From cubane-assembled Mn-oxo clusters to monodispersed manganese oxide colloidal nanocrystals.

The assemblies of [M4O4] (M = metal) cubanes represent a fascinating class of materials for a variety of application fields. Although such a structural characteristic is relatively common in small molecules and in extended bulk solids, high nuclearity clusters composed of multiple [M4O4] units as their backbones are rare. In this work, we report two new Mn-oxo clusters, MnII 8MnIII 10O10(OOCMe)12(OMe)14(py)2 ([Mn18-Ac]) and MnII 4MnIII 14O14(OOCCMe3)8(OMe)14(MeOH)5(py) ([Mn18-Piv]), whose core structures are assemblies of either 6- or 7-cubanes in different packing patterns, which have been unambiguously revealed by single crystal X-ray diffraction technique. The cubane-assembled structural features can be deemed as the embryonic structures of the bulk manganese oxide. Herein, this report demonstrates the first case study of utilizing Mn-oxo clusters as precursors for the preparation of manganese oxide nanocrystals, which has never been explored before. Through a simple colloidal synthetic approach, high-quality, monodisperse Mn3O4 nanocrystals can be readily prepared by employing both precursors, while their morphologies were found to be quite different. This work confirms that the structural similarity between precursors and nanomaterials is instrumental in affording more kinetically efficient pathways for materials formation, and the structure of the precursor has a significant impact on the morphology of final nanocrystal products.

Proteo-genomic characterization of cirrhosis-associated liver cancers reveals potential subtypes and therapeutic targets.

BACKGROUND: This study aimed to identify potential subtypes of hepatocellular carcinoma (HCC) associated with cirrhosis and to investigate key markers using bioinformatic analysis of gene expression datasets-0. METHODS: Three data sets (GSE17548, GSE56140, and GSE87630) were extracted from the Gene Expression Omnibus (GEO) database and normalized using the Limma package in R. Principal component analysis (PCA) and cluster analysis was performed to examine data distribution and identify subtypes. Differential gene expression analysis was performed using the Limma software package. Protein-protein interaction analysis and functional annotation were performed using the STRING database and Cytoscape software. Important signaling pathways and processes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis. RESULTS: The analysis revealed different subtypes of HCC associated with cirrhosis and identified several key genes, including CCNB2, MCM4, and CDC20, with strong binding power and prognostic value. Functional annotation indicated involvement in cell cycle regulation and metabolic pathways. ROC analysis showed high sensitivity and specificity of these genes in predicting HCC prognosis. CONCLUSION: These results suggest that CCNB2, MCM4, and CDC20 may serve as potential biomarkers for predicting HCC prognosis in patients with cirrhosis and provide insights into the molecular mechanisms of HCC progression.

Prognostic model based on B cell marker genes for NSCLC patients under neoadjuvant immunotherapy by integrated analysis of single-cell and bulk RNA-sequencing data.

BACKGROUND: Neoadjuvant immunotherapy has evolved as an effective option to treat non-small cell lung cancer (NSCLC). B cells play essential roles in the immune system as well as cancer progression. However, the repertoire of B cells and its association with clinical outcomes remains unclear in NSCLC patients receiving neoadjuvant immunotherapy. METHODS: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data for LUAD samples were accessed from the TCGA and GEO databases. LUAD-related B cell marker genes were confirmed based on comprehensive analysis of scRNA-seq data. We then constructed the B cell marker gene signature (BCMGS) and validated it. In addition, we evaluated the association of BCGMS with tumor immune microenvironment (TIME) characteristics. Furthermore, we validated the efficacy of BCGMS in a cohort of NSCLC patients receiving neoadjuvant immunotherapy. RESULTS: A BCMGS was constructed based on the TCGA cohort and further validated in three independent GSE cohorts. In addition, the BCMGS was proven to be significantly associated with TIME characteristics. Moreover, a relatively higher risk score indicated poor clinical outcomes and a worse immune response among NSCLC patients receiving neoadjuvant immunotherapy. CONCLUSIONS: We constructed an 18-gene prognostic signature derived from B cell marker genes based on scRNA-seq data, which had the potential to predict the prognosis and immune response of NSCLC patients receiving neoadjuvant immunotherapy.

