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1.
Biol Sport ; 41(3): 137-151, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952921

RESUMO

To observe overall, training, and match injury incidence in female youth football. We also aimed to quantify the incidence of injuries by affected tissue and body location. The following databases were examined: PubMed, Web of Science, Scopus, SPORTDiscus, Cochrane and PEDro. Papers that reported overall injury incidence, training or match injury incidence were included. Additionally, studies had to be performed in adolescent female football players (13-19 years of age). The Newcastle-Ottawa Scale and the checklist of items that must be included in epidemiological football reports were used to assess methodological quality of the included articles. For the meta-analyses, a random effect model was used. A total of 13 studies were included. There were 2,333 injuries; incidence was higher during games (12.7/1000 h) compared to training sessions (2.3/1000 h). The injury match-to-training ratio was 5.8. The lower limbs were the region in which the greatest number of injuries occurred, with the ankle (1.2/1000 h) and knee (0.8/1000 h) having the most injuries. In relation to injured tissue, ligament injuries represented an incidence of 1.3/1000 h, followed by muscle injuries (0.9/1000 h). This study represents the first step towards the creation and implementation of preventative measures in female youth football. The results suggest that attention should be focused on ankle and knee injuries, since they are the most frequent and can lead to sport retirement in some cases depending on the severity.

2.
Front Public Health ; 12: 1386667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957207

RESUMO

Healthcare quality in low- and middle-income countries poses a significant challenge, contributing to heightened mortality rates from treatable conditions. The accreditation of health facilities was part of the former health reform in Mexico, proposed as a mechanism to enhance healthcare quality. This study assesses the performance of hospital accreditation in Mexico, utilizing indicators of effectiveness, efficiency, and safety. Employing a longitudinal approach with controlled interrupted time series analysis (C-ITSA) and fixed effects panel analysis, administrative data from general hospitals in Mexico is scrutinized. Results reveal that hospital accreditation in Mexico fails to enhance healthcare quality and, disconcertingly, indicates deteriorating performance associated with increased hospital mortality. Amidst underfunded health services, the implemented accreditation model proves inadequately designed to uplift care quality. A fundamental redesign of the public hospital accreditation model is imperative, emphasizing incentives for structural enhancement and standardized processes. Addressing the critical challenge of improving care quality is urgent for Mexico's healthcare system, necessitating swift action to achieve effective access as a benchmark for universal healthcare coverage.


Assuntos
Acreditação , Qualidade da Assistência à Saúde , México , Acreditação/normas , Humanos , Qualidade da Assistência à Saúde/normas , Melhoria de Qualidade , Hospitais/normas , Análise de Séries Temporais Interrompida , Mortalidade Hospitalar , Estudos Longitudinais
3.
Am J Clin Nutr ; 120(1): 129-144, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38960570

RESUMO

BACKGROUND: Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status. OBJECTIVES: We aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population. METHODS: A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits. RESULTS: Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control-3 points; 95% confidence interval [CI]: 2.2, 3.8; PN-2.7 points; 95% CI: 2.0, 3.3; and PP-2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (ß: -0.37; 95% CI: -0.56, -0.18), oxidative stress (ß: -0.37; 95% CI: -0.60, -0.15), microbiota (ß: -0.38; 95% CI: -0.63, -0.15), and inflammation (ß: -0.78; 95% CI: -1.24, -0.31) compared with control diet. CONCLUSIONS: Integration of personalized strategies within an e-commerce-like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN. This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1).


Assuntos
Dieta Mediterrânea , Medicina de Precisão , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Método Simples-Cego , Metabolômica , Estado Nutricional , Biomarcadores/sangue , Comportamento Alimentar
4.
Alcohol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969249

RESUMO

The aim of this study was to evaluate the possible impact of the COVID-19 pandemic on prevalence rates and self-reported changes in patterns of alcohol use among first-year university students in Spain, considering the risk of problematic alcohol use. A serial cross-sectional study based on the uniHcos project was carried out. Data from 10,518 first-year university students (73.3% female, mean age 19 (SD=1.6)) collected between 2012 and 2022 were analysed. The evolution of the pooled prevalence rates during the time series was analysed and the risk of problematic alcohol consumption was assessed using the AUDIT. Also, self-reported changes in alcohol use patterns during the pandemic were assessed. According to the results, during the COVID-19 pandemic, the prevalence of alcohol use in the past 30-days was reduced (76.3% in 2019 vs. 63.7% in COVID-19) and increased again in the New Normal period. Thus, a similar pattern in the practice of binge drinking was observed. Regarding the AUDIT score, 21.7% (95%CI 20.9, 22.6) of the students had harmful alcohol consumption, with a higher proportion among males. In the multivariable logistic models, a higher AUDIT score was significantly associated (p-value<0.001) with being male and living with roommates. According to self-reported changes in consumption patterns during the COVID-19 pandemic, a higher proportion of participants with harmful use reported an increase in alcohol consumption compared to those at low-risk (43% vs 19%). Finally, despite the overall reduction in drinking prevalence during COVID-19, changes were not equal for all students and depended on their previous level of problematic drinking, highlighting that this should be considered in the development of strategies against alcohol use in this population.

