Structural and functional insights into the epigenetic regulator MRG15.

MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes.

Identification of potentially high drug-like VEGFR2/c-Met dual-target type II kinase inhibitors with symmetric skeletons based on structural screening.

Vascular endothelial growth factor receptor 2 (VEGFR2) and c-Mesenchymal epithelial transition factor (c-Met) are tyrosine kinase receptors associated with the occurrence of malignant tumors. Studies have shown that inhibition of VEGFR2 promotes a feedback increase in c-Met, a mechanism linked to the emergence of resistance to VEGFR2 inhibitors. Therefore, treatment targeting both VEGFR2 and c-Met will have better application prospects. In this study, hierarchical virtual screening was performed on ZINC15, Molport and Mcule-ULTIMATE databases to identify potential VEGFR2/c-Met dual inhibitors. Firstly, the best pharmacophore model for each target was used to cross-screen the three databases, and the compounds that could match the two pharmacophore models were then retained based on the Fit Value of the respective crystal ligands. Compounds ZINC, MOL, and MLB named after their database sources were retained by binding pattern analysis and docking assessment. ADMET predictions indicated that ZINC had significantly higher oral bioavailability compared to the approved drug cabozantinib. This is likely due to ZINC's unique symmetrical backbone with less structure complexity, which may reduce the occurrence of adverse effects. Molecular dynamics simulations and binding free energy analysis showed that all three hit compounds were able to stably bind at the active site, but only ZINC could form high occupancy of hydrogen bonds with both VEGFR2 and c-Met, and also only ZINC had a higher binding free energy than crystal ligands, suggesting that ZINC was the most likely potential VEGFR2/c-Met dual-target inhibitor. This finding provides a promising starting point for the development of VEGFR2/c-Met dual-target inhibitors.Communicated by Ramaswamy H. Sarma.

Tumor cell SPTBN1 inhibits M2 polarization of macrophages by suppressing CXCL1 expression.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.

The comparison of an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) versus circular stapled hemorrhoidopexy (CSH) in patients with grade IV hemorrhoids: a retrospective cohort study.

OBJECTIVES: The objectives of this study were to present an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) in the treatment of grade IV hemorrhoids and to assess long-term outcomes of this technique compared with circular stapled hemorrhoidopexy (CSH). METHODS: Conventional CSH kits combined with an intestinal spatula were used for performing C-PSH. A total of 256 patients with grade IV hemorrhoids referred to Hangzhou Third People's Hospital between January 2016 and June 2017 were obtained: 122 (47.7%) with C-PSH, and 134 (52.3%) with CSH. After propensity score matching, 222 patients (111 in C-PSH group and 111 in CSH group) were ultimately analyzed. The primary outcome was the five-year recurrence rate of hemorrhoids. Secondary outcomes included intraoperative outcomes, postoperative outcomes and complications. RESULTS: The operative time in the C-PSH group was slightly longer than that in the CSH group (p < 0.01). The vertical length of rectal mucosa specimen in the C-PSH group was shorter than that in the CSH group (p < 0.01). Compared with the CSH group, fecal urgency incidence and numeric rating scale (NRS) score at first defecation were lower in the C-PSH group (p < 0.05). Major complication rate in the CSH group was higher than that in the C-PSH group (p = 0.03). Five-year recurrence rate between the C-PSH group and CSH group was comparable (p > 0.05). Multivariate Cox regression analysis revealed that constipation was an independent prognostic factor for hemorrhoidal recurrence. CONCLUSIONS: The accessible C-PSH seems to be a safe and effective technique in managing grade IV hemorrhoids. It has advantages in alleviating postoperative pain at first defecation, fecal urgency and major complications compared with CSH. It could be an alternative technique in the treatment of grade IV hemorrhoids.

Interfacial Self-assembly of Chiral Selenide Nanomembrane for Enantiospecific Recognition.

