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PAI-1 genetic polymorphisms influence septic patients’outcomes by regulating neutrophil activity

Chinese Medical Journal 2023年第16期136卷 1959-1966页

作者： Shaowei Jiang Yang Wang Liang Chen Honghua Mu connor meaney Yiwen Fan Janesh Pillay Hairong Wang Jincheng Zhang Shuming Pan Chengjin Gao Department of Emergency Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Division of Rheumatology Department of Internal MedicineUniversity of Utah School of MedicineSalt Lake CityUTUSA Department of Pathology Medicine Biology University Medical Center GroningenThe Netherlands Department of Critical Care University Medical Center GroningenThe Netherlands Department of Critical Care Medicine Zhongshan HospitalFudan UniversityShanghai 200032China

Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains *** this study,we investigated the associations among the serum levels of PAI-1,the incidence of 4G/5G promoter PAI-1 gene polymorphisms,immunological indicators,and clinical outcomes in septic ***:A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study,with 28-day mortality as the primary *** initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms(SNPs)were *** logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1,serum level of PAI-1,and 28-day ***:The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1(4G/4G and 4G/5G)(Odds ratio[OR]:2.49;95%confidence interval[CI]:1.09,5.68).Furthermore,a high serum level of PAI-1 strongly influenced 28-day mortality(OR 3.36;95%CI 1.51,7.49).The expression and activation of neutrophils(OR 0.96;95%CI 0.93,0.99),as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils(OR:1.00;95%CI:1.00,1.00),were both regulated by the genotype of ***:Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1,which might contribute to mortality by affecting neutrophil ***,patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

关键词： Gene polymorphism Neutrophil Plasminogen activator inhibitor-1 PAI-1 Sepsis Single nucleotide polymorphism

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Preface to the Special Issue on Modeling and Data Analysis Methods for the SMILE mission

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Earth and Planetary Physics 2024年第1期8卷 1-4页

作者： TianRan Sun Hyunju connor Andrey Samsonov National Space Science Center Chinese Academy of SciencesBeijing 100190China NASA Goddard Space Flight Center US Mullard Space Science Laboratory University College LondonUK

The SMILE(Solar wind Magnetosphere Ionosphere Link Explorer)project(http://***/smile/,https://***/web/smile/mission)is a joint spacecraft mission of the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)with an expected launch in *** aims to study the global interactions of solar wind–magnetosphere–ionosphere innovatively by imaging the Earth’s magnetosheath and cusps in soft X-rays and the northern auroral region in ultraviolet(UV)while simultaneously measuring plasma and magnetic field parameters in the solar wind and magnetosheath along a highly-elliptical and highly-inclined *** special issue is composed of 22 articles,presenting recent progress in modeling and data analysis techniques developed for the SMILE *** this preface,we categorize the articles into the following seven topics and provide brief summaries:(1)instrument descriptions of the Soft X-ray Imager(SXI),(2)numerical modeling of the X-ray signals,(3)data processing of the X-ray images,(4)boundary tracing methods from the simulated images,(5)physical phenomena and a mission concept related to the scientific goals of SMILE-SXI,(6)studies of the aurora,and(7)ground-based support for SMILE.

关键词： SMILE X-ray imaging magnetosphere auroral ionosphere

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Mshpy23:a user-friendly,parameterized model of magnetosheath conditions

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Earth and Planetary Physics 2024年第1期8卷 89-104页

作者： Jaewoong Jung Hyunju connor Andrew Dimmock Steve Sembay Andrew Read Jan Soucek NASA Goddard Space Flight Center GreenbeltMDUSA Department of Astronomy University of MarylandCollege ParkMDUSA Swedish Institude of Space Physics UppsalaSweden University of Leicester LeicesterUK Institute of Atmospheric Physics Academy of Sciences of the Czech Republic

Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind−Magnetosphere−Ionosphere Link Explorer(SMILE)will observe magnetosheath and its boundary motion in soft X-rays for understanding magnetopause reconnection modes under various solar wind conditions after their respective launches in 2024 and *** conditions,namely,plasma density,velocity,and temperature,are key parameters for predicting and analyzing soft X-ray images from the LEXI and SMILE *** developed a userfriendly model of magnetosheath that parameterizes number density,velocity,temperature,and magnetic field by utilizing the global Magnetohydrodynamics(MHD)model as well as the pre-existing gas-dynamic and analytic *** this parameterized magnetosheath model,scientists can easily reconstruct expected soft X-ray images and utilize them for analysis of observed images of LEXI and SMILE without simulating the complicated global magnetosphere ***,we created an MHD-based magnetosheath model by running a total of 14 OpenGGCM global MHD simulations under 7 solar wind densities(1,5,10,15,20,25,and 30 cm)and 2 interplanetary magnetic field Bz components(±4 nT),and then parameterizing the results in new magnetosheath *** compared the magnetosheath model result with THEMIS statistical data and it showed good agreement with a weighted Pearson correlation coefficient greater than 0.77,especially for plasma density and plasma ***,we compiled a suite of magnetosheath models incorporating previous magnetosheath models(gas-dynamic,analytic),and did two case studies to test the *** MHD-based model was comparable to or better than the previous models while providing self-consistency among the magnetosheath ***,we constructed a tool to calculate a soft X-ray image from any given vantage point,which can support the planning and data analysis of the aforementioned LEXI and SMILE missions.A release of the code has been uploaded to a Git

关键词： magnetosheath python modeling

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Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 129-138页

作者： Sudha Kodali Ashton A connor Souhail Thabet Elizabeth W Brombosz R Mark Ghobrial Sherrie and Alan Conover Center for Liver Disease and Transplantation Houston Methodist HospitalHoustonTX 77030USA JC Walter Jr Transplant Center Houston Methodist HospitalHoustonTX 77030USA Department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA Department of Surgery Houston Methodist HospitalHoustonTX 77030USA Department of Surgery Weill Cornell Medical CollegeNew YorkNYUSA School of Medicine New Giza UniversityGizaEgypt

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality *** resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative ***,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor *** transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable ***,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT *** studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced *** selection criterion is the tumor response to neoadjuvant *** with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant *** index that helps predict the treatment outcome is the *** survival outcomes have also opened the door for living donor LT for *** undergoing LT for iCCA now have statistically similar survival rates as patients undergoing *** combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

关键词： Liver transplantation Cholangiocarcinoma Hepatectomy Transplant oncology Liver neoplasm

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Public perspectives on AI diagnosis of mental illness

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General Psychiatry 2024年第3期37卷 348-351页

作者： Cliodhna O'connor University College Dublin DublinIreland

To the editor:Psychiatric theory,policy and practice are currently grappling with the risks and opportunities presented by artificial intelligence(AI)applications in mental *** data to generate diagnosis is an aspect of mental healthcare where AI is anticipated to have the greatest and soonest impact.1-4 While such technologies remain some distance from clinical application,preliminary evidence suggests AI-derived classifications may predict certain treatment outcomes and clinical trajectories,and could soon become available to supplement or replace traditional manual-based diagnostic assessment.

关键词： diagnosis replace editor

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Finding the magnetopause location using soft X-ray observations and a statistical inverse method

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Earth and Planetary Physics 2024年第1期8卷 184-203页

作者： Gonzalo Cucho-Padin Hyunju connor Jaewoong Jung Brian Walsh David G.Sibeck Space Weather Laboratory NASA Goddard Space Flight CenterGreenbeltMDUSA Department of Physics The Catholic University of AmericaWashingtonDCUSA Geospace Physics Laboratory NASA Goddard Space Flight CenterGreenbeltMDUSA Astronomy Department University of Maryland College ParkCollege ParkMDUSA Center for Space Physics Department of Mechanical EngineeringBoston UniversityBostonMAUSA

