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Hypothalamic circuits and aging:keeping the circadian clock updated

Neural Regeneration Research 2024年第9期19卷 1919-1928页

作者： Rosa vázquez-Lizarraga Lucia mendoza-viveros Carolina Cid-Castro Sareni Ruiz-montoya Erick Carreño-vázquez Ricardo Orozco-Solis Instituto Nacional de medicina Genómica(INmEGEN) México CityMéxico Centro de Investigacíon sobre el Envejecimiento Centro de Investigacíon y de Estudios Avanzados(CIE-CINVESTAV)México CityMéxico Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México UNAMMéxico CityMéxico

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of *** on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian *** circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during *** the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy *** brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

关键词： aging astrocytes cellular stress responses circadian clock hypothalamus intranasal drug administration metabolic control nutrient sensor SIRT1 sleep homeostasis

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Isochrone Fitting of Galactic Globular Clusters—Ⅵ.High-latitude Clusters NGC 5024 (m53),NGC 5053,NGC 5272 (m3),NGC 5466,and NGC7099 (m30)

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Research in Astronomy and Astrophysics 2024年第6期24卷 170-190页

作者： G.A.Gontcharov S.S.Savchenko A.A.marchuk C.J.Bonatto O.S.Ryutina m.Yu.Khovritchev v.B.Il'in A.v.mosenkov D.m.Poliakov A.A.Smirnov Central(Pulkovo)Astronomical Observatory Russian Academy of SciencesPulkovskoye chaussee 65/1St.Petersburg 196140Russia Saint Petersburg State University Universitetskij pr.28St.Petersburg 198504Russia Special Astrophysical Observatory Russian Academy of Sciences369167 Nizhnij ArkhyzRussia Departamento de Astronomia Instituto de FísicaUFRGSAv.Bento Gonçalves9500Porto AlegreRSBrazil Saint Petersburg University of Aerospace Instrumentation Bol.Morskaya ul.67ASt.Petersburg 190000Russia Department of Physics and Astronomy Brigham Young UniversityN283 ESCProvoUT 84602USA

We fit various color–magnitude diagrams(CmDs) of the high-latitude Galactic globular clusters NGC 5024(m53),NGC 5053,NGC 5272(m3),NGC 5466,and NGC 7099(m30) by isochrones from the Dartmouth Stellar Evolution Database and Bag of Stellar Tracks and Isochrones for α–enrichment [α/Fe] = +*** the CmDs,we use data sets from Hubble Space Telescope,Gaia,and other sources utilizing,at least,25 photometric filters for each *** obtain the following characteristics with their statistical uncertainties for NGC 5024,NGC 5053,NGC 5272,NGC 5466,and NGC 7099,respectively:metallicities [Fe/H] =-1.93 ± 0.02,-2.08 ± 0.03,-1.60 ± 0.02,-1.95 ± 0.02,and-2.07 ± 0.04 dex with their systematic uncertainty 0.1 dex;ages 13.00 ± 0.11,12.70 ± 0.11,11.63 ± 0.07,12.15 ± 0.11,and 12.80 ± 0.17 Gyr with their systematic uncertainty 0.8 Gyr;distances(systematic uncertainty added) 18.22 ± 0.06 ± 0.60,16.99 ± 0.06 ± 0.56,10.08 ± 0.04 ± 0.33,15.59 ±0.03 ± 0.51,and 8.29 ± 0.03 ± 0.27 kpc;reddenings E(B-v) = 0.023 ± 0.004,0.017 ± 0.004,0.023 ± 0.004,0.023 ± 0.003,and 0.045 ± 0.002 mag with their systematic uncertainty 0.01 mag;extinctions Av= 0.08 ± 0.01,0.06 ± 0.01,0.08 ± 0.01,0.08 ± 0.01,and 0.16 ± 0.01 mag with their systematic uncertainty 0.03 mag,which suggest the total Galactic extinction Av= 0.08 across the whole Galactic dust to extragalactic objects at the North Galactic *** horizontal branch morphology difference of these clusters is explained by their different metallicity,age,mass-loss efficiency,and loss of low-mass members in the evolution of the core-collapse cluster NGC 7099 and loose clusters NGC 5053 and NGC 5466.

