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Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9

Bone Research 2015年第3期3卷 140-151页

作者： Anat Kohn timothy p rutkowski Zhaoyang Liu Anthony J Mirando Michael J Zuscik Regis J O'Keefe Matthew J Hilton Department of Orthopaedics and Rehabilitation The Center for Musculoskeletal Research University of Rochester Medical Center Department of Biomedical Genetics University of Rochester Medical Center Department of Biology University of Rochester Department of Orthopaedic Surgery Duke Orthopaedic Cellular Developmental and Genome Laboratories Duke University School of Medicine Department of Orthopaedic Surgery Washington University School of Medicine

RBpjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBpjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant（prx1Cre;Rbpjkf/f）, Rbpjk mutant/Sox9 haploinsufficient（prx1Cre;Rbpjkf/f;Sox9f/1）,and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.

关键词： Figure Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9 NICD SOX

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Kinetics of glyphosate and aminomethylphosphonic acid sorption onto montmorillonite clays in soil and their translocation to genetically modified corn

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Journal of Environmental Sciences 2024年第1期135卷 669-680页

作者： Meichen Wang Kelly J Rivenbark timothy D phillips Veterinary physiology and pharmacology College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityTX 77845USA

The co-occurrence of glyphosate(GLp)and aminomethylphosphonic acid(AMpA)in contaminated water,soil,sediment and plants is a cause for concern due to potential threats to the ecosystem and human health.A major route of exposure is through contact with contaminated soil and consumption of crops containing GLp and AMpA residues.However,clay-based sorption strategies for mixtures of GLp and AMpA in soil,plants and garden produce have been very limited.In this study,in vitro soil and in vivo genetically modified corn models were used to establish the proof of concept that the inclusion of clay sorbents in contaminated soils will reduce the bioavailability of GLp and AMpA in soils and their adverse effects on plant growth.Effects of chemical concentration(1–10 mg/kg),sorbent dose(0.5%-3%in soil and 0.5%-1%in plants)and duration(up to 28 days)on sorption kinetics were studied.The time course results showed a continuous GLp degradation to AMpA.The inclusion of calcium montmorillonite(CM)and acid processed montmorillonite(ApM)clays at all doses significantly and consistently reduced the bioavailability of both chemicals from soils to plant roots and leaves in a dose-and time-dependent manner without detectable dissociation.plants treated with 0.5%and 1%ApM inclusion showed the highest growth rate(p≤0.05)and lowest chemical bioavailability with up to 76%reduction in roots and57%reduction in leaves.Results indicated that montmorillonite clays could be added as soil supplements to reduce hazardous mixtures of GLp and AMpA in soils and plants.

关键词： Glyphosate AMpA Adsorption Soil remediation plant Hydroponic system

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Bulking Up the Bay-position Substituents Enables Enhanced Selectivity of Cs‑Symmetric Boron Subphthalocyanine−Subnaphthalocyanine Hybrids

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precision Chemistry 2024年第4期2卷 161-181页

作者： Nina F.Farac Alan J.Lough timothy p.Bender Department of Chemical Engineering and Applied Chemistry University of TorontoTorontoOntario M5S 3E5Canada Department of Chemistry University of TorontoTorontoOntario M5S 3H6Canada Department of Materials Science and Engineering University of TorontoTorontoOntario M5S 3E4Canada Department of Mechanical and Industrial Engineering University of TorontoTorontoOntario M5S 3G8Canada

The precise synthesis of subporphyrinoid hybrids withπ-expanded topologies and unique material properties plays a promising role in the design of functional macrocycles.Easy,selective,and controllable routes to boron subphthalocyanine−subnaphthalocyanine hybrids,Bsub(pc_(3‑p)-Ncp)s,are desirable for this purpose yet synthetically challenging due to random mixtures of Cs-,C3v-,and,in some cases,C1-symmetric compounds that form during traditional statistical mixed cyclotrimerizations.Herein,we addressed this issue by developing a sterically driven mixed cyclotrimerization with enhanced selectivity for the targeted Cs-symmetric hybrid and complete suppression of sterically crowded macrocyclic byproducts.This process,coupled with a rationally designed precursor bearing bulky phenyl substituents,enabled the synthesis and characterization of bay-position phenylated ph2-(Rp)8Bsub(pc_(2)-Nc_(1))hybrids with halogens(Rp=Cl or F)in their peripheral isoindole rings.Reaction selectivity ranged between 59 and 72%with remarkable yields,significantly higher than that of conventional mixed cyclotrimerizations.These findings were augmented by theoretical calculations on precursor Lewis basicity as guiding principles into hybrid macrocycle formation.Additionally,the incorporation of unfused phenyl groups and halogen atoms into the hybrid framework resulted in fine-tuned optical,structural,electronic,and electrochemical properties.This straightforward approach achieved improved selectivity and controlled narrowing of the product distribution,affording the efficient synthesis of structurally sophisticated Bsub(pc_(2)-Nc_(1))hybrids.This then expands the library of 3-dimensionalπ-extended macrocycles for use in a range of applications,such as in optoelectronic devices with precisely tailored optical properties.

