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Bone Research 2024年第1期12卷 107-121页

作者： Feng Gao Qimiao Hu Wenwei Chen Jilong Li Cheng Qi Yiwen Yan Cheng Qian Mei Wan james Ficke Junying Zheng Xu Cao Department of orthopedic Surgery Johns Hopkins University School of MedicineBaltimoreMaryland 21205USA Department of Biomedical Engineering Johns Hopkins University School of MedicineBaltimoreMaryland 21205USA

Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading ***,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the *** this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical *** PGE2 levels are in proportion to their weight *** weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing *** of cyclooxygenase-2(CoX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical ***,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone ***,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for ***,we show that elevated PGE2 is associated with ankle osteoarthritis(AoA)and ***,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AoA and implication of potential treatment.

关键词： pain elevated PGE2

Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor

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World Journal of Gastrointestinal oncology 2024年第5期16卷 2060-2073页

作者： Jing Zhou Mei-Ying Zhang Ai-Ai Gao Cheng Zhu Tao He james G Herman Ming-Zhou Guo School of Medicine NanKai UniversityTianjin 300071China Department of Gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China Departments of Pathology Characteristic Medical Center of The Chinese People’s Armed Police ForceTianjin 300162China The Hillman Cancer Center University of Pittsburgh Cancer InstitutePittsburghPA 15213United States National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100853China

BACKGRoUND Targeting DNA damage response(DDR)pathway is a cutting-edge *** has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in ***,the detailed mechanism is *** To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 *** To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse *** Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region ***11 methylation was significantly associated with tumor differentiation and tumor size(both Powever,no significant associations were observed between promoter region methylation and age,gender,smoking,alcohol consumption,TNM stage,or lymph node *** DNA damaged model induced by low dose cisplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling *** silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in *** SLFN11 is frequently methylated in human *** of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

关键词： Schlafen-11 Esophageal squamous cell carcinoma DNA methylation Synthetic lethality AZD0156

Strengthening Active Aging through older People’s Association and Economic Activity of the older People in Nepal

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Advances in Aging Research 2024年第2期13卷 15-24页

作者： Hom Nath Chalise james Brightman Central Department of Population Studies Tribhuvan University Kathmandu Nepal University of Central Florida Orlando Florida USA

Aging is a natural lifelong process ending in death. Many older people are living in poverty. older people are generally considered dependent on others as they grow older. The purpose of this article is to explore the entrepreneurship activities of Nepalese older adults. Data for this study were collected from the project Help Age International (HAI) implemented in Nepal. Qualitative data observations and interviews were used to collect data. The findings of this study show the formation of the older People’s Association (oPA) has supported many older people to participate outside the home in various social activities. Moreover, regular deposits through oPAs offer little help. oPAs support older people in their need of financial support to implement minor entrepreneurship. older people who received support were pleased and were actively involved in their activities and also regularly deposited money in them. Subsequently, older people’s participation in social activities has increased and also helped to lower elderly abuse, loneliness, and depression. Local governments should promote such activities which will help with healthy aging.

关键词： Aging in Nepal Active Aging older People’s Association older People Healthy Aging

Between Quantum Mechanics and General Relativity

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Journal of Modern Physics 2024年第8期15卷 1199-1228页

作者： Walter james Christensen Jr. Department of Physics and Astronomy Cal Poly Pomona University Pomona USA

The origin of elementary particle mass is considered as a function of n-valued graviton quanta. To develop this concept we begin in a cold region of “empty space” comprised of only microscopic gravitons oscillating at angular frequency ω. From opposite directions enters a pair of stray protons. Upon colliding, heat and energy are released. Customarily, this phase and what follows afterward would be described by Quantum Chromodynamics (QCD). Instead, we argue for an intermediary step. one in which neighboring gravitons absorb discrete amounts of plane-wave energy. Captured by the graviton, the planewave becomes a standing wave, whereupon its electromagnetic energy densities are converted into gravitational quanta. Immediately thereafter an elementary particle is formed and emitted, having both mass and spin. From absorption to conversion to emission occurs in less than 3.7 × 10−16 s. During this basic unit of hybrid time, general relativity and quantum physics unite into a common set of physical laws. As additional stray protons collide the process continues. over eons, vast regions of spacetime become populated with low-mass particles. These we recognize to be dark matter by its effects on large scale structures in the universe. Its counterpart, dark energy, arises when the conversion of gravitational quanta to particle emission is interrupted. This causes the gravitational quanta to be ejected. It is recognized by its large scale effects on the universe.

