Melatonin ameliorates 10-hydroxycamptothecin-induced oxidative stress and apoptosis via autophagy-regulated p62/Keap1/Nrf2 pathway in mouse testicular cells.

10-Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT-induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT-induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT-induced DNA damage associated with ataxia-telangiectasia mutated- and Rad3-related and CHK1 phosphorylation levels in the testis. Changes in apoptosis-associated protein levels (Bax, Bcl-2, p53, and Cleaved caspase-3) and in reactive oxygen species-associated proteins (Nrf2 and Keap1) and index (malondialdehyde and glutathione) suggested that melatonin treatment relieved HCPT-induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin-activated autophagy proteins (ATG7, Beclin1, and LC3bII/I) may induce p62-dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1-Nrf2 interaction to promote antioxidant enzyme expression such as HO-1, which would salvage HCPT-induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT-induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.

Cathepsin L promotes oesophageal squamous cell carcinoma development and may be associated with tumour-associated macrophages.

Background: Oesophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide because existing treatments are often insufficient. Therefore, new, reliable biomarkers must be identified. CTSL overexpression is closely associated with tumour progression and poor prognosis. However, the role and mechanism of CTSL as an oncogene in ESCC remain unclear. Methods: Genome-wide association study (GWAS) data were used for Mendelian randomization analysis to investigate the possible relationships between CTSL and ESCC. The correlation between CTSL expression and prognosis was analysed using GEO, TCGA, and GEPIA data. We compared CTSL expression among the cell types using single-cell sequencing. Correlations between CTSL and the tumour microenvironment, immune cell infiltration, tumour mutational load, immunological checkpoints, and treatment sensitivity in patients with ESCC were investigated. Finally, using mouse models and cellular investigations, we assessed the effects of CTSL on the growth, apoptosis, and metastasis of ESCC tumour cells. Results: CTSL was overexpressed in ESCC and correlated with prognosis. We also discovered its close association with cell immunity, especially with tumour-associated macrophages and immune checkpoints in the tumour microenvironment. CTSL may play a key role in ESCC development by affecting M2 macrophage polarisation. CTSL and the M2 macrophage marker genes showed significant positive correlations. Mendelian randomization analysis confirmed a relationship between CTSL and ESCC. Finally, our in vitro and in vivo experiments demonstrated that CTSL promoted the proliferation and migration of ESCC cells, validating our bioinformatic analysis. Conclusion: CTSL emerged as a crucial gene in ESCC that influences patient prognosis and immunity, particularly in association with M2 macrophages. Therefore, targeting or modulating CTSL levels may provide new therapeutic strategies for patients with ESCC.

Temperature-Automated Calibration Methods for a Large-Area Blackbody Radiation Source.

High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody's back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes.

BACKGROUND: Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear. METHOD AND RESULTS: In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes. CONCLUSION: Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

Novel lncRNA Gm33149 modulates metastatic heterogeneity in melanoma by regulating the miR-5623-3p/Wnt axis via exosomal transfer.

The high mortality rate associated with melanoma primarily results from metastasis and recurrence. However, the precise mechanisms driving these processes remain poorly understood. Intercellular communication between cancer cells and non-cancer cells significantly influences the tumor microenvironment and plays a crucial role in metastasis. Therefore, our current study aims to investigate the role and mechanism of long non-coding RNAs (lncRNAs) in regulating the interaction between melanoma cancer stem cells (CSCs) and non-CSCs during the metastatic colonization process. This study has characterized a novel lncRNA called Gm33149. Importantly, we provide evidence for the first time that Gm33149, originating from highly metastatic melanoma stem cells (OL-SD), can be packaged into exosomes and transferred to low-metastatic nonstem cells (OL). Once internalized by OL cells, Gm33149 exerts its function through a competitive endogenous RNA mechanism (ceRNA) involving miR-5623-3p. Specifically, Gm33149 competitively binds to miR-5623-3p, thereby activating the Wnt signaling pathway and promoting the acquisition of a more aggressive metastatic phenotype by OL cells. In summary, our findings suggest that targeting lncRNA Gm33149 within extracellular vesicles could potentially serve as a therapeutic strategy for the treatment of metastatic melanoma. Schematic representation of the mechanisms underlying the pro-metastatic activity of lncRNA Gm33149 mediated by exosomal transfer. The figure illustrates the key mechanisms involved in the pro-metastatic activity of lncRNA Gm33149 through exosomal transfer. Melanoma stem cells (OLSD) release exosomes containing lncRNA Gm33149. These exosomes are taken up by non-stem melanoma cells (OL), delivering lncRNA Gm33149 to the recipient cells. Within OL cells, lncRNA Gm33149 functions as a competitive endogenous RNA (ceRNA), sequestering miR-5623-3p. This sequestration prevents miR-5623-3p from binding to its target genes, thereby activating the Wnt signaling pathway. The activated Wnt signaling pathway enhances the migration, invasion, and metastatic colonization capabilities of OL cells. The transfer of lncRNA Gm33149 via exosomes contributes to OL cells acquiring "metastatic competency" while promoting their metastatic colonization. These findings underscore the importance of lncRNA Gm33149 in intercellular communication and the metastatic progression of melanoma.

