A genome-wide CRISPR screening uncovers that TOB1 acts as a key host factor for FMDV infection via both IFN and EGFR mediated pathways.

The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.

Plasminogen activator urokinase interacts with the fusion protein and antagonizes the growth of Peste des petits ruminants virus.

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.

Building gender-specific sexually transmitted infection risk prediction models using CatBoost algorithm and NHANES data.

BACKGROUND AND AIMS: Sexually transmitted infections (STIs) are a significant global public health challenge due to their high incidence rate and potential for severe consequences when early intervention is neglected. Research shows an upward trend in absolute cases and DALY numbers of STIs, with syphilis, chlamydia, trichomoniasis, and genital herpes exhibiting an increasing trend in age-standardized rate (ASR) from 2010 to 2019. Machine learning (ML) presents significant advantages in disease prediction, with several studies exploring its potential for STI prediction. The objective of this study is to build males-based and females-based STI risk prediction models based on the CatBoost algorithm using data from the National Health and Nutrition Examination Survey (NHANES) for training and validation, with sub-group analysis performed on each STI. The female sub-group also includes human papilloma virus (HPV) infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) program to build males-based and females-based STI risk prediction models using the CatBoost algorithm. Data was collected from 12,053 participants aged 18 to 59 years old, with general demographic characteristics and sexual behavior questionnaire responses included as features. The Adaptive Synthetic Sampling Approach (ADASYN) algorithm was used to address data imbalance, and 15 machine learning algorithms were evaluated before ultimately selecting the CatBoost algorithm. The SHAP method was employed to enhance interpretability by identifying feature importance in the model's STIs risk prediction. RESULTS: The CatBoost classifier achieved AUC values of 0.9995, 0.9948, 0.9923, and 0.9996 and 0.9769 for predicting chlamydia, genital herpes, genital warts, gonorrhea, and overall STIs infections among males. The CatBoost classifier achieved AUC values of 0.9971, 0.972, 0.9765, 1, 0.9485 and 0.8819 for predicting chlamydia, genital herpes, genital warts, gonorrhea, HPV and overall STIs infections among females. The characteristics of having sex with new partner/year, times having sex without condom/year, and the number of female vaginal sex partners/lifetime have been identified as the top three significant predictors for the overall risk of male STIs. Similarly, ever having anal sex with a man, age and the number of male vaginal sex partners/lifetime have been identified as the top three significant predictors for the overall risk of female STIs. CONCLUSIONS: This study demonstrated the effectiveness of the CatBoost classifier in predicting STI risks among both male and female populations. The SHAP algorithm revealed key predictors for each infection, highlighting consistent demographic characteristics and sexual behaviors across different STIs. These insights can guide targeted prevention strategies and interventions to alleviate the impact of STIs on public health.

Associations between low muscle mass and clinical characteristics of health population in China.

Objectives: The primary aim of this study is to discern the association between specific clinical parameters and low muscle mass (LMM). We endeavor to elucidate the determinants of LMM and the predictive potency of individual factors. Methods: In this retrospective cross-sectional study, we encompassed 450 older adult Chinese participants (252 males and 198 females). Muscle mass quantifications were performed using bioelectrical impedance analysis. Comprehensive data encompassing demographic details (age, sex, height, and weight) and laboratory results (complete blood count, thyroid function, liver function, and renal function) were systematically recorded. Logistic regression models, coupled with receiver operating characteristic curve analytics, were employed to ascertain the variables influencing LMM and to evaluate the predictive validity of each parameter on LMM. Results: Upon confounding adjustment for age, gender, body mass index (BMI), and free thyroxine (FT4) persisted as a determinant of LMM. Specifically, individuals with an FT4 exceeding 1.105 ng/dL exhibited a 1.803-fold increased propensity for LMM relative to those with FT4 values below the specified threshold. Incorporating age, gender, BMI, and FT4 in the diagnostic algorithm enhanced the precision of LMM. The results differ between men and women. In the male population, we can still observe that FT4 has a certain value in the diagnosis of LMM, but this phenomenon is not found in the female population. Conclusions: Elevated FT4 concentrations, albeit within clinically accepted limits, are inversely associated with muscle mass. As such, FT4 could be postulated as a potential biomarker for LMM in geriatric individuals, especially in the male group.

