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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James David Hudson Kevin n.Dalby Lin Xu Robert J.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RnA sequencing(scRnA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRnA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Commentary on"An alternative surgical technique for varicoceles:a preliminary experience of the microsurgical spermatic(distal end)-inferior or superficial epigastric vein anastomosis in symptomatic varicoceles associated with perineal pain"

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Asian Journal of Andrology 2022年第6期24卷 680-680页

作者： peter n Schlegel Weill Cornell Medicine New YorkNY10021USA

In the article by Wan et al.,the authors have described a different surgical approach limited to the treatment of men with varicoceles and pelvic floor congestion associated with perineal *** discuss the procedure used,which is essentially a decompression of the varicocele via anastomosis of the distal spermatic veins to the superficial epigastric veins and postoperative *** intervention is distinctly different from the standard approach of occlusion of spermatic veins(surgically or by embolization)typically at the subinguinal,inguinal,or retroperitoneal level.

关键词： superficial surgical varicocele

Influence of MBBR carrier geometrical properties and biofilm thickness restraint on biofilm properties,effluent particle size distribution,settling velocity distribution,and settling behaviour

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Journal of Environmental Sciences 2022年第12期34卷 138-149页

作者： Raheleh Arabgol peter A.Vanrolleghem Robert Delatolla Department of Civil Engineering University of Ottawa161 Louis PasteurK1N 6N5 ONCanada ModelEAU Département de génie civil et de génie des eauxUniversitéLaval1065 av.de la MédecineQuébecCanada

The relatively poor settling characteristics of particles produced in moving bed biofilm reactor(MBBR)outline the importance of developing a fundamental understanding of the characterization and settleability of MBBR-produced *** influence of carrier geometric properties and different levels of biofilm thickness on biofilm characteristics,solids production,particle size distribution(PSD),and particle settling velocity distribution(PSVD)is evaluated in this *** analytical Vi CAs method is applied to the MBBR effluent to assess the distribution of particle settling *** method is combined with microscopy imaging to relate particle size distribution to settling *** conventionally loaded MBBR systems are studied at a similar loading rate of 6.0 g/(m^(2)·day)and with different carrier *** AnoxK^(TM)K5 carrier,a commonly used carrier,is compared to so-called thickness-restraint carriers,AnoxK^(TM)Z-carriers that are newly designed carriers to limit the biofilm ***,two levels of biofilm thickness,200μm and 400μm,are studied using AnoxK^(TM)Z-200 and Z-400 *** analysis confirms that K5 carriers demonstrated a significantly different biofilm mass,thickness,and density,in addition to distinct trends in PSD and PSVD in comparison with ***,in comparison of thickness-restraint carriers,Z-200 carrier results did not vary significantly compared to the Z-400 *** K5 carriers showed the lowest production of suspended solids(0.7±0.3 gTSS/day),thickest biofilm(281.1±8.7μm)and lowest biofilm density(65.0±1.5 kg/m^(3)).The K5 effluent solids also showed enhanced settling behaviour,consisting of larger particles with faster settling velocities.

关键词： MBBR Particle size distribution(PSD) Particle settling velocity distribution(PSVD) Settling behaviour ViCAs z-carriers

Upper bounds of Schubert polynomials

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Science China Mathematics 2022年第6期65卷 1319-1330页

作者： neil Jiuyu Fan peter Long Guo Department of Mathematics Sichuan UniversityChengdu 610064China Center for Combinatorics LPMCNankai UniversityTianjin 300071China

Let w be a permutation of{1,2,...,n},and let D(w)be the Rothe diagram of *** Schubert polynomial■w_(x)can be realized as the dual character of the flagged Weyl module associated with D(w).This implies the following coefficient-wise inequality:Min_(x)≤■_(w)(x)≤Max_(w)xwhere both Min_(w)(x)and Max_(w)(x)are polynomials determined by D(w).Fink et al.(2018)found that■w_(x)equals the lower bound Min_(w)(x)if and only if w avoids twelve permutation *** this paper,we show that■w_(x)reaches the upper bound Max_(w)(x)if and only if w avoids two permutation patterns 1432 and ***,for any given compositionα∈Z^(n)≥0,one can define a lower bound Min_(α)(x)and an upper bound Max_(α)(x)for the key polynomialκ_(α)(x).Hodges and Yong(2020)established thatκ_(α)(x)equals Min_(α)(x)if and only ifαavoids five composition *** show thatκ_(α)(x)equals Max_(α)(x)if and only ifαavoids a single composition pattern(0,2).As an application,we obtain that whenαavoids(0,2),the key polynomialκ_(α)(x)is Lorentzian,partially verifying a conjecture of Huh et al.(2019).

