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LDL,LDL receptors,and PCSK9 as modulators of the risk for type 2 diabetes:a focus on white adipose tissue

The j.urnal of Biomedical Research 2020年第4期34卷 251-259页

作者： may Faraj Cardiovascular and Metabolic Disease Division Montreal Clinical Research InstituteMontrealQuebec H2W 1R7Canada Department of Nutrition Faculty ofMedicineUniversity of MontrealMontrealQuebec H3C 3J7Canada Montreal Diabetes Research Center MontrealQuebec H2X 0A9Canada.

Type 2 diabetes(T2D) and cardiovascular disease(CVD) share many risk factors such as obesity,unhealthy lifestyle,and metabolic syndrome,whose accumulation over years leads to disease ***,while lowering plasma low-density lipoprotein cholesterol(LDLC) is cardio-protective,novel evidence have recognised a role for common LDLC-lowering variants(*** HMGCR,PCSK9,and LDLR) and widely used hypocholesterolemic drugs that mimic the effects of some of these variants(statins) in higher risk for *** these conditions decrease plasma LDLC by increasing tissue-uptake of LDL,a role for LDL receptor(LDLR)pathway was *** underlying mechanisms remain to be fully elucidated,work from our lab reported that native LDL directly provoke the dysfunction of human white adipose tissue(WAT) and the activation of WAT NLRP3(Nucleotide-binding domain and Leucine-rich repeat Receptor,containing a Pyrin domain 3)inflammasome,which play a maj.r role in the etiology of ***,while elevated plasma numbers of apolipoprotein B(apoB)-containing lipoproteins(measured as apoB,mostly as LDL) is associated with WAT dysfunction and related risk factors for T2D in our cohort,this relation was strengthened in regression analysis by lower plasma proprotein convertase subtilisin/kexin type 9(PCSK9).This supports a central role for upregulated pathway of LDLR and/or other receptors regulated by PCSK9 such as cluster of differentiation 36(CD36) in LDL-induced *** receptor-mediated uptake of LDL into WAT may reduce WAT inflammation,WAT dysfunction,and related risk for T2D without increasing the risk for CVD.

关键词： apoB-lipoproteins LDLR CD36 cardiometabolic risk insulin sensitivity apoB-to-PCSK9 ratio

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World j.urnal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K j.cobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy j.Kendall David A Dorward j.nathan A Fallowfield Peter C Hayes j.hn N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** inj.ry(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of inj.ry at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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Caries Patterns in the Primary Dentition: Cluster Analysis of a Sample of 5,169 Arizona Children 5-59 Months of Age

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International j.urnal of Oral Science 2009年第4期1卷 189-195页

作者： walter j. Psoter David G. Pendrys Douglas E. Morse He-ping Zhang Susan T. mayne Department of Epidemiology ＆ Health Promotion College of Dentistry New York University New York USA Department of Oral Health and Diagnostic Sciences School of Dental Medicine University Of Connecticut Health CenterFarmington USA Department of Epidemiology and Public Health School of Medicine Yale University New Haven USA

Aim Cluster analysis was conducted on data from 5,169 United States （U.S.） Arizona children, age＇s 5-59-months with the goal of delineating patterns of caries in the primary dentition of pre-school children without a priori pattern definitions. Methodology Cluster analyses were conducted using all data for children ages 0-4 years in aggregate： 1） for all subj.cts, and 2） for subj.cts without crowned restored teeth. Each of these two sets of analyses consisted of 8 differently specified cluster analyses as a validation procedure. Results The caries patterns identified from the clustering analysis are： 1） smooth surfaces （other than the maxillary incisor）, 2） maxillary incisor, 3） occlusal surfaces of first molars, and 4） pit and fissure surfaces of second molars. Conclusion The cluster analysis findings were consistent with results produced by multidimensional scaling. These cross-validated patterns may represent resulting disease conditions from different risks or the timing of various risk factor exposures. As such, the patterns may be useful case definitions for caries risk factor investigations in children under 60 months of age.

关键词： dental caries cluster analysis multidimensional scaling early childhood caries (ECC) caries patterns

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Surgical outcomes for cutaneous squamous cell carcinoma of the auricle

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World j.urnal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 295-301页

作者： Constantin Manole Liam j.Skinner Martin j.Donnelly Department of Otolaryngology/Head and Neck Surgery University Hospital WaterfordWaterfordRepublic of Ireland Consultant in Otolaryngology/Head and Neck Surgery University Hospital WaterfordWaterfordRepublic of Ireland

