did not consistently affect the numbers of flowers,enlarged cups,empty cups,or mature *** number of flowers in the elevated CO_(2) plots’litter traps was greater in 2018 than 2017,one year after CO_(2) enrichment began,whereas numbers declined in ambient *** with CO_(2) also increased the number o

关键词： Quercus robur L. Acorns masting Pedunculate oak Carbon dioxide