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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

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Source of metals related to gold occurrences in Cameroon, Central African Belt

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Acta Geochimica 2024年第2期43卷 308-324页

作者： kevin Igor Azeuda ndonfack Jinlin Zhang Yuling Xie nSamiratou Yaya Emmanuel Archelaus Afanga Basua JCHX Mining Management Co. LtdBeijing 101500People’s Republic of China Institute of Geology Chinese Academy of Geological SciencesBeijing 100037People’s Republic of China School of Civil and Environmental Engineering University of Science and Technology BeijingBeijing 100083People’s Republic of China Department of Earth Science University of BamendaBamendaRepublic of Cameroon

Suites of granitic and metamorphic rocks form a perfect geological environment in which to investigate the source of metals related to gold *** the East Province of Cameroon,the source of metals-related gold(grade~4.6 g/t)that occurs within metamorphic and granitic rocks remains *** host rocks were subjected to XRF and ICP-MS whole-rock geochemistry and BSE/EDS mineral analyses to investigate the source(s)of metals related to gold in the ***,chalcopyrite-pyrite and magnetite-ilmenite are the main sulfi des and oxides of granites,*** low-grade metamorphic rocks are sulfi de-rich consisting of arsenopyrite,chalcopyrite,pyrite,and sphalerite,and oxides include magnetite,ilmenite,hematite,and ***,ni,Co,Sb,Sc,and Zn concentrations depleted in high-grade metamorphic rocks and granites compared to low-grade metamorphic *** well,Bi,Cd,Co,Cu,ni,Sb,V,W,and Zn concentrations decrease with increasing temperatures from low-grade rocks to high-grade rocks and *** suite of depleted elements in high-grade rocks and granites is almost identical to those enriched in gold *** conclude that metals(Bi,Cd,Co,Cu,ni,Sb,and Zn)related to gold mineralization in the East Province of Cameroon likely originated from metal-rich low-grade metamorphic rocks during prograde metamorphic processes prior to partial melting.

关键词： East Province of Cameroon Metamorphic rocks Granites Oxide–sulﬁdes Metal and gold Geochemistry

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Orthogonal polynomial expansions for the valuation ofoptions under the stochastic volatility models with stochastic correlation

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Journal of Management Science and Engineering 2024年第2期9卷 239-253页

作者： kevin Z.Tong Department of Mathematics and Statistics University of Ottawa585 King EdwardOttawaOntarioK1N 6N5Canada

This work provides a new method for pricing options under the generalized stochastic volatility models with Jacobi stochastic *** method is based on the observation that the generalized models belong to the class of polynomial diffusions and therefore the option prices can be efficiently computed via orthogonal polynomial *** take the Heston and Schöbel-Zhu models with stochastic correlation as two specific examples and are able to derive the analytical formulas for the option *** also illustrate the accuracy of the proposed method through a number of numerical experiments.

关键词： Orthogonal polynomial expansions Polynomial diffusions Stochastic correlation Jacobi process Stochastic volatility

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Cognitive function among military veterans with STEM occupations

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Military Medical Research 2024年第2期11卷 308-310页

作者： Justin T.McDaniel kevin n.Hascup Erin R.Hascup Ugochukwu G.Ezigbo Amanda M.Weidhuner Harvey Henson David L.Albright Dale and Deborah Smith Center for Alzheimer's Research and trEatment(CARE) Southern Illinois University School of MedicineSpringfieldIL 62794USA STEM Education Research Center Southern Illinois UniversityCarbondaleIL 62901USA Department of Political Science The University of AlabamaTuscaloosaAL 35487USA

Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive *** study examines a nationally representative sample of military veterans to address this gap in knowledge.

