The Causal Relationship Between Skin Microbiota and Facial Aging: A Mendelian Randomization Study.

BACKGROUND: Facial aging is a complex process influenced by environmental factors, genetics, and lifestyle. The contribution of the skin microbiota to this process remains poorly understood. METHODS: This two-sample Mendelian randomization (MR) study was performed using genome-wide genotype data from the UK Biobank and previously published studies on skin microbiota. The primary approach for MR analyses included inverse-variance weighting (IVW), MR-Egger regression, simple mode, weighted median, and weighted mode methods. Sensitivity analyses were performed to assess heterogeneity and pleiotropy, and reverse-direction MR analyses were performed to evaluate potential reverse causation. RESULTS: The MR analysis identified ten skin microbiotas with potential causal relationships with facial aging. Protective skin microbiotas included Genus Finegoldia, ASV011 [Staphylococcus (unc.)], ASV008 [Staphylococcus (unc.)], phylum Firmicutes, Family Rhodobacteraceae, and ASV021 [Micrococcus (unc.)], which were negatively associated with facial aging. Conversely, Order Pseudomonadales, Family Moraxellaceae, ASV039 [Acinetobacter (unc.)], and phylum Bacteroidetes were positively associated with facial aging, indicating a risk factor for accelerated aging. Sensitivity analyses confirmed the robustness of these findings, and reverse-direction MR analyses did not suggest any reverse causation. CONCLUSION: This study identified specific skin microbial that may influence facial aging and offered new insights into the rejuvenation strategies. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

HDAC6 inhibitor ACY-1215 protects from nonalcoholic fatty liver disease via inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

Background & aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, for which there is currently no effective treatment. ACY-1215 is a selective inhibitor of histone deacetylation 6, which has shown therapeutic potential in many tumors, as well as acute liver injury. However, no research about ACY-1215 on NAFLD has been published. Therefore, our study aims to explore the role and mechanism of ACY-1215 in the experimental model of NAFLD, to propose a new treatment strategy for NAFLD. Methods: We established cell and animal models of NAFLD and verified the effect of ACY-1215 on NAFLD. The mechanism of ACY-1215 on NAFLD was preliminarily explored through TMT relative quantitative proteomics, and then we verify the mechanism discovered in the experimental model of NAFLD. Results: ACY-1215 can reduce lipid aggregation, IL-1ß, and TNF α mRNA levels in liver cells in vitro. ACY-1215 can reduce the weight gain and steatosis in the liver of the NAFLD mouse model, alleviate the deterioration of liver function, and reduce IL-1ßs and TNF α mRNA levels in hepatocytes. TMT relative quantitative proteomics found that ACY-1215 decreased the expression of CD14 in hepatocytes. It was found that ACY-1215 can inhibit the activation level of CD14/TLR4/MyD88/MAPK/NFκB pathway in the NAFLD experimental model. Conclusions: ACY-1215 has a protective effect on the cellular model of NAFLD induced by fatty acids and lipopolysaccharide, as well as the C57BL/6J mouse model induced by a high-fat diet. ACY-1215 may play a protective role by inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

Ficolin 3 promotes ferroptosis in HCC by downregulating IR/SREBP axis-mediated MUFA synthesis.

BACKGROUND: Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. METHODS: Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. RESULTS: Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor ß (IR-ß) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-ß phosphorylation, ultimately resulting in IR-ß inactivation. This inactivation of IR-ß suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. CONCLUSIONS: These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.

Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Study on the Low-Velocity Impact Response and Damage Mechanisms of Thermoplastic Composites.