Halide-free CO2 cycloaddition onto styrene oxide catalysed by first row transition-metal derivatives of polyoxotungstates.

Quaternary ammonium salts of metal derivatives of polyoxometalates [XW11O39M(H2O)]n- (X = P, Si; M = Cr, Mn, Co, Ni, Zn) were successfully tested instead of quaternary ammonium halides as catalysts in the cycloaddition of CO2 to styrene oxide. Remarkably, they gave very satisfactory yields of styrene carbonate at moderate temperature (80 °C).

GP's GP, general practitioner's health and willingness to contract family doctors in China: a national cross-sectional study.

OBJECTIVES: General practitioners are trained to care for patients with a high level of responsibility and professional competency. However, there are few reports on the physical and mental health status of general practitioners (GPs) in China, particularly regarding help seeking and self-treatment. The primary aims of this study were to explore GPs' expectations of their own family doctors and their reflection on role positioning, and to explore the objective factors that hinder the system of family doctors. STUDY DESIGN: Cross-sectional study. METHODS: We conducted an online survey of Chinese GPs. Descriptive statistics were used to summarize the findings. RESULTS: More than half of the participants (57.20%) reported that their health was normal over the past year. A total of 420 participants (23.35%) reported having chronic diseases. For sleep duration, 1205 participants (66.98%) reported sleeping 6-8 h per day; 473 participants (26.29%) reported chronic insomnia. Two hundred thirty-one participants (12.84%) had possible depression. A total of 595 (33.07%) participants reported that they had contracted a fixed family doctor. In terms of preventing themselves from contracting for a family doctor, the following factors were identified: lack of sufficient time (54.81%), could solve obstacles themselves (50.97%), and embarrassment (24.24%). The proportion of the contract group (12.44%) taking personal relationship as a consideration was higher than that of the non-contract group (7.64%) (χ2 = 10.934 P = 0.01). Most participants (79.90%) in the non-signed group reported never having seen a family doctor. In terms of obstacles, more than half of the signed group thought that they could solve obstacles themselves, while the non-signed group (39.20%) was less confident in the ability of family doctors than the signed group (29.75%) (χ2 = 15.436, P < 0.01). CONCLUSIONS: GPs work under great pressure and lack of self-care awareness, resulting in an increased prevalence of health conditions. Most GPs did not have a regular family doctor. Having a family doctor with a fixed contract is more conducive to the scientific management of their health and provides a reasonable solution to health problems. The main factors hindering GPs from choosing a family doctor were time consumption, abilities to solve obstacles themselves, and trust in the abilities of GPs. Therefore, simplifying the process of family doctor visits, Changing the GPs' medical cognition, and strengthening the policy of GP training would be conducive to promoting a family doctor system that enhances hierarchical diagnosis and treatment. International collaboration could integrate GP health support into global healthcare system.

African Swine Fever Virus I267L Is a Hemorrhage-Related Gene Based on Transcriptome Analysis.

