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cD4^(+)T cells produce IfN-I to license cDc1s for induction of cytotoxic T-cell activity in human tumors

cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël c.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos charlotte L.Zuur noel.f.c.c.de miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of Otorhinolaryngology Leiden University Medical center LeidenThe Netherlands department of Pathology Leiden University Medical CenterLeidenThe Netherlands

cD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDc1s)to induce cD8^(+)cytotoxic T lymphocyte(cTL)anticancer responses,as proven in mouse *** recently identified cDc1s with a transcriptomic imprint of cD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDc1 licensing by cD4^(+)T cells in *** cD4^(+)T cells produce IfNβvia the STING pathway,which promotes MHc-I antigen(cross-)presentation by cDc1s and thereby improves their ability to induce cTL anticancer *** cooperation with cD40 ligand(L),IfNβalso optimizes the costimulatory and other functions of cDc1s required for cTL response ***-I-producing cD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to cTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDcs and tumor-reactive cD8^(+)T *** agreement with this scenario,the presence of IfN-I-producing cD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： cD4^(+)T-cell help cDc1 licensing IfN-I signaling cD40 costimulation (cross-)presentation cTL priming Tumor control

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Assessment of cO_(2)storage prospect based on physical properties of Rio Bonito formation rock units

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Energy Geoscience 2024年第1期5卷 321-330页

作者： Richardson M.Abraham-A Stephanie San Martín cañas Isabella f.S.miranda colombo c.G.Tassinari Institute of Energy and Environment(IEE) University of São Paulo(USP)Brazil Research centre for Greenhouse Gas Innovation(RcGI) University of Sãao Paulo(USP)Brazil

The physical properties of the rock units associated with the Rio Bonito formation are presented in this study with the focus on modelling reservoir quality based on petrophysics-derived parameters to evaluate cO_(2)storage *** involves the modelling of the reservoir depths,thicknesses,flow zone indicators(fZI),and effective permeability(Keff)and presenting the cO_(2)storage efficiency factors peculiar to the rock units of the study *** results presented by this study for the stated objectives are not quite common in the *** values range from 200 mD to higher than 2000 mD,and fZI values are generally above 1.0 mm and up to 13.0 mm within the portions covered by the drilled *** sandstone units recorded are up to 20 m thick in some *** Keff and fZI models indicate the sandstone reservoirs as permeable units to support the injection and circulation of cO_(2)within the potential reservoir units of the Rio Bonio formation across São Paulo *** from some points in the southeastern part of the study location,where the Rio Bonito are delineated at depths less than 800 m(minimum cO_(2)storage depth based on best practices),other portions are deeper,ranging from 950 m to 3500 ***-bedded layers will affect the integrity of the rocks as cO_(2)storage tanks or reservoir seals/traps/overburden within the *** bed thicknesses are up to 20 m in some ***,hybrid cO_(2)reservoir units are feasible,especially in portions where thin siltstone layers are sandwiched between sandstone units to provide considerable thicknesses based on cO_(2)storage *** current study shows that useable areas considering reservoir thickness,depth,and other physical qualities will significantly control the cO_(2)storage efficiency of the study *** studies featuring a detailed geophysical exploration of the site to confirm the availability and saturations of preexisting fluid(hydrocarbon and water)are encouraged

关键词： Rio Bonito Effective permeability fluid transmissibility cO_(2)storage prospect Reservoir quality Overburden integrity flow zones

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Preventing brain aging by the artificial enforcement of the unfolded protein response:future directions

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Neural Regeneration Research 2024年第2期19卷 393-394页

作者： felipe cabral-miranda claudio Hetz Instituto de ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil center for Geroscience Brain Health and MetabolismSantiagoChile、Biomedical Neuroscience InstituteFaculty of MedicineUniversity of ChileSantiagoChile、Program of Cellular and Molecular BiologyInstitute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile、Buck Institute for Research on AgingNovatoCAUSA

As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern *** onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.