Here, we report the synthesis of chiral selenium nanoparticles (NPs) using cysteine and the interfacial assembly strategy to generate a self-assembled nanomembrane on a large-scale with controllable morphology and handedness. The selenide (Se) NPs exhibited circular dichroism (CD) bands in the ultraviolet and visible region with a maximum intensity of 39.96 mdeg at 388 nm and optical anisotropy factors (g-factors) of up to 0.0013 while a self-assembled monolayer nanomembrane exhibited symmetrical CD approaching 72.8 mdeg at 391 nm and g-factors up to 0.0034. Analysis showed that a photocurrent of 20.97±1.55 nA was generated by the D-nanomembrane when irradiated under light while the L-nanomembrane generated a photocurrent of 20.58±1.36 nA. Owing to the asymmetric intensity of the photocurrent with respect to the handedness of the nanomembrane, an ultrasensitive recognition of enantioselective kynurenine (Kyn) was achieved by the ten-layer (10L) D-nanomembrane exhibiting a photocurrent for L-kynurenine (L-Kyn) that was 8.64-fold lower than that of D-Kyn, with a limit of detection (LOD) of 0.0074 nM for the L-Kyn, which was attributed to stronger affinity between L-Kyn and D-Se NPs. Noticeably, the chiral Se nanomembrane precisely distinguished L-Kyn in serum and cerebrospinal fluid samples from Alzheimer's disease patients and healthy subjects.

In Situ Fabrication of SnS2/SnO2 Heterostructures for Boosting Formaldehyde-Sensing Properties at Room Temperature.

Formaldehyde, as a harmful gas produced by materials used for decorative purposes, has a serious impact on human health, and is also the focus and difficulty of indoor environmental polution prevention; hence, designing and developing gas sensors for the selective measurement of formaldehyde at room temperature is an urgent task. Herein, a series of SnS2/SnO2 composites with hollow spherical structures were prepared by a facile hydrothermal approach for the purpose of formaldehyde sensing at room temperature. These novel hierarchical structured SnS2/SnO2 composites-based gas sensors demonstrate remarkable selectivity towards formaldehyde within the concentration range of sub-ppm (0.1 ppm) to ppm (10 ppm) at room temperature. Notably, the SnS2/SnO2-2 sensor exhibits an exceptional formaldehyde-sensing performance, featuring an ultra-high response (1.93, 0.1 ppm and 17.51, 10 ppm), as well as good repeatability, long-term stability, and an outstanding theoretical detection limit. The superior sensing capabilities of the SnS2/SnO2 composites can be attributed to multiple factors, including enhanced formaldehyde adsorption, larger specific surface area and porosity of the hollow structure, as well as the synergistic interfacial incorporation of the SnS2/SnO2 heterojunction. Overall, the excellent gas sensing performance of SnS2/SnO2 hollow spheres has opened up a new way for their detection of trace formaldehyde at room temperature.

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14-valent recombinant human papillomavirus vaccine.

A novel virus-like particle (VLP)-based multivalent recombinant human papillomavirus (HPV) vaccine was developed and evaluated in human, including 14 HPV-type specific VLP antigens (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). The pseudovirus-based neutralizing assay (PBNA) method is widely used for immunogenicity assessment of HPV vaccine in clinical trials. However, as many as 14 antigen-specific antibody levels need be determined, PBNA is, for many reasons, challenging and time-consuming. In this study, we developed a Luminex immunological assay (LIA) and a competitive Luminex immunological assay (cLIA). These methods increase the throughput, reproducibility and precision, as well as reduce the complexity. All assay parameters showed good characteristics in the validation of both methods, benefiting from highly purified and structurally correct VLPs, high specific antibodies, standard VLP-microspheres and PE-mAbs conjugating process, adequate assay development and stable system. Validation data support the use of both methods for immunogenicity assessment in clinical trials. LIA showed higher sensitivity than cLIA, and due to limited epitopes of mAb, cLIA detected lower antibody responses, and therefore, fewer antibodies. This work not only supports clinical trials of 14-valent HPV vaccines more efficiently and reliably, but also provides a set of validation strategies and usable standards for general vaccine immunogenicity testing.

Bilateral subconjunctival haemorrhage in spinal cord injury: a case report.

Neurogenic lower urinary tract dysfunction is a common symptom after spinal cord injury. Here, the case of a 45-year-old male patient who was treated with indwelling urinary catheter during spinal surgery for a fall fracture injury of the T12 thoracic vertebra, associated with decreased muscle strength of both lower extremities, is described. During hospitalization in the rehabilitation department, conventional anticoagulation therapy was administered, and the urinary catheter was removed with the patient urinating by increasing abdominal pressure. At 8 days following urinary catheter removal, the patient was found to have a slight subconjunctival haemorrhage of the left eye, which gradually developed into massive subconjunctival haemorrhage in both eyes. After re-indwelling the urinary catheter, the bilateral subconjunctival haemorrhage gradually improved. No abnormal indicators were found during re-examination of coagulation function and platelet count, and the results of ophthalmological examination were normal. For patients with neurogenic bladder dysfunction associated with spinal cord injury, the risk of bleeding during the anticoagulation period should be carefully assessed to eliminate possible underlying bleeding risk factors (including past medical history and appropriate use of anticoagulant drugs) when considering spontaneous urination through the mode of abdominal pressure.

Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and Aß generation.

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.

Changes in the Strength and Leaching Characteristics of Steel Slag-Oil Shale Residue-Based Filling Paste in a Complex Erosive Environment.

Our research group prepared a new filling paste consisting of steel slag-oil shale residue and no admixtures. It was used as the research object to explore the combined effect of chloride and dry-wet cycling-driven erosion on the long-term stability of a cemented filling paste made of total solid wastes. Macroscopic experiments and microscopic analyses methods were employed. The influence of solutions with different mass fractions of chloride salts and different cycling periods on the uniaxial compressive strength and toxicity of the steel slag-oil shale residue-based filling paste was studied, and the deterioration mechanisms of the steel slag-oil shale residue-based filling paste under combined erosion from chloride and dry-wet cycling were investigated. The test results showed that in the same cycling conditions, the strength of the steel slag-oil shale residue-based filling paste increased first with the increase in the mass fraction of the chloride solution and then decreased with the increase in the mass fraction of the chloride solution after reaching the peak value; the leached concentrations of heavy metal ions decreased with increasing chloride salt mass fraction. With an increase in the number of dry-wet cycles, the compressive strength of the specimens in the chloride salt solution with a mass fraction of 0 (pure water) first increases and then tends to be stable. The strength of samples in 5% and 10% chloride salt solutions increased first and then decreased with an increase in the number of dry-wet cycles. The leached concentrations of heavy metal ions from the samples in all three solutions first decreased and then stabilized. The prehydration products of the steel slag-oil shale residue-based filling paste were C-S-H gels, AFt and Friedel's salt, and these increased with increasing chloride salt mass fraction and the number of dry-wet cycles. However, the hydration reactions of the samples in the 0% chloride solution nearly stopped in the later stages of cycling, and the samples in 5% and 10% chloride salt solutions developed local cracks due to the accumulation of hydration products. The results showed that the number of dry-wet cycles and the chloride salt mass fraction affected the strength and leaching characteristics of the steel slag-oil shale residue-based filling paste by changing the type and amount of erosion products. The test results provide a scientific basis for the promotion and application of backfilling pastes made from total solid wastes.

Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke.

Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders. Loss of GABAergic interneurons after stroke may result in sensorimotor defects. Here, by transplanting human brain organoids resembling the MGE domain (human MGE organoids, hMGEOs) derived from human induced pluripotent stem cells (hiPSCs) into the infarcted cortex of stroke mice, we found that grafted hMGEOs survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time. Our study offers the feasibility of stem cell replacement therapeutics strategy for stroke.

MAGED4B is a Poor Prognostic Marker of Stomach Adenocarcinoma and a Potential Therapeutic Target for Stomach Adenocarcinoma Tumorigenesis.

Background: Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear. Methods: The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α. Results: The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC50; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC50. The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α. Conclusion: MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest.

Immune-Related Genes' Prognostic, Therapeutic and Diagnostic Value in Ovarian Cancer Immune-Related Gene Biomarker in Ovarian Cancer.

OBJECTIVES: The abnormal expression of immune-related genes (IRGs) plays an important role in the occurrence and progression of ovarian cancer (OC), which is the main cause of mortality among gynecological cancer patients. This study aims to establish a prognostic risk model and comprehensively analyze the relationship between OC risk score and prognosis, immune cell infiltration (ICI) and therapeutic sensitivity in OC. METHODS: We retrospectively evaluated the clinicopathological characteristics of consecutive OC patients in the Cancer Genome Atlas (TCGA) database. First, the prognostic risk model was constructed by bioinformatics methods. And then, we systematically assessed model robustness, and correlations between risk score and prognosis, and immune cell infiltration. The ICGC cohort was used to verify the prognostic risk model. Finally, we evaluated their value in the treatment of OC immunotherapy and chemotherapy. RESULTS: A total of 10 IRGs were identified to construct the prognostic risk model. Survival analysis revealed that patients in the low-risk group had a better prognosis (P < .01), and the risk score might be considered an independent predictor for predicting the prognosis. In addition, risk scores and patient clinical information were used to construct clinical nomograms, improving the prediction's precision. We also explored the relationship between the risk score and ICI, immunotherapy and drug sensitivity. CONCLUSIONS: Collectively, we identified a novel ten IRGs signature that may be applied as a prognostic predictor of OC, thereby benefiting clinical decision-making and personalized treatment of patients.