关键词： subphthalocyanine hybrids low-symmetry aromatic macrocycle selective cyclotrimerization sterically driven chemistry broad absorption material properties

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Acetabular cup size trends in total hip arthroplasty

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World Journal of Orthopedics 2024年第1期15卷 39-44页

作者： Daniel patrick McKenna Alex price timothy McAleese Darren Dahly paul McKenna May Cleary Department of Trauma and Orthopaedics University Hospital WaterfordWaterford X91 ER8EIreland Department of Epidemiology and public Health University College CorkCork T12 XF62Ireland

BACKGROUND Total hip arthroplasty(THA)is a common procedure for end stage osteoarthritis.The learning curve for THA is complex and challenging.One of the most difficult skills to master is acetabular reaming.We wish to identify if experience in arthroplasty leads to preservation of more bone stock.AIM To investigate if increasing surgeon experience will predict an ever decreasing acetabular cup size.METHODS A retrospective case series of four attending orthopaedic surgeons was completed.All uncemented elective total hip arthroplasties since appointment were selected for inclusion.The size of acetabular cup used was noted and logistic regression was used to identify if a trend to smaller cups existed.RESULTS A total of 1614 subjects were included with a mean age of 64 years.Overall cups were on average 0.18mm smaller per year(95%confidence interval-0.25 to-0.11,pp sizes to decrease 0.27 mm/year for surgeon A,0.02 mm/year for surgeon B,0.15 mm/year for surgeon C and 0.29 mm/year for surgeon D.Three of the four surgeons had a more pronounced trend to smaller cups for male subjects than their female counterparts.CONCLUSION We found increasing surgeon experience to be associated with an ever-decreasing acetabular cup size.Smaller acetabular cup size may act as a surrogate marker of surgical proficiency by virtue of decreased acetabular reaming.

关键词： Hip Arthroplasty Acetabulum Cup Learning

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The burden and psychosocial impact on immediate caregivers of patients with spinal cord injury in a tertiary health facility,Edo State,Nigeria

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Journal of Integrative Nursing 2024年第2期6卷 103-110页

作者： timothy Aghoghko EHWARIEME Uzezi JOSIAH Auwuli EMINA Department of Nursing Science School of Basic Medical SciencesUniversity of BeninBenin CityEdo StateNigeria Department of Nursing Science Delta State University AbrakaDelta StateNigeria Department of Nursing Science Faculty of Basic Medical and Health SciencesBenson Idahosa UniversityBenin CityEdo StateNigeria

Objective:This study aimed to assess the burden and psychosocial impact of spinal cord injury on the immediate caregivers at a tertiary health facility in Benin City,Edo State.Materials and Methods:A descriptive cross-sectional survey design was adopted among 73 family caregivers in the neurological ward of a tertiary health facility using a structured questionnaire as instrument of data collection.Data collected were analyzed using descriptive statistics and multiple logistic regression.Results:Findings revealed that an overall mean of 2.73 indicates that the burden on the caregivers was moderate with a moderate psychological impact(m=2.88)and a high sociological impact(m=3.12).Factors affecting the caregiving provided by immediate caregivers include social and household responsibilities(94.5%),financial situation(89.0%),family support(83.6%),and health status of the caregiver(80.8%).Age(odds ratio[OR]=5.67,95%confidence interval[CI]:1.23-27.17,p=0.027),education(OR=3.75,95%CI:1.05-13.39,p=0.041),and“others”(spouses,siblings,friends,or extended family members)(OR=3.167,95%CI:1.583-6.337,p=0.001)were predictors for high psychological impact while education(OR=0.074;95%CI:0.015-0.370,p=0.001)and caregiving role(OR=3.167;95%CI:0.1.583-6.337,p=0.001)high sociological impact.Conclusion:Majority of the caregivers experience moderate burden,moderate psychological impact,and high sociological impact.Understanding these factors is essential for developing targeted interventions and support services to address the unique needs of caregivers and mitigate the burden of caregiving on their psychosocial health.