关键词： Dark Matter and Energy Gravitational Quanta Graviton Standing Wave Schwarzschild Metric General Relativity Quantum Physics Unified Field Theory Blackholes

The Rising Burden of Hepatocellular Carcinoma: Is the Gender Gap Narrowing?

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 763-764页

作者： james K.H.Ho Prem H.Thurairajah Daniel Q.Huang Kristie H.Fan Division of Gastroenterology and Hepatology National University HospitalNational University Health SystemSingaporeSingapore

Dear Editors,The landscape of hepatocellular carcinoma(HCC)is continuously *** global trends indicate a significant shift in the epidemiology of HCC from viral-related to non-viral-related ***-associated fatty liver disease has emerged as the fastest-growing contributor to HCC in recent years,due to the increased prevalence of obesity and metabolic risk factors.

关键词： Carcinoma epidemiology obesity

Unveiling the distinctive traits of functional rye centromeres:minisatellites,retrotransposons,and R-loop formation

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Science China(Life Sciences) 2024年第9期67卷 1989-2002页

作者： Chang Liu Shulan Fu Congyang Yi Yang Liu Yuhong Huang Xianrui Guo Kaibiao Zhang Qian Liu james A.Birchler Fangpu Han State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory for Plant Genetics and Breeding Sichuan Agricultural UniversityChengdu 611130China Division of Biological Science University of MissouriColumbia 65211-7400USA

Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle *** their conserved functionality,centromeric DNA sequences exhibit rapid evolution,presenting diverse sizes and compositions across *** functional significance of rye centromeric DNA sequences,particularly in centromere identity,remains *** this study,we comprehensively characterized the sequence composition and organization of rye *** findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs)and interspersed *** systematically classified LTR-RTs into five categories,highlighting the prevalence of younger CRS1,CRS2,and CRS3 of CRSs(centromeric retrotransposons of Secale cereale)were primarily located in the core centromeres and exhibited a higher association with CENH3 *** minisatellites,mainly derived from retrotransposons,along with CRSs,played a pivotal role in establishing functional centromeres in ***,we observed the formation of R-loops at specific regions of CRS1,CRS2,and CRS3,with both rye pericentromeres and centromeres exhibiting enrichment in ***,these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres,suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere *** work provides insights into the DNA sequence composition,distribution,and potential function of R-loops in rye *** knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres,offering implications for the development of synthetic centromeres in future plant modifications and beyond.

关键词： centromere LTR-RTs minisatellite rye R-loop

Nickel sulfate solution fluoride separation with hydrous zirconium oxide

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Tungsten 2024年第2期6卷 367-381页

作者： Elbert M.Nigri Ummul K.Sultana André L.A.Santos james W.Vaughan Sonia D.F.Rocha Department of Mining Engineering Federal University of Minas GeraisBelo Horizonte 31270-901Brazil School of Chemical Engineering University of QueenslandSt Lucia 4072Australia

Fluoride is an impurity in nickel sulfate production,which is required for electric vehicle *** zirconium oxide(HZo)was evaluated for removing fl uoride from nickel sulfate *** fluoride removal occurred at pH value 4 and optimal pH value is 4–5,considering Zr *** availability decreases with pH due to hydrogen fluoride and zirconium fluoride aqueous *** removal is initially rapid,with 50 wt.%removal in 7 min,followed by slow removal up to 68 wt.%after 72 h and follows second order rate *** removal was dominated by an ion exchange mechanism and resulting Zr–F bonds were observed using Fourier-transform infrared *** presence of nickel sulfate decreased loading capacity compared to a salt-free *** maintained adsorption capacity through five cycles of loading and regeneration.