关键词： Schubert polynomial key polynomial flagged Weyl module upper bound Lorentzian polynomial

Deletion or underexpression of the Y-chromosome genes CDY2 and HSFY is associated with maturation arrest in American men with nonobstructive azoospermia

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Asian Journal of Andrology 2012年第5期14卷 676-682页

作者： peter J Stahl Anna n Mielnik Christopher E Barbieri peter n Schlegel Darius A Paduch Department of Urology Weill Cornell Medical CollegeNew York Presbyterian HospitaI-CornellNew YorkNY 10065USA

Maturation arrest （MA） refers to failure of germ cell development leading to clinical nonobstructive azoospermia. Although the azoospermic factor （AZF） region of the human Y chromosome is clearly implicated in some cases, thus far very little is known about which individual Y-chromosome genes are important for complete male germ cell development. We sought to identify single genes on the Y chromosome that may be implicated in the pathogenesis of nonobstructive azoospermia associated with MA in the American population. Genotype-phenotype analysis of 132 men with Y-chromosome microdeletions was performed. Protein-coding genes associated with MA were identified by visual analysis of a genotype-phenotype map. Genes associated with MA were selected as those genes within a segment of the Y chromosome that, when completely or partially deleted, were always associated with MA and absence of retrievable testicular sperm. Expression of each identified gene transcript was then measured with quantitative RT-PCR in testicular tissue from separate cohorts of patients with idiopathic MA and obstructive azoospermia. Ten candidate genes for association with MA were identified within an 8.4-Mb segment of the Y chromosome overlapping the AZFb region. CDY2and HSFYwere the only identified genes for which differences in expression were observed between the MA and obstructive azoospermia cohorts. Men with obstructive azoospermia had 12-fold higher relative expression of CDY2transcript （1.33__.0.40 vs. 0.11＋_0.04; P=O.O003） and 16-fold higher expression of HSFYtranscript （0.78__.0.32 vs. 0.05_0.02; P=O.O005） compared to men with MA. CDY2 and HSFYwere also underexpressed in patients with Sertoli cell only syndrome. These data indicate that CDY2and HSFYare located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with MA. These observations suggest that impairments in CDY2 or HSFYexpression could be impli

关键词： CDY1 protein CDY2 protein genetics histology HSFY human make infertility nonobstructive azoospermia spermato-genesis sperm maturation

Microdissection testicular sperm extraction： an update

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Asian Journal of Andrology 2013年第1期15卷 35-39页

作者： Ali A Dabaja peter n Schlegel Department of Urology Male Reproductive Medicine Weill Cornell Medical College New York NY 10065 USA

Patients with non-obstructive azoospermia （nOA） were once considered to be infertile with few treatment options due to the absence of sperm in the ejaculate. In the last two decades, the advent of intracytoplasmic sperm injection （ICSI）, and the application of various testicular sperm retrieval techniques, including fine needle aspiration （FnA）, conventional testicular sperm extraction （TESE） and microdissection testicular sperm extraction （micro-TESE） have revolutionized treatment in this group of men. Because most men with nOA will have isolated regions of spermatogenesis within the testis, studies have illustrated that sperm can be retrieved in most men with nOA, including Klinefelter＇s syndrome （KS）, prior history of chemotherapy and cryptorchidism. Micro-TESE, when compared with conventional TESE has a higher sperm retrieval rate （SRR） with fewer postoperative complications and negative effects on testicular function. In this article, we will compare the efficacy of the different procedures of sperm extraction, discuss the medical treatment and the role of testosterone optimization in men with nOA and describe the micro-TESE surgical technique. Furthermore, we will update our overall experience to allow counseling on the prognosis of sperm retrieval for the specific subsets of nOA.

关键词： azoospermia genetics male infertility microsurgery non-obstructive azoospermia sperm retrieval testicular sperm extraction

Serological biomarkers for management of primary sclerosing cholangitis

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World Journal of Gastroenterology 2022年第21期28卷 2291-2301页

作者： David Tornai peter Laszlo Ven peter Laszlo Lakatos Maria Papp Division of Gastroenterology Department of Internal MedicineFaculty of MedicineUniversity of DebrecenDebrecen H-4032Hajdu-BiharHungary European Reference network on Hepatological Diseases ERN RARE-LIVERDebrecen H-4032Hajdu-BiharHungary The First Department of Medicine Division of GastroenterologyUniversity of PécsPécs H-7624BaranyaHungary Kálmán Laki Doctoral School of Biomedical and Clinical Sciences Faculty of MedicineUniversity of DebrecenDebrecen H-4032Hajdu-BiharHungary Division of Gastroenterology McGill University Health CentreMontreal QC H4A 3J1QuebecCanada The First Department of Medicine Semmelweis UniversityBudapest H-1083PestHungary

