Enhancing Swimming Performance of Magnetic Helical Microswimmers by Surface Microstructure.

Artificial bacterial flagella (ABF), also known as a magnetic helical microswimmer, has demonstrated enormous potential in various future biomedical applications (e.g., targeted drug delivery and minimally invasive surgery). Nevertheless, when used for in vivo/in vitro treatment applications, it is essential to achieve the high motion efficiency of the microswimmers for rapid therapy. In this paper, inspired by microorganisms, the surface microstructure was introduced into ABFs to investigate its effect on the swimming behavior. It was confirmed that compared with smooth counterparts, the ABF with surface microstructure reveals a smaller forward velocity below the step-out frequency (i.e., the frequency corresponding to the maximum velocity) but a larger maximum forward velocity and higher step-out frequency. A hydrodynamic model of microstructured ABF is employed to reveal the underlying movement mechanism, demonstrating that the interfacial slippage and the interaction between the fluid and the microstructure are essential to the swimming behavior. Furthermore, the effect of surface wettability and solid fraction of microstructure on the swimming performance of ABFs was investigated experimentally and analytically, which further reveals the influence of surface microstructure on the movement mechanism. The results present an effective approach for designing fast microrobots for in vivo/in vitro biomedical applications.

Effects of regulator of G protein signaling 2 (RGS2) overexpression in the paraventricular nucleus on blood pressure in rats with angiotensin II-induced hypertension.

The hypothalamic paraventricular nucleus (PVN) regulates sympathetic activity and blood pressure. The regulator of G protein signaling 2 (RGS2) is a negative G protein regulator, which selectively regulates G⍺q signaling, a potential cause of hypertension. This study aimed to examine angiotensin II (ANG II)-G protein-RGS2 signaling on the central mechanisms of blood pressure control, sympathetic activation, and kidney function. The Sprague Dawley rats were infused with ANG II (200 ng/kg/min) via osmotic mini pump to induce hypertension. Adenovirus (AV) vectors encoding RGS2 was transfected into the PVN in vivo. By radio telemetry measurements, we found AV-RGS2 transfection to the PVN significantly attenuated the increase of mean arterial pressure in ANG II infusion rats from days 2-7 of the 2-week experiment (Day 7: ANG II + AV-RGS2 141.3 ± 10.0 mmHg vs. ANG II 166.9 ± 9.3 mmHg, p < 0.05). AV-RGS2 transfection significantly reduced the serum norepinephrine level and acute volume reflex and increased daily urine volume and sodium excretion in ANG II-infused hypertensive rats. AV-RGS2 transfection significantly reduced G⍺q and PKC protein expressions within the PVN in ANG II infusion rats. In cultured mouse hypothalamic cells, real-time PCR study showed ANG II treatment increased mRNA expression of G⍺q, G⍺s, and RGS2, and AV-RGS2 treatment decreased ANG II-induced mRNA expression of G⍺q and G⍺s. Using confocal imagery, we found that AV-RGS2 attenuated the increase of calcium influx in ANG II-treated cells. Our results suggest that central overexpression of RGS2 in the PVN attenuated the increase of blood pressure and sympathetic outflow, and improves kidney excretory function in hypertensive rats. This may be via the alteration of ANG II-G-protein-RGS2 signaling in the central nervous system.

CEACAM6 expression and function in tumor biology: a comprehensive review.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily protein primarily expressed on epithelial surfaces and myeloid cells. It plays a significant role in cancer progression by inhibiting apoptosis, promoting drug resistance, and facilitating cancer cell invasion and metastasis. Overexpression of CEACAM6 has been observed in various cancers, including lung, breast, colorectal, and hepatocellular cancers, and is associated with poorer overall survival and disease-free survival. Its differential expression on tumor cell surfaces makes it a promising cancer marker. This review aims to provide a comprehensive summary of CEACAM6's role in different cancer types, its involvement in signaling pathways, and recent advancements in CEACAM6-targeted treatments.

Gene features of tumor-specific T cells relevant to immunotherapy, targeted therapy and chemotherapy in lung cancer.