A novel lung cancer stem cell extracellular vesicles lncRNA ROLLCSC modulate non-stemness cancer cell plasticity through miR-5623-3p and miR-217-5p targeting lipid metabolism.

BACKGROUND: The high mortality rate of lung cancer is largely attributed to metastasis. Lung cancer stem cells (CSC) are conducive to cancer heterogeneity. Long noncoding RNAs are known to participate in various biological processes regulating the development of lung cancer. However, characterization of the role and mechanisms of lncRNA in lung cancer metastasis remains a challenge. RESULTS: We demonstrate that ROLLCSC, a highly expressed lncRNA in LLC-SDs, promotes the metastasis of the low metastatic LLCs both in vitro and in vivo. ROLLCSC can be transferred from LLC-SD to LLC through encapsulation in extracellular vesicles (EVs), ultimately leading to the enhancement of the metastatic phenotype of LLCs. Mechanistically, we demonstrate that the pro-metastatic activity of ROLLCSC is achieved through its function as a competing endogenous RNA (ceRNA) of miR-5623-3p and miR-217-5p to stimulate lipid metabolism. CONCLUSION: In this study, we have characterized ROLLCSC, a novel lncRNA, as a pivotal regulator in the metastasis of lung cancer, highlighting its potential as a therapeutic target. Specifically, we show that ROLLCSC is encapsulated by the EVs of LLC-SDs and transmitted to the LLCs, where it acts as a ceRNA of miR-5623-3p and miR-217-5p to stimulate lipid metabolism and ultimately augments metastatic colonization of LLCs.

Effect of different chemotherapy schemes on early-stage breast cancer patients with Low HER-2 expression.

Objective: To explore the effect of different chemotherapy schemes on the prognosis, immune function and adverse reactions of breast cancer patients with low HER-2 expression after surgery. Methods: A retrospective analysis was carried out on the clinical data of 60 breast cancer patients with low HER-2 expression in Wuxi No.2 people's Hospital from January 2018 to December 2019. The enrolled patients were divided into two groups according to the different chemotherapy schemes. Patients in the DC group were treated with polyethylene glycol-coated liposome-encapsulated doxorubicin+cyclophosphamide, and those in the TC group were treated with TC (docetaxel+cyclophosphamide). Further comparison was performed on the difference in prognosis, immune function and adverse reaction between the two groups after different chemotherapy schemes. Results: After four courses of treatment, the IgG, CD4+ and CD4+/CD8+ values in the DC group after treatment were higher than those before treatment, while the IgG, CD3+ and CD4+values in the TC group after treatment were lower than those before treatment(P<0.05). Meanwhile, the IgG, CD4+ and CD4+/CD8+ values in the DC group were better than those in the TC group after treatment(P<0.05). During the treatment, the adverse reactions of leukopenia, alopecia, nausea and vomiting in the DC group were significantly lower than those in the TC group(P<0.05). Conclusion: The chemotherapy combination of liposome-encapsulated doxorubicin+cyclophosphamide can significantly improve immune function and greatly reduce the occurrence of adverse reactions in early-stage breast cancer patients with low HER-2 expression after surgery. It has the same effect as docetaxel+cyclophosphamide in improving the prognosis of patients.

Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p.

BACKGROUND: Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression. METHODS: The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed. RESULTS: This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability. CONCLUSION: We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells. Video Abstract.

Two-step model of paleohexaploidy, ancestral genome reshuffling and plasticity of heat shock response in Asteraceae.

An ancient hexaploidization event in the most but not all Asteraceae plants, may have been responsible for shaping the genomes of many horticultural, ornamental, and medicinal plants that promoting the prosperity of the largest angiosperm family on the earth. However, the duplication process of this hexaploidy, as well as the genomic and phenotypic diversity of extant Asteraceae plants caused by paleogenome reorganization, are still poorly understood. We analyzed 11 genomes from 10 genera in Asteraceae, and redated the Asteraceae common hexaploidization (ACH) event ~70.7-78.6 million years ago (Mya) and the Asteroideae specific tetraploidization (AST) event ~41.6-46.2 Mya. Moreover, we identified the genomic homologies generated from the ACH, AST and speciation events, and constructed a multiple genome alignment framework for Asteraceae. Subsequently, we revealed biased fractionations between the paleopolyploidization produced subgenomes, suggesting the ACH and AST both are allopolyplodization events. Interestingly, the paleochromosome reshuffling traces provided clear evidence for the two-step duplications of ACH event in Asteraceae. Furthermore, we reconstructed ancestral Asteraceae karyotype (AAK) that has 9 paleochromosomes, and revealed a highly flexible reshuffling of Asteraceae paleogenome. Of specific significance, we explored the genetic diversity of Heat Shock Transcription Factors (Hsfs) associated with recursive whole-genome polyploidizations, gene duplications, and paleogenome reshuffling, and revealed that the expansion of Hsfs gene families enable heat shock plasticity during the genome evolution of Asteraceae. Our study provides insights on polyploidy and paleogenome remodeling for the successful establishment of Asteraceae, and is helpful for further communication and exploration of the diversification of plant families and phenotypes.

Synergistic inhibition of NUDT21 by secretory S100A11 and exosomal miR-487a-5p promotes melanoma oligo- to poly-metastatic progression.

Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward 'cause-and-effect relationships'. We have developed a 'dry-lab-driven knowledge discovery and wet-lab validation' approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11-Sec23a) and the exosomal crosstalk (miR-487a-5p) to transfer their 'polymetastatic competency' to the oligometastatic (OL) melanoma cells, via synergistic co-targeting of the tumor-suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.

Competitive Risk Model Nomogram to Predict Prognosis in Patients Aged Over 65 Years with nonmetastatic Cervical Cancer: A SEER Population-Based Study.

Objective: The prognostic factors for elderly patients with cervical cancer differ from those of younger patients. Competitive risk events could cause biases in the Cox proportional hazards (PH) model. This study aimed to construct a competitive risk model (CRM) nomogram for patients aged > 65 years with nonmetastatic cervical cancer. Methods: We retrospectively analyzed data extracted from the Surveillance, Epidemiology, and End Results (SEER) database and a total of 1856 patients from 18 cancer registries across the United States diagnosed between 2010 and 2015 were included. Kaplan-Meier analysis and log-rank tests were used to compare intergroup survival. Univariate and multivariate Cox proportional regression analyses were performed to identify independent prognostic factors. The cumulative incidence function (CIF) and Fine and Gray's test were used to determine the impact of competitive risk events on prognosis. The CRM nomogram was internally and externally validated using time-dependent receiver operator characteristic (ROC) curve (time-AUC), Brier scores, Harrell's concordance index (C-index), calibration curve, and decision curve analysis (DCA). Results: Analyses revealed that histology, age, the International Federation of Gynaecologists and Obstetricians (FIGO) stage, number of in situ malignancies, chemotherapy, radiotherapy (RT), and surgery were independent prognostic factors. The CRM nomogram accurately predicted 1-year, 3-year, and 5-year disease-specific survival (DSS). The C-indexes and Brier scores of the CRM nomogram were 0.641 and 0.094, respectively, at the 1-year cut-off in the training set. The time-AUC of the CRM nomogram at the 1-year, 3-year, and 5-year intervals in the training set were 77.6%, 77.3%, and 74.5%, respectively. The calibration curve demonstrated a favorable concordance. DCA suggested that the nomogram had a good net benefit. Therefore, the Cox model underestimated the weight of risk factors compared to CRM. Conclusions: This study presents the CRM nomogram to predict DSS in patients aged > 65 years with nonmetastatic cervical cancer. It can help clinicians implement more accurate personalized diagnostic and treatment modalities for elderly patients with cervical cancer.

