A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury.

Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.

Jamming on convex deformable surfaces.

Jamming is a fundamental transition that governs the behavior of particulate media, including sand, foams and dense suspensions. Upon compression, such media change from freely flowing to a disordered, marginally stable solid that exhibits non-Hookean elasticity. While the jamming process is well established for fixed geometries, the nature and dynamics of jamming for a diverse class of soft materials and deformable substrates, including emulsions and biological matter, remains unknown. Here we propose a new scenario, metric jamming, where rigidification occurs on a surface that has been deformed from its ground state. Unlike classical jamming processes that exhibit discrete mechanical transitions, surprisingly we find that metric jammed states possess mechanical properties continuously tunable between those of classically jammed and conventional elastic media. The compact and curved geometry significantly alters the vibrational spectra of the structures relative to jamming in flat Euclidean space, and metric jammed systems also possess new types of vibrational mode that couple particle and shape degrees of freedom. Our work provides a theoretical framework that unifies our understanding of solidification processes that take place on deformable media and lays the groundwork to exploit jamming for the control and stabilization of shape in self-assembly processes.

Changes in the gut microbiota of patients with Graves' orbitopathy according to severity grade.

BACKGROUND: To explore the changes of gut microbiota in Graves' orbitopathy (GO) patients of different severity grades and to identify the pathogenic bacteria of GO and the associated mechanism. METHODS: A total of 18 healthy controls and 62 GO patients were recruited. The baseline information and faecal samples of all subjects were collected for gut microbiota analysis and metabolic function prediction analysis. 16SrDNA sequencing was used for microbial diversity detection. The operational taxonomic unit (OTU) was divided using the Mothur software, and the dominant microbiota was analysed. OTU number, Chao1 index, ACE index, and Shannon index of microbiota in faecal samples were analysed using the QIIME1.9.0 software. The relative abundance of microbiota in faecal samples was analysed through principal component analysis (PCA) using the Canoco Software 5.0. The metabolic function of microbiota in faecal samples was predicted using PICRUSt 2.0. RESULTS: There was no remarkable difference in gut microbiota diversity between groups; however, the gut microbial community and dominant microbiota significantly differed among groups. Klebsiella_pneumoniae was deemed the potentially pathogenic bacteria of GO, and its abundance was positively correlated with disease severity. The metabolic prediction results revealed that inorganic nutrition metabolism, fatty acid and lipid degradation, electron transfer, aromatic compound degradation, and alcohol degradation were notably different between groups with high and low abundance of Klebsiella_pneumoniae and among groups with different GO severity grades, thereby showing a positive correlation with GO clinical risks. CONCLUSIONS: Klebsiella_pneumoniae was a potential GO-related pathogen, which may regulate the metabolic pathways to affect GO progression.

Improving speed and strength in long-distance running training / Aperfeiçoamento de velocidade e força no treinamento de corrida de longa distância / Perfeccionamiento de la velocidad y de la fuerza en el entrenamiento de carreras de larga distancia