1 Background: In lung cancer, the use of small-molecule inhibitors, chemotherapy and immunotherapy has led to unprecedented survival benefits in selected patients. Considering most patients will experience a relapse within a short period of time due to single drug resistance, combination therapy is also particularly important to improve patient prognosis. Therefore, more robust biomarkers to predict responses to immunotherapy, targeted therapy, chemotherapy and rationally drug combination therapies may be helpful in clinical treatment choices. 2 Methods: We defined tumor-specific T cells (TSTs) and their features (TSTGs) by single-cell RNA sequencing. We applied LASSO regression to filter out the most survival-relevant TSTGs to form the Tumor-specific T cell score (TSTS). Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low TSTS groups. 3 Results: We identified six clusters of T cells as TSTs in lung cancer, and four most robust genes from 9 feature genes expressed only on tumor-specific T cells were screened to construct a tumor-specific T cells score (TSTS). TSTS was positively correlated with immune infiltration and angiogenesis and negatively correlated with malignant cell proliferation. Moreover, potential vascular-immune crosstalk in lung cancer provides the theoretical basis for combined anti-angiogenic and immunotherapy. Noticeable, patients in high TSTS had better response to ICB and targeted therapy and patients in the low TSTS group often benefit from chemotherapy. 4 Conclusion: The proposed TSTS is a promising indicator to predict immunotherapy, targeted therapy and chemotherapy responses in lung cancer patients for helping clinical treatment choices.

A Five-gene Signature based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma.

AIMS: We aimed to classify molecular subtypes and establish a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in Stomach adenocarcinoma (STAD). BACKGROUND: STAD is a common diagnosed gastrointestinal malignancy and its heterogeneity is a big challenge that influences prognosis and precision therapies. Present study was designed to classify molecular subtypes and construct a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in STAD. OBJECTIVE: The objective of this study is to investigate the molecular subtypes and prognostic model for STAD. METHODS: A STAD specific miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was generated using the RNA-Seq and miRNA expression profiles from The Cancer Genome Atlas (TCGA) database, in which miRNA-related mRNAs were screened. Molecular subtypes were then determined using miRNA-related genes. Through univariate Cox analysis and multivariate regression analysis, a prognostic model was established in GSE84437 Train dataset and validated in GSE84437 Test, TCGA, GSE84437 and GSE66229 datasets. Immunotherapy datasets were employed for assessing the performance of the risk model. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to validate the expression of hub genes used for the risk score signature. RESULTS: We constructed a ceRNA network containing 84 miRNAs and 907 mRNAs and determined two molecular subtypes based on 26 genes from the intersection of TCGASTAD and GSE84437 datasets. Subtype S2 had poor prognosis, lower tumor mutational burden, higher immune score and lower response to immunotherapy. Subtype S1 was more sensitive to Sorafenib, Pyrimethamine, Salubrinal, Gemcitabine, Vinorelbine and AKT inhibitor VIII. Next, a five-gene signature was generated and its robustness was validated in Test and external datasets. This risk model also had a good prediction performance in immunotherapy datasets. CONCLUSION: This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.

Fatty acid metabolism-related lncRNA prognostic signature for serous ovarian carcinoma.

Background: To explore the role of fatty acid metabolism (FAM)-related lncRNAs in the prognosis and antitumor immunity of serous ovarian cancer (SOC). Materials & methods: A SOC FAM-related lncRNA risk model was developed and evaluated by a series of analyses. Additional immune-related analyses were performed to further assess the associations between immune state, tumor microenvironment and the prognostic risk model. Results: Five lncRNAs associated with the FAM genes were found and used to create a predictive risk model. The patients with a low-risk profile exhibited favorable prognostic outcomes. Conclusion: The established prognostic risk model exhibits better predictive capabilities for the prognosis of patients with SOC and offers novel potential therapy targets for SOC.

Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis.

OBJECTIVE: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered. DESIGN: We performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism. RESULTS: Integrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary. CONCLUSION: We uncover a mechanism for organ-specific CRC metastasis.

Effecting mechanisms of iron-rich sludge on ash fusion characteristics of coal with high ash fusion temperature under reducing atmosphere.