Atomistic Origins of Reversible Noncatalytic Gas-Solid Interfacial Reactions.

Noncatalytic gas-solid reactions are a large group of heterogeneous reactions that are usually assumed to occur irreversibly because of the strong driving force to favor the forward direction toward the product formation. Using the example of Ni oxidation into NiO with CO2, herein, we demonstrate the existence of the reverse element that results in the NiO reduction from the countering effect of the gaseous product of CO. Using in situ electron microscopy observations and atomistic modeling, we show that the oxidation process occurs via preferential CO2 adsorption along step edges that results in step-flow growth of NiO layers, and the presence of Ni atoms on the flat NiO surface promotes the nucleation of NiO layers. Simultaneously, the NiO reduction happens via preferential step-edge adsorption of CO that leads to the receding motion of atomic steps, and the presence of Ni vacancies in the NiO surface facilitates the CO-adsorption-induced surface pitting. Temperature and CO2 pressure effect maps are constructed to illustrate the spatiotemporal dynamics of the competing NiO redox reactions. These results demonstrate the rich gas-solid surface reaction dynamics induced by the coexisting forward and reverse reaction elements and have practical applicability in manipulating gas-solid reactions via controlling the gas environment or atomic structure of the solid surface to steer the reaction toward the desired direction.

Mitochondrial iron overload mediated by cooperative transfer of plasma membrane ATP5B and TFR2 to mitochondria triggers hepatic insulin resistance under PFOS exposure.

In general populations, insulin resistance (IR) is related to perfluorooctane sulfonate (PFOS), a persistent organic pollutant. However, the underlying mechanism remains unclear. In this study, PFOS induced mitochondrial iron accumulation in the liver of mice and human hepatocytes L-O2. In the PFOS-treated L-O2 cells, mitochondrial iron overload preceded the occurrence of IR, and pharmacological inhibition of mitochondrial iron relieved PFOS-caused IR. Both transferrin receptor 2 (TFR2) and ATP synthase ß subunit (ATP5B) were redistributed from the plasma membrane to mitochondria with PFOS treatment. Inhibiting the translocation of TFR2 to mitochondria reversed PFOS-induced mitochondrial iron overload and IR. In the PFOS-treated cells, ATP5B interacted with TFR2. Stabilizing ATP5B on the plasma membrane or knockdown of ATP5B disturbed the translocation of TFR2. PFOS inhibited the activity of plasma-membrane ATP synthase (ectopic ATP synthase, e-ATPS), and activating e-ATPS prevented the translocation of ATP5B and TFR2. Consistently, PFOS induced ATP5B/TFR2 interaction and redistribution of ATP5B and TFR2 to mitochondria in the liver of mice. Thus, our results indicated that mitochondrial iron overload induced by collaborative translocation of ATP5B and TFR2 was an up-stream and initiating event for PFOS-related hepatic IR, providing novel understandings of the biological function of e-ATPS, the regulatory mechanism for mitochondrial iron and the mechanism underlying PFOS toxicity.

Exosomal miR-211-5p regulates glucose metabolism, pyroptosis, and immune microenvironment of melanoma through GNA15.