关键词： Hydrous zirconium oxide Nickel sulfate Fluoride Adsorption Anion exchange

Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

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Acta Pharmaceutica Sinica B 2024年第2期14卷 653-666页

作者： Shining Loo Antony Kam Bamaprasad Dutta Xiaohong Zhang Nan Feng Siu Kwan Sze Chuan-Fa Liu Xiaoliang Wang james P.Tam School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Department of Biological Sciences Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Institute of Materia Medica Chinese Academy of Medical SciencesBeijing 100050China Department of Health Sciences Brock UniversityNiagara RegionON L2S 3A1Canada

Stress and illness connection is complex and involves multiple physiological *** ginsengs,reputed for their broad-spectrum“cure-all”effect,are widely prescribed to treat stress and related ***,the identity of ginseng’s“cure-all”medicinal compounds that relieve stress remains ***,we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to *** are disulfide-rich,cell-penetrating and proteolytic-stable *** affinity-enrichment mass spectrometry target identification together with in vitro,ex vivo and in vivo validations,we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway,alleviate a1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta,decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet *** administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation,to prevent collagen and adrenalineinduced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in ***,these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra-and intra-cellular proteins to reverse stress-induced damages.

关键词： Ginseng Cysteine-rich peptides Microproteins Cure-all Stress Homeostasis

Radiofrequency ablation versus microwave ablation for colorectal liver metastases:long-term results of a retrospective cohort surgical experience

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 759-770,I0001页

作者： Ali Gunduz Sarioglu Chase J.Wehrle Ege Akgun Arturan Ibrahimli james F.Bena Eren Berber Department of Endocrine Surgery Cleveland ClinicClevelandOHUSA Department of General Surgery Cleveland ClinicClevelandOHUSA Department of Quantitative Health Sciences Cleveland ClinicClevelandOHUSA

Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablation(MWA)is being preferred due to its perceived superiority in creating the ablation *** aim of this study is to compare the long-term efficacy of these two modalities performed ***:Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved *** were compared using Wilcoxon,Chi-square,Kaplan-Meier,and Cox multivariate regression *** data are presented as median(interquartile range).Results:There were a total of 242 *** RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 *** was no difference between the groups regarding operative time(161 vs.147 minutes,respectively,P=0.4),perioperative morbidity(3%vs.8%,respectively,P=0.2)or hospital stay(1 vs.1 day,P=0.05).Local recurrence(LR)per lesion with at least 1 year of imaging follow-up was 29%in the RFA and 13%in the MWA group(Pon univariate survival analysis,tumor size,blood vessel proximity,ablation margin,and ablation modality were independent predictors of *** control these variables,direct matching was *** cohort included 189 ***-Meier analysis of these cohorts showed increased LR-free survival in the MWA group *** RFA group(P=0.005).Conclusions:This large study confirms our initial observation that local tumor control rate is better after MWA ***.

关键词： Colorectal cancer liver metastasis liver ablation radiofrequency ablation(RFA) microwave ablation(MWA) local recurrence(LR)

Momentum as Translations at Conformal Infinity

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Journal of Applied Mathematics and Physics 2024年第4期12卷 1522-1540页

作者： Richard james Petti Jacob Luke Graham Arlington MA USA Newton MA USA

Although General Relativity is the classic example of a physical theory based on differential geometry, the momentum tensor is the only part of the field equation that is not derived from or interpreted with differential geometry. This work extends General Relativity and Einstein-Cartan theory by augmenting the Poincaré group with projective (special) conformal transformations, which are translations at conformal infinity. Momentum becomes a part of the differential geometry of spacetime. The Lie algebra of these transformations is represented by vectorfields on an associated Minkowski fiber space. Variation of projective conformal scalar curvature generates a 2-index tensor that serves as linear momentum in the field equations of General Relativity. The computation yields a constructive realization of Mach’s principle: local inertia is determined by local motion relative to mass at conformal infinity in each fiber. The vectorfields have a cellular structure that is similar to that of turbulent fluids.

关键词： Projective Symmetry Conformal Symmetry Momentum General Relativity Einstein-Cartan Mach’s Principle