Background:Cutaneous squamous cell carcinoma (CSCC) on the auricle is believed to carry a higher risk of metastatic *** rates of lymphatic metastasis reported in the literature have varied *** are no established prognostic criteria to determine which of these tumors are higher risk and warrant prophylactic treatment of the associated lymphatic ***:To retrospectively evaluate outcomes after surgical treatment of auricular CSCC in our department,examining excision completeness,tumor recurrence,and lymphatic ***,to identify factors associated with lymphatic ***:One hundred and thirty‐eight consecutive cases of auricular SCC were excised from 126 patients in our department over a 7‐year period (j.nuary 2012–December 2018).Data were retrospectively collected on patient characteristics,tumor histology,surgical procedures,and follow‐***:Incomplete initial excision occurred in 17 cases (12.32%).Six patients (4.76%) had a local *** metastasis occurred in eight patients (6.35%),on average within 10.25 months after primary *** patients with metastasis died during follow‐up,with a mean survival of 10.2 *** age was associated with lymphatic metastasis (P = 0.0267).Other factors,including tumor recurrence,size,grade,cartilage invasion,and positive margins,were evaluated and not significantly associated with ***:In this study,the metastatic rate of auricular SCC was 6.35%,which is within the previously reported *** histological prognostic factors were identified in this study,which may be due to our limited sample *** the absence of established prognostic criteria,decisions regarding prophylactic treatment should be made on an individual basis with multidisciplinary support.

关键词： cutaneous malignancy external ear metastasis squamous cell carcinoma

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Overlooked uneven progress across sustainable development goals at the global scale: Challenges and opportunities

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The Innovation 2024年第2期5卷 42-50页

作者： Yali Liu j.anqing Du Yanfen Wang Xiaoyong Cui j.chang Dong Pan Gu Yanbin Hao Kai Xue Hongbo Duan Anquan Xia Yi Hu Zhi Dong Bingfang Wu j.urgen P.Kropp Boj.e Fu School of Grassland Science Beijing Forestry UniversityBeijing 100083China Beij.ng Yanshan Earth Critical Zone National Research Station University of Chinese Academy of SciencesBeijing 101408China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Tibetan Plateau Earth System Environment and ResourcesChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China School of Economics and Management University of Chinese Academy of SciencesBeijing 100190China School of Humanities University of Chinese Academy of SciencesBeijing 100049China Key Laboratory of Adaptation and Evolution of Plateau Biota Northwest Institute of Plateau BiologyChinese Academy of SciencesXining 810001China School of Innovation and Entrepreneurship University of Chinese Academy of SciencesBeijing 100190China State Key Laboratory of Remote Sensing Science Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100101China Potsdam Institute for Climate Impact Research 14412 PotsdamGermany Institute for Environmental Science and Geography University of Potsdam14412 PotsdamGermany State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Differences in progress across sustainable development goals(SDGs)are widespread globally;meanwhile,the rising call for prioritizing specific SDGs may exacerbate such ***,how these progress differences would influence global sustainable development has been long ***,we present the first quantitative assessment of SDGs’progress differences globally by adopting the SDGs progress evenness *** results highlight that the uneven progress across SDGs has been a hindrance to sustainable development because(1)it is strongly associated with many public health risks(e.g.,air pollution),social inequalities(e.g.,gender inequality,modern slavery,wealth gap),and a reduction in life expectancy;(2)it is also associated with deforestation and habitat loss in terrestrial and marine ecosystems,increasing the challenges related to biodiversity conservation;(3)most countries with low average SDGs performance show lower progress evenness,which further hinders their fulfillment of SDGs;and(4)many countries with high average SDGs performance also showcase stagnation or even retrogression in progress evenness,which is partly ascribed to the antagonism between climate actions and other *** findings highlight that while setting SDGs priorities may be more realistic under the constraints of multiple global stressors,caution must be exercised to avoid new problems from intensifying uneven progress across ***,our study reveals that the urgent needs regarding SDGs of different regions seem complementary,emphasizing that regional collaborations(e.g.,demand-oriented carbon trading between SDGs poorly performed and well-performed countries)may promote sustainable development achievements at the global scale.

关键词： globally priori inequality

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A novel diagnostic gene region for distinguishing between two pest fruit flies:Bactrocera tryoni(Froggatt)and Bactrocera neohumeralis(Hardy)(Diptera:Tephritidae)

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Insect Science 2024年第4期31卷 1285-1295页

作者： Melissa L.Starkie Elizabeth V.Fowler Alexander M.Piper Xiaocheng Zhu Pauline Wyatt David Gopurenko Matt N.Krosch Francesca Strutt Karen F.Armstrong Hamish Patrick Mark K.Schutze Mark j.Blacket Department of Agriculture and Fisheries BiosecurityBrisbaneQueenslandAustralia Agriculture Victoria AgriBioBundooraVictoriaAustralia Department of Primary Industries Wagga Wagga Agricultural InstituteWagga WaggaNew South WalesAustralia Forensic Services Group Queensland Police ServiceBrisbaneQueenslandAustralia Department of Pest-management and Conservation Lincoln UniversityLincolnNew Zealand Better Border Biosecurity(B3 B3nz.org.nz)LincolnNew Zealand