Variability in the location and shape of the dayside magnetopause is attributed to magnetic reconnection,a fundamental process that enables the transfer of mass,energy,and momentum from the solar wind into the *** spatial and temporal properties of the magnetopause,under varying solar and magnetospheric conditions,remain largely unknown because empirical studies using in-situ observations are challenging to *** wide field-of-view(FOV)imaging is the only means to simultaneously observe the spatial distribution of the plasma properties over the vast dayside magnetospheric region and,subsequently,quantify the energy transport from the interplanetary medium into the terrestrial *** upcoming missions,ESA/CAS SMILE and NASA’s LEXI will provide wide-field imagery of the dayside magnetosheath in soft X-rays,an emission generated by charge exchange interactions between high charge-state heavy ions of solar wind origin and exospheric neutral ***-cadence two-dimensional observations of the magnetosheath will allow the estimation of dynamic properties of its inner boundary,the magnetopause,and enable studies of its response to changes in the solar wind dynamic pressure and interplanetary magnetic field *** work introduces a statistically-based estimation approach based on inverse theory to estimate the spatial distribution of magnetosheath soft X-ray emissivities and,with this,identify the location of the magnetopause over the Sun−Earth *** do so,we simulate the magnetosheath structure using the MHD-based OpenGGCM model and generate synthetic soft X-ray images using LEXI’s orbit and attitude *** results show that 3-D estimations using the described statistically-based technique are robust against Poisson-distributed shot noise inherent to soft X-ray ***,our proposed methodology shows that the accuracy of both three-dimensional(3-D)estimation and the magnetopause standoff distance calculation hi

关键词： magnetopause soft X-ray tomography

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Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

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Neural Regeneration Research 2025年第1期20卷 205-206页

作者： Sarah Fullam Sean O’Dowd Antoinette O’connor Department of Neurology Tallaght University HospitalDublinIreland Academic Unit of Neurology Trinity College DublinIreland

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of *** evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic *** the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for ***,the expensive and invasive nature of these tests limits their scalability.

关键词： Blood Alzheimer diagnosis

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晚白垩世真兽类Zalamdalestes揭示哺乳动物独特的枢椎及其复杂的进化过程

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Science Bulletin 2024年第11期69卷 1767-1775页

作者： Patrick Arnold Katarzyna Janiszewska 李茜 Jingmai K.O'connor Lucja Fostowicz-Frelik Institute of Biochemistry and Biology University of PotsdamPotsdam D-14476Germany Environmental Paleobiology Department Institute of PaleobiologyPolish Academy of SciencesWarsaw 00-818Poland Key Laboratory of Evolutionary Systematics of Vertebrates Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China The Field Museum of Natural History Chicago IL 60605USA Department of Organismal Biology and Anatomy The University of ChicagoChicago IL 60637USA Evolutionary Paleobiology Department Institute of PaleobiologyPolish Academy of SciencesWarsaw 00-818Poland

The typical mammalian neck consisting of seven cervical vertebrae(C1–C7)was established by the Late Permian in the cynodont forerunners of modern *** structure is precisely adapted to facilitate movements of the head during feeding,locomotion,predator evasion,and social ***,the clade including crown placentals,has a fossil record extending back more than 125 million years revealing significant morphological diversification in the *** very little is known concerning the early evolution of eutherian cervical morphology and its functional adaptations.A specimen of Zalambdalestes lechei from the Late Cretaceous of Mongolia boasts exceptional preservation of an almost complete series of cervical vertebrae(C2–C7)revealing a highly modified axis(C2).The significance of this cervical morphology is explored utilizing an integrated approach combining comparative anatomical examination across mammals,muscle reconstruction,geometric morphometrics and virtual range of motion *** compared the shape of the axis in Zalambdalestes to a dataset of 88 mammalian species(monotremes,marsupials,and placentals)using three-dimensional landmark *** results indicate that the unique axis morphology of Zalambdalestes has no close analog among living *** range of motion analysis of the neck strongly implies Zalambdalestes was capable of exerting very forceful head movements and had a high degree of ventral flexion for an animal its *** findings reveal unexpected complexity in the early evolution of the eutherian cervical morphology and suggest a feeding behavior similar to insectivores specialized in vermivory and defensive behaviors in Zalambdalestes akin to modern spiniferous mammals.