关键词： Alzheimer's disease Veterans Science technology engineering and mathematics(STEM) Animal fluency test Dementia

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Direct anterior compared to posterior approach for hip hemiarthroplasty following femoral neck fractures

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World Journal of Orthopedics 2024年第6期15卷 605-607页

作者： kevin A Wu Alexandra n Krez Albert T Anastasio Department of Orthopaedic Surgery Duke University HospitalDurhamNC 27710United States Department of Orthopaedic Surgery Duke University School of MedicineDurhamNC 27710United States

The differences in complication rates between the direct anterior and posterior approaches for hemiarthroplasty in elderly patients with femoral neck fractures are not yet fully ***,a severe complication associated with increased mortality and often requiring additional surgery,may occur less frequently with the direct anterior approach compared to the posterior *** consideration of patient demographics is essential when planning the surgical *** research in this area should focus on robust randomized controlled trials involving elderly patients recovering from femoral neck fractures.

关键词： Direct anterior approach Posterior approach Hemiarthroplasty Femoral neck fractures Arthroplasty Dislocation Surgical technique

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Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： kevin Tak-Pan ng Li Pang Jia-Qi Wang Wong Hoi She Simon Hing-Yin Tsang Chung Mau Lo Kwan Man Tan To Cheung Department of Surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not *** study was to find out whether systemic inflammation plays an important ***:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex *** relationships of the cytokines and the postoperative outcomes were compared between LLR and ***:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative *** to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly *** POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during *** levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital ***,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver ***:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

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Arthroscopic Treatment of Gonarthrosis in a Low-Income Setting

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Open Journal of Orthopedics 2024年第1期14卷 75-82页

作者： kevin Parfait Bienvenu Bouhelo-Pam Affleck Romaric Ledier Angalla norbert Edgard Lamini n’soundhat Marius Monka Arnauld Sledje Wilfrid Bilongo Bouyou Paul Yèlai Ikounga Térence Olivier Etsaka-Ohoya Department of Orthopaedic Surgery and Traumatology University Hospital of Brazzaville Brazzaville Congo Faculty of Health Sciences Marien N’GOUABI University Brazzaville Congo Department of Rhumatology University Hospital of Brazzaville Brazzaville Congo

Background: Knee osteoarthritis is a frequent, debilitating, and degenerative condition. It is the most common operative indication for surgical arthroscopy. Hypothesis: Arthroscopy allows painless treatment of knee osteoarthritis and functional recovery. Patients and Methods: Our study was conducted in a private medical center in the city of Brazzaville in Congo, during the period from September 2020 to February 2023. It was prospective and based on patients with mechanical knee pain caused by osteoarthritis. A mobile arthroscopy device was used. The IKDC and KOOS scores allowed the evaluation of the treatment. Results: Our work involved 15 men and 7 women, with an average age of 39.9 years. Knee osteoarthritis was classified as type 2 according to Ahlbäck in 26 cases (70.27%) and type 3 in 11 cases (29.73%). In 7 patients, arthroscopy revealed lesions not visualized on MRI. Joint lavage was performed in all cases, synovial debridement in 17 cases (45.94%), and extraction of cartilaginous foreign bodies in 10 cases (27.03%). 20 patients were very satisfied with the surgery and 2 moderately satisfied. The EVA, subjective IKDC and KOOS scores were acceptable on a long-term follow-up. Discussion: Arthroscopy is a modern surgical technique for the management of intra-articular lesions of the knee. It relieves pain and stabilizes the degenerative process. A mobile arthroscopy device used here was preferred because of the low cost of installation and production.

关键词： Arthroscopy Surgery Imaging Knee

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Effect of Ultraviolet Radiation on Hsp70 Protein Expression in HaCaT Cells

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World Journal of nuclear Science and Technology 2024年第1期14卷 59-71页

作者： Sergio Hugo Sánchez Rodríguez Jesús Rodríguez Vergil Manuel Venancio Muñoz Juárez kevin Said Ramírez Dávila Luis Martín García Ortiz Germán Flores Cortés Luz Elena Vidales Rodríguez Jesús Adrián López David Alejandro García López Laboratorio de Biología Celular y neurobiología Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México Laboatorio de Bacterias y Hongos Filamentosos Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México Laboratorio de MicroRnAs Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México