关键词： (stars:)Hertzsprung Russell and C-m diagrams (ISm:)dust extinction (Galaxy:)globular clusters:general (Galaxy:)globular clusters:individual(NGC 5024,NGC 5053,NGC 5272,NGC 5466,NGC7099)

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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred m.Whitlock Zachary michel Kristen Pan Jocelyn Taylor vivian Szymczuk Brendan Boyce Daniel martin vardit Kram Rebeca Galisteo Kamran melikov Leonid v.Chernomordik michael T.Collins Alison m.Boyce Skeletal Disorders and mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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In vivo femtosecond laser nanosurgery of the cell wall enabling patch-clamp measurements on filamentous fungi

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microsystems & Nanoengineering 2024年第2期10卷 251-267页

作者： Tanja Pajić Katarina Stevanović Nataša v.Todorović Aleksandar J.Krmpot miroslav Živić Svetlana Savić-Šević Steva m.Lević marina Stanić Dejan Pantelić Brana Jelenković mihailo D.Rabasović Institute of Physiology and Biochemistry“Ivan Djaja” Faculty of BiologyUniversity of BelgradeStudentski trg 1611158BelgradeSerbia Institute for Biological Research“Siniša Stanković” University of BelgradeNational Institute of the Republic of SerbiaBulevar Despota Stefana 14211000BelgradeSerbia Institute of Physics Belgrade University of BelgradeNational Institute of the Republic of SerbiaPregrevica 11811080BelgradeSerbia University of Belgrade Faculty of AgricultureNemanjina Street 611080BelgradeSerbia Institute for multidisciplinary Research University of BelgradeKneza Višeslava 111030BelgradeSerbia

Studying the membrane physiology of filamentous fungi is key to understanding their interactions with the environment and crucial for developing new therapeutic strategies for disease-causing ***,their plasma membrane has been inaccessible for a micron-sized patch-clamp pipette for pA current recordings due to the rigid chitinous cell ***,we report the first femtosecond IR laser nanosurgery of the cell wall of the filamentous fungi,which enabled patch-clamp measurements on protoplasts released from hyphae.A reproducible and highly precise(diffraction-limited,submicron resolution)method for obtaining viable released protoplasts was *** release from the nanosurgery-generated incisions in the cell wall was achieved from different regions of the *** plasma membrane of the obtained protoplasts formed tight and high-resistance(GΩ)contacts with the recording *** entire nanosurgical procedure followed by the patch-clamp technique could be completed in less than 1 *** to previous studies using heterologously expressed channels,this technique provides the opportunity to identify new ionic currents and to study the properties of the ion channels in the protoplasts of filamentous fungi in their native environment.

关键词： patch recording laser

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Spatial Attention Integrated EfficientNet Architecture for Breast Cancer Classification with Explainable AI

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Computers, materials and Continua 2024年第3期80卷 5029-5045页

作者： Chakravarthy S. Nagarajan B. Khan S.B. venkatesan v.K. Ramakrishna m.T. Al musharraf A. Aurungzeb K. Department of Electronics and Communication Engineering Bannari Amman Institute of Technology Sathyamangalam 638402 India School of Computer Science Engineering and Information Systems (SCORE) Vellore Institute of Technology Vellore 632014 India School of Science Engineering and Environment University of Salford Manchester M54WT United Kingdom Adjunct Research Faculty Centre for Research Impact and Outcome Chitkara University Rajpura 140401 India Department of Computer Science and Engineering Faculty of Engineering and Technology JAIN (Deemed-to-be University) Bengaluru 562112 India Department of management College of Business Administration Princess Nourah Bint Abdulrahman University Riyadh 11671 Saudi Arabia Department of Computer Engineering College of Computer and Information Sciences King Saud University Riyadh 11543 Saudi Arabia

Breast cancer is a type of cancer responsible for higher mortality rates among women. The cruelty of breast cancer always requires a promising approach for its earlier detection. In light of this, the proposed research leverages the representation ability of pretrained EfficientNet-B0 model and the classification ability of the XGBoost model for the binary classification of breast tumors. In addition, the above transfer learning model is modified in such a way that it will focus more on tumor cells in the input mammogram. Accordingly, the work proposed an EfficientNetB0 having a Spatial Attention Layer with XGBoost (ESA-XGBNet) for binary classification of mammograms. For this, the work is trained, tested, and validated using original and augmented mammogram images of three public datasets namely CBIS-DDSm, INbreast, and mIAS databases. maximum classification accuracy of 97.585% (CBIS-DDSm), 98.255% (INbreast), and 98.91% (mIAS) is obtained using the proposed ESA-XGBNet architecture as compared with the existing models. Furthermore, the decision-making of the proposed ESA-XGBNet architecture is visualized and validated using the Attention Guided GradCAm-based Explainable AI technique. © 2024 The Authors.