African swine fever (ASF) is an acute and severe disease transmitted among domestic pigs and wild boars. This disease is notorious for its high mortality rate and has caused great losses to the world's pig industry in the past few years. After infection, pigs can develop symptoms such as high fever, inflammation, and acute hemorrhage, finally leading to death. African swine fever virus (ASFV) is the causal agent of ASF; it is a large DNA virus with 150-200 genes. Elucidating the functions of each gene could provide insightful information for developing prevention and control methods. Herein, to investigate the function of I267L, porcine alveolar macrophages (PAMs) infected with an I267L-deleted ASFV strain (named ∆I267L) and wild-type ASFV for 18 h and 36 h were taken for transcriptome sequencing (RNA-seq). The most distinct different gene that appeared at both 18 hpi (hours post-infection) and 36 hpi was F3; it is the key link between inflammation and coagulation cascades. KEGG analysis (Kyoto encyclopedia of genes and genomes analysis) revealed the complement and coagulation cascades were also significantly affected at 18 hpi. Genes associated with the immune response were also highly enriched with the deletion of I267L. RNA-seq results were validated through RT-qPCR. Further experiments confirmed that ASFV infection could suppress the induction of F3 through TNF-α, while I267L deletion partially impaired this suppression. These results suggest that I267L is a pathogenicity-associated gene that modulates the hemorrhages of ASF by suppressing F3 expression. This study provides new insights into the molecular mechanisms of ASFV pathogenicity and potential targets for ASFV prevention and control.

Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vß2+ T cell malignancy.

Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vß2 as a model, here we demonstrate the rapid generation of an off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vß chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity. Second generation 4-1BB/CD3zeta CAR containing high affinity humanized anti-Vß scFv is expressed efficiently on donor T cells via both lentivirus and adeno-associated virus transduction with limited detectable pre-existing immunoreactivity. Our optimized CAR-T cells demonstrate specific and persistent killing of Vß2+ Jurkat cells and Vß2+ patient derived malignant T cells, in vitro and in vivo, without affecting normal T cells. In parallel, we generate humanized anti-Vß2 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) by Fc-engineering for NK cell ADCC therapy.

Vimentin inhibits peste des petits ruminants virus replication by interaction with nucleocapsid protein.

The Peste des petits ruminant virus (PPRV) is a member of the Paramyxoviridae family and is classified into the genus Measles virus. PPRV predominantly infects small ruminants, leading to mortality rates of nearly 100%, which have caused significant economic losses in developing countries. Host proteins are important in virus replication, but the PPRV nucleocapsid (N) protein-host interacting partners for regulating PPRV replication remain unclear. The present study confirmed the interaction between PPRV-N and the host protein vimentin by co-immunoprecipitation and co-localization experiments. Overexpression of vimentin suppressed PPRV replication, whereas vimentin knockdown had the opposite effect. Mechanistically, N was subjected to degradation via the ubiquitin/proteasome pathway, where vimentin recruits the E3 ubiquitin ligase NEDD4L to fulfill N-ubiquitination, resulting in the degradation of the N protein. These findings suggest that the host protein vimentin and E3 ubiquitin ligase NEDD4L have an anti-PPRV effect.

Biofilm Formation, Motility, and Virulence of Listeria monocytogenes Are Reduced by Deletion of the Gene lmo0159, a Novel Listerial LPXTG Surface Protein.

Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen that causes listeriosis in humans and other animals. Surface proteins with the LPXTG motif have important roles in the virulence of L. monocytogenes. Lmo0159 is one such protein, but little is known about its role in L. monocytogenes virulence, motility, and biofilm formation. Here, we constructed and characterized a deletion mutant of lmo0159 (∆lmo0159). We analyzed not only the capacity of biofilm formation, motility, attachment, and intracellular growth in different cell types but also LD50; bacterial load in mice's liver, spleen, and brain; expression of virulence genes; and survival time of mice after challenge. The results showed that the cross-linking density of the biofilm of ∆lmo0159 strain was lower than that of WT by microscopic examination. The expression of biofilm-formation and virulence genes also decreased in the biofilm state. Subsequently, the growth and motility of ∆lmo0159 in the culture medium were enhanced. Conversely, the growth and motility of L. monocytogenes were attenuated by ∆lmo0159 at both the cellular and mouse levels. At the cellular level, ∆lmo0159 reduced plaque size; accelerated scratch healing; and attenuated the efficiency of adhesion, invasion, and intracellular proliferation in swine intestinal epithelial cells (SIEC), RAW264.7, mouse-brain microvascular endothelial cells (mBMEC), and human-brain microvascular endothelial cells (hCMEC/D3). The expression of virulence genes was also inhibited. At the mouse level, the LD50 of the ∆lmo0159 strain was 100.97 times higher than that of the WT strain. The bacterial load of the ∆lmo0159 strain in the liver and spleen was lower than that of the WT strain. In a mouse model of intraperitoneal infection, the deletion of the lmo0159 gene significantly prolonged the survival time of the mice, suggesting that the lmo0159 deletion mutant also exhibited reduced virulence. Thus, our study identified lmo0159 as a novel virulence factor among L. monocytogenes LPXTG proteins.