5.
Sci Immunol ; 9(96): eadj8526, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905326

RESUMO

Memory CD4 T cells are critical to human immunity, yet it is unclear whether viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)-specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly 2 years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely because of a chromatin accessibility landscape altered by inflammation. Moreover, S-specific CD4 T cells primed by infection had reduced proliferative capacity in vitro relative to vaccine-primed cells. Furthermore, the transcriptional state of S-specific memory CD4 T cells was minimally altered by booster immunization and/or breakthrough infection. Thus, infection-associated inflammation durably imprints CD4 T cell memory, which affects the function of these cells and may have consequences for long-term immunity.


Assuntos
Linfócitos T CD4-Positivos , COVID-19 , Memória Imunológica , Inflamação , Células T de Memória , SARS-CoV-2 , Humanos , COVID-19/imunologia , SARS-CoV-2/imunologia , Linfócitos T CD4-Positivos/imunologia , Memória Imunológica/imunologia , Inflamação/imunologia , Células T de Memória/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Feminino , Masculino , Adulto , Vacinas contra COVID-19/imunologia
6.
Front Cell Infect Microbiol ; 14: 1415162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919702

RESUMO

Taenia crassiceps has been used for decades as an experimental model for the study of human and porcine cysticercosis. Even though, its life cycle, tissue organization, ultrastructure and immune response elicited in the host, have been extensively described, there are many other biological questions remaining to be addressed. In the present study we revisited the muscle and neural architecture of cysticerci in two of the most frequently used strains (WFU and ORF), using conventional staining and confocal microscopy imaging, aiming to assemble an updated anatomy. Differences between both strains, including polarization processes during development of the young budding larvae, are emphasized. We also performed a search for genes that have been related to peptidergic neural processes in other related flatworms. These findings can help to understand the anatomical and molecular consequences of the scolex presence or absence in both strains.


Assuntos
Cysticercus , Larva , Músculos , Taenia , Animais , Cysticercus/imunologia , Músculos/parasitologia , Taenia/fisiologia , Microscopia Confocal , Cisticercose/parasitologia , Suínos , Humanos , Sistema Nervoso
7.
Arch Bronconeumol ; 60(7): 417-422, 2024 Jul.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38729884

RESUMO

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.


Assuntos
Álcoois Benzílicos , Combinação de Medicamentos , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Prospectivos , Álcoois Benzílicos/uso terapêutico , Álcoois Benzílicos/administração & dosagem , Clorobenzenos/uso terapêutico , Clorobenzenos/administração & dosagem , Quinuclidinas/uso terapêutico , Quinuclidinas/administração & dosagem , Quimioterapia Combinada , Antagonistas Muscarínicos/uso terapêutico , Antagonistas Muscarínicos/administração & dosagem , Androstadienos/uso terapêutico , Androstadienos/administração & dosagem , Resultado do Tratamento , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Administração por Inalação , Masculino , Feminino , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Eosinófilos , Pessoa de Meia-Idade
8.
Inorg Chem ; 63(23): 10500-10510, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38805658

RESUMO

The direct conversion of solar energy into chemical energy represents an enormous challenge for current science. One of the commonly proposed photocatalytic systems is composed of a photosensitizer (PS) and a catalyst, together with a sacrificial electron donor (ED) when only the reduction of protons to H2 is addressed. Layered double hydroxides (LDH) have emerged as effective catalysts. Herein, two Co-Al LDH and their composites with graphene oxide (GO) or graphene quantum dots (GQD) have been prepared by coprecipitation and urea hydrolysis, which determined their structure and so their catalytic performance, giving H2 productions between 1409 and 8643 µmol g-1 using a ruthenium complex as PS and triethanolamine as ED at 450 nm. The influence of different factors, including the integration of both components, on their catalytic behavior, has been studied. The proper arrangement between the particles of both components seems to be the determining factor for achieving a synergistic interaction between LDH and GO or GQD. The novel Co-Al LDH composite with intercalated GQD achieved an outstanding catalytic efficiency (8643 µmol H2 g-1) and exhibited excellent reusability after 3 reaction cycles, thus representing an optimal integration between graphene materials and Co-Al LDH for visible light driven H2 photocatalytic production.