A worldwide bibliometric analysis of the research trends and hotspots of bruxism in adults during 1991-2021.

BACKGROUND AND OBJECTIVES: With the increasing attention to bruxism, the research on bruxism is increasing rapidly. However, there is still a lack of systematic bibliometric analysis in the field of bruxism in adults. This study aimed to comprehensively explore and visualize the global trends and research hotspots in the field of bruxism in adults during 1991-2021. METHODS: The study searched the literature published during 1991-2021 in the Web of Science Core Collection database without language restrictions. VOSviewer, CiteSpace and Microsoft Excel were applied to analyse the authors, institutions, journals, countries, cited references, keywords and other information of the included publications, and construct visualized cooperation networks. RESULTS: A total of 878 articles were finally included. The top two most productive authors in the past 30 years were Lobbezoo F and Manfredini D. ACTA-Amsterdam, Univ Sao Paulo, Univ Helsinki, Univ Padua, Univ Montreal, et al. were prominent institutions in this field. Journal of Oral Rehabilitation made outstanding contributions in this field. The United States produced the most documents in this field, followed by Brazil. Both countries and authors cooperated closely around the world. The two most cited articles focused on the definition, assessment and classification of bruxism. In recent years, diagnostic criteria and stress have begun to receive a lot of attention. CONCLUSION: From 1991 to 2021, the attention to bruxism in adults continued to increase. Diagnostic criteria and stress may be potential research hotspots in this field. This study references relevant scholars on development trends and research hotspots.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma.

Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma

ABSTRACT Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

Sex differences in mortality among children, adolescents, and young people aged 0-24 years: a systematic assessment of national, regional, and global trends from 1990 to 2021.

BACKGROUND: Differences in mortality exist between sexes because of biological, genetic, and social factors. Sex differentials are well documented in children younger than 5 years but have not been systematically examined for ages 5-24 years. We aimed to estimate the sex ratio of mortality from birth to age 24 years and reconstruct trends in sex-specific mortality between 1990 and 2021 for 200 countries, major regions, and the world. METHODS: We compiled comprehensive databases on the mortality sex ratio (ratio of male to female mortality rates) for individuals aged 0-4 years, 5-14 years, and 15-24 years. The databases contain mortality rates from death registration systems, full birth and sibling histories from surveys, and reports on household deaths in censuses. We modelled the sex ratio of age-specific mortality as a function of the mortality in both sexes using Bayesian hierarchical time-series models. We report the levels and trends of sex ratios and estimate the expected female mortality and excess female mortality rates (the difference between the estimated female mortality and the expected female mortality) to identify countries with outlying sex ratios. FINDINGS: Globally, the mortality sex ratio was 1·13 (ie, boys were more likely to die than girls of the same age) for ages 0-4 years (90% uncertainty interval 1·11 to 1·15) in 2021. This ratio increased with age to 1·16 (1·12 to 1·20) for 5-14 years, reaching 1·65 for 15-24 years (1·52 to 1·75). In all age groups, the global sex ratio of mortality increased between 1990 and 2021, driven by faster declines in female mortality. In 2021, the probability of a newborn male reaching age 25 years was 94·1% (93·7 to 94·4), compared with 95·1% for a newborn female (94·7 to 95·3). We found a disadvantage of females versus males (compared with countries with similar total mortality) in 2021 in five countries for ages 0-4 years (Algeria, Bangladesh, Egypt, India, and Iran), one country (Suriname) for ages 5-14 years, and 13 countries for ages 15-24 years (including Bangladesh and India). We found the reverse pattern (disadvantage of males vs females compared with countries of similar total mortality) in one country in ages 0-4 years (Vietnam) and eight countries in ages 15-24 years (including Brazil and Mexico). Globally, the number of excess female deaths from birth to age 24 years was 86 563 (-6059 to 164 000) in 2021, down from 544 636 (453 982 to 633 265) in 1990. INTERPRETATION: The global sex ratio of mortality for all age groups in the first 25 years of life increased between 1990 and 2021. Targeted interventions should focus on countries with outlying sex ratios of mortality to reduce disparities due to discrimination in health care, nutrition, and violence. FUNDING: The Bill & Melinda Gates Foundation, US Agency for International Development, and King Abdullah University of Science and Technology.