关键词： diseases aging directions

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comparison between care Strategies for Patients with Osteoarthritis of the Hands Based on the Use of Joint Protection, Assistive Technology and Exercises

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Open Journal of Orthopedics 2024年第7期14卷 295-311页

作者： Daniele dos Santos Scarcella Talita Dias da Silva Victoria Yanara Hernandes da Silva Maria cândida de miranda Luzo Selma Lancman Marcia Uchoa de Rezende carlos Bandeira de Mello Monteiro Instituto de Ortopedia e Traumatologia Hospital das Clnicas HCFMUSP Faculdade de Medicina Universidade de So Paulo So Paulo Brazil Programa de Ps-Graduao em cincias da Reabilitao Faculdade de Medicina Universidade de So Paulo So Paulo Brazil Escola de Artes Cincias e Humanidades Universidade de So Paulo So Paulo Brazil

Background: Osteoarthritis (OA) is a disabling disease that can affect 6% to 12% of the adult population and more than a third of people over 65 years of age. Purpose: To assess whether a group of people with hand osteoarthritis (hOA) who received different types of treatment improved their function after two years of follow-up. Method: The entire sample (n = 97) underwent three follow-up assessments regarding anthropometric parameters of the upper limbs and ability to perform functional activities. Subsequently, the sample was divided into two groups for the intervention periods, called the first Period (n = 73) and the Second Period (n = 24);the first Period kept the same protocol with orientations, and the Second Period went to an intervention with orientation strength exercises and use of orthosis. findings: In the separate analysis of the three questions of the DASH pain module, no differences were found between the assessment moments for groups of guidelines, treatment, or symptoms. Significant effects were observed for f(2, 162) = 3.5, p = 0.033, η2 = 0.04, and interaction for moments and intervention f(2, 162) = 4.3, p = 0.016, η2 = 0.05. Implications: It can be concluded that only guidance treatment does not benefit patients with hand osteoarthritis. In contrast, guidance, exercise, and orthosis treatment can significantly improve the disease.

关键词： Hand Osteoarthritis Hand deformities Occupational Therapy

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Application of a Pulsed Electric field to Modify the free Energy of the Active Site of an Azoreductase

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Journal of Applied Mathematics and Physics 2024年第1期12卷 249-255页

作者： Jesus Magyber de Jesus miranda Pedro Guillermo Reyes-Romero Jorge Mulia-Rodríguez Daniel Osorio-González Molecular Biophysics Laboratory Faculty of Sciences Autonomous University of State of Mexico Toluca Mexico Advanced Physics Laboratory Faculty of Sciences Autonomous University of State of Mexico Toluca Mexico

The Gibbs free energy is strongly related to the stability and catalytic function of an enzyme through the energetic changes that occur in the chemical reactions the enzyme catalyzes. In this in silico study, a pulsed electric field was applied to an azoreductase, and its effect on the Gibbs free energy of molecular docking with two dyes was measured. We propose that certain stimuli from a pulsed electric field favor the structural stability of the enzyme by promoting an arrangement in the active site, potentially leading to an enhancement of enzymatic activity overall.

关键词： Pulsed Electric field Molecular Dynamics Docking Azoreductase

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Polygenic Profile and Magnitude Impact of Inflammatory Response in Soccer Athletes

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Open Journal of Genetics 2024年第3期14卷 47-76页

作者： Tane Kanope caleb Guedes miranda dos Santos christiano Eduardo Veneroso Andre fornazieiro Miller Gomes de Assis Eduardo Mendonça Pimenta UfMG Soccer Science center Program in Sport Sciences School of Physical Education Physiotherapy and Occupational Therapy Federal University of Minas Gerais Belo Horizonte MG Brazil Army Institute of Biology IBEX Rio de Janeiro Brazil Graduate Program in Physical Education Federal University of Maranho So Lus MA Brazil