A comparative experimental and numerical study of the impact behaviour of carbon-fiber-reinforced thermoplastic (TP) and thermoset (TS) composites has been carried out. On the one hand, low velocity impact (LVI) tests were performed on TP and TS composites with different lay-up sequences at different energy levels, and the damage modes and microscopic damage mechanisms after impact were investigated using macroscale inspection, C-scan inspection, and X-ray-computed tomography. The comparative results show that the initial damage valve force under LVI depends not only on the material, but also on the layup sequence. The initial valve force of the P2 soft layer with lower stiffness is about 11% lower than that of the P1 quasi-isotropic layer under the same material, while the initial valve force of thermoplastic composites is about 28% lower than that of thermoset composites under the same stacking order. Under the same stacking order and impact energy level, the damage area and depth of TP composites are smaller than those of TS composites; while under the same material and impact energy level, the indentation depth of P2 plies is greater than that of P1 plies, and the damage area of P2 plies is smaller than that of P1 plies, but the change of thermoplastic composites is not as obvious as that of thermoset composites. This indicates that TP composites have a higher initial damage threshold energy and impact resistance at the same lay-up order, while increasing the lay-up ratio of the same material by 45° improves the impact resistance of the structure. In addition, a damage model based on continuum damage mechanics (CDM) was developed to predict different damage modes of thermoplastic composites during low velocity impact, and the analytical results were compared with the experimental results. At an impact energy of 4.45 J/mm, the error of the initial damage valve force is 5.26% and the error of the maximum impact force is 4.36%. The simulated impact energy and impact velocity curves agree with the experimental results, indicating that the finite element model has good reliability.

Nanosheet-structured ZnCo-LDH microsphere as active material for rechargeable zinc batteries.

We report zinc cobalt-layered double hydroxides (ZnCo-LDH) as the active cathode materials for the development of high-performance Zn-ZnCo batteries. Electrochemical investigations show the battery's capacity increases linearly with increasing the ZnCo-LDH loading (up to 60 mg cm-2). The resulting Zn-ZnCo battery exhibits excellent rate performance and cycle stability, retaining 86% of its capacity even after 5000 cycles of testing. By incorporating ZnCo-LDH with a Pt/C-coated gas diffusion layer to form an integrated multifunctional air-cathode, we demonstrate a hybrid Zn battery, which combines the merits of Zn-ZnCo and Zn-air batteries to show a characteristic two-stage charge-discharge voltage profile. The current work demonstrates the linear relationship between the battery capacity and the active material loading. The results also highlight that a greater battery capacity requires further increasing of loading though very challenging.

A Comparative Study on the Mechanical Properties of Open-Hole Carbon Fiber-Reinforced Thermoplastic and Thermosetting Composite Materials.

In this paper, the damage initiation/propagation mechanisms and failure modes of open-hole carbon fiber-reinforced thermoplastic composites and thermosetting composites with tension, compression, and bearing loads are investigated, respectively, by experiments and finite element simulations. The experimental evaluations are performed on the specimens using the Combined Loading Compression (CLC) test method, the tensile test method, and the single-shear test method. The differences in macroscopic damage initiation, evolution mode, and damage characteristics between thermoplastic composite materials and thermosetting composite material open-hole structures are obtained and analyzed under compressive load. Based on scanning electron microscope SEM images, a comparative analysis is conducted on the micro-failure modes of fibers, matrices, and fiber/matrix interfaces in the open-hole structures of thermoplastic and thermosetting composites under compressive load. The differences between thermoplastic and thermosetting composites were analyzed from the micro-failure mechanism. Finally, based on continuum damage mechanics (CDM), a damage model is also developed for predicting the initiation and propagation of damage in thermoplastic composites. The model, which can capture fiber breakage and matrix crack, as well as the nonlinear response, is used to conduct virtual compression tests, tensile test, and single-shear test, respectively. Numerical simulation results are compared with the extracted experimental results. The displacement-load curve and failure modes match the experimental result, which indicates that the finite element model has good reliability.

The relationship between longer leukocyte telomeres and dNCR in non-cardiac surgery patients: a retrospective analysis.

BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P < 0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P < 0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P < 0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%. CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.

Pharmacotherapies of NAFLD: updated opportunities based on metabolic intervention.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that is becoming increasingly prevalent, and it ranges from simple steatosis to cirrhosis. However, there is still a lack of pharmacotherapeutic strategies approved by the Food and Drug Administration, which results in a higher risk of death related to carcinoma and cardiovascular complications. Of note, it is well established that the pathogenesis of NAFLD is tightly associated with whole metabolic dysfunction. Thus, targeting interconnected metabolic conditions could present promising benefits to NAFLD, according to a number of clinical studies. Here, we summarize the metabolic characteristics of the development of NAFLD, including glucose metabolism, lipid metabolism and intestinal metabolism, and provide insight into pharmacological targets. In addition, we present updates on the progresses in the development of pharmacotherapeutic strategies based on metabolic intervention globally, which could lead to new opportunities for NAFLD drug development.