关键词： breast cancer deep-learning EfficientNet Explainable AI mammograms transfer learning

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Extracellular vesicles-coupled miRNAs from oviduct and uterus modulate signaling pathways related to lipid metabolism and bovine early embryo development

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1528-1549页

作者： Rosane mazzarella Karina Canon‑Beltran Yulia N.Cajas meriem Hamdi Encina m.Gonzalez Juliano C.da Silveira Claudia L.v.Leal D.Rizos Department of Animal Reproduction INIA-CSICMadridSpain Department of Biochemistry and molecular Biology Veterinary FacultyComplutense University of Madrid(UCM)MadridSpain Department Agrarian Production Technical University of MadridUPMMadridSpain Departamento de Ciencias Biologicas Universidad Tecnica Particular de LojaUTPLLojaEcuador Department of Anatomy and Embryology FV-UCMMadridSpain Department of veterinary medicine FZEA-USPPirassunungaBrazil

Background Extracellular vesicles(Evs) present in oviductal(OF) and uterine fluid(UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes(LmGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabo-lism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within Evs in maternal reproductive fluids, such as micro RNAs(miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional *** This study evaluated miRNA cargo in OF-Evs from the early luteal phase and UF-Evs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LmGs and sign-aling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups. From the 20 differentially expressed miRNAs, 19 up-regulated in UF-Evs(bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one(bta-miR-148b) in OF-Evs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, mAPK, and lipid metabolism and degradation. Differ-ences in miRNAs found in OF-Evs from the early luteal phase and UF-Evs from mid-luteal phase may reflect differ-ent environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and *** Our study su

关键词： Embryo-maternal interaction Epigenetic Exosomes mammalian Preimplantation Reproductive fluids

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Increasingβ-hexosaminidase A activity using genetically modified mesenchymal stem cells

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Neural Regeneration Research 2024年第1期19卷 212-219页

作者： Alisa A.Shaimardanova Daria S.Chulpanova valeriya v.Solovуeva Shaza S.Issa Aysilu I.mullagulova Angelina A.Titova Yana O.mukhamedshina Anna v.Timofeeva Alexander m.Aimaletdinov Islam R.Nigmetzyanov Albert A.Rizvanov Institute of Fundamental medicine and Biology Kazan Federal UniversityKazanRussia Department of Histology Cytology and EmbryologyKazan State Medical UniversityKazanRussia

Gm2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorde *** diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for Gm2 ganglioside *** deficiency causes the accumulation of Gm2-gangliosides mainly in the nervous system cells,leading to severe progressive neurodegeneration and *** date,there is no treatment for these ***-mediated gene therapy is considered a promising treatment for Gm2 *** study aimed to evaluate the ability of genetically modified mesenchymal stem cells(mSCs-HEXA-HEXB)to restore HexA deficiency in Tay-Sachs disease patient cells,as well as to analyze the functionality and biodistribution of mSCs in *** effectiveness of HexA deficiency cross-correction was shown in mutant mSCs upon intera ction with *** results also showed that the mSCs-HEXA-HEXB express the functionally active HexA enzyme,detectable in vivo,and intravenous injection of the cells does not cause an immune response in *** data suggest that genetically modified mesenchymal stem cells have the potentials to treat Gm2 gangliosidoses.

关键词： adeno-associated viral vectors cell therapy cell-mediated gene therapy gene therapy Gm2 gangliosidosis Sandhoff disease Tay-Sachs disease β-hexosaminidase

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Preliminary results of lithological and palynological study of Svobodny,ancient man’s parking relic in Amur region,Russia

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Global Geology 2024年第3期27卷 121-131页

作者： Kovalenko S.v. Kezina T.v. Kryuchko E.I. mironov m.A. Center for the Preservation of Historical and Cultural Heritage of the Amur Region Blagoveshchensk 675000Russia Amur State University Blagoveshchensk 675027Russia

A single-layer monument Svobodny,ancient man's parking lot-1,discovered in 2021 as part of archaeological work to study the zone of economic development of the Amur region was investigated lithologically and *** on the results of geomorphological analysis of the territory,the study of artifacts,palynological data,as well as analogy with previously identified and sufficiently studied relics in the region,the existence of the Osinoozersk late Neolithic culture in this territory is *** time of its expansion in the Amur region is determined within the framework of the second half of theⅣmillennium BC to the first half of theⅡmillennium *** preliminary results of palynological analysis suggest the existence of a temperate climate here,was close to the modern one,which does not contradict the reconstructed paleoclimate and environments of the region during the Holocene period.