The practice of soccer involves carrying-out actions of high intensity, which demand a great generation of eccentric strength, which in turn results in an increase in the inflammatory response after training practice and game matches. The study aimed to investigate, in combination and individually, the association of 28 polymorphisms with the inflammatory responses of soccer athletes. The sample consisted of 47 male under-20 soccer athletes who belong to clubs in the first division of Brazilian soccer. Blood samples were collected at Pre, and 03, 24, and 48 hours after the training session to evaluate the inflammatory responses (hematological analyzes (hemogram), creatine phosphokinase (cK), high sensitivity quantitative c-reactive protein (cRP), tumor necrosis factor-alpha, (TNfα), interleukin 6 (IL-6) and insulin-like growth factor 1 (IGf-1)). DNA was obtained through scraping of buccal cells, where a sterile swab was rubbed on the inner side of the mouth of each participant 06 times. The database was built using the TruSeq DNA PcRfree kit (Illumina®) and the covaris equipment for shearing genomic DNA (gDNA) by ultrasound. Of the analyzed SNPs, 09 (AcTN3 rs1815739, cOL5A1 rs12722, cOL5A1 rs3196378, HGf rs5745697, IGf1 rs35767, IL-6 rs1800795, MMP3 rs679620, SLc30A8 rs13266634, SOX15 rs4227) were individually associated with biomarkers and 07 SNPs, (cOL5A1 rs12722, cOL5A1 rs3196378, cOL5A1 rs1800012, HGf rs5745697, IGf1 rs35767, IL-6 rs1800795 and MMP3 rs679620) analyzed in combination, explained 16% to 40% of the variation of inflammatory responses in soccer athletes. The results suggest that the genotypic profile can be taken into account for a more individualized distribution of the training load, along with the elaboration of recovery strategies for high-level athletes between training sessions and games of high physical and physiological demand.

关键词： Polymorphism Genotype Soccer Inflammation

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Temperature Drop of Molten Metals in Open channels

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World Journal of Engineering and Technology 2024年第3期12卷 493-500页

作者： Miguel A. Barron-Meza Joan Reyes-miranda departamento de Materiales Universidad Autonoma Metropolitana Azcapotzalco Ciudad de Mexico Mexico

The temperature drop of molten metal flowing in open channels is numerically determined. Rectangular, trapezoidal and triangular geometries are considered. The overall heat transfer coefficients for the bottom, side walls and free surface of the channel have been taken from the literature. for each geometry, the volumetric flow rate, mean residence time and temperature drop as a function of the channel inclination angle were determined. The rectangular and trapezoidal geometries present the smallest temperature drops, while the triangular geometry presents the greatest temperature drop. The factors that most affect this drop are the value of the free surface area of the channel, and the average residence time of the molten metal in the channel.

关键词： free Surface Heat Transfer Molten Metal Open channel Geometry Residence Time Temperature Drop

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Non-Darcy flow in Molding Sands

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Open Journal of Applied Sciences 2024年第4期14卷 976-982页

作者： Miguel A. Barron-Meza Joan Reyes-miranda Daniel flores-Sanchez departamento de Materiales Universidad Autonoma Metropolitana Azcapotzalco Ciudad de Mexico Mexico

Darcy’s law is widely used to describe the flow in porous media in which there is a linear relationship between fluid velocity and pressure gradient. However, it has been found that for high numbers of Reynolds this law ceases to be valid. In this work, the Ergun equation is employed to consider the non-linearity of air velocity with the pressure gradient in casting sands. The contribution of non-linearity to the total flow in terms of a variable defined as a non-Darcy flow fraction is numerically quantified. In addition, the influence of the shape factor of the sand grains on the non-linear flow fraction is analyzed. It is found that for values of the Reynolds number less or equal than 1, the contribution of non-linearity for spherical particles is around 1.15%.