Novel ginsenoside monomer RT4 promotes colitis repair in mice by regulating miR-144-3p/SLC7A11 signaling pathway.

BACKGROUND: Ginsenoside RT4 (RT4) is a new biologically active compound extracted from ginseng that possesses numerous medicinal and pharmacological properties. However, its potential therapeutic effect of ginsenoside RT4 on ulcerative colitis remains unknown. METHODS AND RESULTS: In this study, we investigated the anti-inflammatory effects of ginsenoside RT4 and its underlying molecular mechanism in the treatment of ulcerative colitis mice induced with dextran sulfate sodium (DSS). Our results demonstrate that ginsenoside RT4 effectively reduced weight, shortening of colonic tract length, colonic bowel damage, and disease activity index (DAI) scores in DSS-induced colitis mice. Additionally, ginsenoside RT4 regulates miR-144-3p expression in DSS-induced colitis mice, and we further confirmed that the solute carrier family 7 member 11 (SLC7A11) was the target gene of miR-144-3p by database analysis. Finally, ginsenoside RT4 inhibits the activation of the miR-144-3p/SLC7A11 signaling pathway, which alleviates colitis. Ginsenoside RT4 significantly decreased the expression of pro-inflammatory cytokines TNF-α and IL-1ß and increased the anti-inflammatory cytokine IL-10. CONCLUSIONS: These findings suggest that ginsenoside RT4 may have therapeutic potential for treating ulcerative colitis by downregulating levels of miR-144-3p/SLC7A11 signaling pathway, which are expected to be useful in treating clinical ulcerative colitis.

The effect of ginsenosides on liver injury in preclinical studies: a systematic review and meta-analysis.

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported. Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis. Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity. Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.

Characterisation of kapok fibre's biochar for arsenate adsorption removal from aqueous solution.

Al-KBC was produced through the simple pyrolysis of Al-modified kapok fibres at high temperatures. Using the N2 adsorption Brunauer Emmett Teller (BET) process, Fourier transforms infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), the energy-dispersive X-ray spectroscopy (EDS) spectroscopy, and X-ray photoelectron spectroscopy (XPS), the sorbent changes and characteristics were analysed. As a result of Al's addition to the fibre's surface, Al-KBC exhibited superior As(V) adsorption performance compared to KBC due to better pore structures. Experiments on the kinetics of As(V) adsorption revealed that the adsorption followed the pseudo-second-order model and that intradiffusion was not the only factor governing the adsorption. Experiments with isotherms indicated that the adsorption mechanism corresponded to the Langmuir model, and the adsorption capacity Qm of Al-KBC at 25 °C was 483 µg/g. The thermodynamic experiments suggested that the adsorption reactions were spontaneous endothermic with a random approach at the adsorption interface. 25 mg/L of coexisting ions such as sulphate and phosphate reduced the sorbent As(V) removal ability to 65% and 39%. After seven cycles of adsorption/desorption, Al-KBC demonstrated satisfactory performance in terms of reusability, adsorbing 53% of 100 µg/L As(V) from the water. This novel BC can probably be used as a filter to purify groundwater with high As(V) concentration in the rural zone.

Seasonal variations, source apportionment and dry deposition of chemical species of total suspended particulate in Pengjia Yu Island, East China Sea.

Total of 172 total suspended particulate (TSP) samples and its chemical compositions were collected and analyzed from January to December 2010 in Pengjia Yu Island, an open region in East China Sea (ECS). Despite the predominance of sea-salt major ions (Na+, Cl-), the presence of non-sea-salt SO42- (nss-SO42-) and NO3- as well as combustion-derived trace metals clearly establishes the impact of anthropogenic sources over ECS. The annual contributions of coal, heavy-fuel oil and traffic to the measured chemical species were 21.0 %, 15.0 % and 15.5 %, respectively. Especially in spring, the contributions of crustal minerals to measured chemical species during dust period (33.6 %) were higher than that (13.2 %) during non-dust period. The calculated annual average dry deposition fluxes for trace metals and total inorganic nitrogen were 246.1 ± 345.8 µg/m2/d and 2950.4 ± 2245.0 µg/m2/d, suggesting that atmospheric deposition is an important source of nutrient elements for the south of ECS.