Melatonin attenuated chronic visceral pain by reducing Nav1.8 expression and nociceptive neuronal sensitization.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and its specific pathogenesis is still unclear. We have previously reported that TTX-resistant (TTX-R) sodium channels in colon-specific dorsal root ganglion (DRG) neurons were sensitized in a rat model of visceral hypersensitivity induced by neonatal colonic inflammation (NCI). However, the detailed molecular mechanism for activation of sodium channels remains unknown. This study was designed to examine roles for melatonin (MT) in sensitization of sodium channels in NCI rats. METHODS: Colorectal distention (CRD) in adult male rats as a measure of visceral hypersensitivity. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. Western blot and Immunofluorescence were employed to detect changes in expression of Nav1.8 and MT2. RESULTS: The results showed that rats exhibited visceral hypersensitivity after NCI treatment. Intrathecal application of melatonin significantly increased the threshold of CRD in NCI rats with a dose-dependent manner, but has no role in the control group. Whole-cell patch clamp recording showed that melatonin remarkably decreased the excitability and the density of TTX-R sodium channel in DRG neurons from NCI rats. The expression of MT2 receptor at the protein level was markedly lower in NCI rats. 8MP, an agonist of MT2 receptor, enhanced the distention threshold in NCI rats. Application of 8MP reversed the enhanced hypersensitivity of DRG neurons from NCI rats. 8MP also reduced TTX-R sodium current density and modulated dynamics of TTX-R sodium current activation. CONCLUSIONS: These data suggest that sensitization of sodium channels of colon DRG neurons in NCI rats is most likely mediated by MT2 receptor, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.

Effects of sodium tanshinone IIA sulfonate injection on inflammatory factors and vascular endothelial function in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized clinical trials.

Background: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) therapy may experience further damage to the vascular endothelium, leading to increased inflammatory response and in-stent thrombosis. In many clinical studies, sodium tanshinone IIA sulfonate injection (STS) has been found to reduce inflammatory factors and enhance vascular endothelial function in patients with ACS while improving the prognosis of PCI. However, to date, there has been no systematic review assessing the effectiveness and safety of STS on inflammatory factors and vascular endothelial function. Purpose: The aim of this study is to systematically review the effects of STS on inflammatory factors and endothelial function in patients with ACS treated with PCI. Methods: Until October 2022, eight literature databases and two clinical trial registries were searched for randomized controlled trials (RCTs) investigating STS treatment for ACS patients undergoing PCI. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool 2.0. Meta-analysis was performed using RevMan 5.4 software. Results: Seventeen trials met the eligibility criteria, including 1,802 ACS patients undergoing PCI. The meta-analysis showed that STS significantly reduced high-sensitivity C-reactive protein (hs-CRP) levels (mean difference [MD = -2.35, 95% CI (-3.84, -0.86), p = 0.002], tumor necrosis factor-alpha (TNF-α) levels (standard mean difference [SMD = -3.29, 95%CI (-5.15, -1.42), p = 0,006], matrix metalloproteinase-9 (MMP-9) levels [MD = -16.24, 95%CI (-17.24, -15.24), p < 0.00001], and lipid peroxidation (LPO) levels [MD = -2.32, 95%CI (-2.70, -1.93), p < 0.00001], and increased superoxide dismutase (SOD) levels [SMD = 1.46, 95%CI (0.43, 2.49), p = 0,006] in patients with ACS. In addition, STS significantly decreased the incidence of major adverse cardiovascular events (relative risk = 0.54, 95%CI [0.44, 0.66], p < 0.00001). The quality of evidence for the outcomes was assessed to be very low to medium. Conclusion: STS can safely and effectively reduce the levels of hs-CRP, TNF-α, MMP-9, and LPO and increase the level of SOD in patients with ACS treated with PCI. It can also reduce the incidence of adverse cardiovascular events. However, these findings require careful consideration due to the small number of included studies, high risk of bias, and low to moderate evidence. In the future, more large-scale and high-quality RCTs will be needed as evidence in clinical practice.

