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macrophage-specific inhibition of the histone demethylase JmJD3 decreases STING and pathologic inflammation in diabetic wound repair

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Cellular & molecular Immunology 2022年第11期19卷 1251-1262页

作者： Christopher O.Audu William J.melvin Amrita D.Joshi Sonya J.Wolf Jadie Y.moon frank m.davis Emily C.Barrett Kevin D.mangum Hongping Deng Xianying Xing Rachel Wasikowski Lam C.Tsoi Sriganesh B.Sharma Tyler m.Bauer James Shadiow matthew A.Corriere Andrea TObi Steven LKunkel Benjamin Levi Bethany Bmoore Johann EGudjonsson Andrew mSmith Katherine A.Gallagher Department of Surgery Section of Vascular SurgeryUniversity of MichiganAnn ArborMIUSA Department of microbiology and Immunology University of MichiganAnn ArborMIUSA Department of medicinal Chemistry University of MichiganAnn ArborMIUSA Department of Surgery Section of General SurgeryUniversity of MichiganAnn ArborMIUSA Department of Bioengineering University of IllinoisUrbana-ChampaignChampaignILUSA Department of Dermatology University of MichiganAnn ArborMIUSA Department of Pathology University of MichiganAnn ArborMIUSA Department of Surgery University of Texas Southwestern Medical CenterDallasTXUSA

macrophage plasticity is critical for normal tissue repair following injury.In pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are unknown.Here,using single-cell RNA sequencing of human diabetic wounds,we identified increased JmJD3 in diabetic wound macrophages,resulting in increased inflammatory gene expression.mechanistically,we report that in wound healing,JmJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling.However,in the diabetic state,we found that IL-6,a cytokine increased in diabetic wound tissue at later time points post-injury,regulates JmJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JmJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism.Interestingly,RNA sequencing of wound macrophages isolated from mice with JmJD3-deficient myeloid cells(Jmjd3f/fLyz2Cre+)identified that the STING gene(Tmem173)is regulated by JmJD3 in wound macrophages.STING limits inflammatory cytokine production by wound macrophages during healing.However,in diabetic mice,its role changes to limit wound repair and enhance inflammation.This finding is important since STING is associated with chronic inflammation,and we found STING to be elevated in human and murine diabetic wound macrophages at late time points.Finally,we demonstrate that macrophage-specific,nanoparticle inhibition of JmJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING.Taken together,this work highlights the central role of JmJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

关键词： wound healing epigenetics diabetes JmJD3 STING

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Solving traffic data occlusion problems in computer vision algorithms using DeepSORT and quantum computing

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第1期11卷 1-15页

作者： frank Ngeni Judith mwakalonge Saidi Siuhi Department of Engineering South Carolina State UniversityOrangeburgSC 29117USA

Inaccuracies of traffic sensors during traffic counting and vehicle classification have persisted as transportation agencies have been prompted to calibrate sensors periodically.Detection of multiple objects,heavy occlusions,and similar appearances in congested places are some causes of computer vision model inaccuracies.This paper used the YOLOv5 model for detection and the DeepSORT model for tracking objects.Due to the nature of the reported problem caused by many misses and mismatches,the power of quantum computing with the alternating direction method of multipliers(ADmm)optimizer was leveraged.A basic Kalman filter and the Hungarian algorithm features were used in combination with a quantum optimizer to present robust multiple object tracking(mOT)algorithms.This hybrid combination of the classical and quantum model has fastened learning the occludes during frame matching of tracks and detections by generating minimum quantum cost function value.Comparisons with the existing models indicated a significant increase in the primary mOT metric multiple object tracking accuracy(mOTA)by 16%more than the regular YOLOv5-DeepSORT model when using a quantum optimizer.Also,a 6%multiple object tracking precision(mOTP)increases and a 6%identification metrics(F_(1))score increase were observed using the quantum optimizer with identity switching reduced from 6 to 4.This model is expected to assist transportation officials in improving the accuracy of traffic counts and vehicle classification and reduce the need for regular computer vision software calibration.