9.
Heliyon ; 10(9): e29959, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707309

RESUMO

In the teaching of the operating systems course, which is part of computer engineering degrees, a thorough understanding of processor scheduling algorithms is crucial. However, it has been identified that the current knowledge of classical algorithms is insufficient in the present context. Therefore, it is proposed to conduct a review of the state of the art in the field to identify new trends and algorithms that can enhance the teaching of the subject and improve student training. As a result, the state of the art is thoroughly reviewed, and study sheets are designed to facilitate the comprehension of the algorithms. Additionally, a software simulator is developed to compare different algorithms in a controlled environment, allowing for the validation of the most promising ones for classroom teaching.

10.
Heliyon ; 10(10): e31230, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813160

RESUMO

Research for the development of noble metal-free electrodes for hydrogen evolution has blossomed in recent years. Transition metal carbides compounds, such as W2C, have been considered as a promising alternative to replace Pt-family metals as electrocatalysts towards hydrogen evolution reaction (HER). Moreover, hybridization of TMCs with graphene nanostructures has emerged as a reliable strategy for the preparation of compounds with high surface to volume ratio and abundant active sites. The present study focuses in the preparation of tungsten carbide/oxide compounds deposited in a three-dimensional vertical graphene nanowalls (VGNW) substrate via chemical vapor deposition, magnetron sputtering and thermal annealing processes. Structural and chemical characterization reveals the partial carburization and oxidation of the W film sputtered on the VGNWs, due to C and O migration from VGNWs towards W during the high temperature annealing process. Electrochemical characterization shows the enhanced performance of the nanostructured hybrid W2C/WOx on VGNW compound towards HER, when compared with planar W2C/WOx films. The W2C/WOx nanoparticles on VGNWs require an overpotential of -252 mV for the generation of 10 mA cm-2. Chronoamperometry tests in high overpotentials reveal the compounds stability while sustaining high currents, in the order of hundreds of mA. Post-chronoamperometry test XPS characterization unveils the formation of a W hydroxide layer which favours hydrogen evolution in acidic electrolytes. We aspire that the presented insights can be valuable for those working on the preparation of hybrid electrodes for electrochemical processes.

11.
Eur J Dent ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776981

RESUMO

OBJECTIVE: The focus of this triple-blind randomized study was to evaluate the biocompatibility of a new root canal filling sealer (RCFS) based on tristrontium aluminate and dodecacalcium hepta-aluminate in living tissue. MATERIAL AND METHODS: Forty-five Wistar rats (Rattus norvegicus) were divided into three groups: control (polyethylene), sealer (Bio-C Sealer, Londrina, PR, Brazil), and experimental (tristrontium aluminate and dodecacalcium hepta-aluminate). The tissues were analyzed under an optical microscope to assess different cellular events at different time intervals (7, 15, and 30 days). STATISTICAL ANALYSIS: Data were analyzed using the Kruskal-Wallis and Dunn (p < 0.05) tests. RESULTS: In the initial period, a moderate inflammatory infiltrate was observed, similar between the endodontic cements groups (p = 0.725). The intensity of the infiltrate decreased with time, with no significant difference among the groups (p > 0.05). The number of young fibroblasts was elevated in all groups evaluated at 7 days. The experimental group showed the highest number of cells at all time intervals, but the difference with the sealer group at 7 (p = 0.001) and 15 days (p = 0.002) and the control group at 30 days was not significant (p = 0.001). Regarding tissue repair events, the amount of collagen fibers increased over the experimental intervals, with no significant difference between the sealer and control groups (p > 0.05). CONCLUSION: The experimental RCFS based on calcium and strontium aluminates proved to be biocompatible for use in close contact with periapical tissue, inducing a low inflammatory reaction and favoring rapid tissue repair.