Recovery methods for athletes during high-intensity training / Métodos de recuperação sobre os atletas durante o treinamento de alta intensidade / Métodos de recuperación en atletas durante el entrenamiento de alta intensidad

ABSTRACT Introduction: The continuous improvement of the level of modern sports competition compels continuous reform and constant updates on sports training theory; sports training research is migrating from continuous low-intensity to high-intensity interval, and many studies have shown that high-intensity interval training has a good effect on athletes. Objective: Investigate the effect of different recovery modalities during high-intensity interval training on the athletic performance of young male runners. Methods: Using body morphological index measurement, high-intensity intermittent exhaustion test, and statistical analysis, forty young male long-distance runners from sports schools were randomly divided into active recovery group (AR, n=20) and passive recovery group (PR, n=20), maximal oxygen uptake (VO2max) and maximal aerobic speed (MAV) were measured by incremental load exercise test, and interval exercise capacity and time to exhaustion (ET) were recorded. Results: Compared with pre-training, MAV and ET in both groups increased significantly after training (P<0.05); there was no significant difference in MAV on RA group after training (P>0.05). Conclusion: High-intensity interval training with active recovery can significantly improve athletic ability and performance in young male runners in the long term. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O aprimoramento contínuo do nível de competição esportiva moderna compele a reforma contínua e constantes atualizações sobre a teoria do treinamento esportivo, a pesquisa esportiva de treinamento está migrando de contínuo de baixa intensidade para intervalado de alta intensidade e muitos estudos demonstraram que o treinamento intervalado de alta intensidade tem um bom efeito sobre os atletas. Objetivo: Investigar o efeito de diferentes modalidades de recuperação durante o treinamento intervalado de alta intensidade no desempenho atlético de jovens corredores masculinos. Métodos: Usando medição do índice morfológico corporal, teste de exaustão intermitente de alta intensidade e análise estatística, quarenta jovens corredores masculinos de longa distância de escolas esportivas foram divididos aleatoriamente em grupo de recuperação ativa (AR, n=20) e grupo de recuperação passiva (PR, n=20), o consumo máximo de oxigênio (VO2max) e a velocidade aeróbica máxima (MAV) foram medidos pelo teste de exercício de carga incremental, e a capacidade de exercício intervalado e o tempo até a exaustão (ET) foram registrados. Resultados: Em comparação com o pré-treino, MAV e ET nos dois grupos aumentaram significativamente após o treinamento (P<0,05); não houve diferença significativa em MAV no grupo AR após o treinamento (P>0,05). Conclusão: O treinamento em intervalos de alta intensidade com recuperação ativa pode melhorar significativamente a capacidade atlética e o desempenho em corredores jovens masculinos em longo prazo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La mejora continua del nivel de la competición deportiva moderna obliga a la reforma continua y a la actualización constante de la teoría del entrenamiento deportivo, la investigación del entrenamiento deportivo está migrando de la baja intensidad continua a la alta intensidad interválica y muchos estudios han demostrado que el entrenamiento interválico de alta intensidad tiene un buen efecto en los atletas. Objetivo: Investigar el efecto de diferentes modalidades de recuperación durante el entrenamiento de intervalos de alta intensidad en el rendimiento atlético de jóvenes corredores masculinos. Métodos: Mediante la medición del índice morfológico corporal, la prueba de agotamiento intermitente de alta intensidad y el análisis estadístico, se dividió aleatoriamente a cuarenta jóvenes corredores masculinos de larga distancia de escuelas deportivas en el grupo de recuperación activa (AR, n=20) y en el grupo de recuperación pasiva (PR, n=20), se midió el consumo máximo de oxígeno (VO2max) y la velocidad aeróbica máxima (MAV) mediante la prueba de ejercicio de carga incremental, y se registraron la capacidad de ejercicio a intervalos y el tiempo hasta el agotamiento (ET). Resultados: En comparación con el preentrenamiento, MAV y ET en ambos grupos aumentaron significativamente después del entrenamiento (P<0,05); no hubo diferencias significativas en MAV en el grupo de AR después del entrenamiento (P>0,05). Conclusión: El entrenamiento de intervalos de alta intensidad con recuperación activa puede mejorar significativamente la capacidad atlética y el rendimiento de los corredores masculinos jóvenes a largo plazo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Physicochemical properties of bone marrow mesenchymal stem cells encapsulated in microcapsules combined with calcium phosphate cement and their ectopic bone formation.