The safety and efficacy of percutaneous transforaminal endoscopic discectomy and fenestration discectomy in the treatment of lumbar disc herniation.

BACKGROUND: The aim of the study was to explore the safety and efficacy of percutaneous transforaminal endoscopic discectomy (PTED) and fenestration discectomy (FD) in the treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS: The complete clinical data from 87 patients with LDH from our hospital were retrospectively analyzed. Patients were divided into a control group (n = 39, treated with FD) and a research group (n = 48, treated with PTED) according to the prescribed treatments. The basic operation conditions were compared across the two groups. Surgical outcomes were assessed. The incidences of complications and the life quality of patients were evaluated 1 year after surgery. RESULTS: The patients in both groups completed the operation. The visual analog scale and Oswestry Disability Index score of patients in the research group was significantly lower while the Orthopaedic Association Score was significantly higher after surgery. The success rate of the operation in the research group which was significantly higher and the rate of complications was significantly lower. No statistical differences in the quality of life were observed between the patients (p > 0.05). CONCLUSIONS: PTED and FD are effective in the treatment of LDH. However, our study showed that PTED has a higher rate of treatment success, faster recovery times and is safer than FD.

OBJETIVO: Investigar la seguridad y la eficacia de la discectomía endoscópica percutánea (DEP) y de la discectomía fenestrada (DF) en el tratamiento de la hernia de disco lumbar. MÉTODO: Se analizaron retrospectivamente los datos clínicos completos de 87 pacientes con hernia de disco lumbar. De acuerdo con el tratamiento prescrito, los pacientes fueron divididos en grupo control (DF, n = 39) y grupo de estudio (DEP, n = 48). Se compararon las condiciones básicas de funcionamiento de los dos grupos y se evaluaron los resultados de la cirugía, la incidencia de complicaciones y la calidad de vida al año de la operación. RESULTADOS: Ambos grupos completaron la operación. En el grupo de estudio, las puntuaciones en la escala visual análoga y ODI disminuyeron significativamente, mientras que las puntuaciones JOA aumentaron significativamente. La tasa de éxito de la operación en el grupo de estudio fue significativamente mayor que en el grupo control, y la incidencia de complicaciones fue significativamente menor que en el grupo control. No hubo diferencia significativa en la calidad de vida entre los dos grupos (p > 0.05). CONCLUSIONES: La tasa de éxito del tratamiento con DEP fue mayor, y el tiempo de recuperación fue más rápido y más seguro que con la DF.

C5aR antagonist inhibits LPS-induced inflammation in human gingival fibroblasts via NF-κB and MAPK signaling pathways.

OBJECTIVE: Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). METHODOLOGY: HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. RESULTS: Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1ß, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. CONCLUSION: These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study.