Co-gasification is crucial for large-scale clean conversion of coal and sludge. In this study, the effects of municipal sewage sludge (MSS, Fe2O3:48.11 %) and pharmaceutical sewage sludge (PSS, Fe2O3: 67.80 %) on ash fusion temperature (AFT) of high AFT Xiangyuan coal (XY) were explored using an AFT analysis, X-ray fluorescence spectrometry, X-ray diffraction, scanning electronic microscopy, and thermodynamics FactSage calculation. The results showed that when MSS or PSS ash mass ratios reached 20 % or 16 % (for XY mixtures, the mass ratio of MSS or PSS should be >5.81 wt% or 5.07 wt%), respectively, the AFT met the requirement of liquid-slag discharge for entrained-flow bed gasification. Under a reducing atmosphere (6:4, CO/CO2, volume ratio), Fe2+ destroyed the bridging-oxygen bonds in the network structure and generated low melting-point (MP) hercynite (FeAl2O4). This resulted in the AFT decreases in the XY mixtures with the additions of PSS or MSS. Meanwhile, the high calcium content (CaO: 13.40 %) easily reacted with Al2O3 and SiO2 and formed anorthite (CaAl2SiO8), which inhibited high-MP mullite formation and decreased the mixed XY AFT. With the increasing SS mass ratio, the surface of the ash sample and thermodynamic FactSage calculation were in good agreement with the experimental results.

Current Situation and Prospect of Adoptive Cellular Immunotherapy for Malignancies.

Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and non-specific) into patients to kill tumor cells either directly or indirectly by stimulating the body's immune system. The patient's (autologous) or a donor's (allogeneic) immune cells are used to improve immune function. Chimeric antigen receptor (CAR) T cells (CAR-T) is a type of ACT that has gained attention. T cells from the peripheral blood are genetically engineered to express CARs that rapidly proliferate and specifically recognize target antigens to exert its anti-tumor effects. Clinical application of CAR-T therapy for hematological tumors has shown good results, but adverse reactions and recurrence limit its applicability. Tumor infiltrating lymphocyte (TIL) therapy is effective for solid tumors. TIL therapy exhibits T cell receptor (TCR) clonality, superior tumor homing ability, and low targeted toxicity, but its successful application is limited to a number of tumors. Regardless, TIL and CAR-T therapies are effective for treating cancer. Additionally, CAR-natural killer (NK), CAR-macrophages (M), and TCR-T therapies are currently being researched. In this review, we highlight the current developments and limitations of several types of ACT.

The prevalence rate, mortality, and 5-year overall survival of Schistosoma japonicum patients with human malignancy.

Background: Only a few studies have focused on the association between Schistosoma japonicum and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall survival of S. japonicum patients with human malignancy. Methods: From January 20, 2018, to January 31, 2021, 5,866 inpatients were included in the study. A total of 656 S. japonicum patients with malignancy were identified. Cases were stratified by gender and age groups. The cancer sites, prevalence rate, mortality, and 5-year overall survival of the patients were reported. The S. japonicum patients with malignancy were further divided into a non-digestive system tumor group (n = 309) and a digestive system tumor group (n = 347), including those with cancer in the esophagus, stomach, colon, rectum, liver, gallbladder, bile duct, or pancreas. Chi-squared test and odds ratio with confidence intervals were performed between these two groups. Results: Lung cancer was found the most common malignancy, accounting for 18.6% of all malignancies, followed by colorectal, stomach, liver, and gallbladder cancers. These five leading malignancies accounted for approximately 61.8% of all cases. Colorectal cancer was the leading cause of malignancy death, followed by lung, stomach, gallbladder, and liver cancers. These five leading causes of death accounted for approximately 55.6% of all death cases. Statistical significance was found in the prevalence rate between S. japonicum and non-S. japonicum patients with/without digestive system tumor (p < 0.001). The odds ratio of S. japonicum patients with digestive system tumors was 1.6 (95%CI: 1.4-1.9). Conclusion: S. japonicum contributes to a significant prevalence and mortality in digestive system tumors, including colorectal, stomach, liver, and gallbladder cancers.