关键词： Darcy’s Law Molding Sands Non-Darcy flow Reynolds Number Shape factor

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Immunoregulatory and Anti-cancer Activities of combination Treatment of Novel four-Herb formula and Doxorubicin in 4T1-Breast cancer Bearing Mice

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chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben chung-Lap chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi miranda Sin-Man Tsang clara Bik-San Lau Ping-chung Leung chun-Kwok Wong Institute of chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina department of chemical Pathology The Chinese University of Hong KongHong Kong SARChina china-Australia International Research centre for chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio chin R&D centre for chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel four-Herb formula(4Hf)and doxorubicin in triple-negative breast cancer(TNBc).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4Hf(low dose 4Hf),HD 4Hf(high dose 4Hf),LD 4Hf+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4Hf,*** LD 4Hf+D group received daily oral gavage of 658 mg/kg 4Hf and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4Hf and doxorubicin resulted in significantly reduced tumor and spleen burdens(Pcyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as c-c motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(Pf-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines chinese medicine tumor microenvironment

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Social determinants of gastrointestinal malformation mortality in Brazil:a national study

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World Journal of Pediatric Surgery 2024年第2期7卷 134-141页

作者： Ayla Gerk Amanda Rosendo Luiza Telles Aricia Gomes miranda Madeleine carroll Bruna Oliveira Trindade Sarah Bueno Motter Esther freire Gabriella Hyman Julia ferreira fabio Botelho Roseanne ferreira David P Mooney Joaquim Bustorff-Silva Program in Global Surgery and Social change Harvard Medical SchoolBostonMassachusettsUSA faculty of Medicine and Health Sciences McGill UniversityMontrealQuebecCanada Harvey E.Beardmore Division of Pediatric Surgery The Montreal Children's HospitalMcGill University Health CentreMontrealQuebecCanada department of Surgery Universidade Estadual de Campinas(UNICAMP)CampinasBrazil Instituto de Educação Médica(IDOMED/Estácio Campus Vista Carioca)Rio de JaneiroBrazil faculty of Medicine Universidade Federal do Delta do ParnaibaParnaibaPiauiBrazil Universidade federal de ciencias da Saude de Porto Alegre Porto AlegreBrazil Universidade federal da Bahia SalvadorBrazil department of Health Research Methods McMaster UniversityHamiltonSouthern OntarioCanada department of Pediatric Surgery Boston Children's HospitalBostonMassachusettsUSA

Introduction In Brazil,approximately 5%are born with a congenital disorder,potentially fatal without *** study aims to evaluate the relationship between gastrointestinal congenital malformation(GIcM)mortality,health indicators,and socioeconomic factors in *** GIcM admissions(Q39-Q45)between 2012 and 2019 were collected using national *** demographics,socioeconomic factors,clinical management,outcomes,and the healthcare workforce density were also accounted *** Surgical Workforce density and the number of neonatal intensive care units in a region were extracted from national datasets and combined to create a clinical index termed'NeoSurg'.Socioeconomic variables were combined to create a socioeconomic index termed SocEcon'.Simple linear regression was used to investigate if the temporal changes of both indexes were *** correlation between mortality and the different indicators in Brazil was evaluated using Pearson's correlation *** Over 8 years,Brazil recorded 12804 GIcM *** Southeast led with 6147 cases,followed by the Northeast(2660),South(1727),North(1427),and Midwest(843).The North and Northeast reported the highest mortality,lowest NeoSurg,and SocEcon Index ***,mortality rates declined across regions from 7.7%(2012)to 3.9%(2019),a 51.7%*** North and Midwest experienced the most substantial reductions,at 63%and 75%,*** significantly correlated with the indexes in nearly all regions(pconclusion Our study highlights the correlation between social determinants of health and GIcM mortality in Brazil,using two novel indexes in the pediatric *** findings provide an opportunity to rethink and discuss new indicators that could enhance our understanding of our country and could lead to the development of necessary solutions to tackle existing challenges in Brazil and globally.

关键词： Northeast Brazil globally

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