Bactrocera tryoni and Bactrocera neohumeralis are morphologically similar sibling pest fruit fly species that possess different biological attributes,geographic distributions,and host *** need to differentiate between the two species is critical for accurate pest status assessment,management,biosecurity,and maintenance of reference *** morphologically similar,adults may be separated based on subtle characters;however,some characters exhibit intraspecific variability,creating overlap between the two ***,there is currently no single molecular marker or rapid diagnostic assay that can reliably distinguish between *** and ***;therefore,ambiguous samples remain *** we report the first molecular marker that can consistently distinguish between *** and *** diagnostic region consists of two adj.cent single nucleotide polymorphisms(SNPs)within the pangolin(pan)gene *** confirmed the genotypes of each species are consistent across their distributional range,then developed a tetra-primer amplification refractory mutation system(ARMS)PCR assay for rapid diagnosis of the *** assay utilizes four primers in multiplex,with two outer universal primers,and two internal primers:one designed to target two adj.cent SNPs(AA)present in *** and the other targeting adj.cent SNPs present in ***(GG).The assay accurately discriminates between the two species,but their SNP genotypes are shared with other nontarget tephritid fruit fly ***,this assay is most suited to adult diagnostics where species confirmation is necessary in determining ambiguous surveillance trap catches;maintaining pure colony lines;and in Sterile Insect Technique management responses.

关键词： ARMS-PCR colony molecular diagnostics pangolin tetra-primer

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj.j.nny Cheung j.nnifer Zhang Kaveh Mirmoeini j.aul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adj.stable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve inj.ry nerve regeneration nerve wrap tacrolimus

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Sport and exercise during viral acute respiratory illness——Time to revisit

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j.urnal of Sport and Health Science 2024年第5期13卷 663-665页

作者： Olli Ruuskanen Maarit Valtonen Matti Waris Raakel Luoto Olli j.einonen Department of Pediatrics and Adolescent Medicine Turku University Hospital and University of TurkuTurku 20521Finland Finnish Institute of High Performance Sport KIHU Jyvaskyla 40700Finland Institute of Biomedicine University of Turku and Department of Clinical VirologyTurku University HospitalTurku 20520Finland Paavo Nurmi Centre and Unit for Health and Physical Activity University of TurkuTurku 20520Finland

Athletes are commonly advised not to compete or train during maj.r symptoms of a viral acute respiratory illness(ARI),which most commonly is a common *** has been traditionally thought that heavy physical stress could induce the worsening of symptoms of ARI and possibly cause potentially severe complications like myocarditis or sudden cardiac death(SCD).In addition,viral ARI may decrease athlete's performance.1 These concerns have been recently stressed during the coronavirus disease 2019(COVID-19)pandemic.2 However,it is anecdotally well-known that athletes commonly compete while experiencing common colds,most commonly due to picornaviral *** this perspective,we discuss what is known or not known regarding the risks of exercising during the viral ARI.

关键词： traditionally illness tally

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Impact of temporal modulations on laser-induced damage of fused silica at 351 nm

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High Power Laser Science and Engineering 2023年第2期11卷 1-9页

作者： C.Bouyer R.Parreault N.Roquin j.-Y.Natoli L.Lamaignère CEA CESTA Le BarpFrance Aix-Marseille Univ CNRSCentrale MarseilleInstitut FresnelMarseilleFrance

Laser-induced damage(LID)on high-power laser facilities is one of the limiting factors for the increase in power and *** confinement fusion(ICF)facilities such as Laser Mégaj.ule or the National Ignition Facility use spectral broadening of the laser pulse that may induce power modulations because of frequency modulation to amplitude modulation *** this paper,we study the impact of low and fast power modulations of laser pulses both experimentally and *** MELBA experimental testbed was used to shape a wide variety of laser pulses and to study their impact on LID.A 1D Lagrangian hydrodynamic code was used to understand the impact of different power profiles on LID.

关键词： fused silica high-power laser laser diagnostics laser-induced damage

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Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

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World j.urnal of Gastrointestinal Oncology 2022年第2期14卷 511-524页

作者： Lauren Midthun Sungj.n Kim Andrew Hendifar Arsen Osipov Samuel j.Klempner j.seph Chao may Cho Michelle Guan Veronica R Placencio-Hickok Alexandra Gangi Miguel Burch De-Chen Lin Kevin Waters Katelyn Atkins Mitchell Kamrava j.n Gong Department of Medicine Division of Hematology and OncologyCedars-Sinai Medical CenterLos AngelesCA 90048United States Biostatistics and Bioinformatics Research Center Cedars Sinai Medical CenterLos AngelesCA 90048United States Samuel Oschin Cancer Center Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Beth Israel Deaconess Medical Center/Harvard Medical SchoolBrigham and Women's Hospital/Harvard Medical SchoolBostonMA 02114United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaIrvineCA 92697United States Department of Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Pathology and Laboratory Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal ***,not all patients with metastatic disease receive *** To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and *** We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without *** A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving *** median follow-up was 69.45 *** median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no *** of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving *** the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on ***,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic

关键词： Esophageal cancer Metastatic Chemotherapy Predictors Survival

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