A C1qTNF3 collagen domain fusion chaperones diverse secreted proteins and anti-Aß scFvs: Applications for gene therapies.

Enhancing production of protein cargoes delivered by gene therapies can improve efficacy by reducing the amount of vector or simply increasing transgene expression levels. We explored the utility of a 126-amino acid collagen domain (CD) derived from the C1qTNF3 protein as a fusion partner to chaperone secreted proteins, extracellular "decoy receptor" domains, and single-chain variable fragments (scFvs). Fusions to the CD domain result in multimerization and enhanced levels of secretion of numerous fusion proteins while maintaining functionality. Efficient creation of bifunctional proteins using the CD domain is also demonstrated. Recombinant adeno-associated viral vector delivery of the CD with a signal peptide resulted in high-level expression with minimal biological impact as assessed by whole-brain transcriptomics. As a proof-of-concept in vivo study, we evaluated three different anti-amyloid Aß scFvs (anti-Aß scFvs), alone or expressed as CD fusions, following viral delivery to neonatal CRND8 mice. The CD fusion increased half-life, expression levels, and improved efficacy for amyloid lowering of a weaker binding anti-Aß scFv. These studies validate the potential utility of this small CD as a fusion partner for secretory cargoes delivered by gene therapy and demonstrate that it is feasible to use this CD fusion to create biotherapeutic molecules with enhanced avidity or bifunctionality.

PD1hi CD200hi CD4+ exhausted T cell increase immunotherapy resistance and tumour progression by promoting epithelial-mesenchymal transition in bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is one of the most diagnosed cancers in humans worldwide. Recently, immunotherapy has become a main treatment option for BC. However, most BLCA patients do not respond to immune checkpoint inhibitors or relapse after immunotherapy. Therefore, it is very important to identify novel biomarkers for the prediction of immunotherapy response in B patients. METHODS: Pancancer single-cell RNA sequencing (scRNA-seq) data were used to identify the clusters of CD4+ T cells in the tumour microenvironment (TME). The clinical significance of key CD4+ T-cell clusters was evaluated based on the survival data of two independent immunotherapy bladder cancer (BLCA) cohorts. We also investigated the function of key clusters of CD4+ T cell in the TME of BC cells in vitro. RESULTS: This study identified two novel exhausted CD4+ T-cell subpopulations with the expression of PD1hi CD200hi or PD1hi CD200low in BC patients. Moreover, BLCA patients with a high level of PD1hi CD200hi CD4+ exhausted T cell showed immunotherapy resistance. Cell function analysis demonstrated that PD1hi CD200hi CD4+ exhausted T cell can promote epithelial-mesenchymal transition (EMT) and angiogenesis in BLCA cells. In addition, PD1hi CD200hi CD4+ exhausted T cells were shown to communicate with malignant BLCA cells through the GAS6-AXL axis. Finally, we also found that GAS6 expression is upregulated in B cells by METTL3-mediated m6A modification. CONCLUSIONS: PD1hi CD200hi CD4+ exhausted T cell may serve as a novel biomarker for poor prognosis and immunotherapy resistance in B. Targeted inhibitors of PD1hi CD200hi CD4+ exhausted T cells may help improve the efficacy of immunotherapy.

Ferrous sulfate reverses cerebral metabolic abnormality induced by minimal hepatic encephalopathy.