INTRODUCTION: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. METHODS: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. RESULTS: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. CONCLUSIONS: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Impacts of physical coordination training on speed in short track speed skating / Impactos do treinamento de coordenação física sobre a velocidade na patinação de velocidade em pista curta / Efectos del entrenamiento de la coordinación física sobre la velocidad en el patinaje de velocidad en pista corta

ABSTRACT Introduction Although the development time of short-track speed skating in China is relatively short, with the joint efforts of many athletes and coaches, the special technical level can be comparable with that of European and American countries. Objective Verify the impacts of physical coordination training on speed in short track speed skating. Methods Athletes from the provincial skating team were randomly selected and distributed into control and experimental groups to apply the training method on physical coordination in short track speed skating. Results The average body fat rate of the skaters in the control group was 15.24%, the average body fat rate in the control group was 15.20%, and the T value of the experimental group and control group was 1.00, P = 0.374 < 0.05. Conclusion Because they are special equipment, the turn resistance training device and the air resistance parachute played an important role in improving the special fitness of Chinese short track speed skaters. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Embora o tempo de desenvolvimento da patinação em pista curta na China seja relativamente curto, com os esforços conjuntos de muitos atletas e treinadores, o nível técnico especial pode ser comparável com o dos países europeus e americanos. Objetivo Verificar os impactos do treinamento de coordenação física sobre a velocidade na patinação de velocidade em pista curta. Métodos Atletas da equipe de patinação provincial foram aleatoriamente selecionados e distribuídos em grupos controle e experimental para aplicar o método de treinamento na coordenação física de patinação de velocidade em pista curta. Resultados A taxa média de gordura corporal dos patinadores no grupo controle foi 15,24%, a taxa média de gordura corporal no grupo de controle foi 15,20%, e o valor de T do grupo experimental e do grupo de controle foi 1,00, P = 0,374 < 0,05. Conclusão Por serem equipamentos especiais, o dispositivo de treinamento de resistência à curva e o paraquedas de resistência ao ar desempenharam um papel importante na melhoria da aptidão física especial dos patinadores chineses de velocidade em pista curta. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Aunque el tiempo de desarrollo del patinaje de velocidad en pista corta en China es relativamente corto, con el esfuerzo conjunto de muchos atletas y entrenadores, el nivel técnico especial puede ser comparable al de los países europeos y americanos. Objetivo Verificar los impactos del entrenamiento de la coordinación física sobre la velocidad en el patinaje de velocidad en pista corta. Métodos Se seleccionaron aleatoriamente atletas del equipo provincial de patinaje y se distribuyeron en grupos de control y experimentales para aplicar el método de entrenamiento de la coordinación física en el patinaje de velocidad en pista corta. Resultados El índice medio de grasa corporal de los patinadores del grupo de control fue del 15,24%, el índice medio de grasa corporal del grupo de control fue del 15,20%, y el valor T del grupo experimental y del grupo de control fue de 1,00, P = 0,374 < 0,05. Conclusión Debido a que son equipos especiales, el dispositivo de entrenamiento de resistencia en curva y el paracaídas de resistencia al aire desempeñaron un papel importante en la mejora de la aptitud física especial de los patinadores de velocidad de pista corta chinos. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Improving explosive body capacity in female short track speed skaters / Melhoria da capacidade explosiva corporal em patinadoras de velocidade em pista curta / Mejora de la capacidad explosiva corporal en patinadoras de velocidad en pista corta