ABSTRACT Introduction: Long-distance running is a typical physical endurance sport. The athletes' fitness level plays a dominant and central role in the components of their competitive ability. Whether long-distance runners can win in fierce competition depends mainly on the endurance of their physical fitness. Objective: To analyze the physical training methods of long-distance runners and discuss the improvement of speed and strength of long-distance runners through physical training. Methods: This paper uses literature materials, expert interviews, and experimental methods to research the training practice of middle and long-distance runners in colleges and universities. The data collected comprised an experimental protocol performed on volunteer long-distance runners. The above research determined the effect of physical training on speed and strength in long-distance runners. Results: After the 12-week experimental intervention, the overall strength, flexibility, and flexibility of the long-distance runners were improved, and the data were statistically significant (P<0.05). The aerobic workability and anaerobic capacity of the athletes were improved through the experiment. Conclusion: Physical training can improve the speed and strength of long-distance runners. Athletes can increase physical training with this protocol in their daily training. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A corrida de longa distância é um esporte típico de resistência física. O nível de aptidão física dos atletas desempenha um papel dominante e central nos componentes de sua capacidade competitiva. Se os corredores de longa distância podem vencer em competições acirradas depende principalmente da resistência de sua aptidão física. Objetivo: Analisar os métodos de treinamento físico dos corredores de longa distância e discutir o aperfeiçoamento da velocidade e da força dos corredores de longa distância através do treinamento físico. Métodos: Este artigo utiliza materiais de literatura, entrevistas com especialistas e métodos experimentais para conduzir pesquisas aplicadas na prática de treinamento de corredores de média e longa distância em faculdades e universidades. Os dados coletados compuseram um protocolo experimental executado em atletas de longa distância voluntários. A pesquisa acima determinou o efeito do treinamento físico sobre a velocidade e a força dos corredores de longa distância. Resultados: Após as 12 semanas de intervenção experimental, a força geral, flexibilidade e flexibilidade dos corredores de longa distância foram aprimoradas e os dados foram estatisticamente significativos (P<0,05). A trabalhabilidade aeróbica e a capacidade anaeróbica dos atletas foram melhoradas através do experimento. Conclusão: O treinamento físico pode melhorar a velocidade e a força dos corredores de longa distância. Os atletas podem incrementar o treinamento físico com este protocolo em seu treinamento diário. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La carrera de larga distancia es un deporte típico de resistencia física. El nivel de forma física de los deportistas desempeña un papel dominante y central en los componentes de su capacidad competitiva. La posibilidad de que los corredores de larga distancia puedan ganar en competiciones feroces depende principalmente de la resistencia de su estado físico. Objetivo: Analizar los métodos de entrenamiento físico de los corredores de larga distancia y discutir la mejora de la velocidad y la fuerza de los corredores de fondo mediante el entrenamiento físico. Métodos: Este trabajo utiliza materiales bibliográficos, entrevistas a expertos y métodos experimentales para llevar a cabo una investigación aplicada a la práctica del entrenamiento de corredores de media y larga distancia en colegios y universidades. Los datos recogidos comprendían un protocolo experimental realizado en atletas voluntarios de larga distancia. La investigación anterior determinó el efecto del entrenamiento físico sobre la velocidad y la fuerza en corredores de larga distancia. Resultados: Tras la intervención experimental de 12 semanas, la fuerza, la flexibilidad y la flexibilidad generales de los corredores de fondo mejoraron y los datos fueron estadísticamente significativos (P<0,05). La capacidad de trabajo aeróbico y la capacidad anaeróbica de los atletas mejoraron con el experimento. Conclusión: El entrenamiento físico puede mejorar la velocidad y la fuerza de los corredores de larga distancia. Los atletas pueden aumentar el entrenamiento físico con este protocolo en su entrenamiento diario. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Influence of upper body stretching exercises on shot put / Influência dos exercícios de alongamento da parte superior do corpo no arremesso de peso / Influencia de los ejercicios de estiramiento de la parte superior del cuerpo en el lanzamiento de peso

ABSTRACT Introduction The technique in the shot put and the ability in the throwing stage are two important factors that determine the ability of athletes. Qualified experts and coaches attach great importance to training and research on the ability of the throwing stage and the ability to throw. Objective Compare gravity load training and single incremental load training through practical means, analyzing the impacts on throwing ability in athletes. Methods The self-assessment method was used to conduct the comparative experiment on different forms of strength training in 20 college students. The experimental scheme adopts the single incremental load strength training, and the control scheme adopts the traditional barbell training. Results : After the experiment, the hand angle of group I was significantly higher than that of group II (P < 0.05); after the experiment, the shoulder angle of group I was significantly higher than that of group II (P < 0.05); after the experiment, the performance of the seated shot placed in group I was significantly higher than that of group II (P < 0.05), and there was no significant difference in the standing performance (P > 0.05). Conclusion Single incremental load training can significantly improve the throwing ability of shot put athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A técnica no arremesso de peso e a habilidade na etapa de arremessar são dois fatores importantes que determinam a habilidade dos atletas Especialistas e treinadores qualificados atribuem grande importância ao treinamento e pesquisa sobre a habilidade da fase de arremesso e a capacidade de arremessar. Objetivo Comparar o treinamento com carga gravitacional e o treinamento com carga incremental única através de meios experimentais, analisando os impactos na habilidade de arremesso nos atletas. Métodos O método de auto-avaliação foi usado para realizar o experimento comparativo de diferentes formas de treinamento de força em 20 estudantes universitários. O esquema experimental adota o treinamento único de força de carga incremental, e o esquema de controle adota o treinamento tradicional de barra. Resultados : Após o experimento, o ângulo da mão do grupo I foi significativamente maior do que o do grupo II (P < 0,05); após o experimento, o ângulo do ombro do grupo I foi significativamente maior do que o do grupo II (P < 0,05); após o experimento, o desempenho do tiro sentado colocado no grupo I foi significativamente maior do que o do grupo II (P < 0,05), e não houve diferença significativa no desempenho em pé (P > 0,05). Conclusão O treinamento com carga incremental única pode melhorar significativamente a capacidade de arremesso dos atletas de arremesso de peso. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La técnica en el lanzamiento de peso y la habilidad en la fase de lanzamiento son dos factores importantes que determinan la habilidad de los atletas. Los especialistas y entrenadores cualificados atribuyen gran importancia a la formación y a la investigación sobre la habilidad de la fase de lanzamiento y la habilidad de lanzamiento. Objetivo Comparar el entrenamiento con carga gravitacional y el entrenamiento con carga incremental única a través de medios experimentales, analizando los impactos en la capacidad de lanzamiento en los atletas. Métodos Se utilizó el método de autoevaluación para realizar el experimento comparativo de diferentes formas de entrenamiento de fuerza en 20 estudiantes universitarios. El esquema experimental adopta el entrenamiento de fuerza con una sola carga incremental, y el esquema de control adopta el entrenamiento tradicional con barra. Resultados : Después del experimento, el ángulo de la mano del grupo I fue significativamente mayor que el del grupo II (P < 0,05); después del experimento, el ángulo del hombro del grupo I fue significativamente mayor que el del grupo II (P < 0,05); después del experimento, el rendimiento del lanzamiento de peso sentado del grupo I fue significativamente mayor que el del grupo II (P < 0,05), y no hubo diferencias significativas en el rendimiento de pie (P > 0,05). Conclusión El entrenamiento con una sola carga incremental puede mejorar significativamente la capacidad de lanzamiento de los atletas de lanzamiento de peso. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The correlation of EZH2 expression with the progression and prognosis of hepatocellular carcinoma.