Orally administered ferrous iron was previously reported to significantly improve the cognition and locomotion of patients with minimal hepatic encephalopathy (MHE). However, the metabolic mechanisms of the therapeutic effect of ferrous iron are unknown. In this study, MHE was induced in rats by partial portal vein ligation (PPVL), and was treated with ferrous sulfate. The Morris water maze was used to evaluate the cognitive condition of the rats. The metabolites observed by NMR and validated by liquid chromatography-mass spectrometry were defined as the key affected metabolites. The enzyme activities and trace element contents in the rat brains were also investigated. The Mn content was found to be increased but the ferrous iron content decreased in the cortex and striatum in MHE. Decreased oxoglutarate dehydrogenase activity and increased glutamine synthetase (GS) and pyruvate carboxylase (PC) activity were observed in the cortex of MHE rats. Decreased pyruvate dehydrogenase activity and increased GS and PC activity were observed in the striatum of MHE rats. The levels of BCAAs and taurine were significantly decreased, and the contents of GABA, lactate, arginine, aspartate, carnosine, citrulline, cysteine, glutamate, glutamine, glycine, methionine, ornithine, proline, threonine and tyrosine were significantly increased. These metabolic abnormalities described above were restored after treatment with ferrous sulfate. Pathway enrichment analysis suggested that urea cycle, aspartate metabolism, arginine and proline metabolism, glycine and serine metabolism, and glutamate metabolism were the major metabolic abnormalities in MHE rats, but these processes could be restored and cognitive impairment could be improved by ferrous sulfate administration.

Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance.

It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.

Network Analysis and Nomogram in the Novel Classification and Prognosis Prediction of Advanced Schistosomiasis Japonica.

Clinical classification of advanced schistosomiasis japonica is important for treatment options and prognosis prediction. Network analysis was used to solve the problem of complexity and co-occurrence complications in classification of advanced schistosomiasis. A total of 4,125 retrospective patients were enrolled and divided randomly into a training cohort (n = 2,888) and a validation cohort (n = 1,237). Network analysis was used to cluster the isolated complications of advanced schistosomiasis. The accuracy of the network was evaluated. Nomograms based on the clustered complications were built to predict 1- to 5-year survival rates in advanced schistosomiasis. The predictive performance of the nomogram was also evaluated and validated. Fifteen isolated complications were identified: metabolic syndromes, minimal hepatic encephalopathy, hepatic encephalopathy, chronic obstructive pulmonary disease, pulmonary hypertension, respiratory failure, right heart failure, gastroesophageal variceal bleeding, gastrointestinal ulcer bleeding, splenomegaly, fibrosis, chronic kidney disease, ascites, colorectal polyp, and colorectal cancer. Through network analysis, three major clustered complications were achieved-namely, schistosomal abnormal metabolic syndromes (related to chronic metabolic abnormalities), schistosomal abnormal hemodynamics syndromes (related to severe portal hypertension and portosystemic shunting), and schistosomal inflammatory granulomatous syndromes (related to granulomatous inflammation). The nomograms showed a good performance in prognosis prediction of advanced schistosomiasis. The novel classification-based nomogram was useful in predicting the survival rate in advanced schistosomiasis japonica.

TIGER: A Web Portal of Tumor Immunotherapy Gene Expression Resource.

Immunotherapy is a promising cancer treatment method; however, only a few patients benefit from it. The development of new immunotherapy strategies and effective biomarkers of response and resistance is urgently needed. Recently, high-throughput bulk and single-cell gene expression profiling technologies have generated valuable resources. However, these resources are not well organized and systematic analysis is difficult. Here, we present TIGER, a tumor immunotherapy gene expression resource, which contains bulk transcriptome data of 1508 tumor samples with clinical immunotherapy outcomes and 11,057 tumor/normal samples without clinical immunotherapy outcomes, as well as single-cell transcriptome data of 2,116,945 immune cells from 655 samples. TIGER provides many useful modules for analyzing collected and user-provided data. Using the resource in TIGER, we identified a tumor-enriched subset of CD4+ T cells. Patients with melanoma with a higher signature score of this subset have a significantly better response and survival under immunotherapy. We believe that TIGER will be helpful in understanding anti-tumor immunity mechanisms and discovering effective biomarkers. TIGER is freely accessible at http://tiger.canceromics.org/.

