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Mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： joséM.Izquierdo Centro de Biología Molecular Severo Ochoa(CBM) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Optimization of high-speed railway pantographs for improving pantograph-catenary contact

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Theoretical & Applied Mechanics Letters 2013年第1期3卷 51-57页

作者： Jorge ambrósio Joo Pombo Manuel Pereira IdMEC-IST Technical Univ. of Lisbon Av. Rovisco Pais

A crucial system for the operation of high-speed trains is the pantograph catenary interface as it is the sole responsible to deliver electrical power to the train. Being the catenary a stationary system with a long lifespan it is also less likely to be redesigned and upgraded than the pantographs that fit the train vehicles. This letter proposes an optimization procedure for the improvement of the contact quality between the pantograph and the catenary solely based on the redesign of the pantograph head suspension characteristics. A pantograph model is defined and validated against experimental dynamic characteristics of existing pantographs. An optimization strategy based on the use of a global optimization method, to find the vicinity of the optimal solution, followed by the use of a deterministic optimization algorithm, to fine tune the optimal solution, is applied here. The spring stiffness, damping characteristics and bow mass are the design variables used for the pantograph optimization. The objective of the optimal problem is the minimization of the standard deviation of the contact force history, which is the most important quantity to define the contact quality. The pantograph head suspension characteristics are allowed to vary within technological realistic limits. It is found that current high-speed railway pantographs have a limited potential for mechanical improvements, not exceeding 10% 15% on the decrease of the standard deviation of the contact force. C 2013 The Chinese Society of Theoretical and Applied Mechanics. [doi：10.1063/2.1301306]

关键词： high-speed railway pantograph

Autophagy, apoptosis and organelle features during cell exposure to cadmiumč

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BIOCELL 2013年第2期37卷 45-54页

作者： CRISTIANE dOS SANTOS VERGILIO EdÉsio josÉTENÓRIO dE MELO Universidade Estadual do Norte Fluminense Centro de Biociências e BiotecnologiaLaboratório de Biologia Celular e TecidualCampos dos GoytacazesRJBrasil28013-602.

Cadmium(Cd)induces several effects in different tissues,but our knowledge of the toxic effects on organelles is insuffi *** observe the progression of Cd effects on organelle structure and function,HuH-7 cells(human hepatic carcinoma cell line)were exposed to CdCl2 in increasing concentrations(1μM–20μM)and exposure times(2 h–24 h).during Cd treatment,the cells exhibited a progressive decrease in viability that was both time-and *** treated cells displayed progressive morphological changes that included cytoplasm retraction and nuclear condensation preceding a total loss of cell *** with 10μM for 12 h led to irreversible *** these drastic and irreparable damages,treated cells(5μM for 12 h)presented a progressive loss of mitochondrial function and cytoplasm acidifi cation as well as dysfunction and disorganization of microfi laments and endoplasmic *** damages led to the induction of apoptotic events and an increase in autophagic bodies in the *** results revealed that Cd affects multiple intra-cellular targets that induce alterations in the mitochondria,cytoskeleton,endoplasmic reticulum and acidic compartments,ultimately culminating in cell death via apoptotic and autophagic pathways.

关键词： Cd cell death hepatocyte HuH-7 cells mitochondria

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María joséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOd-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOd-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOd-,LRR-and pyrin domain-containing protein 3(NLRP3)

Influence of physical-anatomical wood variables on charcoal physical-mechanical properties

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Journal of Forestry Research 2023年第2期34卷 531-538页

作者： Allan Motta Couto Thiago Campos Monteiro Paulo Fernando Trugilho joséTarcísio Lima joséReinaldo Moreira da Silva Alfredo Napoli diego Pierre de Almeida department of Forestry Science State University of Mato Grosso do Sul–UEMSAv.Graziela Maciel BarrosoKm 12 Zona RuralAquidauanaMS 79200000Brazil department of Forestry Engineering and Technology Federal University of Paraná–UFPRA V.Pref.Lothário Meissner 632Jardim BotânicoCuritibaPR 80210170Brazil department of Forestry Science Federal UniversityLavras–UFLALavrasMG 37200000Brazil département de Performance des Systèmes de Production Et de Transformation Tropicaux Centre de Coopération Internationale em Recherche Agronomique pour le Développement–CIRADMontpellierFrance

This research assessed the relationship between wood physical-anatomical variables and charcoal physical-mechanical *** trees were harvested and mechanically processed into standard pieces for laboratory *** following variables were determined:wood density,fiber length and width,fiber lumen diameter and wall thickness,fiber wall fraction,and vessel *** charcoal was produced in a laboratory and gravimetric yield,relative density,and mechanical properties ***’s correlation coefficients,multivariate statistical analysis of canonical correlation,and principal component analysis were used to evaluate the relationship between wood and charcoal *** width was not significantly correlated with charcoal *** bulk density,hardness,and strength were positively correlated with wood density,fiber length,wall thickness,and wall *** properties were negatively correlated with fiber lumen diameter and vessel *** results will help identify the best wood with adequate physical-mechanical properties for industrial charcoal proces sing.