A few-shot disease diagnosis decision making model based on meta-learning for general practice.

BACKGROUND: Diagnostic errors have become the biggest threat to the safety of patients in primary health care. General practitioners, as the "gatekeepers" of primary health care, have a responsibility to accurately diagnose patients. However, many general practitioners have insufficient knowledge and clinical experience in some diseases. Clinical decision making tools need to be developed to effectively improve the diagnostic process in primary health care. The long-tailed class distributions of medical datasets are challenging for many popular decision making models based on deep learning, which have difficulty predicting few-shot diseases. Meta-learning is a new strategy for solving few-shot problems. METHODS AND MATERIALS: In this study, a few-shot disease diagnosis decision making model based on a model-agnostic meta-learning algorithm (FSDD-MAML) is proposed. The MAML algorithm is applied in a knowledge graph-based disease diagnosis model to find the optimal model parameters. Moreover, FSDD-MAML can learn learning rates for all modules of the knowledge graph-based disease diagnosis model. For n-way, k-shot learning tasks, the inner loop of FSDD-MAML performs multiple gradient update steps to learn internal features in disease classification tasks using n×k examples, and the outer loop of FSDD-MAML optimizes the meta-objective to find the associated optimal parameters and learning rates. FSDD-MAML is compared with the original knowledge graph-based disease diagnosis model and other meta-learning algorithms based on an abdominal disease dataset. RESULT: Meta-learning algorithms can greatly improve the performance of models in top-1 evaluation compared with top-3, top-5, and top-10 evaluations. The proposed decision making model FSDD-MAML outperforms all the other models, with a precision@1 of 90.02 %. We achieve state-of-the-art performance in the diagnosis of all diseases, and the prediction performance for few-shot diseases is greatly improved. For the two groups with the fewest examples of diseases, FSDD-MAML achieves relative increases in precision@1 of 29.13 % and 21.63 % compared with the original knowledge graph-based disease diagnosis model. In addition, we analyze the reasoning process of several few-shot disease predictions and provide an explanation for the results. CONCLUSION: The decision making model based on meta-learning proposed in this paper can support the rapid diagnosis of diseases in general practice and is especially capable of helping general practitioners diagnose few-shot diseases. This study is of profound significance for the exploration and application of meta-learning to few-shot disease assessment in general practice.

Eâ ¡B Mutation Reduces the Pathogenicity of Listeria monocytogenes by Negatively Regulating Biofilm Formation Ability, Infective Capacity, and Virulence Gene Expression.

To explore the role of the membrane permease ⅡB (EⅡB) gene of Listeria pathogenicity island 4 (LIPI-4) in the virulence of Listeria monocytogenes, both an EⅡB deletion strain (∆EⅡB) and a complemented strain were constructed. In vitro experiments demonstrated that EⅡB deletion affected the biofilm formation ability of the wild-type strain (Lm928). Moreover, this deletion decreased the intracellular proliferation abilities of L. monocytogenes. Mice infected with ∆EⅡB survived longer and experienced less weight loss on days 1, 2, and 3 post-infection. The bacterial load in the liver tissue of ∆EⅡB-infected mice was significantly reduced, and a considerable decrease in the blood levels of inflammatory cytokines IL-ß, IL-6, IL-10, and TNF-α were observed. Following EⅡB deletion, 65% (13/20) of genes were downregulated, 25% (5/20) were upregulated, and 10% (2/20) showed no change. These findings suggest that EⅡB deletion may reduce both the in vivo and in vitro virulence levels as well as the biofilm formation ability of Lm928 by downregulating the transcription levels of genes associated with virulence and biofilm formation. These findings provide a foundation for further examining the pathogenic mechanisms of LIPI-4 and EⅡB in L. monocytogenes.