12.
Org Biomol Chem ; 22(19): 3854-3859, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38639197

RESUMO

The molecular recognition of saccharides by synthetic hosts has become an appealing but elusive task in the last decades. Herein, we combine Dynamic Combinatorial Chemistry (DCC) for the rapid self-assembly and screening of virtual libraries of receptors, with the use of ITC and NMR to validate the hits and molecular modelling to understand the binding mechanisms. We discovered a minimalistic receptor, 1F (N-benzyl-L-phenylalanine), with considerable affinity for fructose (Ka = 1762 M-1) and remarkable selectivity (>50-fold) over other common monosaccharides. The approach accelerates the discovery process of receptors for saccharides.


Assuntos
Técnicas de Química Combinatória , Monossacarídeos , Monossacarídeos/química , Modelos Moleculares , Fenilalanina/química , Fenilalanina/análogos & derivados , Fenilalanina/síntese química
13.
Nanoscale ; 16(17): 8470-8478, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38590267

RESUMO

Transition metal dichalcogenides, including WSe2, have gained significant attention as promising nanomaterials for various applications due to their unique properties. In this study, we explore the temperature-dependent photoluminescent properties of WSe2 nanomaterials to investigate their potential as luminescent nanothermometers. We compare the performance of WSe2 quantum dots and nanorods synthesized using sonication synthesis and hot injection methods. Our results show a distinct temperature dependence of the photoluminescence, and conventional ratiometric luminescence thermometry demonstrates comparable relative thermal sensitivity (0.68-0.80% K-1) and temperature uncertainty (1.3-1.5 K), irrespective of the morphology of the nanomaterials. By applying multiple linear regression to WSe2 quantum dots, we achieve enhanced thermal sensitivity (30% K-1) and reduced temperature uncertainty (0.1 K), highlighting the potential of WSe2 as a versatile nanothermometer for microfluidics, nanofluidics, and biomedical assays.

14.
Biol Trace Elem Res ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676876

RESUMO

The presence of arsenic (As) and fluoride (F-) in drinking water is of concern due to the enormous number of individuals exposed to this condition worldwide. Studies in cultured cells and animal models have shown that As- or F-induced hepatotoxicity is primarily associated with redox disturbance and altered mitochondrial homeostasis. To explore the hepatotoxic effects of chronic combined exposure to As and F- in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and/or 25 mg/L F- (sodium fluoride). The male offspring continued the exposure treatment up to 30 (P30) or 90 (P90) postnatal days. GSH levels, cysteine synthesis enzyme activities, and cysteine transporter levels were investigated in liver homogenates, as well as the expression of biomarkers of ferroptosis and mitochondrial biogenesis-related proteins. Serum transaminase levels and Hematoxylin-Eosin and Masson trichrome-stained liver tissue slices were examined. Combined exposure at P30 significantly reduced GSH levels and the mitochondrial transcription factor A (TFAM) expression while increasing lipid peroxidation, free Fe 2+, p53 expression, and serum ALT activity. At P90, the upregulation of cysteine uptake and synthesis was associated with a recovery of GSH levels. Nevertheless, the downregulation of TFAM continued and was now associated with a downstream inhibition of the expression of MT-CO2 and reduced levels of mtDNA and fibrotic liver damage. Our experimental approach using human-relevant doses gives evidence of the increased risk for early liver damage associated with elevated levels of As and F- in the diet during intrauterine and postnatal period.

15.
Comput Methods Programs Biomed ; 250: 108188, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657382

RESUMO

BACKGROUND AND OBJECTIVE: The protein-protein interaction (PPI) network alignment has proven to be an efficient technique in the diagnosis and prevention of certain diseases. However, the difficulty in maximizing, at the same time, the two qualities that measure the goodness of alignments (topological and biological quality) has led aligners to produce very different alignments. Thus making a comparative study among alignments of such different qualities a big challenge. Multi-objective optimization is a computer method, which is very powerful in this kind of contexts because both conflicting qualities are considered together. Analysing the alignments of each PPI network aligner with multi-objective methodologies allows you to visualize a bigger picture of the alignments and their qualities, obtaining very interesting conclusions. This paper proposes a comprehensive PPI network aligner study in the multi-objective domain. METHODS: Alignments from each aligner and all aligners together were studied and compared to each other via Pareto dominance methodologies. The best alignments produced by each aligner and all aligners together for five different alignment scenarios were displayed in Pareto front graphs. Later, the aligners were ranked according to the topological, biological, and combined quality of their alignments. Finally, the aligners were also ranked based on their average runtimes. RESULTS: Regarding aligners constructing the best overall alignments, we found that SAlign, BEAMS, SANA, and HubAlign are the best options. Additionally, the alignments of best topological quality are produced by: SANA, SAlign, and HubAlign aligners. On the contrary, the aligners returning the alignments of best biological quality are: BEAMS, TAME, and WAVE. However, if there are time constraints, it is recommended to select SAlign to obtain high topological quality alignments and PISwap or SAlign aligners for high biological quality alignments. CONCLUSIONS: The use of the SANA aligner is recommended for obtaining the best alignments of topological quality, BEAMS for alignments of the best biological quality, and SAlign for alignments of the best combined topological and biological quality. Simultaneously, SANA and BEAMS have above-average runtimes. Therefore, it is suggested, if necessary due to time restrictions, to choose other, faster aligners like SAlign or PISwap whose alignments are also of high quality.