ABSTRACT Introduction The peculiar characteristics of short track speed skating should be integrated into the psychology of competitions; it is considered that elite athletes engaged in this particular sport should have a healthy psychic condition. Objective Investigate the explosive power of female speed skaters in short track speed skating. Methods 10 key athletes from the national short track speed skating team were selected, and explosive power was tested by T-test, hexagonal test, and pro sensitivity test. Data analysis was performed using an independent sample t-test, differences in the results of related test indicators between groups were analyzed, and repeated measures analysis of variance was used. Results During the explosive kick phase, knee extension speed increased linearly from 210°/S to 600°/S, and hip extension speed increased linearly from 200°/S to 400°/S. Conclusion The development of muscle group strength and explosive power during training often shows differences in the degree of contraction, which is related to the arrangement of training methods. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução As características peculiares da patinação de velocidade em pista curta devem ser integradas na psicologia das competições; considera-se que os atletas de elite engajados nesta modalidade especial devem ter boa condição psíquica. Objetivo Investigar o poder explosivo das patinadoras de patinação de velocidade em pista curta. Métodos 10 atletas-chave da equipe nacional de patinação de velocidade em pista curta foram selecionadas, o poder explosivo foi testado por teste T, teste hexagonal e teste de sensibilidade pro. A análise dos dados foi realizada utilizando um teste t de amostra independente, as diferenças nos resultados dos indicadores de teste relacionados entre os grupos foram analisadas, e foi utilizada a análise de medidas repetidas de variação. Resultados Durante a fase de pontapé explosivo, a velocidade da extensão do joelho aumentou linearmente de 210°/S para 600°/S, e a velocidade da extensão do quadril aumentou linearmente de 200°/S para 400°/S. Conclusão O desenvolvimento da força do grupo muscular e do poder explosivo durante o treinamento muitas vezes apresenta diferenças no grau de contração, o que está relacionado com a disposição dos métodos de treinamento. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Las características peculiares del patinaje de velocidad en pista corta deben integrarse en la psicología de las competiciones; se considera que los atletas de élite que se dedican a esta modalidad especial deben tener una buena condición psíquica. Objetivo Investigar la potencia explosiva de las patinadoras de velocidad en pista corta. Métodos Se seleccionaron 10 atletas clave del equipo nacional de patinaje de velocidad en pista corta, se probó la potencia explosiva mediante la prueba T, la prueba hexagonal y la prueba de sensibilidad pro. El análisis de los datos se realizó mediante una prueba t de muestras independientes, se analizaron las diferencias en los resultados de los indicadores de las pruebas relacionadas entre los grupos y se utilizó el análisis de varianza de medidas repetidas. Resultados Durante la fase de patada explosiva, la velocidad de extensión de la rodilla aumentó linealmente de 210°/S a 600°/S, y la velocidad de extensión de la cadera aumentó linealmente de 200°/S a 400°/S. Conclusión El desarrollo de la fuerza y la potencia explosiva de los grupos musculares durante el entrenamiento suele mostrar diferencias en el grado de contracción, lo que está relacionado con la disposición de los métodos de entrenamiento. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Situation and prevention strategies of sports injuries in community home sports under the background of covid-19 / A situação e estratégias de prevenção de lesões esportivas em esportes domésticos comunitários sob o pano de fundo da covid-19 / La situación y las estrategias de prevención y tratamiento de las lesiones deportivas en el hogar en la comunidad en el contexto del covid - 19