关键词： Burden caregivers predictors of psychosocial impact psychological impact sociological impact spinal cord injury

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腕足动物支撑的关山生物群层状底栖群落揭示寒武纪早期生态系统复杂性

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地球科学 2024年第6期49卷 2277-2295页

作者：陈飞扬张志飞 Topper timothy p. 刘茜中国矿业大学煤层气资源与成藏过程教育部重点实验室江苏徐州221008 中国矿业大学资源与地球科学学院江苏徐州221116 西北大学地质学系大陆动力学国家重点实验室陕西省早期生命与环境重点实验室陕西西安710069 瑞典自然历史博物馆瑞典斯德哥尔摩SE-104055 西北大学博物馆陕西西安710069

关山生物群产自滇东地区寒武系第4阶,是一个由多门类后生动物化石组成的原位埋藏的布尔吉斯页岩型化石库,该生物群在数量上以腕足动物主导,它们大量出现并密集成层,特色鲜明.综述了近年来关山生物群的最新研究进展,包括群落构成、腕足... 详细信息

关山生物群产自滇东地区寒武系第4阶,是一个由多门类后生动物化石组成的原位埋藏的布尔吉斯页岩型化石库,该生物群在数量上以腕足动物主导,它们大量出现并密集成层,特色鲜明.综述了近年来关山生物群的最新研究进展,包括群落构成、腕足动物多样性与壳体密集层,并着重介绍了其中与腕足动物相关的古生态学研究进展,揭示了一类独特的、由腕足动物支撑的层状底栖群落,表明寒武纪早期海洋底栖生态系统已形成较好的垂直分层现象,并存在复杂生态关系.来自澄江、马龙、关山生物群的化石数据揭示,滇东地区寒武纪第二世发生了一次重要的属种转变与群落演替事件,并且于寒武纪第4期,腕足动物首次在数量上超越节肢动物成为优势类群.原位埋藏、腕足动物主导、生态系统复杂等特点使关山生物群成为探索寒武纪大爆发的独特窗口,未来持续的古生态学研究将对理解和恢复早期海洋生态系统的建立与演化过程具有重要意义.同时,开展该时期古环境的纵向演变研究,探索影响群落演替的关键控制因素,将对寒武系第二统全球地层对比工作提供重要参考.

关键词：关山生物群腕足动物底栖群落演替生态系统复杂性寒武纪第4期滇东地区生态学

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Effect of age on the standardized ileal amino acid digestibility of soybean meal and canola meal in broilers

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Animal Nutrition 2024年第1期16卷 11-22页

作者： Mukti Barua M.Reza Abdollahi Faegheh Zaefarian timothy J.Wester Channarayapatna K.Girish peter V.Chrystal Velmurugu Ravindran Monogastric Research Center School of Agriculture and Environment Massey University Department of Animal Science and Nutrition Faculty of Veterinary Medicine Chattogram Veterinary and Animal Sciences University Nutrition and Care Animal NutritionEvonik (SEA) Pte. Ltd Complete Feed Solutions

Standardized ileal digestibility coefficients (SIDC) of nitrogen (N) and amino acids (AA) in two protein sources (soybean meal [SBM] and canola meal [CM]) were investigated at six broiler ages (d 7, 14, 21, 28, 35, and 42). Two assay diets were formulated to contain either SBM (413 g/kg) or CM (553 g/kg) as the sole dietary AA source. Titanium dioxide (5 g/kg) was added as an indigestible marker. A total of 696 male broilers at 1 d old were allotted to 12 replicate cages per age group. Each assay diet was offered to birds for 4 d prior to the ileal digesta collection on d 7 (14 birds/cage), 14 (12 birds/cage), 21 (10 birds/cage), 28 (8 birds/cage), 35 (8 birds/cage) and 42 (6 birds/cage), respectively. The apparent digestibility coefficients were standardized using age-specific basal endogenous AA flows. In the SBM group, though the SIDC of N tended to be influenced (quadratic; p=0.075) by age, no linear or quadratic response of age effect was observed on the average SIDC of indispensable (IAA) and total AA (TAA). An age effect (quadratic; ppensable AA (DAA) in SBM with the highest value recorded at d 7, followed by a decrease from d 14 to 28, which increased beyond d 35. The SIDC of some individual AA (Arg, Thr, Trp, Cys, pro) were affected (pppppppending on the protein source and AA. The results demonstrate that age-specific SIDC AA data might need consideration in broiler feed formulations.

