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Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation

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Bone Research 2018年第1期6卷 83-94页

作者： Heather A.Carey Blake E.Hildreth III Jennifer A.Geisler Mara C.Nickel Jennifer Cabrera Sankha Ghosh Yue Jiang Jing Yan James Lee Sandeep Makam Nicholas A.Young Giancarlo R.Valiente Wael N.Jarjour Kun Huang Thomas J.Rosol Ramiro E.Toribio julia f.charles Michael C.Ostrowski Sudarshana M.Sharma Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State University Wexner Medical Center College of Veterinary Medicine The Ohio State University Department of Biochemistry and Molecular Biology and Hollings Cancer Center Medical University of South Carolina Division of Rheumatology Immunology and Allergy Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Division of Rheumatology and Immunology Department of Internal Medicine The Ohio State University Wexner Medical Center Department of Biomedical Informatics The Ohio State University Wexner Medical Center

Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(Tf)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. functional genomic analysis indicated PU.1 and MITf orchestrated a Tf network essential for OC differentiation. Several of these Tfs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.

关键词： Genome-wide GWASs MITf

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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika fujii charles f.Zorumski Yukitoshi Izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi Izumi Kazuko A.O'Dell charles f.Zorumski Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao charles K.f.Chan Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of MedicineStanford CA 94305USA Department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA Department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

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Otolaryngology residency program factors associated with female resident representation

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 7-11页

作者： julia E.Canick James C.Campbell charles R.Woodard Lars J.Grimm Alissa M.Collins Duke University School of Medicine DurhamNorth CarolinaUSA Department of Head and Neck Surgery&Communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Department of Radiology Duke University School of MedicineDurhamNorth CarolinaUSA

Objective:female representation in the field of otolaryngology is *** is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female *** study sought to identify program factors associated with greater female representation among resident ***:Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto Rico were examined for a list of *** programs with a resident roster available,the genders of residents,faculty,program directors,and chairpersons were *** and city population for each program was also recorded,as was female resident *** were compared using Pearson Chi‐squared univariate ***:1,632 residents and 2,605 faculty were included in the analysis of 109 *** median female resident representation was 40%.Programs with larger faculty sizes,more female faculty,and urban location were associated with an above‐median female resident *** with a larger residency cohort approached significance regarding above‐median female resident *** female faculty representation,program director gender,chairperson gender,and US region were not associated with variation in female resident ***:Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total *** was also likely that a larger resident cohort size may affect female resident *** proportions of female faculty,program director,and chairperson gender,as well as the US region,were not associated with variation in female resident gender representation.

关键词： gender program director recruitment residency training

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Rheological and stability analysis of cement pastes incorporating silica-based wastes

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Particuology 2024年第6期89卷 144-152页

作者： julia da Rosa Martins Janaíde Cavalcante Rocha Dachamir Hotza Luciano Senff Graduate Program in Materials Science and Engineering(PPGMAT) Federal University of Santa Catarina(UFSC)Florianópolis88040-900SCBrazil Graduate Program in Civil Engineering(PPGEC) Federal University of Santa Catarina(UFSC)Florianópolis88040-900SCBrazil Graduate Program in Chemical Engineering(POSENQ) Federal University of Santa Catarina(UFSC)Florianópolis88040-900SCBrazil Department of Mobility Engineering Federal University of Santa Catarina(UFSC)Joinville89219-600SCBrazil

This study investigates the influence of waste characteristics,especially zeta potential,on the properties of cement pastes and *** focus is to evaluate the impact of the zeta potential of cement particles and waste materials on the sedimentation speed,rheology,and hardening time of stabilized cement *** Cement II f 40,retarder additive,silica,and fly ash were used in the *** pastes were prepared,and during the stabilization period,their rheological properties and pH were *** zeta potential and sedimentation speed of the cement and waste particles were measured at the pH that the pastes presented during the entire stabilization *** the stabilization period,the pastes were subjected to the hardening time *** zeta potential analyses revealed diverse values for the different powder types,with the cement particles exhibiting a zeta potential of−3.0 mV,the silica particles exhibiting−10.5 mV,and the fly ash particles exhibiting−20.3 *** influence of the high zeta potential modulus was observed on the sedimentation speed,with the solution containing fly ash exhibiting a speed of 40.01μm/s,whereas the solution containing only cement exhibited a speed of 99.38μm/*** the pastes,the results indicate that the presence of fly ash particles with a significantly negative zeta potential led to a 16%reduction in hardening time compared to particles with a lower modulus of zeta *** tests showed that the inclusion of fly ash particles prevented the formation of *** the zeta potential influenced agglomerate formation and hardening time,it was found to have no effect on yield stress or viscosity.