Assuntos
Algoritmos , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , Software , Alinhamento de Sequência , Biologia Computacional/métodos , Proteínas/química , Proteínas/metabolismo , Humanos
16.
Biol Sex Differ ; 15(1): 34, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589872

RESUMO

BACKGROUND: Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. METHODS: Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. RESULTS: Reduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3ß, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females. CONCLUSIONS: Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.


Understanding the physiological role of pregnancy-associated plasma protein-A2 (PAPP-A2), a proteinase involved in the insulin-like growth factor-1 (IGF1) availability to regulate growth, could provide insight into new treatments for patients with short stature and skeletal abnormalities. Although progressive postnatal growth retardation in patients with PAPP-A2 mutations can differ between males and females, we do not know the underlying differences in IGF1 system and signaling, and their response to treatment that contribute to growth improvement. The present study examines whether Pappa2 deficiency and pharmacological administration of rhGH, rhIGF1 and rhPAPP-A2 are associated with sex-specific differences in IGF1 ternary complexes and IGF1 signaling pathways. Reduced body and femur length of Pappa2-deficient mice was associated with sex- and tissue-specific alteration of IGF ternary/binary complexes and IGF1 signaling pathways. rhPAPP-A2 treatment induced female-specific increase in body and femur length and reduction in IGF ternary/binary complexes through STAT5-AKT-ERK2-AMPK signaling pathways in liver. The involvement of PAPP-A2 in sex-based growth physiology supports the use of promising drugs to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.


Assuntos
Piperazinas , Proteína Plasmática A Associada à Gravidez , Proteínas Proto-Oncogênicas c-akt , Humanos , Masculino , Criança , Camundongos , Feminino , Animais , Proteína Plasmática A Associada à Gravidez/genética , Proteína Plasmática A Associada à Gravidez/metabolismo , Transtornos do Crescimento/metabolismo
17.
Front Chem ; 12: 1379587, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633984

RESUMO

We report the synthesis and single-crystal X-ray diffraction, magnetic, and luminescence measurements of a novel family of luminescent cage-like tetranuclear silsesquioxanes (PhSiO1.5)8(LnO1.5)4(O)(C5H8O2)6(EtOH)2(CH3CN)2⋅2CH3CN (where Ln = Tb, 1; Tb/Eu, 2; and Gd, 3), featuring seven-coordinated lanthanide ions arranged in a one-capped trigonal prism geometry. Compounds 1 and 2 exhibit characteristic Tb3+ and Tb3+/Eu3+-related emissions, respectively, sensitized by the chelating antenna acetylacetonate (acac) ligands upon excitation in the UV and visible spectral regions. Compound 3 is used to assess the energies of the triplet states of the acac ligand. For compound 1, theoretical calculations on the intramolecular energy transfer and multiphonon rates indicate a thermal balance between the 5D4 Stark components, while the mixed Tb3+/Eu3+ analog 2, with a Tb:Eu ratio of 3:1, showcases intra-cluster Tb3+-to-Eu3+ energy transfer, calculated theoretically as a function of temperature. By utilizing the intensity ratio between the 5D4→7F5 (Tb3+) and 5D0→7F2 (Eu3+) transitions in the range 11-373 K, we demonstrate the realization of a ratiometric luminescent thermometer with compound 2, operating in the range 11-373 K with a maximum relative sensitivity of 2.0% K-1 at 373 K. These findings highlight the potential of cage-like silsesquioxanes as versatile materials for optical sensing-enabled applications.