ABSTRACT Introduction: In the context of COVID-19, many physical activities have been restricted to the home environment, including traditional community sports. The situation of bodily injuries and prevention strategies during this period urges investigation and adaptation for a preventive approach. Objective: Explore the current scenario by devising means of prevention for sports injuries caused in the home environment. Methods: A total of 60 people were selected as experimental volunteers for home sports injury analysis, 30 in the experimental group and 30 in the control group, the cases were studied, and hypotheses were raised corroborating a preventive system of the cataloged home sports injuries, as well as the mitigation of their intercurrences. Results: In the experimental group, the flexion amplitude increased from 74.55±5.30 to 95.19±6.54; the extension amplitude increased from −3.88±3.29 to 1.57±2.17; the walking index evolved from 22.61±7.00 to 28.53±5.74; the stair activity index increased from 18.70±6.79 to 18.70±6.79. The same data measured in the control group showed no significant changes. Conclusion: Prevention of sports injuries during the current pandemic begins with the care of the immune system; care of the home environment was also described, as well as validation of effective treatment for timely rehabilitation of home sports injuries. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: No contexto da COVID-19, muitas atividades físicas restringiram-se ao ambiente doméstico, incluindo os esportes tradicionalmente comunitários. A situação das lesões corporais e as estratégias de prevenção durante este período urgem investigações e adaptações para uma abordagem preventiva. Objetivo: Explorar o cenário atual elaborando meios de prevenção para as lesões esportivas ocasionadas em ambiente domiciliar. Métodos: Um total de 60 pessoas foram selecionadas como voluntários experimentais para análise de lesão esportiva domiciliar, 30 no grupo experimental e 30 no grupo de controle, estudou-se os casos e foram levantadas hipóteses corroborando para um sistema preventivo das lesões esportivas domiciliares catalogadas, bem como a atenuação de suas intercorrências. Resultados: No grupo experimental, a amplitude de flexão aumentou de 74,55±5,30 para 95,19±6,54; a amplitude de extensão aumentou de −3,88±3,29 para 1,57±2,17; o índice de caminhada evoluiu de 22,61±7,00 para 28,53±5,74; o índice de atividade em escadas aumentou de 18,70±6,79 para 18,70±6,79. Os mesmos dados aferidos no grupo controle não apresentaram alterações significativas. Conclusão: A prevenção de lesões esportivas durante a pandemia atual inicia-se no cuidado do sistema imunológico, cuidados com o ambiente doméstico também foram descritos, bem como a validação de tratamento eficaz para a reabilitação das lesões esportivas domésticas em tempo hábil. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: En el contexto del COVID-19, muchas actividades físicas se han restringido al ámbito doméstico, incluidos los deportes comunitarios tradicionales. La situación de las lesiones corporales y las estrategias de prevención durante este período urgen investigaciones y adaptaciones para un abordaje preventivo. Objetivo: Explorar el escenario actual ideando medios de prevención para las lesiones deportivas causadas en el entorno doméstico. Métodos: Un total de 60 personas fueron seleccionadas como voluntarios experimentales para el análisis de las lesiones deportivas domiciliarias, 30 en el grupo experimental y 30 en el grupo control, se estudiaron los casos y se plantearon hipótesis corroborando para un sistema preventivo de las lesiones deportivas domiciliarias catalogadas, así como la mitigación de sus intercurrencias. Resultados: En el grupo experimental, la amplitud de flexión aumentó de 74,55±5,30 a 95,19±6,54; la amplitud de extensión aumentó de −3,88±3,29 a 1,57±2,17; el índice de marcha evolucionó de 22,61±7,00 a 28,53±5,74; el índice de actividad en escaleras aumentó de 18,70±6,79 a 18,70±6,79. Los mismos datos medidos en el grupo de control no mostraron cambios significativos. Conclusión: La prevención de las lesiones deportivas durante la pandemia actual comienza en el cuidado del sistema inmunológico, también se describió el cuidado del entorno del hogar, así como la validación de un tratamiento eficaz para la rehabilitación de las lesiones deportivas en el hogar de manera oportuna. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

C5aR antagonist inhibits LPS-induced inflammation in human gingival fibroblasts via NF-κB and MAPK signaling pathways

Abstract Objective Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). Methodology HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. Results Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1β, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. Conclusion These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways.

Cardioprotective action of aprepitant in a rat model of ischemia-reperfusioninduced myocardial injury: role of PI3K-AkT-GSK-3ß-HIF-1α signaling pathway.

PURPOSE: The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury. METHODS: The isolated hearts of Wistar male albino rats were subjected to ischemia-reperfusion injury on Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase 1 and CK-MB release in the coronary effluent. The rats were treated with aprepitant (5, 10 and 20 mg/kg) before isolating hearts. After injury, the levels of HIF-1α, p-AkT, p-GSK-3ß/GSK-3ß were measured in heart homogenates. LY294002 was employed as PI3K inhibitor. RESULTS: Ischemia-reperfusion led to significant myocardial injury and decreased the levels of HIF-1α, p-AkT and ratio of p-GSK-3ß/GSK-3ß. Aprepitant attenuated myocardial injury and restored the biochemical changes in a dose-dependent manner. Pre-treatment with LY294002 (10 and 20 mg/kg) abolished aprepitant-mediated cardioprotective effects and restored the biochemical parameters in the heart homogenate. CONCLUSIONS: Aprepitant may be effective in preventing ischemia-reperfusion-induced myocardial injury, which may be due to activation of PI3K-AkT-GSK-3ß and HIF-1α signaling pathway.