关键词： Traffic classification Traffic counting DeepSORT YOLOv5 Quantum computing

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Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & Vascular Neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam Longting Lin Christina Lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel matthew Lee-Archer Andrew Wong michael Roizman Amanda Gilligan Andrew Lee Kee meng Tan Susan Day Christopher Levi Stephen m.davis mark Parsons Bernard Yan melbourne Brain Centre at Royal melbourne Hospital ParkvilleVictoriaAustralia University of New South Wales South Western Sydney Clinical School LiverpoolNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of Neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of Neurology Northern Hospital EppingEppingVictoriaAustralia Department of Neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland School of medicine HerstonQueenslandAustralia Neurosciences Clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of Neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of medicine and Public Health AdelaideSouth AustraliaAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of Sydney Northern Clinical School St LeonardsNew South WalesAustralia Department of Neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic lesions.We aimed to quantify silent ischaemic lesions and haemorrhages on mRI at 1month in patients commenced on early(mic lesions and more haemorrhages in the early anticoagulant group at 1-month mRI.methods A prospective multicentre,observational cohort study was performed at 11 Australian stroke centres.Clinical and mRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two authors.Timing of commencement of anticoagulation was at the discretion of the treating stroke physician.Results We recruited 276 patients of whom 208 met the eligibility criteria.The average age was 74.2 years(SD±10.63),and 79(38%)patients were female.median National Institute of Health Stroke Scale score was 5(IQR 1–12).median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up mRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation timing.Conclusion Commencing anticoagulationmic lesions at 1month in AF patients.There is no increased rate of haemorrhage with early anticoagulation.These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe,but randomised controlled s

关键词： patients lesions ischaemic

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两种富含甘氨酸的RNA结合蛋白参与选择性剪接实现对水稻耐热性的昼夜节律调控

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Science Bulletin 2024年第1期69卷 59-71页

作者：杨闯罗安妮芦海平 Seth Jon davis 刘建祥 State Key Laboratory of Plant Environmental Resilience College of Life SciencesZhejiang UniversityHangzhou 310027China Department of Biology University of YorkYork YO105DDUK

Rice(Oryza sativa L.)production is threatened by global warming associated with extreme high temperatures,and rice heat sensitivity is differed when stress occurs between daytime and nighttime.However,the underlying molecular mechanism are largely unknown.We show here that two glycine-rich RNA binding proteins,Os GRP3 and Os GRP162,are required for thermotolerance in rice,especially at nighttime.The rhythmic expression of Os GRP3/Os GRP162 peaks at midnight,and at these coincident times,is increased by heat stress.This is largely dependent on the evening complex component Os ELF3-2.We next found that the double mutant of Os GRP3/Os GRP162 is strikingly more sensitive to heat stress in terms of survival rate and seed setting rate when comparing to the wild-type plants.Interestingly,the defect in thermotolerance is more evident when heat stress occurred in nighttime than that in daytime.Upon heat stress,the double mutant of Os GRP3/Os GRP162 displays globally reduced expression of heat-stress responsive genes,and increases of m RNA alternative splicing dominated by exon-skipping.This study thus reveals the important role of Os GRP3/Os GRP162 in thermotolerance in rice,and unravels the mechanism on how Os GRP3/Os GRP162 regulate thermotolerance in a diurnal manner.

关键词： Alternative splicing Diurnal regulation Glycine-rich protein Oryza sativa L. Thermotolerance

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Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis

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Genes & Diseases 2022年第1期9卷 108-115页

作者： Joy m.davis Binglu Cheng madeline m.Drake Qiang Yu Baibing Yang Jing Li Chunhui Liu mamoun Younes Xiurong Zhao Jennifer m.Bailey Qiang Shen Tien C.Ko Yanna Cao Department of Surgery The University of Texas Health Science Center at HoustonHoustonTX 77030USA Department of Pathology&Laboratory medicine The University of Texas Health Science Center at HoustonHoustonTX 77030USA Department of Neurology The University of Texas Health Science Center at HoustonHoustonTX 77030USA Department of Internal medicine The University of Texas Health Science Center at HoustonHoustonTX 77030USA Department of Genetics Louisiana State University Health Sciences CenterNew OrleansLA 70112USA

Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment,composed of activated fibroblasts and macrophages.macrophages can be characterized as m1 or m2,with tumor-inhibiting or-promoting functions,respectively.We reported that Gremlin 1(GREm1),a key pro-fibrogenic factor,is upregulated in the stroma of CP.The current study aimed to investigate the expression of GREm1 and correlation between GREm1 and macrophages within the pancreas during chronic inflammation and the development of PDAC.By mRNA in situ hybridization,we detected GREm1 mRNA expression withinα-smooth muscle actin(SmA)-positive fibroblasts of the pancreatic stroma.These designated FibroblastsGrem1+marginally increased from CP to pancreatic intraepithelial neoplasia(PanIN)and PDAC.Within PDAC,FibroblastsGrem1+increased with higher pathological tumor stages and in a majority of PDAC subtypes screened.Additionally,FibroblastsGrem1+positively correlated with total macrophages(macCD68+)and m2 macrophages(m2CD163+)in PDAC.To begin exploring potential molecular links between FibroblastsGrem1+and macrophages in PDAC,we examined the expression of macrophage migration inhibitory factor(mIF),an endogenous counteracting molecule of GREm1 and an m1 macrophage promoting factor.By IHC staining of mIF,we found mIF to be expressed by tumor cells,positively correlated with GREm1;by IHC co-staining,we found mIF to be negatively correlated with m2CD163+expression.Our findings suggest that GREm1 expression by activated fibroblasts may promote PDAC development,and GREm1/mIF may play an important role in macrophage phenotype.

关键词： Fibroblasts Gremlin 1 macrophage migration inhibitory factor macrophages

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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy miriam E.A.Tschaffon-müller Shan Jiang Tobias malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa melanie Haffner-Luntzer David J.Beech frank Timo Beil michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and metabolic medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell types.While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage.Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)development.mice with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate postnatally.moreover,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth plates.While skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age.Likewise,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage degeneration.Importantly,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) mice.We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes.Finally,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes.Collectively,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Impact on Soil Organic C and Total Soil N from Cool- and Warm-Season Legumes Used in a Green manure-Forage Cropping System

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Agricultural Sciences 2024年第3期15卷 333-357页

作者： Clark B. Neely Francis m. Rouquette Jr. Cristine L.S. morgan frank m. Hons William L. Rooney Gerald R. Smith Department of Soil and Crop Science Washington State University Pullman WA USA Texas A&m AgriLife Research Overton TX USA Chief Scientific Officer Soil Health Institute Morrisville NC USA Department of Soil and Crop Science Texas A&M University College Station TX USA

Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t Dm ha-1) and contributed the most total N (167 kg∙ha-1) and total C (3043 kg∙ha-1) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t Dm ha-1 with a total

关键词： Annual Legumes Soil N Soil Organic C Green manure Deer Browse Forage Cropping Systems

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Estimating the effects of meteorology on Pm_(2.5) reduction during the 2008 Summer Olympic Games in Beijing, China

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Frontiers of Environmental Science & Engineering 2011年第3期5卷 331-341页

作者： Liu YANG Ye WU Jerry m.davis Jiming HAO School of Environment Tsinghua UniversityBeijing 100084China Office of Air Quality Planning and Standards Health and Environmental Impacts DivisionUS Environmental Protection AgencyRaleighNC 27513USA

Particulate pollution was a critical challenge to the promise of good air quality during the 2008 Beijing Olympic Games,which took place from August 8th to 24th.To ensure good air quality for the Games,several temporary emission control measures were implemented in Beijing and surrounding areas.Ambient particulate matter concentration decreased significantly during the Olympic period;however,it is difficult to distinguish the effectiveness of those control measures since meteorology also affects ambient Pm_(2.5) concentration.In this work,a multiple linear regression model based on continuous field monitoring at a roadside site was conducted to evaluate the effects of meteorology and emission control measures on the reduction of Pm_(2.5) during the 2008 Olympic Games.The hourly data set was divided into two time periods,the no control period,June 22nd to July 4th,and the control period,July 28th to August 21st.The response variable was Pm_(2.5) and the meteorology covariates used in the model were hourly temperature,dew point temperature,wind speed and precipitation.Wind direction was not a significant predictor of Pm_(2.5) levels in either the control or the no control period.Using the meteorologically-based regression coefficients from the two time periods,meteorology was found to contribute to at least a 16%reduction in Pm_(2.5) levels in the roadside microenvironment;while the pollution control measures contributed to at least a 43%reduction in Pm_(2.5) levels.