The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells.

CD8+ T cells play an important role in anti-tumor immunity. Better understanding of their regulation could advance cancer immunotherapies. Here we identify, via stepwise CRISPR-based screening, that CUL5 is a negative regulator of the core signaling pathways of CD8+ T cells. Knocking out CUL5 in mouse CD8+ T cells significantly improves their tumor growth inhibiting ability, with significant proteomic alterations that broadly enhance TCR and cytokine signaling and their effector functions. Chemical inhibition of neddylation required by CUL5 activation, also enhances CD8 effector activities with CUL5 validated as a major target. Mechanistically, CUL5, which is upregulated by TCR stimulation, interacts with the SOCS-box-containing protein PCMTD2 and inhibits TCR and IL2 signaling. Additionally, CTLA4 is markedly upregulated by CUL5 knockout, and its inactivation further enhances the anti-tumor effect of CUL5 KO. These results together reveal a negative regulatory mechanism for CD8+ T cells and have strong translational implications in cancer immunotherapy.

Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can lead to a cytokine storm, unleashed in part by pyroptosis of virus-infected macrophages and monocytes. Interleukin-6 (IL-6) has emerged as a key participant in this ominous complication of COVID-19. IL-6 antagonists have improved outcomes in patients with COVID-19 in some, but not all, studies. IL-6 signaling involves at least 3 distinct pathways, including classic-signaling, trans-signaling, and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130. IL-6 has become a therapeutic target in COVID-19, cardiovascular diseases, and other inflammatory conditions. However, the efficacy of inhibition of IL-6 signaling in metabolic diseases, such as obesity and diabetes, may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism, glucose uptake, and insulin sensitivity owing to complexities that remain to be elucidated. The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications, focusing predominantly on metabolic and cardiovascular diseases.

Effect of balance training on the physical fitness of marathon runners / Efeito do treinamento de equilíbrio sobre a aptidão física dos maratonistas / Efecto del entrenamiento del equilibrio en la aptitud física de corredores de maratón

