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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.zor.mski 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.zor.mski 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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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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Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

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World Journal of Orthopedics 2024年第8期15卷 754-763页

作者： Mahad M Hassan Aliya G feroe Brenton W Douglass Andrew E Jimenez Benjamin Kuhns charles f Mitchell Robert L Parisien Daniel A Maranho Eduardo N Novais Young-Jo Kim Ata M Kiapour Department of Orthopedic Surgery University of MinnesotaMinneapolisMN 55454United States Department of Orthopedic Surgery TRIA Orthopaedic CenterBloomingtonMN 55122United States Department of Orthopedic Surgery Boston Children’s HospitalBostonMA 02115United States Department of Orthopedic Surgery Mayo ClinicRochesterMN 55901United States Department of Orthopaedics and Rehabilitation Yale School of MedicineNew HavenCT 06510United States Department of Orthopedic Surgery American Hip Institute Research FoundationDes PlainesIL 60018United States Department of Orthopedic Surgery Mount SinaiNew YorkNY 10029United States Department of Biomechanics Medicineand Rehabilitation of the Locomotor SystemRibeirao Preto Medical SchoolUniversity of São PauloRibeirao Preto 14048-900São PauloBrazil

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular *** To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric *** hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both *** Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip *** femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head *** In both sexes,the residual volume increased by age(Pficantly smaller femoral head size in older ages(>13 years)in females,there were no sex-differences in residual volume and aspherity *** were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age *** 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

关键词： Hip femoral head Sphericity Skeletal growth Sex differences

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The siphonic energy transfer between hot solar wind and cold martian ionosphere through open magnetic flux rope

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fundamental Research 2024年第4期4卷 882-889页

作者： Xiaojun Xu Lou-Chuang Lee Qi Xu Qing Chang Jing Wang Ming Wang Shaosui Xu Christian Mosti charles J.farrugia Xing Wang Yudong Ye Zilu Zhou Lei Luo Peishan He Shaoguan Cheng State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao 999078China CNSA Macao Center for Space Exploration and Science Macao 999078China Institute of Earth Science Academia SinicaTaipei 115029China Institute of Space Science and Applied Technology Harbin Institute of TechnologyShenzhen 518000China Planetary Environmental and Astrobiological Research Laboratory(PEARL) School of Atmospheric SciencesSun Yat-sen UniversityZhuhai 519000China Nanjing University of Information Science and Technology Nanjing 210000China Space ScienceLaboratory Universityof CaliforniaBerkeleyCA94320USA Space Research Institute Austrian Academy of SciencesGraz 8010Austria University of New Hampshire NH 03824USA

A mechanism for energy transfer from the solar wind to the Martian ionosphere through open magnetic flux rope is proposed based on the observations by Mars Atmosphere and Volatile EvolutioN(MAVEN).The satellite was located in the dayside magnetosheath at an altitude of about 70o km above the northern *** between the hot solar wind protons and the cold heavy ions/neutrals in the subsolar region can cool the protons and heat the heavy *** a result,the magnetosheath protons are siphoned into the ionosphere due to the thermal pressure gradient of protons and the heated heavy ions escape along the open magnetic field *** direct collisions in the lower-altitude region were not detected,this physical process is demonstrated by MAVEN measurements of enhanced proton density,decreased proton temperature and oppositely directed motions of hot and cool protons within the flux rope,which are very different from the observational features of the flux transfer events near the Earth's *** mechanism could universally exist in many contexts where a collisionless plasma region is connected to a collisional plasma *** reconstructing the magnetic geometry and the cross-section of the flux rope using the Grad-Shafranov technique,the ion loss rates are quantitatively estimated to be on the order of 1023 s-l,which is much higher than previously estimated.

关键词： Mars flux rope Solarwind Ionosphere Ion loss

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Doublecortin-like kinase 1 exhibits cancer stem cell-like characteristics in a human colon cancer cell line

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Chinese Journal of Cancer Research 2013年第2期25卷 134-142页

作者： Lianna Li charles f. Bellows Department of Surgery Tulane University University of Mississippi Cancer Institute

Objective： Colon cancer stem cells （CSCs） are implicated in colorectal cancer carcinogenesis, metastasis, and therapeutic resistance. The identification of these cells could help to develop novel therapeutic strategies. Doublecortin-like kinase 1 （DCLK1） has been viewed as a marker for gastrointestinal stem cells that fuel the self-renewal process, however others view them as a marker of Tuft cells or as an enteroendocrine subtype. The purpose of this study was to use a colon cancer cell line to identify and characterize the stem-like characteristics of the DCLKI＋ cell population. Methods： To enrich stem-like cells, HCT116 cells （derived from colon adenocarcinomas） were cultured using serum-free media to form spheres under both normal oxygen and hypoxia condition. DCLK1 transcript expression in the adherent parental cells and spheroids was quantified using quantitative real time reverse transcription- polymerase chain reaction [（q）RT-PCR]. DCLK1 protein expression was determined using flow cytometry. Self-renewal capability from adherent parental cells and spheroids was determined using extreme limiting dilution analysis （ELDA）. Results： Under both normal oxygen and hypoxia condition, the adherent parental cells were composed of cells that express low levels of DCLK1. However, spheroids exhibited an increased frequency of cells expressing DCLK1 on both mRNA and protein levels. Cells derived from spheroids also possess stronger self-renewal capability. Conclusions： The higher fraction of DCLK1 ＋ cells exhibited by spheroids and hypoxia reflects the stem- like characteristics of these cells. DCLK1 may represent an ideal marker to study and develop effective strategies to overcome chemo-resistance and relapse of colon cancer.

关键词： Doublecortin-like kinase 1 (DCLK1) colorectal cancer cancer stem cells stem cell marker spheroids

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