关键词： meteorology emission control measures Beijing Olympic Games Pm_(2.5) linear statistical models

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Legume Green manure and Intercropping for High Biomass Sorghum Production

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Agricultural Sciences 2024年第6期15卷 605-621页

作者： Clark B. Neely Francis m. Rouquette Jr. Cristine L. S. morgan frank m. Hons William L. Rooney Gerald R. Smith Department of Soil and Crop Science Washington State University Pullman WA USA Texas A&m AgriLife Research Overton TX USA Soil Health Institute Morrisville NC USA Department of Soil and Crop Science Texas A&M University College Station TX USA

Before the advent of cheap, synthetic fertilizers, legumes were commonly used as green manure crops for their ability to fix atmospheric nitrogen (N). A three-year study at Overton, TX examined legume integration into high-biomass sorghum (Sorghum bicolor L.) production systems on a Lilbert loamy fine sand recently cultivated after a fertilized bermudagrass [Cynodon dactylon (L.) Pers.] pasture. In this split-split plot design, ‘Dixie’ crimson clover (Trifolium incarnatum L.) and ‘Iron and Clay’ cowpea (Vigna unguiculata L.) were integrated into a high-biomass sorghum production system to evaluate impacts on N concentration, C concentration, and yield of high-biomass sorghum and their impacts on soil total N and soil organic carbon (SOC). main plots were split into crimson clover green manure (CLGm) and winter fallow (FALL) followed by three sub-plots split into warm-season crop rotations: cowpea green manure (CPGm), cowpea-sorghum intercrop (CPSR), and sorghum monocrop (SORG). Three N fertilizer treatments (0, 45, 90 kg N∙ha−1) were randomized and applied as sub-sub plots. The CLGm increased (P sorghum biomass yield (16.5 t Dm∙ha−1) 28% in year three but had no effect in the first two years. The CPSR treatment reduced sorghum yield up to 62% compared to SORG;whereas CPGm increased sorghum yield 56% and 18% the two years following cowpea incorporation. Rate of N fertilizer had no effect on sorghum biomass yield. Decrease in SOC and soil N over time indicated mineralization of organic N and may explain why no N fertilizer response was observed in sorghum biomass yield. Cowpea showed strong potential as a green manure crop but proved to be too competitive for successful intercropping in high-biomass sorghum production systems.

关键词： High-Biomass Sorghum Legumes Green manure Intercrop Cowpea Crimson Clover Soil Organic Carbon Soil Nitrogen

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A pentaploid-based linkage map of the ancestral octoploid strawberry Fragaria virginiana reveals instances of sporadic hyper-recombination

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Horticulture Research 2020年第1期7卷 1796-1810页

作者： Thomas m.davis Yilong Yang Lise L.mahoney Daniel C.Frailey Department of Agriculture Nutritionand Food SystemsUniversity of New HampshireDurhamNH 03824USA

The first high-resolution genetic linkage map of the ancestral octoploid(2n=8x=56)strawberry species,Fragaria virginiana,was constructed using segregation data obtained from a pentaploid progeny population.This novel mapping population of size 178 was generated by crossing highly heterozygous F.virginiana hybrid“LB48”as a paternal parent with diploid(2n=2x=14)Fragaria vesca“Hawaii 4”.The LB48 linkage map comprises 6055 markers genotyped on the Axiom®IStraw90 strawberry SNP array.The map consists of 28 linkage groups(LGs)organized into seven homoeology groups of four LGs each,and excludes a small 29th LG of undefined homoeology.One member of each homoeology group was assignable to an“A”subgenome associated with ancestral diploid Fragaria vesca,while no other subgenomes were defined.Despite an intriguing discrepancy within homoeology group VI,synteny comparisons with the previously published Fragaria×ananassa DA×mO linkage map revealed substantial agreement.Following initial map construction,examination of crossover distributions revealed that six of the total 5162(=29 chromosomes/individual×178 individuals)chromosomes making up the data set exhibited abnormally high crossover counts,ranging from 15 to 48 crossovers per chromosome,as compared with the overall mean of 0.66 crossovers per chromosome.Each of these six hyper-recombinant(HypR)chromosomes occurred in a different LG and in a different individual.When calculated upon exclusion of the six HypR chromosomes,the canonical(i.e.,broadly representative)LB48 map had 1851 loci distributed over a total map length of 1873 cm,while their inclusion increased the number of loci by 130,and the overall map length by 91 cm.Discovery of these hyper-recombinant chromosomes points to the existence of a sporadically acting mechanism that,if identified and manipulable,could be usefully harnessed for multiple purposes by geneticists and breeders.

关键词： Fragaria straw linkage

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