关键词： Osinoozersk culture palynological spectra Zeya River paleoclimate

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Joint Rain Streaks & Haze Rem.v.l Network for Object Detection

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Computers, materials & Continua 2024年第6期79卷 4683-4702页

作者： Ragini Thatikonda Prakash Kodali Ramalingaswamy Cheruku Eswaramoorthy K.v Department of Electronics and Communication Engineering National Institute of TechnologyWarangal506004India Department of Computer Science and Engineering National Institute of TechnologyWarangal506004India Department of Electronics and Communication Engineering Indian Institute of Information TechnologyDesign and ManufacturingKurnool518008India

In the realm of low-level vision tasks,such as image deraining and dehazing,restoring images distorted by adverse weather conditions remains a significant *** emergence of abundant computational resources has driven the dominance of deep Convolutional Neural Networks(CNNs),supplanting traditional methods reliant on prior ***,the evolution of CNN architectures has tended towards increasing complexity,utilizing intricate structures to enhance performance,often at the expense of computational *** response,we propose the Selective Kernel Dense Residual m-shaped Network(SKDRmNet),a flexible solution adept at balancing computational efficiency with network accuracy.A key innovation is the incorporation of an m-shaped hierarchical structure,derived from the U-Net framework as m-Network(m-Net),within which the Selective Kernel Dense Residual module(SDRm)is introduced to reinforce multi-scale semantic feature *** methodology employs two sampling techniques-bilinear and pixel unshuffled and utilizes a multi-scale feature fusion approach to distil more robust spatial feature map *** the reconstruction phase,feature maps of varying resolutions are seamlessly integrated,and the extracted features are effectively merged using the Selective Kernel Fusion module(SKFm).Empirical results demonstrate the comprehensive superiority of SKDRmNet across both synthetic and real rain and haze datasets.

关键词： Image deraining Selective Dense Residual module(SDRm) Selective Kernel Fusion module(SKFm) Selective KernelDense Residual m-Shaped Network(SKDRmNet)

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Old-growth mixed dipterocarp forests show variable losses and gains in aboveground biomass and standing carbon over forty years

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Forest Ecosystems 2024年第1期11卷 14-23页

作者： Sisira Ediriweera Champika Bandara Tithira Lakkana Shanika Jayasinghe David Woodbury Arun Dayanandan B.m.P.Singhakumara Xiangcheng mi I.A.U.N.Gunatilleke C.v.S.Gunatilleke mark SAshton Department of Science and Technology Uva Wellassa UniversityBadullaSri Lanka The Forest School Yale School of the EnvironmentYale UniversityNew HavenCT06511USA Department of Forestry and Environmental Science University of Sri JayewardenepuraNugegodaSri Lanka State Key Laboratory of vegetation and Environmental Change Institute of BotanyChinese Academy of SciencesBeijing100093China Botany Department University of PeradeniyaPeradeniyaSri Lanka

Background:No studies have documented long-term trends in aboveground biomass(AGB)for mixed-dipterocarp forests(mDF),the dominant rain forest type in tropical wet equatorial *** our study,we sought to document such trends over forty years across three sites representing lowland to lower montane ***:To do this,we established fifty 100 m×25 m plots in 1978 across three sites sampled along an elevation gradient,identified as mature old-growth *** measured trees for diameter at breast height that we identified to species and *** took wood samples to calculate species wood-specific *** re-measured plots in 1998 and again in ***:We show standing AGB for all sites combined to be 517.52 mg·ha^(-1)in 1978,but this declined by 17%over 40 years to 430.11 mg·ha^(-1).No differences exist among sites in AGB primarily because of considerable within site variation;but interactions of time with site show declines across sites were not uniform,one remained about the *** few species represented a high proportion of the AGB with the top five species comprising between 34%and 65%,depending upon site and year *** species,mesua nagassarium,represented a disproportionately large amount of AGB and decline over time,particularly at the low elevation ***:Our results are directly relevant to estimating AGB and standing carbon sequestered in *** study is the first to demonstrate varying but overall,declining trends in amounts of AGB among forests making predictions of biomass and standing carbon in mDF difficult over wide regions.

关键词： Western ghats Shorea spp. Southeast Asia Sri Lanka Tropical rain forest Wood specific gravity

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