Influence of ladder training on motor coordination in basketball players / Influência do treinamento de escada na coordenação motora dos jogadores de basquetebol / Influencia del entrenamiento de escalera en la coordinación motora de los jugadores de baloncesto

ABSTRACT Introduction: The ladder training method was implemented in the USA in the late 20th century to train the agility the motor coordination of athletes in the United States. It is believed that this exercise can be a beneficial addition to the training of basketball players. Objective: Study the ladder training method's influences on basketball players' sensitivity. Methods: Following the parameters of the current scientific literature, an experimental ladder training protocol was designed. Basketball players aged 10-12 years in sports schools were selected as volunteers for the experiment. The influence of motor coordination qualities was measured pre and post-test. The collected data were statistically analyzed and discussed. Results: The experimental group had significant differences in the activities of running for 30 meters, and vertical jump. Very significant changes were also found in the cross jump repeated in 20 seconds, cross quadrant jump, and 5-meter triangular slide. Conclusion: Ladder training beneficially influenced the motor coordination of young basketball players, implementing general and sport-specific agility. Combining it with standardized training is recommended for further promotion of motor quality in young basketball players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O método de treinamento por escada foi implementado nos EUA no final do século 20 para treinar a agilidade a coordenação motora dos atletas nos Estados Unidos. Acredita que esse exercício possa ser um complemento benéfico aos treinamentos dos jogadores de basquetebol. Objetivo: Estudar as influências do método de treinamento com escada na sensibilidade dos jogadores de basquetebol. Métodos: Seguindo os parâmetros da literatura científica atual, foi elaborado um protocolo experimental de treinamento de escada. Esportistas de basquetebol entre 10 a 12 anos nas escolas esportivas foram selecionados como voluntários para o experimento. Aferiu-se a influência das qualidades relativas à coordenação motora pré e pós teste. Os dados coletados foram analisados estatisticamente e discutidos. Resultados: O grupo experimental teve diferenças significativas nas atividades de corrida por 30 metros e salto vertical, alterações muito significativas também foram encontradas no salto cruzado repetido em 20 segundos, salto em quadrante cruzado e deslizamento triangular de 5 metros. Conclusão: O treinamento de escada influenciou beneficamente na coordenação motora dos jovens jogadores de basquetebol, implementando a agilidade geral e específica dos esportistas. Recomenda-se a sua combinação ao treinamento padronizado para maior promoção da qualidade motora nos jovens jogadores de basquetebol. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El método de entrenamiento en escalera se implantó en Estados Unidos a finales del siglo XX para entrenar la agilidad la coordinación motriz de los atletas en Estados Unidos. Se cree que este ejercicio puede ser un complemento beneficioso para los entrenamientos de los jugadores de baloncesto. Objetivo: Estudiar las influencias del método de entrenamiento en escalera sobre la sensibilidad de los jugadores de baloncesto. Métodos: Siguiendo los parámetros de la literatura científica actual, se elaboró un protocolo experimental de entrenamiento en escalera. Se seleccionaron como voluntarios para el experimento jugadores de baloncesto de entre 10 y 12 años de las escuelas deportivas. La influencia de las cualidades relacionadas con la coordinación motriz se midió antes y después de la prueba. Los datos recogidos se analizaron y discutieron estadísticamente. Resultados: El grupo experimental tuvo diferencias significativas en las actividades de carrera de 30 metros y salto vertical, también se encontraron cambios muy significativos en el salto cruzado repetido en 20 segundos, salto en cuadrante cruzado y deslizamiento triangular de 5 metros. Conclusión: El entrenamiento en escalera ha influido beneficiosamente en la coordinación motriz de los jóvenes jugadores de baloncesto, implementando la agilidad general y específica de los deportistas. Se recomienda combinarlo con el entrenamiento estandarizado para fomentar aún más la calidad motriz de los jóvenes jugadores de baloncesto. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Loss of Myostatin Alters Mitochondrial Oxidative Phosphorylation, TCA Cycle Activity, and ATP Production in Skeletal Muscle.