BACKGROUND: Enhancer of Zeste homologue 2 (EZH2) is a polycomb group gene and an epigenetic regulator that inhibits transcription, a modification associated with gene silencing. EZH2 plays an essential role in humoral and cell-mediated adaptive immunity. The purpose of the current study is to investigate the prognostic potential of EZH2 and to comprehensively analyse the correlation between EZH2 and immune infiltration in multiple cancer cases, especially liver hepatocellular carcinoma. METHODS: EZH2 expression across cancers was explored through Oncomine, HPA, and GEPIA2. Additionally, the prognostic value of EZH2 analysis across cancers was based on the GEPIA2, TCGA portal, Kaplan-Meier Plotter, and LOGpc databases. Based on GO and KEGG analyses, GSEA helped demonstrate the biological processes through which EZH2 might lead to HCC development. GEPIA and TIMER were adopted to detect the possible relationship of EZH2 expression with tumour-infiltrating immune cells (TIICs). RESULTS: EZH2 overexpression levels were associated with poor prognosis of cancer, especially hepatocellular carcinoma. A high EZH2 expression level is related to a poor prognosis of HCC, especially in disease histology and stage III. The EZH2 expression level was positively correlated with critical gene markers of TAMs, M2 macrophages, M1 macrophages, and monocytes. Further analysis revealed that EZH2 genes were mainly related to DNA recombination, mitotic cell cycle phase transition, and chromosome segregation. CONCLUSION: EZH2 plays an essential role in the immune microenvironment and is a potential prognostic marker and immunotherapy target for hepatocellular carcinoma.

Botox-A improve the thyroid-associated ophthalmopathy (TAO) orbital fibroblast activation through inhibiting the TGF-ß/Smad signaling.

The activation of orbital fibroblasts can result in fibrosis, finally contributing to thyroid-associated ophthalmopathy (TAO) progression. Although the effect of BTX-A on the treatment of TAO-related strabismus and upper eyelid retraction has long been recognized in clinical work, the underlying mechanism of BTX-A improving TAO-related strabismus and upper eyelid retraction has not been uncovered yet. In the present study, we successfully isolated and authenticated normal and TAO orbital fibroblasts. Compared with PBS, BTX-A and TACA exerted similar inhibitory effects on TAO orbital fibroblast proliferation and ECM production. TGF-ß stimulation induced the proliferation and ECM production by TAO orbital fibroblast, which was significantly inhibited by BTX-A or TACA treatment. Under TGF-ß stimulation, the inhibitory effects of BTX-A or TACA treatment on TAO orbital fibroblast proliferation and ECM production were reversed by TGF-ß/Smad signaling agonist SRI-011381. Collectively, BTX-A inhibited TGF-ß-induced TAO orbital fibroblast activation through inhibiting the TGF-ß/Smad signaling. Considering that TACA shows no satisfactory curative effects on symptoms closely related to the function of extraocular muscles, such as eye movement and diplopia, BTX-A might be a promising agent in TAO treatment.

Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma.

BACKGROUND: MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). METHODS: Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan-Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene-miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. RESULTS: MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. CONCLUSION: MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.

Elongation and percolation of defect motifs in anisotropic packing problems.

We examine the regime between crystalline and amorphous packings of anisotropic objects on surfaces of different genus by continuously varying their size distribution or shape from monodispersed spheres to bidispersed mixtures or monodispersed ellipsoidal particles; we also consider an anisotropic variant of the Thomson problem with a mixture of charges. With increasing anisotropy, we first observe the disruption of translational order with an intermediate orientationally ordered hexatic phase as proposed by Nelson, Rubinstein and Spaepen, and then a transition to amorphous state. By analyzing the structure of the disclination motifs induced, we show that the hexatic-amorphous transition is caused by the growth and connection of disclination grain boundaries, suggesting this transition lies in the percolation universality class in the scenarios considered.