关键词： Biomass density Energy Fiber Vessel

Oral pharmacological treatment for patent ductus arteriosus in premature neonates with hemodynamic repercussions

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Asian Pacific Journal of Tropical Medicine 2017年第11期10卷 1080-1083页

作者： Clarissa de Albuquerque Botura Bruno ambrósio da Rocha Thiely Balensiefer Franciele Queiroz Ames Ciomar Aparecida Bersani-Amado Roberto Kenji Nakamura Cuman department of Medicine Faculdade Uningá department of Pharmacology and Therapeutics State University of Maringá Hospital Pharmacy at Santa Rita Hospital

Objective: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus(PdA) in premature neonates with significant clinical and hemodynamic repercussions(CHRs) and to determine the effect of these respective treatments on renal ***: A retrospective study of cases of PdA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin[0.2 mg/(kg$d), 3-day cycle], ibuprofen [10 mg/(kg$d) followed by 5 mg/(kg$d), 3-day cycle], and paracetamol(15 mg/kg every 6 h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age,newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels(sodium and potassium).Results: Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5 d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of9.66 d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ***: Oral indomethacin was effective for closure of the PdA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PdA closure in premature neonates with severe CHRs and contraindications for indomethacin was ***, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.

关键词： Patent ductus arteriosus Premature neonatal Indomethacin Ibuprofen Paracetamol

Evaluation of markers of outcome in realworld treatment of diabetic macular edema

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Eye and Vision 2018年第1期5卷 240-249页

作者： António Campos Elisa J Campos Anália do Carmo Francisco Caramelo João Martins João P Sousa António Francisco ambrósio Rufino Silva Coimbra Institute for Clinical and Biomedical Research(iCBR) Faculty of MedicineUniversity of CoimbraAzinhaga de Santa CombaCelas3000-548 CoimbraPortugal CNC.iCBR Consortium University of CoimbraCoimbraPortugal department of Ophthalmology Leiria HospitalLeiriaPortugal Clinical Pathology department Centro Hospitalar Universitário de Coimbra(CHUC)CoimbraPortugal Laboratory of Biostatistics and Medical Informatics Faculty of MedicineUniversity of CoimbraCoimbraPortugal Medical Sciences department Faculty of Health SciencesUniversity of Beira InteriorCovilhãPortugal Association for Innovation and Biomedical Research on Light and Image(AIBILI) CoimbraPortugal department of Ophthalmology Centro Hospitalar Universitário de Coimbra(CHUC)CoimbraPortugal

Objective:To evaluate short-term markers of outcome in diabetic macular edema(dME).Methods:Prospective interventional case series included 122 eyes of 122 patients with recently diagnosed *** were treated with a 3-monthly loading dose of ranibizumab or aflibercept and pro re nata *** enhanced deep imaging Sd-OCT high resolution scans were used to measure subfoveal choroidal thickness(SFCT)and central retinal thickness(CRT).Anatomic(10%CRT decrease)and functional responses(best corrected visual acuity,BCVA gain≥5 letters)were assessed at 3 months and 6 months using univariate and multivariate *** tested were gender,duration of diabetes,HbA1c,hypertension,CRT,SFCT,BCVA,ellipsoid zone(EZ)status,subfoveal neuroretinal detachment(SNd),anti-VEGF used and laser naivety.A logistic regression model was applied to find independent markers ***:BCVA increased,CRT and SFCT decreased at 3 months and 6 *** metabolic control(p=0.003),intact baseline EZ(p=0.030),EZ re-grading at 3 M(pd laser naivety(p=0.001)were associated with better functional *** multivariate linear regression model showed that baseline SNd and CRT are predictors of anatomic response,while lower baseline BCVA and intact EZ are predictors of functional ***:The presence of SNd predicts anatomic response only,while an intact EZ is critical to achieve a good functional outcome in dME.