Myostatin (MSTN) is an important negative regulator of skeletal muscle growth in animals. A lack of MSTN promotes lipolysis and glucose metabolism but inhibits oxidative phosphorylation (OXPHOS). Here, we aimed to investigate the possible mechanism of MSTN regulating the mitochondrial energy homeostasis of skeletal muscle. To this end, MSTN knockout mice were generated by the CRISPR/Cas9 technique. Expectedly, the MSTN null (Mstn-/-) mouse has a hypermuscular phenotype. The muscle metabolism of the Mstn-/- mice was detected by an enzyme-linked immunosorbent assay, indirect calorimetry, ChIP-qPCR, and RT-qPCR. The resting metabolic rate and body temperature of the Mstn-/- mice were significantly reduced. The loss of MSTN not only significantly inhibited the production of ATP by OXPHOS and decreased the activity of respiratory chain complexes, but also inhibited key rate-limiting enzymes related to the TCA cycle and significantly reduced the ratio of NADH/NAD+ in the Mstn-/- mice, which then greatly reduced the total amount of ATP. Further ChIP-qPCR results confirmed that the lack of MSTN inhibited both the TCA cycle and OXPHOS, resulting in decreased ATP production. The reason may be that Smad2/3 is not sufficiently bound to the promoter region of the rate-limiting enzymes Idh2 and Idh3a of the TCA cycle, thus affecting their transcription.

Myostatin Knockout Affects Mitochondrial Function by Inhibiting the AMPK/SIRT1/PGC1α Pathway in Skeletal Muscle.

Myostatin (Mstn) is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes. The deletion of the Mstn gene in mice leads to reduced mitochondrial functions. However, the underlying regulatory mechanisms remain unclear. In this study, we used CRISPR/Cas9 to generate myostatin-knockout (Mstn-KO) mice via pronuclear microinjection. Mstn-KO mice exhibited significantly larger skeletal muscles. Meanwhile, Mstn knockout regulated the organ weights of mice. Moreover, we found that Mstn knockout reduced the basal metabolic rate, muscle adenosine triphosphate (ATP) synthesis, activities of mitochondrial respiration chain complexes, tricarboxylic acid cycle (TCA) cycle, and thermogenesis. Mechanistically, expressions of silent information regulator 1 (SIRT1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) were down-regulated, while peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) acetylation modification increased in the Mstn-KO mice. Skeletal muscle cells from Mstn-KO and WT were treated with AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR), and the AMPK inhibitor Compound C, respectively. Compared with the wild-type (WT) group, Compound C treatment further down-regulated the expression or activity of pAMPK, SIRT1, citrate synthase (CS), isocitrate dehydrogenase (ICDHm), and α-ketoglutarate acid dehydrogenase (α-KGDH) in Mstn-KO mice, while Mstn knockout inhibited the AICAR activation effect. Therefore, Mstn knockout affects mitochondrial function by inhibiting the AMPK/SIRT1/PGC1α signaling pathway. The present study reveals a new mechanism for Mstn knockout in regulating energy homeostasis.

Salmonid alphavirus non-structural protein 2 is a key protein that activates the NF-κB signaling pathway to mediate inflammatory responses.

Salmonid alphavirus (SAV) infection of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) causes pancreas disease (PD) with typical inflammatory responses, such as necrosis of the exocrine pancreas, cardiomyopathy and skeletal myopathy. However, the pathogenic mechanism underlying SAV infection is still unclear. Inflammation may cause damage to the body, but it is a defense response against infection by pathogenic microorganisms, of which nuclear factor-kappa B (NF-κB) is the main regulator. This study revealed that SAV can activate NF-κB, of which the viral nonstructural protein Nsp2 is the major activating protein. SAV activates the NF-κB signaling pathway by simultaneously up-regulating TLR3, 7, 8 and then the expression of the signaling molecule myeloid differentiation factor 88 (Myd88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). We found that Nsp2 can induce IκB degradation and p65 phosphorylation and transnucleation, and activate NF-κB downstream inflammatory cytokines. Nsp2 may simultaneously activate NF-κB through TLR3,7,8-dependent signaling pathways. Overexpression of Nsp2 can up-regulate mitochondrial antiviral signaling protein (MAVS) and then promote the expression of IFNa1 and antiviral protein Mx, which inhibits viral replication. This study shows that Nsp2 acts as a key activator protein for the NF-κB signaling pathway, which induces inflammation post-SAV infection. This study systematically analyzes the molecular mechanism of SAV activation of the NF-κB signaling pathway, and provides a theoretical basis for revealing the mechanism of innate immune response and inflammatory injury caused by SAV.