Geometry and kinetics determine the microstructure in arrested coalescence of Pickering emulsion droplets.

Arrested coalescence occurs in Pickering emulsions where colloidal particles adsorbed on the surface of the droplets become crowded and inhibit both relaxation of the droplet shape and further coalescence. The resulting droplets have a nonuniform distribution of curvature and, depending on the initial coverage, may incorporate a region with negative Gaussian curvature around the neck that bridges the two droplets. Here, we resolve the relative influence of the curvature and the kinetic process of arrest on the microstructure of the final state. In the quasistatic case, defects are induced and distributed to screen the Gaussian curvature. Conversely, if the rate of area change per particle exceeds the diffusion constant of the particles, the evolving surface induces local solidification reminiscent of jamming fronts observed in other colloidal systems. In this regime, the final structure is shown to be strongly affected by the compressive history just prior to arrest, which can be predicted from the extrinsic geometry of the sequence of surfaces in contrast to the intrinsic geometry that governs the static regime.

Periodontal ligament fibroblasts migration injury via ROS/TXNIP/Nlrp3 inflammasome pathway with Porphyromonas gingivalis lipopolysaccharide.

Inflammasomes serve as an intracellular machinery to initiate inflammatory response to various danger signals. However, the chronic periodontitis pathological relevance of this inflammasome activation, particularly in periodontal ligament fibroblasts, remains largely unknown. The present study demonstrated that Nlrp3 inflammasome components abundantly expressed in cultured mouse periodontal ligament fibroblasts (mPDLFs). In addition, our data demonstrated that P.g-LPS (Porphyromonas gingivalis Lipopolysaccharide), a major injurious factor during chronic periodontitis, could induce the mPDLFs migration dysfunction and the inhibition of Nlrp3 inflammasome by Isoliquiritigenin (ISO) markedly recovered the migration dysfunction in mPDLFs. And Nlrp3 inflammasome components could be aggregated to form an inflammasome complex on stimulation of P.g-LPS, as shown by fluorescence confocal microscopy. Correspondingly, P.g-LPS induced Nlrp3 inflammasome activation, caspase-1 activation, IL-1ß and HMGB1 release, which were blocked by Nlrp3 inflammasome inhibitor (ISO). Interestingly, reactive oxygen species, TXNIP protein and TXNIP binding to Nlrp3 were markedly increased in mPDLFs with P.g-LPS. Furthermore, ROS generation inhibitor (Apocynin; APO) significantly reduced Nlrp3 inflammasome formation and IL-1ß production in mPDLFs with P.g-LPS. And APO attenuated P.g-LPS-induced TXNIP protein expression and mPDLFs injury. In conclusion, our results demonstrate that ROS/TXNIP/Nlrp3 Inflammasome pathway is a key initiating mechanism necessary for P.g-LPS-induced subsequent mPDLFs inflammatory response leading to chronic periodontitis.

Arrested Coalescence of Viscoelastic Droplets: Ellipsoid Shape Effects and Reorientation.

The stable configurations formed by two poroelastic, ellipsoid-shaped droplets during their arrested coalescence have been investigated using micromanipulation experiments. Ellipsoidal droplets are produced by millifluidic emulsification of petrolatum into a yield stress fluid that preserves their elongated shape. The liquid meniscus between droplets can transmit stress and instigate movement of the droplets, from their initial relative position, in order to minimize doublet surface energy. The action of the liquid meniscus causes the ellipsoidal droplets to undergo rolling and reorientation events because of their unique ellipsoid shape and associated variation in the surface curvature. The final configuration of the droplets is controlled by the balance between interfacial Laplace pressure and internal elasticity, as well as a constraint force that resists complete minimization of surface energy. Geometric and surface energy calculations are used to map the possible and most likely configurations of the droplet pairs. Experimental deviations from the calculations indicate the magnitude and potential origin of the constraint force resisting full equilibration. Droplet aspect ratio and elasticity are both shown to influence the degree of reorientation and stability of the droplets at energy extrema. Higher aspect ratios drive greater reorientation and better agreement with final doublet configurations predicted by energy minimization. Lower elasticity droplets undergo secondary deformations at high aspect ratios, further broadening the space of possible morphologies.

Primary leptomeningeal melanoma.

Primary melanoma of the central nervous system is a rare melanocytic tumor typically located in the leptomeninges. We report a 57-year-old woman with an intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was completely removed and leptomeningeal melanoma was proven pathologically. Follow-up imaging studies up to 19 months showed no recurrence of the disease. Here we present radiological, gross, and pathological images of leptomeningeal melanoma, discuss its characteristics, and review the relevant literature.