Long-term effects of antipsychotics on mortality in patients with schizophrenia: a systematic review and meta-analysis

Objective: To gather current evidence on the impact of antipsychotics on long-term mortality in patients with schizophrenia. Methods: We systematically searched for articles in Embase, PubMed, and PsycINFO reporting the long-term mortality (follow-up > 1 year) of patients with schizophrenia who were using any antipsychotics. We then conducted multiple meta-analyses to determine differences in long-term mortality between different types of antipsychotics. Results: We identified 45 articles that provided unadjusted long-term mortality rates, including 46,171 deaths during 2,394,911 person-years. The pooled mortality rate was 9.9 (95%CI = 7.4-12.7) per 1,000 person-years. The unadjusted crude mortality rate of antipsychotic drug users was lower than that of non-users (risk ratio [RR] = 0.546, 95%CI = 0.480-0.621), first-generation antipsychotics caused higher all-cause mortality than second-generation antipsychotics (RR = 1.485, 95%CI = 1.361-1.620), and polypharmacy had better effects than monotherapy on long-term mortality (RR = 0.796, 95%CI = 0.689-0.921). As for the causes of death, heart disease and cardiovascular disease ranked highest among cause-specific mortality (5.6 per 1,000 person-years). Conclusion: Since antipsychotics had a beneficial effect on long-term mortality in schizophrenia, greater precaution should be taken with patients who do not take them. However, since disease severity, comorbidities, and other confounding factors cannot be fully controlled, further research and verification are needed.

Multiple-trait analyses improved the accuracy of genomic prediction and the power of genome-wide association of productivity and climate change-adaptive traits in lodgepole pine.

BACKGROUND: Genomic prediction (GP) and genome-wide association (GWA) analyses are currently being employed to accelerate breeding cycles and to identify alleles or genomic regions of complex traits in forest trees species. Here, 1490 interior lodgepole pine (Pinus contorta Dougl. ex. Loud. var. latifolia Engelm) trees from four open-pollinated progeny trials were genotyped with 25,099 SNPs, and phenotyped for 15 growth, wood quality, pest resistance, drought tolerance, and defense chemical (monoterpenes) traits. The main objectives of this study were to: (1) identify genetic markers associated with these traits and determine their genetic architecture, and to compare the marker detected by single- (ST) and multiple-trait (MT) GWA models; (2) evaluate and compare the accuracy and control of bias of the genomic predictions for these traits underlying different ST and MT parametric and non-parametric GP methods. GWA, ST and MT analyses were compared using a linear transformation of genomic breeding values from the respective genomic best linear unbiased prediction (GBLUP) model. GP, ST and MT parametric and non-parametric (Reproducing Kernel Hilbert Spaces, RKHS) models were compared in terms of prediction accuracy (PA) and control of bias. RESULTS: MT-GWA analyses identified more significant associations than ST. Some SNPs showed potential pleiotropic effects. Averaging across traits, PA from the studied ST-GP models did not differ significantly from each other, with generally a slight superiority of the RKHS method. MT-GP models showed significantly higher PA (and lower bias) than the ST models, being generally the PA (bias) of the RKHS approach significantly higher (lower) than the GBLUP. CONCLUSIONS: The power of GWA and the accuracy of GP were improved when MT models were used in this lodgepole pine population. Given the number of GP and GWA models fitted and the traits assessed across four progeny trials, this work has produced the most comprehensive empirical genomic study across any lodgepole pine population to date.

Integrating genomic information and productivity and climate-adaptability traits into a regional white spruce breeding program.

