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Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

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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 P<0.05).However,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

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

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

Surgical management of the diabetic foot:The current evidence

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World Journal of Orthopedics 2024年第5期15卷 404-417页

作者： Richard Henry Randall Roberts Gareth Rhys Davies-Jones james Brock Vaishnav Satheesh Greg AJ Robertson Department of Trauma and Orthopaedics Wrexham Maelor HospitalWrexham LL137TDUnited Kingdom Department of Trauma and Orthopaedics The Robert Jones and Agnes Hunt Orthopaedic HospitalOswestry SY107AGUnited Kingdom

The prevalence of diabetes mellitus and its associated complications,particularly diabetic foot pathologies,poses significant healthcare challenges and economic burdens *** review synthesises current evidence on the surgical management of the diabetic foot,focusing on the interplay between neuropathy,ischemia,and infection that commonly culminates in ulcers,infections,and,in severe cases,*** escalating incidence of diabetes mellitus underscores the urgency for effective management strategies,as diabetic foot complications are a leading cause of hospital admissions among diabetic patients,significantly impacting morbidity and mortality *** review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers,infections,and skeletal pathologies such as Charcot arthropathy,emphasising the critical role of early diagnosis,comprehensive management strategies,and interdisciplinary care in mitigating adverse *** addressing surgical interventions,this review evaluates conservative surgeries,amputations,and reconstructive procedures,highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot *** integration of advanced diagnostic tools,novel surgical techniques,and postoperative care,including offloading and infection control,are discussed in the context of optimising healing and preserving limb function.

关键词： Diabetes Diabetic foot Charcot Osteomyelitis Amputation Diabetic foot attack Conservative surgery

Fully integrated and broadband Si-rich silicon nitride wavelength converter based on Bragg scattering intermodal four-wave mixing

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Photonics Research 2024年第3期12卷 I0001-I0010页

作者： VALERIO VITALI THALÍA DOMÍNGUEZ BUCIO HAO LIU JOSÉMANUEL LUQUE GONZÁLEZ FRANCISCO JURADO-ROMERO ALEJANDRO ORTEGA-MOÑUX GLENN CHURCHILL james C.GATES james HILLIER NIKOLAOS KALFAGIANNIS DANIELE MELATI JENS H.SCHMID ILARIA CRISTIANI PAVEL CHEBEN J.GONZALO WANGÜEMERT-PÉREZ ÑIGO MOLINA-FERNÁNDEZ FREDERIC GARDES COSIMO LACAVA PERIKLIS PETROPOULOS Optoelectronics Research Centre University of SouthamptonSouthampton SO171BJUK 2ElectricalComputer and Biomedical Engineering DepartmentUniversity of PaviaPavia 27100Italy 3Telecommunication Research Institute(TELMA)Universidad de MálagaCEI Andalucı´a TECHE.T.S.I.Telecomunicación29010 MálagaSpain 4School of Science and TechnologyNottingham Trent UniversityNottingham NG118NSUK 5Department of Electrical EngineeringEindhoven University of TechnologyEindhoven 5600 MBThe Netherlands 6Department of Materials Science and EngineeringUniversity of IoanninaIoannina 45110Greece 7Centre de Nanosciences et de NanotechnologiesUniversitéParis-SaclayCNRS91120 PalaiseauFrance 8Advanced Electronics and Photonics Research CenterNational Research Council CanadaOttawaOntario K1A 0R6Canada

Intermodal four-wave mixing(FWM)processes have recently attracted significant interest for all-optical signal processing applications thanks to the possibility to control the propagation properties of waves exciting distinct spatial modes of the same *** allows,in principle,to place signals in different spectral regions and satisfy the phase matching condition over considerably larger bandwidths compared to intramodal ***,the demonstrations reported so far have shown a limited bandwidth and suffered from the lack of on-chip components designed for broadband manipulation of different *** demonstrate here a silicon-rich silicon nitride wavelength converter based on Bragg scattering intermodal FWM,which integrates mode conversion,multiplexing and de-multiplexing functionalities *** system enables wavelength conversion between pump waves and a signal located in different telecommunication bands(separated by 60 nm)with a 3 dB bandwidth exceeding 70 nm,which represents,to our knowledge,the widest bandwidth ever achieved in an intermodal FWM-based system.

关键词： scattering pump modal