Despite the unprecedented advancement of cancer treatment, the prognosis for patients with metastatic stage of cancer remains poor. The challenge that underlines this clinical dilemma is the complexity of metastasis. The conventional experiment-driven discovery approaches (the "wet lab") yield overly simplified one-to-one mechanistic relationships that are inept of elucidating the complexity of metastasis. Metastasis research also suffers from the knowledge and skill deficiency of the individual investigators. The importance of the present study is the demonstration that the "dry-lab-driven discovery and wet-lab validation" approach can improve the efficiency of studying complex biological behaviors, and can yield more reliable, objective and comprehensive mechanistic findings that are have clinical significance. Specifically, we applied this approach to study the mechanisms that underline the involvement of exosomal miRNAs in transferring the metastatic capability between heterogenous melanoma cancer cells. We show that the highly metastatic melanoma tumor cells (POL) can transfer their metastatic competency to the low-metastatic melanoma tumor cells (OL) by exosomal miR-211-5p. The oncogenic activity of miR-211-5p is mediated by the target gene guanine nucleotide-binding protein subunit alpha-15 (GNA15) through modifying the immune function of the tumor microenvironment extrinsically; as well as through inhibiting pyroptosis and augmenting glycolysis within OL cells intrinsically. In addition, we show that exosomal sorting of miR-211-5p is like selective and is subjected to regulation by a transcriptional feedback loop between miR-211-5p and zinc finger FYVE-type containing 26 (ZFYVE26). Furthermore, the "8-genes pyroptosis Risk model" derived from LASSO regression analysis was verified as an independent prognostic factor for melanoma.

Exosomal microRNA-4535 of Melanoma Stem Cells Promotes Metastasis by Inhibiting Autophagy Pathway.

High mortality rate and poor survival in melanoma are associated with efficient metastatic colonization. The underlying mechanisms remain elusive. Elucidating the role of exosomes in mediating the interactions between cancer cells and the metastatic microenvironment has been focused on cancer cell derived exosomes in modulating the functions of stromal cells. Whether cancer stem cells (CSCs) can modify the metastatic properties of non-CSC cells, and whether exosomal crosstalk plays a role have not been demonstrated prior to this report. In this study, a paired M14 melanoma derivative cell line, i.e., melanoma parental cell (MPC) and its CSC derivative cell line melanoma stem cell (MSC) were employed. We demonstrated that exosomal crosstalk betwen MSCs and non-CSC MPCs is a new mechanism that underlies melanoma metastasis. Low metastatic melanoma cells (MPCs) can acquire the "metastatic power" from highly metastatic melanoma CSCs (MSCs). We illustrated an uncharacterized microRNA, miR-4535 in mediating such exosomal crosstalk. MSCs deliver its exosomal miR-4535 to the targeted MPCs. Upon entering MPCs, miR-4535 augments metastatic colonization of MPCs by inactivating the autophagy pathway.

Effects of high-intensity training on endurance in basketball players / Efeitos do treinamento de alta intensidade na resistência dos jogadores de basquetebol / Efectos del entrenamiento de alta intensidad en la resistencia de los jugadores de baloncesto