Clinical manifestations and progression of primary sclerosing cholangitis(PSC)are heterogeneous,and its pathogenesis is poorly *** importance of gut-liver interactions in the pathogenesis has been clinically confirmed and highlighted in different *** advances regarding biomarkers of biliarygut crosstalk may help to identify clinically relevant PSC subgroups assisting everyday clinical work-up(e.g.,diagnosis,disease stratification,or surveillance)and the exploration of potential therapeutic *** phosphatase produced by the biliary epithelium is consistently associated with ***,its level shows natural fluctuation limiting its use in individual ***,cell activation,and tissue remodeling markers have been reported to predict clinical *** immunoglobulin(Ig)G4 level is associated with a shorter transplantation-free *** type atypical perinuclear anti-neutrophil cytoplasmic antibodies(P-AnCAs)are non-specific markers of various autoimmune liver diseases and may reflect an abnormal B-cell response to gut microbial *** type atypical P-AnCA identifies PSC patients with particular clinical and genetic(for human leukocyte antigens)*** presence of IgA type anti-F-actin antibody(AAA)may predict a progressive disease course,and it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte *** type anti-glycoprotein 2(GP2)antibodies identify patients with a severe disease phenotype and poor survival due to enhanced fibrogenesis or development of *** soluble vascular adhesion protein-1(sVAP-1)level is associated with adverse disease outcomes in *** sVAP-1 levels correlate with mucosal addressin cell adhesion molecule-1(MAdCAM-1)expression in the liver that contributes to gut activated T-cell homing to the hepatobiliary *** the present paper,we review the evidence on these possible serological ma

关键词： Primary sclerosing cholangitis Hepatobiliary Serological biomarker Immunoglobulin Inflammatory Tissue remodeling

Complementary effect of zoo compost with mineral nitrogen fertilisation increases wheat yield and nutrition in a low-nutrient soil

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Pedosphere 2022年第2期32卷 339-347页

作者： Muhammad S.A.KHAn Lynette K.ABBOTT Zakaria M.SOLAIMAn peter R.MAWSOn Ian S.WAITE Sasha n.JEnKInS School of Agriculture and Environment Institute of AgricultureThe University of Western AustraliaPerth WA 6009Australia Perth Zoo Department of BiodiversityConservation and AttractionsPerth WA 6151Australia Agricultural Officer(Headquarters) DirectorateSoil Fertility Research InstituteAgriculture DepartmentGovernment of the PunjabLahore 53700Pakistan

Excess nitrogen(n) fertiliser use in agriculture is associated with water pollution and greenhouse gas *** practices and programs to reduce n fertiliser application continue to be developed,inefficient fertiliser use *** that reduce mineral n fertiliser application are needed in a sustainable agricultural ecosystem to control leaching and gaseous losses for environmental *** study evaluated whether fully or partially replacing mineral n fertiliser with zoo compost(Perth Zoo) could be a good mitigation strategy to reduce mineral n fertiliser application without affecting wheat yield and *** achieve this,a glasshouse experiment was conducted to assess the complementary effect of zoo compost and mineral n fertiliser on wheat yield and nutrition in a sandy soil of southwestern ***,a chlorophyll meter was used to determine whether there was a correlation between chlorophyll content and soil mineral n content,grain n uptake,and grain protein content at the tillering(42 d after sowing(DAS)) and heading(63 DAS) growth *** standard practice for n application for this soil type in this area,100 kg ha^(-1),was used with a soil bulk density of 1.3 g cm^(-3) to calculate the amount of mineral n(urea,46% n) and Perth Zoo compost(ZC)(0.69% n) for each *** comprised a control(no nutrients added,T1),mineral n only(100 kg n ha^(-1),T2),ZC only(100 kg n ha^(-1),T7),and combinations of mineral n and ZC at different rates(mineral n at 100 kg n ha^(-1)+ ZC at 25 kg n ha^(-1)(T3),mineral n at 75 kg n ha^(-1)+ ZC at 25 kg n ha^(-1)(T4),mineral n at 75 kg n ha^(-1)+ ZC at 50 kg n ha^(-1)(T5),and mineral n at 50 kg n ha^(-1)+ ZC at 50 kg n ha^(-1)(T6)).The T6 treatment significantly increased grain yield(by 26%) relative to the T2 ***,the T7 treatment did not affect grain yield when compared to the T2 *** treatments with mineral n and ZC in combination significantly improved the

关键词： chlorophyll meter SPAD measurement integrated nutrient management nitrogen use efficiency reduced n fertiliser application wheat yield

Isolated Bell's palsy-An unusual presentation of dengue infection

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Asian Pacific Journal of Tropical Medicine 2013年第1期6卷 82-84页

作者： Soumia peter Malhotra n peter P Sood R Department of Medicine Christian Medical College & Hospital Department of Radiodiagnosis Christian Medical College & Hospital

Dengue fever is a very common arthropod-borne infection in tropical *** complications in dengue fever are relatively uncommon and among these,isolated cranial neuropathies have been reported only very *** present an unusual neurological complication of Bell’s palsy(lower motor neuron 7 th nerve palsy) associated with dengue *** the best of our knowledge,there have been very few documented cases of Flavivirus causing isolated Bell’s palsy.

关键词： Dengue infection Bell’s palsy