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Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge Lexiang Yu Zhongzhi Wu Jianwen Que Wei Li Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNY 10032USA Department of Molecular Pharmacology and Therapeutics Columbia UniversityNew YorkNY 10032USA Department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and Liver Diseases Columbia UniversityNew YorkNY 10032USA Center for Human Development Columbia UniversityNew YorkNY 10027USA Department of Pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA Department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism Small molecule conjugates Regeneration Adiposity

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The energetics of cellular life transitions

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Life Metabolism 2024年第3期3卷 12-20页

作者： Anna S.Monzel Michael Levin Martin Picard Department of Psychiatry Division of Behavioral MedicineCollege of Physicians and SurgeonsColumbia University Irving Medical CenterNew YorkNY 10032United States Department of Biology Tufts UniversityMedfordMA 02155United States Allen Discovery Center at Tufts University MedfordMA 02155United States Wyss Institute for Biologically Inspired Engineering Harvard UniversityBostonMA 02115United States Department of Neurology H.Houston Merritt CenterColumbia Translational Neuroscience InitiativeCollege of Physicians and SurgeonsColumbia University Irving Medical CenterNew YorkNY 10032United States New York State Psychiatric Institute New YorkNY 10032United States Robert N Butler Columbia Aging Center Columbia University Mailman School of Public HealthNew YorkNY 10032United States

Major life transitions are always difficult because change costs *** findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that excessive integrated stress response(ISR)signaling may prevent cellular identity transitions during *** this perspective,we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift *** energetic cost of cellular differentiation has not been directly quantified,representing a gap in *** propose that the ISR is an energetic checkpoint evolved to(i)prevent OxPhos-deficient cells from engaging in excessively costly transitions and(ii)allow ISR-positive cells to recruit systemic energetic resources by signaling via GDF15 and the brain.

关键词： energy mitochondria signaling pathway growth differentiation factor 15 energy balance development

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Towards data-efficient mechanical design of bicontinuous composites usinggenerative AI

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Theoretical & Applied Mechanics Letters 2024年第1期14卷 57-64页

作者： Milad Masrouri Zhao Qin Department of Civil and Environmental Engineering Syracuse UniversitySyracuseNY 13244USA Laboratory for Multiscale Material Modelling Syracuse UniversitySyracuseNY 13244USA The BioInspired Institute Syracuse UniversitySyracuseNY 13244USA

The distribution of material phases is crucial to determine the composite’s mechanical *** the full structure-mechanics relationship of highly ordered material distributions can be studied with finite number of cases,this relationship is difficult to be revealed for complex irregular distributions,preventing design of such material structures to meet certain mechanical *** noticeable developments of artificial intelligence(AI)algorithms in material design enables to detect the hidden structure-mechanics correlations which is essential for designing composite of complex *** is intriguing how these tools can assist composite ***,we focus on the rapid generation of bicontinuous composite structures together with the stress distribution in *** find that generative AI,enabled through fine-tuned Low Rank Adaptation models,can be trained with a few inputs to generate both synthetic composite structures and the corresponding von Mises stress *** results show that this technique is convenient in generating massive composites designs with useful mechanical information that dictate stiffness,fracture and robustness of the material with one model,and such has to be done by several different experimental or simulation *** research offers valuable insights for the improvement of composite design with the goal of expanding the design space and automatic screening of composite designs for improved mechanical functions.

关键词： Generative artificial intelligence Stable diffusion Composite design Phase field model Molecular dynamics simulation

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Violent collisions can reveal hexadecapole deformation of nuclei

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Nuclear Science and Techniques 2024年第7期35卷 1-3页

作者： Björn Schenke Physics Department Brookhaven National LaboratoryUptonNY 11973USA

A new observable in heavy ion collision experiments was identified to be sensitive to the hexadecapole deformation of the colliding *** deformation is difficult to measure in traditional nuclear electric transition measurements,as it is often overwhelmed by the nuclear quadrupole *** opens the door to gain new insight into nuclear structure with experiments that were designed to study hot and dense nuclear matter.

关键词： deformation. collision insight

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Imprinting at the KBTBD6 locus involves species-specific m ternal methylation and monoallelic expression in livestock animals

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Journal of Animal Science and Biotechnology 2024年第1期15卷 127-145页

作者： Jinsoo Ahn In-Sul Hwang Mi-Ryung Park Seongsoo Hwang Kichoon Lee Department of Animal Sciences The Ohio State UniversityColumbusOH 43210USA Animal Biotechnology Division Rural Development AdministrationNational Institute of Animal ScienceJeonbuk 55365Republic of Korea Columbia Center for Translational Immunology Columbia University Irving Medical CenterColumbia UniversityNew YorkNY 10032USA Animal Welfare Research Team National Institute of Animal ScienceRDA1500Kongjwipatjwi‑roJeollabuk‑do 55365Republic of Korea

Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of *** Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent *** In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