ABSTRACT Introduction: The aerobic endurance training of sports athletes has become the focus of research in institutions and related units. One of the recent proposals is high-intensity interval training to develop athletic aerobic endurance. Objective: Study the effect of high-intensity interval training on aerobic endurance in basketball players. Methods: Fifteen athletes from a university were randomly selected and divided into a high-intensity interval training group, a moderate-intensity continuous training group, and a low-intensity continuous training group, with the control of external influence factors. The indicators analyzed were the average aerobic endurance index of maximal oxygen consumption, average anaerobic capacity, and average maximal power output. The data were obtained before and after the experiment. They were compared and discussed using statistical analysis. Results: The average maximal oxygen consumption in the three training groups increased significantly, and the effect was most evident under the high-intensity intermittent training conditions. This training method could increase the maximal exercise time of the normal groups by up to two times. Conclusion: Intermittent high-intensity training can effectively improve the aerobic endurance of basketball players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento da resistência aeróbica dos atletas esportivos tornou-se o foco na pesquisa de instituições e unidades relacionadas. No intuito de desenvolver a resistência aeróbica atlética, uma das propostas recentes é o treinamento intervalado de alta intensidade. Objetivo: Estudar o efeito do treinamento intervalado de alta intensidade sobre a resistência aeróbica nos jogadores de basquetebol. Métodos: Foram selecionados aleatoriamente 15 atletas de uma universidade, que foram divididos em um grupo de treinamento de intervalo de alta intensidade, um grupo de treinamento contínuo de intensidade moderada e um grupo de treinamento contínuo de baixa intensidade, com o controle dos fatores de influência externa. Entre os indicadores analisados estão o índice de resistência aeróbica média de consumo máximo de oxigênio, a capacidade anaeróbica média e a potência máxima média. Os dados foram obtidos antes e após o experimento. Foram comparados e discutidos através de análise estatística. Resultados: O consumo máximo médio de oxigênio nos três grupos de treinamento aumentou significativamente, e o efeito foi mais evidente sob as condições de treinamento intermitente de alta intensidade. Este método de treinamento apresentou o potencial de aumentar o tempo máximo de exercício dos grupos normais em até duas vezes. Conclusão: O treinamento intermitente de alta intensidade pode efetivamente melhorar a resistência aeróbica dos jogadores de basquete. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento de la resistencia aeróbica de los atletas deportivos se ha convertido en el centro de la investigación en instituciones y unidades relacionadas. Para desarrollar la resistencia aeróbica atlética, una de las propuestas recientes es el entrenamiento de intervalos de alta intensidad. Objetivo: Estudiar el efecto del entrenamiento interválico de alta intensidad sobre la resistencia aeróbica en jugadores de baloncesto. Métodos: Se seleccionaron aleatoriamente quince atletas de una universidad y se dividieron en un grupo de entrenamiento por intervalos de alta intensidad, un grupo de entrenamiento continuo de intensidad moderada y un grupo de entrenamiento continuo de baja intensidad, con el control de los factores de influencia externos. Entre los indicadores analizados estaban el índice medio de resistencia aeróbica de consumo máximo de oxígeno, la capacidad anaeróbica media y la potencia máxima media. Los datos se obtuvieron antes y después del experimento. Se compararon y discutieron mediante un análisis estadístico. Resultados: El consumo medio máximo de oxígeno en los tres grupos de entrenamiento aumentó significativamente, y el efecto fue más evidente en las condiciones de entrenamiento intermitente de alta intensidad. Este método de entrenamiento presentaba el potencial de aumentar el tiempo máximo de ejercicio de los grupos normales hasta dos veces. Conclusión: El entrenamiento intermitente de alta intensidad puede mejorar eficazmente la resistencia aeróbica de los jugadores de baloncesto. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Revealing the Potential Markers of N(4)-Acetylcytidine through acRIP-seq in Triple-Negative Breast Cancer.

Understanding the causes of tumorigenesis and progression in triple-receptor negative breast cancer (TNBC) can help the design of novel and personalized therapies and prognostic assessments. Abnormal RNA modification is a recently discovered process in TNBC development. TNBC samples from The Cancer Genome Atlas database were categorized according to the expression level of NAT10, which drives acetylation of cytidine in RNA to N(4)-acetylcytidine (ac4C) and affects mRNA stability. A total of 703 differentially expressed long non-coding RNAs (lncRNAs) were found between high- and low-expressed NAT10 groups in TNBC. Twenty of these lncRNAs were significantly associated with prognosis. Two breast cancer tissues and their paired normal tissues were sequenced at the whole genome level using acetylated RNA immunoprecipitation sequencing (acRIP-seq) technology to identify acetylation features in TNBC, and 180 genes were significantly differentially ac4c acetylated in patients. We also analyzed the genome-wide lncRNA expression profile and constructed a co-expression network, containing 116 ac4C genes and 1080 lncRNAs. Three of these lncRNAs were prognostic risk lncRNAs affected by NAT10 and contained in the network. The corresponding reciprocal pairs were "LINC01614-COL3A1", "OIP5-AS1-USP8", and "RP5-908M14.9-TRIR". These results indicate that RNA ac4c acetylation involves lncRNAs and affects the tumor process and prognosis of TNBC. This will aid the prediction of drug targets and drug sensitivity.

Isoquercitrin from Apocynum venetum L. produces an anti-obesity effect on obese mice by targeting C-1-tetrahydrofolate synthase, carbonyl reductase, and glutathione S-transferase P and modification of the AMPK/SREBP-1c/FAS/CD36 signaling pathway in mice in vivo.