关键词： Atlas Axis Vertebral column Stem placental Morphology paleoecology

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Hybrid-Vlasov simulation of soft X-ray emissions at the Earth’s dayside magnetospheric boundaries

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Earth and Planetary Physics 2024年第1期8卷 70-88页

作者： M.Grandin H.K.connor S.Hoilijoki M.Battarbee Y.Pfau-Kempf U.Ganse K.Papadakis M.Palmroth Department of Physics University of HelsinkiHelsinkiFinland NASA Goddard Space Flight Center GreenbeltMD20771USA Space and Earth Observation Centre Finnish Meteorological InstituteHelsinkiFinland

Solar wind charge exchange produces emissions in the soft X-ray energy range which can enable the study of near-Earth space regions such as the magnetopause,the magnetosheath and the polar cusps by remote sensing *** Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)and Lunar Environment heliospheric X-ray Imager(LEXI)missions aim to obtain soft Xray images of near-Earth space thanks to their Soft X-ray Imager(SXI)*** earlier modeling works have already simulated soft X-ray images as might be obtained by SMILE SXI during its mission,the numerical models used so far are all based on the magnetohydrodynamics description of the space *** investigate the possible signatures of ion-kinetic-scale processes in soft Xray images,we use for the first time a global hybrid-Vlasov simulation of the geospace from the Vlasiator *** simulation is driven by fast and tenuous solar wind conditions and purely southward interplanetary magnetic *** first produce global X-ray images of the dayside near-Earth space by placing a virtual imaging satellite at two different locations,providing meridional and equatorial *** then analyze regional features present in the images and show that they correspond to signatures in soft X-ray emissions of mirrormode wave structures in the magnetosheath and flux transfer events(FTEs)at the *** results suggest that,although the time scales associated with the motion of those transient phenomena will likely be significantly smaller than the integration time of the SMILE and LEXI imagers,mirror-mode structures and FTEs can cumulatively produce detectable signatures in the soft X-ray *** instance,a local increase by 30%in the proton density at the dayside magnetopause resulting from the transit of multiple FTEs leads to a 12%enhancement in the line-of-sight-and time-integrated soft X-ray emissivity originating from this ***,a proton density increase by 14%in the magnetosheath

关键词： magnetosphere magnetosheath numerical simulation SMILE LEXI soft X-ray emissions hybrid-Vlasov model polar cusp flux transfer events mirror-mode waves

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Steroidal scaffold decorations in Solanum alkaloid biosynthesis

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Molecular Plant 2024年第8期17卷 1236-1254页

作者： Rosalind Lucier Mohamed O.Kamileen Yoko Nakamura Sofiia Serediuk Ranjit Barbole Jens Wurlitzer Maritta Kunert Sarah Heinicke Sarah E.O'connor Prashant D.Sonawane Department of Natural Product Biosynthesis Max Planck Institute for Chemical Ecology07745 JenaGermany Research Group Biosynthesis and NMR Max Planck Institute for Chemical Ecology07745 JenaGermany Biochemical Sciences Division CSIR-National Chemical LaboratoryPune 411008MaharashtraIndia

Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and *** it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic *** these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory ***,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum ***,it is still unknown how plants synthesize these bioactive steroidal *** comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from *** that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA *** further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation *** work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.

关键词： steroidal glycoalkaloids Solanum biosynthetic pathway α-solamargine malonyl-solamargine specialized metabolites

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