Ultraviolet radiation by its wavelength is divided into: UVA, UVB and UVC. Only UVA and UVB manage to penetrate the ozone layer, but due to anthropological activities, all of them are capable of interacting with humans to a greater or lesser extent, and can generate adverse effects such as cellular stress when interacting with intra-and extracellular biomolecules. The skin is the first organ in contact with UV radiation, and the stress it generates can be analyzed by the expression of a bioindicator of cellular damage such as Hsp70. Therefore, the objective of the project was: to determine the effect of UVA, UVB and UVC radiation on HaCaT epithelial cells, by analyzing the expression of Hsp70. Materials and methods: HaCaT cells were cultured in vitro, which were irradiated with UVA, UVB and UVC light at different doses, to subsequently determine the degree of Hsp70 expression by Immunodetection by PAGE-SDS and Western Blot. Results: Basal expression of Hsp70 was observed in no irradiated HaCaT cells. When HaCaT cells were irradiated with UVA, UVB, UVC, an increase in this Hsp70 protein was observed. With UVA, a higher degree of expression was observed at a time of 30 minutes of irradiation. With UVB the highest expression shifted to a time of 20 minutes. With UVC, overexpression was observed after 10 minutes. Conclusion: UV radiation generates cellular stress on HaCaT cells, evaluated by the stress bioindicator Hsp70. According to the wavelength of UV radiation, those that have a shorter wavelength have a greater potential for cellular damage, such as UVC.

关键词： Ultraviolet A Light (UVA) Ultraviolet B Light (UVB) Ultraviolet C Light (UVC) Heat Shock Protein 70 (Hsp70) HaCaT

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Dynamics of self-hybridized exciton–polaritons in 2D halide perovskites

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Light(Science & Applications) 2024年第1期13卷 13-22页

作者： Surendra B.Anantharaman Jason Lynch Christopher E.Stevens Christopher Munley Chentao Li Jin Hou Hao Zhang Andrew Torma Thomas Darlington Francis Coen kevin Li Arka Majumdar PJames Schuck Aditya Mohite Hayk Harutyunyan Joshua R.Hendrickson Deep Jariwala Department of Electrical and Systems Engineering University of PennsylvaniaPhiladelphiaPA19104USA KBR Inc. BeavercreekOH45431USA Air Force Research Laboratory Sensors DirectorateWright-Patterson Air Force BaseOH45433USA Department of Physics University of WashingtonSeattleWA98195USA Department of Physics Emory UniversityAtlantaGA30322USA Department of Chemical and Biomolecular Engineering Rice UniversityHoustonTX77005USA Department of Materials Science and nanoengineering Rice UniversityHoustonTX77005USA Applied Physics Program Smalley‐Curl InstituteRice UniversityHoustonTX77005USA Department of Mechanical Engineering Columbia UniversityNew YorkNY10027USA Department of Electrical and Computer Engineering University of WashingtonSeattleWA98195USA

Excitons,bound electron–hole pairs,in two-dimensional hybrid organic inorganic perovskites(2D HOIPs)are capable of forming hybrid light-matter states known as exciton-polaritons(E–Ps)when the excitonic medium is confined in an optical *** the case of 2D HOIPs,they can self-hybridize into E–Ps at specific thicknesses of the HOIP crystals that form a resonant optical cavity with the ***,the fundamental properties of these self-hybridized E–Ps in 2D HOIPs,including their role in ultrafast energy and/or charge transfer at interfaces,remain ***,we demonstrate that>0.5µm thick 2D HOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E–P *** E–Ps have high Q factors(>100)and modulate the optical dispersion for the crystal to enhance sub-gap absorption and *** varying excitation energy and ultrafast measurements,we also confirm energy transfer from higher energy E–Ps to lower energy E–***,we also demonstrate that E–Ps are capable of charge transport and transfer at *** findings provide new insights into charge and energy transfer in E–Ps opening new opportunities towards their manipulation for polaritonic devices.

关键词： charge polar excitation

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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew n.Lane kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRnAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRnA splicing CD8 T cells ARS2 PKM2

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