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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

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Nano Research 2024年第10期17卷 9052-9064页

作者： Savannah e.est-Witte Sydney R.Shannon Dennis H.Gong Kaitlyn G.Calabresi jawaun j.Harris Kaitlyn Storm edwin j.Yoo Ariel Isser Vivek P.jani Natalie K.Livingston Mary o.omotoso Kelly Rhodes elana Ben-Akiva Randall A.Meyer Zoe T.Hsieh Simone Sidoli Stephany Y.Tzeng jonathan P.Schneck jordan j.Green Translational Tissue engineering Center Institute for NanobiotechnologyDepartment of Biomedical EngineeringJohns Hopkins School of Medicine400 N BroadwayBaltimoreMD 21231USA Institute for Cell engineering Department of PathologyJohns Hopkins School of Medicine733 N BroadwayBaltimoreMD 21205USA Department of Biochemistry Albert Einstein College of MedicineThe BronxNew York CityNY 10461USA

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical *** ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor *** effective,this process is resource-intensive and logistically impossible for many *** artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo *** particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after *** to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of *** properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell *** literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in *** the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive *** this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

关键词： adoptive cell therapy artificial antigen presenting cells particle drug delivery elasticity protein corona poly(ethylene glycol)

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Surgeon preferences in the treatment of thumb carpometacarpal osteoarthritis

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World journal of orthopedics 2024年第5期15卷 435-443页

作者： edward j Wu Bradley W Fossum Wyatt Vander Voort Christopher o Bayne Robert M Szabo Department of orthopedic Surgery University of Minnesota Medical SchoolMinneapolisMN 55455United States Department of orthopaedic Surgery UC Davis School of MedicineSacramentoCA 95817United States

BACKGRoUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand *** the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy *** The purpose of our study was to determine why surgeons opt for their technique in treating CMC *** A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC *** were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic *** of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their *** who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their *** of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional *** of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and freque

关键词： Thumb carpometacarpal osteoarthritis Trapeziectomy Ligament reconstruction tendon interposition Suspensionplasty Preferences Trends

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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.o.Beeren G.Dos Santos P.j.Dijkstra C.Mota j.Bauer H.Ferreira Rui L.Reis N.Neves S.Camarero-espinosa M.B.Baker L.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal PoLYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKeRBASQUe Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(Me-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for Me-AM community that desires to tune the bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending Surface functionalization Surface density Click chemistry Human

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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton o.McDonald Laxman Pokhrel Duy H.Hua evan C.Titgemeyer Barry j.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

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Physical activity volume,frequency,and intensity:Associations with hypertension and obesity over 21 years in Australian women

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journal of Sport and Health Science 2024年第5期13卷 631-641页

作者： Gregore I.Mielke Ding Ding Shelley e.Keating Bruno P.Nunes Ruth Brady Wendy j.Brown School of Public Health The University of QueenslandBrisbaneQLD 4006Australia Sydney School of Public Health Faculty of Medicine and HealthThe University of SydneySydneyNSW 2006Australia The Charles Perkins Centre The University of SydneySydneyNSW 2006Australia School of Human Movement and Nutrition Sciences The University of QueenslandBrisbaneQLD 4072Australia School of Nursing Federal University of PelotasPelotasRio Grande do Sul 96010-610Brazil Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4226Australia

Background:optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not *** overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 ***,we investigated whether,for the same weekly volume of PA,the number of sessions(frequency)and vigorousness of PA(intensity)were associated with a reduction in the occurrence of hypertension and obesity in ***:Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed(n=20,588;12%-16%with a Bachelor's or higher degree).Self-reported PA,hypertension,height,and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/*** estimating equation models with a 3-year lag model were used to investigate the association of PA volume(metabolic equivalent min/week)(none;33-499;500-999;≥1000,weekly frequency(none;1-2 times;3-4times;5-7 times;≥8 times),and the proportion of vigorous PA to total volume of PA(none;0%;1%-33%;34%-66%;67%-100%)with odds of hypertension and obesity from 2000 to ***:The cumulative incidence of hypertension was 6%in the 1973-1978 and 23%in the 1946-1951 cohort;27%of women in the 1973-1978;and 15%in the 1946-1951 cohort developed obesity over the ***,a higher volume of PA was associated with reduced odds of hypertension and *** the volume of PA was considered,the odds of hypertension did not vary according to the frequency or intensity of ***,increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obe ***:PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and *** more sessions,particularly of vigorous-intensity PA,may provide extr

关键词： Physical activity Frequency Intensity Incidences epidemiology Women

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Cavity-agnostic acoustofluidic manipulations enabled by guided flexural waves on a membrane acoustic waveguide actuator

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Microsystems & Nanoengineering 2024年第2期10卷 153-171页

作者： Philippe Vachon Srinivas Merugu jaibir Sharma Amit Lal eldwin j.Ng Yul Koh joshua e.-Y.Lee Chengkuo Lee Department of electrical and Computer engineering National University of SingaporeSingaporeSingapore Institute of Microelectronics Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore SonicMeMS Laboratory School of Electrical and Computer EngineeringCornell UniversityIthacaNYUSA School of electrical and Data engineering University of Technology SydneyUltimoNSWAustralia

This article presents an in-depth exploration of the acoustofluidic capabilities of guided flexural waves(GFWs)generated by a membrane acoustic waveguide actuator(MAWA).By harnessing the potential of GFWs,cavity-agnostic advanced particle manipulation functions are achieved,unlocking new avenues for microfluidic systems and lab-on-a-chip *** localized acoustofluidic effects of GFWs arising from the evanescent nature of the acoustic fields they induce inside a liquid medium are numerically investigated to highlight their unique and promising *** traditional acoustofluidic technologies,the GFWs propagating on the MAWA’s membrane waveguide allow for cavity-agnostic particle manipulation,irrespective of the resonant properties of the fluidic ***,the acoustofluidic functions enabled by the device depend on the flexural mode populating the active region of the membrane *** demonstrations using two types of particles include in-sessile-droplet particle transport,mixing,and spatial separation based on particle diameter,along with streaming-induced counter-flow virtual channel generation in microfluidic PDMS *** experiments emphasize the versatility and potential applications of the MAWA as a microfluidic platform targeted at lab-on-a-chip development and showcase the MAWA’s compatibility with existing microfluidic systems.