ABSTRACT Introduction: As a comprehensive sport, Marathon presents high demands concerning the athletes' comprehensive capacity. Objective: This paper explores to what extent balance skill training can effectively contribute to improving physical fitness for marathon runners. Methods: 120 marathon runners were selected for the pilot experiment. The experimental group received balance training, while the control group underwent no intervention. Results: In the experimental group, the time with eyes closed and feet apart increased from 33.559 ± 15.8570 to 37.203 ± 15.5865s, the time spent in the T-shaped run from 10.144 ± 0.5063s to 9.908 ± 0.5225s, the time spent in the standing long jump from 2.831 ± 0.2648m to 3.058 ± 0.3183m, and the time spent in the T-shaped run from 55.544 ± 2.2581 to 60.845 ± 2.4367 times/min. The total FMS score changed from 14.618 ± 0.9392 to 18.481 ± 1.3909. Shoulder flexibility increased from 2.777 ± 0.4756 to 2.917 ± 0.2994, and active straight knee raise changed from 2.306 ± 0.4692 to 2.803 ± 0.403. Conclusion: Daily balance training can be added to usual marathon training to improve the fitness of its athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A maratona, enquanto esporte integral, apresenta altas exigências relativas à capacidade plena dos atletas. Objetivo: Este artigo tenta explorar em que medida o treinamento da habilidade de equilíbrio pode efetivamente contribuir para o aprimoramento da aptidão física aos praticantes do esporte de corrida de maratona. Métodos: 120 corredores de maratona foram selecionados para o experimento piloto. O grupo experimental recebeu treinamento de equilíbrio, enquanto o grupo de controle não sofreu qualquer intervenção. Resultados: No grupo experimental, o tempo com olhos fechados e pés separados aumentou de 33,559 ± 15,8570 para 37,203 ± 15,5865s, o tempo gasto na corrida em forma de T de 10,144 ± 0,5063s para 9,908 ± 0,5225s, o tempo gasto no salto em pé em distância de 2,831 ± 0,2648m para 3,058 ± 0,3183m, e o tempo gasto na corrida em forma de T de 55,544 ± 2,2581 para 60,845 ± 2,4367 vezes/min. A pontuação total de FMS mudou de 14,618 ± 0,9392 para 18,481 ± 1,3909. A flexibilidade do ombro aumentou de 2,777 ± 0,4756 para 2,917 ± 0,2994, e o levantamento reto do joelho ativo mudou de 2,306 ± 0,4692 para 2,803 ± 0,403. Conclusão: O treinamento de equilíbrio diário pode ser adicionado ao treino de maratona habitual para melhorar a aptidão física de seus atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El maratón, como deporte integral, presenta grandes exigencias en cuanto a la capacidad integral de los atletas. Objetivo: Este trabajo pretende explorar hasta qué punto el entrenamiento de las habilidades de equilibrio puede contribuir eficazmente a la mejora de la condición física de los corredores de maratón. Métodos: Se seleccionaron 120 corredores de maratón para el experimento piloto. El grupo experimental recibió entrenamiento de equilibrio, mientras que el grupo de control no se sometió a ninguna intervención. Resultados: En el grupo experimental, el tiempo con los ojos cerrados y los pies separados aumentó de 33,559 ± 15,8570 a 37,203 ± 15,5865s, el tiempo empleado en la carrera en forma de T de 10,144 ± 0,5063s a 9,908 ± 0,5225s, el tiempo empleado en el salto de longitud de pie de 2,831 ± 0,2648m a 3,058 ± 0,3183m, y el tiempo empleado en la carrera en forma de T de 55,544 ± 2,2581 a 60,845 ± 2,4367 veces/min. La puntuación total de FMS pasó de 14,618 ± 0,9392 a 18,481 ± 1,3909. La flexibilidad de los hombros aumentó de 2,777 ± 0,4756 a 2,917 ± 0,2994, y la elevación activa de la rodilla pasó de 2,306 ± 0,4692 a 2,803 ± 0,403. Conclusión: El entrenamiento diario del equilibrio puede añadirse al entrenamiento habitual de maratón para mejorar la forma física de sus atletas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Effects of resistance training on exercise tolerance in marathon runners / Efeitos do treinamento de resistência sobre a tolerância ao exercício em corredores de maratona / Efectos del entrenamiento de resistencia sobre la tolerancia al ejercicio en corredores de maratón