Calcium phosphate bone cement (CPC) serves as an excellent scaffold material for bone tissue engineering owing to its good biocompatibility, injectability, self-setting property and three-dimensional porous structure. However, its clinical use is limited due to the cytotoxic effect of its setting reaction on cells and difficulties in degradation into bone. In this study, bone marrow mesenchymal stem cells (BMSCs) were encapsulated in alginate chitosan alginate (ACA) microcapsules and compounded with calcium phosphate bone cement. Changes in the compressive strength, porosity, injectability and collapsibility of CPC at different volume ratios of microcapsules were evaluated. At a 40% volume ratio of microcapsules, the composite scaffold displayed high porosity and injectability with good collapsibility and compressive strength. Cell live/dead double staining, Cell Counting Kit-8 (CCK-8) assays and scanning electron microscopy were used to detect the viability, proliferation and adhesion of cells after cell microcapsules were combined with CPC. The results revealed that cells protected by microcapsules proliferated and adhered better than those that were directly combined with CPC paste, and cell microcapsules could effectively form macropores in scaffold material. The composite was subsequently implanted subcutaneously on the backs of nude mice, and ectopic osteogenesis of the scaffold was detected via haematoxylin-eosin (H&E), Masson's trichrome and Goldner's trichrome staining. CPC clearly displayed better new bone formation function and degradability after addition of pure microcapsules and cell microcapsules. Furthermore, the cell microcapsule treatment group showed greater osteogenesis than the pure microcapsule group. Collectively, these results indicate that BMSCs encapsulated in ACA microcapsules combined with CPC composite scaffolds have good application prospects as bone tissue engineering materials.

Gene signature of m6A RNA regulators in diagnosis, prognosis, treatment, and immune microenvironment for cervical cancer.

Continuing studies imply that m6A RNA modification is involved in the development of cervical cancer (CC), but lack strong support on recurrence and diagnosis prediction. In this research, a comprehensive analysis of 33 m6A regulators was performed to fulfill them. Here, we performed diagnostic and prognosis models and identified key regulators, respectively. Then the CC patients were separated into two clusters in accordance with 33 regulators, and participants in the cluster 1 had a worse prognosis. Subsequently, the m6AScore was calculated to quantify the m6A modification pattern based on regulators and we found that patients in cluster 1 had higher m6AScore. Afterwards, immune microenvironment, cell infiltration, escape analyses and tumor burden mutation analyses were executed, and results showed that m6AScore was correlated with them, but to a limited extent. Interestingly, HLAs and immune checkpoint expression, and immunophenoscore in patients with high-m6AScores were significantly lower than those in the low-m6AScore group. These suggested the m6AScores might be used to predict the feasibility of immunotherapy in patients. Results provided a distinctive perspective on m6A modification and theoretical basis for CC diagnosis, prognosis, clinical treatment strategies, and potential mechanism exploration.

Research advances in the structures and biological activities of secondary metabolites from Talaromyces.

The genus Talaromyces belongs to the phylum Ascomycota of the kingdom Fungi. Studies have shown that Talaromyces species yield many kinds of secondary metabolites, including esters, terpenes, steroids, alkaloids, polyketides, and anthraquinones, some of which have biological activities such as anti-inflammatory, bacteriostatic, and antitumor activities. The chemical constituents of fungi belonging to the genus Talaromyces that have been studied by researchers over the past several years, as well as their biological activities, are reviewed here to provide a reference for the development of high-value natural products and innovative uses of these resources.

Fluorescence probe for selectively monitoring biothiols within cells and mouse depression diagnosis.

As a global mental disorder, depression is associated with oxidative stress in the brain. Cysteine, a reductive biothiols, regulates the oxidative situation in many biological events including the stress that occurs in the tissues. Exploring the pathology and physiology of depression is still a challenge and always in an urgent need. Thus, developing a new method that could track Cys level without the interferes from other competing substances is of great importance. Herein, we developed a fluorescence probe that could selectively sensing Cys over other biothiols. Besides, we have demonstrated its desirable performance in cellular applications and mouse brain. This work provides a new method for Cys imaging and understanding pathogenesis of depression. We hope the work described here could be used as a potential chemical approach for the diagnosis of Cys associated diseases in clinical applications.