关键词： Wastes Zeta potential Setting time Rheometry

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Applying Earth Observation Technologies to Economic Consequence Modeling:A Case Study of COVID‑19 in Los Angeles County,California

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International Journal of Disaster Risk Science 2024年第1期15卷 18-31页

作者： fynnwin Prager Marina T.Mendoza charles K.Huyck Adam Rose Paul Amyx Gregory Yetman Kristy f.Tiampo California State University Dominguez HillsCarsonCA 90747USA ImageCat Inc.Long BeachCA 90802USA University of Southern California Los AngelesCA 90015USA CIESIN–Center for International Earth Science Information Network Columbia UniversityPalisadesNY 10964USA Cooperative Institute for Research in Environmental Sciences(CIRES) University of Colorado BoulderBoulderCO 80309USA

Earth observation(EO) technologies,such as very high-resolution optical satellite data available from Maxar,can enhance economic consequence modeling of disasters by capturing the fine-grained and real-time behavioral responses of businesses and the *** investigated this unique approach to economic consequence modeling to determine whether crowd-sourced interpretations of EO data can be used to illuminate key economic behavioral responses that could be used for computable general equilibrium modeling of supply chain repercussions and resilience *** applied our methodology to the COVID-19 pandemic experience in Los Angeles County,California as a case *** also proposed a dynamic adjustment approach to account for the changing character of EO through longer-term disasters in the economic modeling *** found that despite limitations,EO data can increase sectoral and temporal resolution,which leads to significant differences from other data sources in terms of direct and total impact *** findings from this analytical approach have important implications for economic consequence modeling of disasters,as well as providing useful information to policymakers and emergency managers,whose goal is to reduce disaster costs and to improve economic resilience.

关键词： Computable general equilibrium models COVID-19 Disaster economic impacts Earth observation Economic consequence analysis Los Angeles County

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Complication rates after direct anterior vs posterior approach for hip hemiarthroplasty in elderly individuals with femoral neck fractures

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World Journal of Orthopedics 2024年第1期15卷 22-29页

作者： Tatiana charles Nicolas Bloemers Bilal Kapanci Marc Jayankura Department of Orthopedic Surgery and Traumatology HUB-Hospital ErasmeBrussels 1070Belgium

BACKGROUND Dislocation rates after hemiarthroplasty reportedly vary from 1%to 17%.This serious complication is associated with increased morbidity and mortality *** to this surgery are still debated,with no consensus regarding the superiority of any single *** To compare early postoperative complications after implementing the direct anterior and posterior approaches(PL)for hip hemiarthroplasty after femoral neck *** This is a comparative,retrospective,single-center cohort study conducted at a university *** March 2008 and December 2018,273 patients(a total of 280 hips)underwent bipolar hemiarthroplasties(n=280)for displaced femoral neck fractures using either the PL(n=171)or the minimally invasive direct anterior approach(DAA)(n=109).The choice of approach was related to the surgeons’practices;the implant types were similar and unrelated to the *** rates and other complications were reviewed after a minimum followup of 6 *** Both treatment groups had similarly aged patients(mean age:82 years),sex ratios,patient body mass indexes,and patient *** data(surgery delay time,operative time,and blood loss volume)did not differ significantly between the *** 30 d mortality rate was higher in the PL group(9.9%)than in the DAA group(3.7%),but the difference was not statistically significant(P=0.052).Among the one-month survivors,a significantly higher rate of dislocation was observed in the PL group(14/154;9.1%)than in the DAA group(0/105;0%)(P=0.002).Of the 14 patients with dislocation,8 underwent revision surgery for recurrent instability(posterior group),and one of them had 2 additional procedures due to a deep *** rate of other complications(e.g.,perioperative and early postoperative periprosthetic fractures and infection-related complications)did not differ significantly between the *** These findings suggest that the DAA to bipolar hemiarthroplasty f

关键词： Hemiarthroplasty femoral neck fracture Direct anterior approach Posterior approach Dislocation Mortality

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A Modified Transitional Korteweg-De Vries Equation: Posed in the Quarter Plane

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Journal of Applied Mathematics and Physics 2024年第7期12卷 2691-2701页

作者： charles Bu Department of Mathematics Wellesley College Wellesley MA USA

This paper is concerned with a modified transitional Korteweg-de Vries equation ut+f(t)u2ux+uxxx=0, (x,t)∈R+×R+with initial value u(x,0)=g(x)∈H4(R+)and inhomogeneous boundary value u(0,t)=Q(t)∈C2([ 0,∞ )). Under the conditions either 1) f(t)≤0, f′(t)≥0or 2) f(t)≤−αwhere α>0, we prove the existence of a unique global classical solution.

关键词： Modified Transitional KdV Equation Initial-Boundary Value Problem Semi-Group Local and Global Existence

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骨骼干细胞表观遗传调控的新证据（英文）

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Science Bulletin 2024年第13期 2004-2006页

作者：赵黎明肖骏 charles K.f.Chan Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine Department of Surgery Division of Plastic and Reconstructive Surgery Stanford University School of Medicine Department of Orthopaedic Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Skeletal stem cells (SSCs) are crucial for skeletal development and regeneration, yet the epigenetic regulation of these cells remains poorly understood. Recent studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout life. Skeletal stem cells (SSCs), residing within the skeleton and lineage-restricted, serve as a cellular reserve to foster development and maintain skeletal homeostasis. Historically categorized within the broader mesenchymal stromal/stem cells (MSCs), SSCs have been differentiated due to MSCs’ recognized heterogeneity, which has generated inconsistencies and controversies in the field [1].

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