关键词： Differentially methylated region Domesticated mammal Imprinting KBTBD6 Parthenogenetic

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Spatio-temporal coupled mode theory for nonlocal metasurfaces

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Light(Science & Applications) 2024年第2期13卷 267-282页

作者： Adam Overvig Sander A.Mann Andrea Alù Photonics Initiative Advanced Science Research CenterCity University of New YorkNew YorkNY10031USA Physics Program Graduate Center of the City University of New YorkNew YorkNY10016USA

Diffractive nonlocal metasurfaces have recently opened a broad range of exciting developments in nanophotonics research and applications,leveraging spatially extended—yet locally patterned—resonant modes to control light with new degrees of *** conventional grating responses are elegantly captured by temporal coupled mode theory,current approaches are not well equipped to capture the arbitrary spatial response observed in the nascent field of nonlocal ***,we introduce spatio-temporal coupled mode theory(STCMT),capable of elegantly capturing the key features of the resonant response of wavefront-shaping nonlocal *** framework can quantitatively guide nonlocal metasurface design while maintaining compatibility with local metasurface frameworks,making it a powerful tool to rationally design and optimize a broad class of ultrathin optical *** validate this STCMT framework against full-wave simulations of various nonlocal metasurfaces,demonstrating that this tool offers a powerful semi-analytical framework to understand and model the physics and functionality of these devices,without the need for computationally intense full-wave *** also discuss how this model may shed physical insights into nonlocal phenomena in photonics and the functionality of the resulting *** a relevant example,we showcase STCMT’s flexibility by applying it to study and rapidly prototype nonlocal metasurfaces that spatially shape thermal emission.

关键词： theory resonant spatially

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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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PETG:Applications in Modern Medicine

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Engineered Regeneration 2024年第1期5卷 45-55页

作者： Catherine Yan Corinne Kleiner Aaron Tabigue Veer Shah Gregory Sacks Darshi Shah Vincent DeStefano Renaissance School of Medicine at Stony Brook University Stony BrookNYUSA Department of Biology Niagara UniversityLewistonNYUSA Stony Brook University Stony BrookNYUSA Department of Mechanical and Industrial Engineering Northeastern UniversityBostonMAUSA

Polyethylene terephthalate glycol,PETG,is a miscible,transparent thermoplastic known to have strong tensile properties,high ductility,as well as resistance to heat and chemical *** may be manufactured in several ways,most notably 3D printing *** such,PETG has emerged as a viable biomaterial for a variety of medical applications such as tissue engineering,dentistry,optometry,vascular health,cardiology,orthopedics,neurology,gynecology,and *** also serves a valuable role in biomedical research and engineering by offering improvements in cell studies,drug carriers,and anti-bacterial *** medical research and innovation utilizing PETG will better characterize its value as an inexpensive and versatile biomaterial.

关键词： Polyethylene terephthalate glycol Tissue Engineering 3D Printing Clinical Applications Biomedical Research

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Modeling urban scale human mobility through big data analysis and machinelearning

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Building Simulation 2024年第1期17卷 3-21页

作者： Yapan Liu Bing Dong Department of Mechanical&Aerospace Engineering Syracuse University263 Link HallSyracuseNY 13244USA

In the United States,the buildings sector consumes about 76%of electricity use and 40% of all primary energy use and associated greenhouse gas *** behavior has drawn increasing research interests due to its impacts on the building energy ***,occupant behavior study at urban scale remains a challenge,and very limited studies have been *** an effort to couple big data analysis with human mobility modeling,this study has explored urban scale human mobility utilizing three months Global Positioning System(GPS)data of 93,o00 users at Phoenix Metropolitan *** research extracted stay points from raw data,and identified users'home,work,and other locations by Density-Based Spatial Clustering ***,daily mobility patterns were constructed using different types of *** propose a novel approach to predict urban scale daily human mobility patterns with 12-hour prediction horizon,using Long Short-Term Memory(LSTM)neural network *** shows the developed models achieved around 85%average accuracy and about 86%mean *** developed models can be further applied to analyze urban scale occupant behavior,building energy demand and flexibility,and contributed to urban planning.

关键词： urban human mobility big data analysis urban scale occupant behavior recurrent neural networks

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Probing turbulence in galaxies with fast radio burst scintillation

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Science China(Physics,Mechanics & Astronomy) 2024年第1期67卷 177-178页

作者： James M.Cordes Department of Astronomy the Cornell Center for Astrophysics and Planetary ScienceCornell UniversityIthaca NY 14853USA

Interstellar scintillation(ISS)is a well-known phenomenon observed from pulsars in the Milky *** comprises intensity variations *** and frequency caused by constructive and destructive interference from multipath propagation,which is due to diffraction from fluctuations in electron density in the interstellar medium(ISM)on scales as small as~100 *** density fluctuations appear to be part of a turbulence process combined with discrete structures in electron density from other astrophysical processes;together these fluctuations extend to scales of pc or larger.

关键词： scales galaxies turbulence

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