关键词： Age Amino acid Broiler Digestibility protein source

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Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps:A pilot study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 29-36页

作者： Jorge A.Gutierrez III Jeremy L.Barth Rodney J.Schlosser Thomas S.Edwards timothy L.Smith Zachary M.Soler Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Regenerative Medicine&Cell Biology Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery Oregon Health&Science UniversityPortlandOregonUSA

Objectives:prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNp).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNp at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)and normosmic(n=4)patients.Results:Differential gene expression analysis comparing dysosmic and normosmic CRSsNp patients showed upregulation of 563 genes and downregulation of 327 genes.Using stringent criteria for multiple comparisons,one upregulated gene(Immediate Early Response 3[IER3])had an false discovery rate(FDR)correction adjustedp value considered statistically significant(ppathways significantly different between dysosmic and normosmic patients(ppsin-like receptors.Conclusions:RNA sequencing of the superior turbinates in patients with CRSsNp can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction.This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNp.This study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,andIER3 in the pathogenesis of olfactory dysfunction.

关键词： chronic rhinosinusitis without nasal polyps olfactory dysfunction RNA sequencing

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Impact of pre- and peri-operative risk factors on length of stay and hospital readmission following minimally-invasive partial nephrectomy

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Asian Journal of Urology 2024年第1期11卷 72-79页

作者： Vanessa A.Lukas Rahul Dutta Ashok K.Hemal Matvey Tsivian timothy E.Craven Nicholas A.Deebel David D.Thiel Ram Anil pathak Brigham and Women's Hospital Division of UrologyDepartment of Surgery75 Francis StreetBostonMAUSA Atrium Health Wake Forest Baptist Medical Center Department of Urology1 Medical Center BlvdWinston-SalemNCUSA Mayo Clinic Florida Department of Urology4500 San Pablo RoadJacksonvilleFLUSA

Objective:We conducted an analysis of the American College of Surgeons National Surgical Quality Improvement program database for minimally-invasive partial nephrectomy cases reported with the goal to identify pre-and peri-operative variables associated with length of stay(LOS)greater than 3 days and readmission within 30 days.Methods:Records from 2008 to 2018 for“laparoscopy,surgical;partial nephrectomy”for prolonged LOS and readmission cohorts were compiled.Univariate analysis with Chi-square,t-tests,and multivariable logistic regression analysis with odds ratios(ORs),p-values,and 95%confidence intervals assessed statistical associations.Results:Totally,20306 records for LOS greater than 3 days and 15854 for readmission within 30 days were available.Univariate and multivariable analysis exhibited similar results.For LOS greater than 3 days,undergoing non-elective surgery(OR=5.247),transfusion of greater than four units within 72 h prior to surgery(OR=5.072),pre-operative renal failure or dialysis(OR=2.941),and poor pre-operative functional status(OR=2.540)exhibited the strongest statistically significant associations.For hospital readmission within 30 days,loss in body weight greater than 10%in 6 months prior to surgery(OR=2.227)and bleeding disorders(OR=2.081)exhibited strongest statistically significant associations.Conclusion:Multiple pre-and peri-operative risk factors are independently associated with prolonged LOS and hospital readmission within 30 days of surgery using the American College of Surgeons National Surgical Quality Improvement program data.Recognizing the risks factors that can potentially be improved prior to minimally-invasive partial nephrectomy is crucial to informing patient selection,optimization strategies,and patient education.

关键词： Minimally-invasive partial nephrectomy The American College of Surgeons National Surgical Quality Improvement program Lengthof stay Hospital readmission

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Finding biomarkers of experience in animals

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Journal of Animal Science and Biotechnology 2024年第3期15卷 925-944页

作者： Sarah Babington Alan J.Tilbrook Shane K.Maloney Jill N.Fernandes Tamsyn M.Crowley Luoyang Ding Archa H.Fox Song Zhang Elise A.Kho Daniel Cozzolino timothy J.Mahony Dominique Blache School of Agriculture and Environment The University of Western AustraliaCrawleyWA 6009Australia Centre for Animal Science The Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia School of Veterinary Science The University of QueenslandGattonQLD 4343Australia School of Human Sciences The University of Western AustraliaCrawleyWA 6009Australia School of Medicine Deakin UniversityGeelongVIC 3217Australia poultry Hub Australia University of New EnglandArmidaleNSW 2350Australia College of Animal Science and Technology Yangzhou UniversityYangzhou 225009China Centre for Nutrition and Food Sciences The Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia

At a time when there is a growing public interest in animal welfare,it is critical to have objective means to assess the way that an animal experiences a situation.Objectivity is critical to ensure appropriate animal welfare outcomes.Existing behavioural,physiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes.But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal,from negative to positive.In this review,we draw from the knowledge of human biomedical science to propose a list of candidate biological markers(biomarkers)that should reflect the experiential state of non-human animals.The proposed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological markers.We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

关键词： Animal experience Animal welfare Biomarker Stress Welfare assessment

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