Tree improvement programs often focus on improving productivity-related traits; however, under present climate change scenarios, climate change-related (adaptive) traits should also be incorporated into such programs. Therefore, quantifying the genetic variation and correlations among productivity and adaptability traits, and the importance of genotype by environment interactions, including defense compounds involved in biotic and abiotic resistance, is essential for selecting parents for the production of resilient and sustainable forests. Here, we estimated quantitative genetic parameters for 15 growth, wood quality, drought resilience, and monoterpene traits for Picea glauca (Moench) Voss (white spruce). We sampled 1,540 trees from three open-pollinated progeny trials, genotyped with 467,224 SNP markers using genotyping-by-sequencing (GBS). We used the pedigree and SNP information to calculate, respectively, the average numerator and genomic relationship matrices, and univariate and multivariate individual-tree models to obtain estimates of (co)variance components. With few site-specific exceptions, all traits examined were under genetic control. Overall, higher heritability estimates were derived from the genomic- than their counterpart pedigree-based relationship matrix. Selection for height, generally, improved diameter and water use efficiency, but decreased wood density, microfibril angle, and drought resistance. Genome-based correlations between traits reaffirmed the pedigree-based correlations for most trait pairs. High and positive genetic correlations between sites were observed (average 0.68), except for those pairs involving the highest elevation, warmer, and moister site, specifically for growth and microfibril angle. These results illustrate the advantage of using genomic information jointly with productivity and adaptability traits, and defense compounds to enhance tree breeding selection for changing climate.

Mutation of MtrA at the Predicted Phosphorylation Site Abrogates Its Role as a Global Regulator in Streptomyces venezuelae.

The global regulator MtrA controls development and primary and secondary metabolism in Streptomyces species. However, residues critical for its function have not yet been characterized. In this study, we identified residue D53 as the potential phosphorylation site of MtrA from Streptomyces venezuelae, a model Streptomyces strain. MtrA variants with amino acid substitutions at the D53 site were generated, and the effects of these substitutions were evaluated in vitro and in vivo. We showed that, although substitutions at D53 did not alter MtrA's secondary structure, the MtrA D53 protein variants lost the ability to bind known MtrA recognition sequences (MtrA sites) in electrophoretic mobility shift assays. Complementation of the ΔmtrA strain with MtrA D53 protein variants did not affect overall strain growth. However, in comparison to the wild-type strain, chloramphenicol and jadomycin production were aberrant in the D53 variant strains, with levels similar to the levels in the ΔmtrA strain. Transcriptional analysis showed that the expression patterns of genes were also similar in the ΔmtrA strain and the D53 variant strains. Although the D53 protein variants and wild-type MtrA were produced at similar levels in S. venezuelae, chromatin immunoprecipitation-quantitative PCR results indicated that replacing the D53 residue rendered the altered proteins unable to bind MtrA sites in vivo, including MtrA sites that regulate genes involved in nitrogen metabolism and in chloramphenicol and jadomycin biosynthesis. In conclusion, our study demonstrates that the predicted phosphorylation site D53 is critical for the role of MtrA in regulation and suggests that MtrA functions in a phosphorylated form in the genus Streptomyces. IMPORTANCE Although phosphorylation has been shown to be essential for the activation of many response regulator proteins of two-component systems, the role of the phosphorylation site in the function of the global regulator MtrA in the genus Streptomyces has not been reported. In this study, we generated Streptomyces mutants that had amino acid substitutions at the predicted phosphorylation site of MtrA, and the effects of the substitutions were investigated by comparing the phenotypes of the resulting strains and their gene expression patterns with those of the wild-type strain and an MtrA deletion mutant. The ability of the altered proteins to bind known promoter targets in vitro was also evaluated. Our analyses showed that the predicted phosphorylation site D53 is critical for MtrA binding in vitro and for the normal functioning of MtrA in vivo. These studies further demonstrate the importance of MtrA as a global regulator in the genus Streptomyces.