In the present study, mice with high-fat-diet-induced obesity were used in investigating the anti-obesity effects of an aqueous extract and isoquercitrin from Apocynum venetum L. The aqueous extract and the signal molecule isoquercitrin significantly reduced the body weight gain, food intake, water consumption, and fasting blood glucose, plasma triglyceride and total cholesterol levels of the obese mice. Furthermore, the mechanism of action of isoquercitrin was explored through RT-PCR analyses and uptake experiments of adenosine 5'-monophosphate-activated protein kinase (AMPK) and sterol regulatory-element binding protein (SREBP-1c) inhibitors and glucose. The indexes of SREBP-1c, fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD), and cluster of differentiation 36 (CD36) in obese mice significantly increased but returned to normal levels after the administration of isoquercitrin. Meanwhile, the anti-obesity effect of isoquercitrin was diminished by the inhibitors of AMPK and SREBP-1c. In addition, intestinal glucose uptake in normal mice was significantly inhibited after the oral administration of isoquercitrin. Moreover, 2D gel electrophoresis based proteome-wide cellular thermal shift assay (CETSA) showed that the potential target proteins of isoquercitrin were C-1-tetrahydrofolate synthase, carbonyl reductase, and glutathione S-transferase P. These results suggested that isoquercitrin produces an anti-obesity effect by targeting the above-mentioned proteins and regulating the AMPK/SREBP-1c signaling pathway and potentially prevents obesity and obesity-related metabolic disorders.

One case of wrist cyst rupture with nerve and blood vessel compression.

INTRODUCTION AND IMPORTANCE: Tendon sheath cysts are mostly located around the joint capsule and tendon sheath, which often occur in the wrist, ankle, and wrist back (O'Valle et al., 2014; Nguyen et al., 2004 [1, 2]). The palmar side of the wrist is relatively rare, which is often associated with the wrist. Ultrasound and MRI can detect and diagnose early. CASE PRESENTATION: In this case report, we discussed an elderly woman with palmar carpal tendon sheath cyst and ruptured. She communicated with the outside world through the skin sinus, and at the same time pressed the radial artery and the median nerve to produce obvious clinical symptoms. CLINICAL DISCUSSION: Because of its deep position and close relationship with the surrounding important nerves and vessels, the operation was relatively difficult. In particular, in this case, tendon sheath cyst ruptured to form sinus, so there were some difficulties. CONCLUSION: Pathological diagnosis was tendon sheath cyst. The analysis of the relationship between the tumor and the surrounding tissue by preoperative MRI and other imaging examinations has important guiding significance for surgery.

Deer antler extract promotes tibia fracture healing in mice by activating BMP-2/SMAD4 signaling pathway.

BACKGROUND: Deer antler is a traditional Chinese medicine with the function of tonifying kidney and strengthening bone, which is often used to treat orthopedic diseases. METHODS: Eight-week-old C57BL/6 mice were used as the fixation model of open tibial fracture with intramedullary nail. The mice were treated with deer antler extract (DAE) or PBS by oral gavage once daily. The tibial fracture samples were collected and performed to the tissue analysis, including X-ray, micro-CT, histology, qRT-PCR, immunohistochemistry. MC3T3-E1 cells were used to detect the effect of deer antler extract on ability of cell proliferation and migration by CCK-8 assay and cell scratch test. RESULTS: Imaging and micro-CT showed that DAE could promote the healing of tibial fracture in mice, and histological analysis showed that DAE could promote the transformation of cartilage callus to bone callus in fracture area. The results of qRT-PCR and immunohistochemistry showed that DAE could promote intrachondral ossification in fracture zone and the mechanism of promoting fracture healing may be related to the activation of BMP-2/SMAD4 signaling pathway. In the cytological experiment of DAE, it can be found that DAE promoted the proliferation of MC3T3-E1 cells and the migration of MC3T3-E1 cells at a certain concentration, which is also related to the promotion of fracture healing by DAE. CONCLUSION: DAE can promote fracture healing by activating BMP-2/SMAD4 signaling pathway. DAE has the potential to be used in clinic as an important means of promoting fracture healing.