关键词： diabetic macular edema Outcome factors Spectral-domain optical coherence tomography Antivascular endothelial growth factor Laser

Biomechanical diagnostics of the cornea

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Eye and Vision 2020年第1期7卷 87-98页

作者： Louise Pellegrino Gomes Esporcatte Marcella Q.Salomão Bernardo T.Lopes Paolo Vinciguerra Riccardo Vinciguerra Cynthia Roberts Ahmed Elsheikh daniel G.dawson Renato ambrósio Jr Rio de Janeiro Corneal Tomography and Biomechanics Study Group Rio de JaneiroBrazil Instituto de Olhos Renato ambrósio Rua Conde de Bonfim 211/712Rio de JaneiroRJ 20520-050Brazil department of Ophthalmology Hospital São Vicente de PauloRio de JaneiroBrazil Brazilian Study Group of Artificial Intelligence and Corneal Analysis–BrAIN Rio de Janeiro&MaceióBrazil department of Ophthalmology Federal University of São PauloSão PauloBrazil Instituto Benjamin Constant Rio de JaneiroBrazil School of Engineering University of LiverpoolLiverpool L693GHUK department of Biomedical Science Humanitas UniversityRozzanoItaly Eye Center Humanitas Clinical and Research CenterRozzanoItaly department of Ophthalmology Humanitas San Pio X HospitalMilanItaly department of Ophthalmology and Visual Science Department of Biomedical EngineeringThe Ohio State UniversityColumbusOHUSA School of Biological Science and Biomedical Engineering Beihang UniversityBeijingChina NIHR Biomedical Research Centre for Ophthalmology Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyLondonUK The University of Florida department of Ophthalmology GainesvilleFLUSA department of Ophthalmology Federal University the State of Rio de Janeiro(UNIRIO)Rio de JaneiroBrazil

Corneal biomechanics has been a hot topic for research in contemporary ophthalmology due to its prospective applications in diagnosis,management,and treatment of several clinical conditions,including glaucoma,elective keratorefractive surgery,and different corneal *** clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia after laser vision *** review discusses the latest developments in the detection of corneal ectatic *** developments should be considered in conjunction with multimodal corneal and refractive imaging,including Placido-disk based corneal topography,Scheimpflug corneal tomography,anterior segment tomography,spectral-domain optical coherence tomography(Sd-OCT),very-high-frequency ultrasound(VHF-US),ocular biometry,and ocular wavefront *** ocular response analyzer(ORA)and the Corvis ST are non-contact tonometry systems that provide a clinical corneal biomechanical *** recently,Brillouin optical microscopy has been demonstrated to provide in vivo biomechanical *** integration of tomographic and biomechanical data into artificial intelligence techniques has demonstrated the ability to increase the accuracy to detect ectatic disease and characterize the inherent susceptibility for biomechanical failure and ectasia progression,which is a severe complication after laser vision correction.

关键词： Corneal biomechanics Corneal ectasia Corneal imaging

Improved rate-distortion optimized video coding using non-integer bit estimation and multiple Lambda search

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Frontiers of Computer Science 2016年第1期10卷 157-166页

作者： sio Kei IM Mohammad Mahdi GHANdI MPI-QMUL Information Systems Research Centre Macao Polytechnic Institute Macao China department of Electronic Systems Engineering University of Essex Colchestey CO4 3SQ UK

Many modern video encoders use the Lagrangian rate-distortion optimization （RdO） algorithm for mode deci- sions during the compression procedure. For each encoding stage, this approach involves minimizing a cost, which is a function of rate, distortion and a multiplier called Lambda. This paper proposes to improve the RdO process by applying two modifications. The first modification is to increase the ac- curacy of rate estimation, which is achieved by computing a non-integer number of bits for arithmetic coding of the syntax elements. This leads to a more accurate cost computation and therefore a better mode decision. The second modification is to search and adjust the value of Lambda based on the char- acteristics of each coding stage. For the encoder used, this paper proposes to search multiple values of Lambda for the intra-4x4 mode decision. Moreover, a simple shift in Lambda value is proposed for motion estimation. Each of these modi- fications offers a certain gain in RdO performance, and, when all are combined, an average bit-rate saving of up to 7.0% can be achieved for the H.264/AVC codec while the same concept is applicable to the H.265/HEVC codec as well. The extra added complexity is contained to a certain level, and is also adjustable according to the processing resources available.

关键词： rate distortion optimization Lambda adjust-ment non-integer bit estimation H.264/AVC H265/HEVCvideo coding