18.
PLoS One ; 19(4): e0301604, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635649

RESUMO

The red abalone (Haliotis rufescens) represents North America's most important aquaculture species. Its hepatopancreas is rich in cellulases and other polysaccharide-degrading enzymes, which provide it the remarkable ability to digest cellulose-rich macroalgae; nevertheless, its cellulolytic systems are poorly explored. This manuscript describes some functional and structural properties of an endogenous trimeric glycosylated endoglucanase from H. rufescens. The purified enzyme showed a molecular mass of 23.4 kDa determined by MALDI-TOF mass spectrometry, which behaved as a homotrimer in gel filtration chromatography and zymograms. According to the periodic acid-Schiff reagent staining, detecting sugar moieties in SDS-PAGE gel confirmed that abalone cellulase is a glycoprotein. Hydrolysis of cello-oligosaccharides and p-nitrophenyl-ß-D-glucopyranosides confirmed its endo/exoactivity. A maximum enzyme activity toward 0.5% (w/v) carboxymethylcellulose of 53.9 ± 1.0 U/mg was achieved at 45°C and pH 6.0. We elucidated the abalone cellulase primary structure using proteases and mass spectrometry methods. Based on these results and using a bioinformatic approach, we identified the gene encoding this enzyme and deduced its full-length amino acid sequence; the mature protein comprised 177 residues with a calculated molecular mass of 19.1 kDa and, according to sequence similarity, it was classified into the glycosyl-hydrolase family 45 subfamily B. An AlphaFold theoretical model and docking simulations with cellopentaose confirmed that abalone cellulase is a ß-sheet rich protein, as also observed by circular dichroism experiments, with conserved catalytic residues: Asp26, Asn109, and Asp134. Interestingly, the AlphaFold-Multimer analysis indicated a trimeric assembly for abalone cellulase, which supported our experimental findings. The discovery and characterization of these enzymes may contribute to developing efficient cellulose bioconversion processes for biofuels and sustainable bioproducts.


Assuntos
Celulase , Gastrópodes , Animais , Celulase/metabolismo , Gastrópodes/genética , Sequência de Aminoácidos , Celulose/metabolismo , Polissacarídeos
19.
Chem Mater ; 36(7): 3452-3463, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617804

RESUMO

This work challenges the conventional approach of using NdIII 4F3/2 lifetime changes for evaluating the experimental NdIII → YbIII energy transfer rate and efficiency. Using near-infrared (NIR) emitting Nd:Yb mixed-metal coordination polymers (CPs), synthesized via solvent-free thermal grinding, we demonstrate that the NdIII [2H11/2 → 4I15/2] → YbIII [2F7/2 → 2F5/2] pathway, previously overlooked, dominates energy transfer due to superior energy resonance and J-level selection rule compatibility. This finding upends the conventional focus on the NdIII [4F3/2 → 4I11/2] → YbIII [2F7/2 → 2F5/2] transition pathway. We characterized Nd0.890Yb0.110(BTC)(H2O)6 as a promising cryogenic NIR thermometry system and employed our novel energy transfer understanding to perform simulations, yielding theoretical thermometric parameters and sensitivities for diverse Nd:Yb ratios. Strikingly, experimental thermometric data closely matched the theoretical predictions, validating our revised model. This novel perspective on NdIII → YbIII energy transfer holds general applicability for the NdIII/YbIII pair, unveiling an important spectroscopic feature with broad implications for energy transfer-driven materials design.

20.
Environ Sci Technol ; 58(16): 7056-7065, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38608141

RESUMO

The sources and sinks of nitrous oxide, as control emissions to the atmosphere, are generally poorly constrained for most environmental systems. Initial depth-resolved analysis of nitrous oxide flux from observation wells and the proximal surface within a nitrate contaminated aquifer system revealed high subsurface production but little escape from the surface. To better understand the environmental controls of production and emission at this site, we used a combination of isotopic, geochemical, and molecular analyses to show that chemodenitrification and bacterial denitrification are major sources of nitrous oxide in this subsurface, where low DO, low pH, and high nitrate are correlated with significant nitrous oxide production. Depth-resolved metagenomes showed that consumption of nitrous oxide near the surface was correlated with an enrichment of Clade II nitrous oxide reducers, consistent with a growing appreciation of their importance in controlling release of nitrous oxide to the atmosphere. Our work also provides evidence for the reduction of nitrous oxide at a pH of 4, well below the generally accepted limit of pH 5.


Assuntos
Óxido Nitroso , Óxido Nitroso/metabolismo , Bactérias/metabolismo , Oxirredutases/metabolismo , Desnitrificação
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