关键词： waveguide fluid cavity

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Numerical analysis of high‑speed railway slab tracks using calibrated and validated 3D time‑domain modelling

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Railway engineering Science 2024年第1期32卷 36-58页

作者： A.F.esen o.Laghrouche P.K.Woodward D.Medina‑Pineda Q.Corbisez j.Y.Shih D.P.Connolly Institute for High‑Speed Rail and System Integration University of LeedsLeeds LS29JTUK Institute for Infrastructure and environment Heriot-Watt UniversityEdinburgh EH144ASUK Alstom Transport Saint‑OuenFrance Birmingham Centre for Railway Research and education University of BirminghamBirmingham B152TTUK

Concrete slabs are widely used in modern railways to increase the inherent resilient quality of the tracks,provide safe and smooth rides,and reduce the maintenance *** this paper,the elastic performance of a novel slab trackform for high-speed railways is investigated using three-dimensional finite element modelling in *** is then compared to the performance of a ballasted ***,slab and ballasted track models are developed to replicate the full-scale testing of track *** the models are calibrated with the experimental results,the novel slab model is developed and compared against the calibrated slab track *** slab and ballasted track models are then extended to create linear dynamic models,considering the track geodynamics,and simulating train passages at various speeds,for which the Ledsgard documented case was used to validate the *** travelling at low and high speeds are analysed to investigate the track deflections and the wave propagation in the soil,considering the issues associated with critical *** train loading methods are discussed,and the most practical approach is retained and ***,correlations are made between the geotechnical parameters of modern high-speed rail and conventional *** is found that considering the same ground condition,the slab track deflections are considerably smaller than those of the ballasted track at high speeds,while they show similar behaviour at low speeds.

关键词： High-speed railways Slab track New ballastless track Ballasted track Critical speeds Finite element modelling Calibration of numerical models

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SARS-CoV-2 triggers Dickkopf-1(Dkk-1)modulation of T helper cells and lung pathology in mice

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Genes & Diseases 2024年第4期11卷 9-12页

作者： Yifan Wu Freedom M.Green Stephen A.Shaw Lauren j.Bonilla Shannon e.Ronca Maria elena Bottazzi Farrah Kheradmand jill e.Weatherhead Department of Pathology&Immunology One Baylor PlazaHoustonTX 77030USA Department of Pediatrics One Baylor PlazaHoustonTX 77030USA Department of Medicine One Baylor PlazaHoustonTX 77030USA National School of Tropical Medicine One Baylor PlazaHoustonTX 77030USA Molecular Virology&Microbiology One Baylor PlazaHoustonTX77030USA Biologyof Inflammation Center Baylor College of MedicineOne BaylorPlazaHoustonTX77030USA Michael e.DeBakey VA Center for Translational Research on Inflammatory Diseases HoustonTX 77030USA

Severe acute respiratory syndrome coronavirus 2(SARSCov-2)is the etiologic agent of the coronavirus disease 19(CoVID-19)*** viral infections like SARS-CoV-2,a robust anti-viral type 1 immune response,including upregulation of type 1 CD4+T helper cells(Th1),is required for effective viral clearance while minimizing end-organ pathology and collateral tissue damage.

关键词： pathology acute respiratory

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Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

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journal of Sport and Health Science 2024年第3期13卷 409-418页

作者： jérémy Raffin Yves Rolland Annelise Genoux Guillaume Combes Mikael Croyal Bertrand Perret Sophie Guyonnet Bruno Vellas Laurent o.Martinez Philipe de Souto Barreto For the MAPT/DSA Group Institut du Vieillissement Gérontopôle de ToulouseCentre Hospitalo-Universitaire de ToulouseToulouse 31000France Centre d'epidémiologie et de Recherche en Santédes Populations UnitéMixte de Recherche 1295Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse-III-Paul-SabatierToulouse 31000France LimitAging Team Institut des Maladies Métaboliques et CardiovasculairesUnitéMixte de Recherche 1297Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse III-Paul SabatierToulouse 31432France Service de Biochimie Pôle de biologieHôpital de PurpanCentre Hospitalo-Universitaire de ToulouseToulouse 31300France L'Institut du Thorax Institut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France BioCore US16Structure Fédérative de Recherche BonamyInstitut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France Plate-forme de spectrométrie de masse Centre de Recherche en Nutrition HumaineOuestNantes 44000France 不详

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy ***1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains ***,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP *** examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these ***:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were ***1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year *** linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 *** analyses were conducted to examine whether apoA-I mediated these *** linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in ***:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;Se=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;Se=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;Se=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly med

关键词： Aging Apolipoprotein Bioenergetics exerkine Mitochondria

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Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas eduardo e.Rodriguez Laura M.jensen Raluca G.Mateescu Peter j.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PeBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PeBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PeBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

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