ABSTRACT Introduction: A high index of exercise tolerance is fundamental for marathon runners, indicating a good capacity to perform the exercises considering their maximum duration and workload. Objective: Evaluate the effects of resistance training with different loads on exercise tolerance of marathon runners. Methods: 120 professional long-distance runners were selected as volunteers for the experiment. Divided into experimental groups A, B and Control, the intervention had a 9-week period. The experimental groups A and B received resistance training with different loads, while the Control group did not undergo training intervention. Results: Upper limb muscle mass increased from 3.38 ± 0.18 to 3.75 ± 0.37 in group A; from 3.40 ± 0.15 to 3.66 ± 0.31 in group B; peak biceps brachii moment increased from 53.60 ± 6.27 to 62.97 ± 8.87 in group A; from 53.67 ± 5.68 to 58.48 ± 6.16 in group B; from 5. 37 ± 2.16 to 5.73 ± 2.67 in group A; from 7.21 ± 2.62 to 6.76 ± 4.36 in group B; and from 154.86 ± 19.69 to 108.30 ± 31.75 in group A; group B presented a reduction from 156.97 ± 46.13 to 116.45 ± 39.09, and the data from the control group did not change significantly. Conclusion: Resistance training with different loads in daily training can effectively improve the endurance of long-distance runners. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Um índice elevado de tolerância ao exercício é fundamental para corredores de maratona, sinalizando uma boa capacidade para a realização dos exercícios considerando sua duração máxima e carga de trabalho. Objetivo: Avaliar os efeitos do treinamento de resistência com distintas cargas sobre a tolerância ao exercício dos corredores de maratona. Métodos: Foram selecionados 120 corredores profissionais de longa distância como voluntários para o experimento. Divididos em grupo experimental A, B e Controle, a intervenção teve um período de 9 semanas. Os grupos experimentais A e B receberam treinamento de resistência com cargas diferentes, enquanto o grupo Controle não sofreu intervenção de treinamento. Resultados: A massa muscular dos membros superiores elevou-se de 3,38 ± 0,18 para 3,75 ± 0,37 no grupo A; de 3,40 ± 0,15 para 3,66 ± 0,31 no grupo B; o momento de pico do bíceps braquial aumentou de 53,60 ± 6,27 para 62,97 ± 8,87 no grupo A; de 53,67 ± 5,68 para 58,48 ± 6,16 no grupo B; de 5. 37 ± 2,16 para 5,73 ± 2,67 no grupo A; de 7,21 ± 2,62 para 6,76 ± 4,36 no grupo B; e de 154,86 ± 19,69 para 108,30 ± 31,75 no grupo A; o grupo B apresentou redução de 156,97 ± 46,13 para 116,45 ± 39,09, e os dados do grupo de controle não sofreram alterações significativas. Conclusão: O treinamento de resistência com diferentes cargas no treinamento diário pode efetivamente melhorar a resistência dos corredores de longa distância. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Un alto índice de tolerancia al ejercicio es fundamental para los corredores de maratón, indicando una buena capacidad para realizar los ejercicios, considerando su máxima duración y carga de trabajo. Objetivo: Evaluar los efectos del entrenamiento de resistencia con diferentes cargas sobre la tolerancia al ejercicio de corredores de maratón. Métodos: 120 corredores profesionales de larga distancia fueron seleccionados como voluntarios para el experimento. Divididos en los grupos experimentales A, B y Control, la intervención tuvo una duración de 9 semanas. Los grupos experimentales A y B recibieron entrenamiento de resistencia con diferentes cargas, mientras que el grupo Control no se sometió a intervención de entrenamiento. Resultados: La masa muscular del miembro superior aumentó de 3,38 ± 0,18 a 3,75 ± 0,37 en el grupo A; de 3,40 ± 0,15 a 3,66 ± 0,31 en el grupo B; el momento máximo del bíceps braquial aumentó de 53,60 ± 6,27 a 62,97 ± 8,87 en el grupo A; de 53,67 ± 5,68 a 58,48 ± 6,16 en el grupo B; de 5. 37 ± 2,16 a 5,73 ± 2,67 en el grupo A; de 7,21 ± 2,62 a 6,76 ± 4,36 en el grupo B; y de 154,86 ± 19,69 a 108,30 ± 31,75 en el grupo A; el grupo B presentó una reducción de 156,97 ± 46,13 a 116,45 ± 39,09, y los datos del grupo control no sufrieron cambios significativos. Conclusión: El entrenamiento de resistencia con diferentes cargas en el entrenamiento diario puede mejorar eficazmente la resistencia de los corredores de fondo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Upregulation of miR-129-5p increases the sensitivity to Taxol through inhibiting HMGB1-mediated cell autophagy in breast cancer MCF-7 cells

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.