Analysis of rainwater storage and use recommendations: From the perspective of DBPs generation and their risks.

As a vital freshwater resource, rainwater is usually stored in water cellars in arid regions to solve the daily drinking water problems of the population. However, the status of disinfection by-products (DBPs) generation in cellar water under intermittent disinfection conditions is unclear. Therefore, we investigated the formation and distribution characteristics of DBPs in cellar water under intermittent disinfection conditions for the first time. The results demonstrated that six categories of DBPs were selected for detection after chlorination, including trihalomethanes (THMs), haloacetic acids (HAAs), haloketones (HKs), haloacetonitriles (HANs), halonitromethanes (HNMs), and nitrosamines (NAs), among which HAAs, HKs, and HANs were the major DBPs. Only bromoacetic acid (MBAA), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA) showed an increasing trend of accumulation as the number of disinfections increased. Meanwhile, the precursor composition was gradually transformed from humic substances to amino acids, and both organic substances were the main precursors of HAAs. The health risk assessment showed that the main carcinogenic and non-carcinogenic risks of cellar water were contributed by NAs and HAAs, respectively, and children are more susceptible to the risks than adults. The best time to drink cellar water is after approximately 12 days of storage, when the total carcinogenic risk is the minimum.

Appraising the quality of guidelines for peripheral arterial catheters care: A systematic review of reviews.

INTRODUCTION: Catheter-related bloodstream infections are among the most critical adverse events in critical patients with peripheral arterial catheters (ACs). Adherence to evidence-based guidelines can prevent and reduce arterial bloodstream infections. OBJECTIVE: The objectives of this study were to assess clinical practice guidelines for AC care and analyse methodological factors related to their development for effective dissemination and implementation in clinical practice. REVIEW METHOD USED: This was a systematic review of guidelines. DATA SOURCES: We searched PubMed, CINAHL, EMBASE, CNKI, and WANFANG databases from inception until September 2021 and evaluated websites of organisations that complied or produced guidelines. REVIEW METHODS: A comprehensive list of guidelines for ACs care was included. We excluded incomplete guidelines, guidelines translated in other languages, duplicate publications, and summaries of multiple guidelines. Two reviewers independently extracted and collected the data, and three authors conducted quality assessments independently using the Appraisal of Guidelines for Research and Evaluation, Second Edition (AGREE II) tool. The intraclass correlation coefficient (two-way random) with a 95% confidence interval was used to evaluate the concordance between reviewers. RESULTS: Of the 738 total publications screened, seven were selected for evaluation. The concordance between observers was substantial (intraclass correlation coefficient >0.9, P < 0.001). Most guidelines (4/6) were developed in the United States and the United Kingdom. The median scores for the six domains were 89.0%, 65.5%, 58.0%, 86.0%, 65.0%, and 86.0%. The domains of stakeholder involvement, rigour of development, and applicability had the lowest scores. Guidelines by the United Kingdom's National Institute for Health and Care Excellence showed the highest quality. CONCLUSIONS: The guidelines we included scored poorly on crucial domains (rigour of development, applicability, and stakeholder involvement). Most of the current recommendations on ACs were included in the guidelines for vascular catheter-related bloodstream infections. Therefore, targeted guidelines created specifically for ACs are warranted to reduce the incidence of catheter-related complications and ensure patient safety.

Evaluative index system in physical training of basketball players / Sistema de índice avaliativo no treinamento físico dos jogadores de basquetebol / Sistema de índice de evaluación en la preparación física de los jugadores de baloncesto

ABSTRACT Introduction: The training should be performed according to the characteristics of basketball by establishing a scientific evaluation index system to fully exploit the potential of its players. Objective: Evaluate the index system for measuring physical training specific to basketball players. Methods: The physical training evaluation indexes of athletes were studied by checking the scientific literature and mathematical statistics, and an evaluation index for the physical training of young basketball players was designed and experimented. Results: The highest proportion of the special fitness score in athletic average was 46.25%; the proportion of the players' general fitness score represented 15% above and 13.75% below. The specific fitness level of basketball players is mainly at the average level. Conclusion: The effects of training can be effectively evaluated by the experienced index system, and it is useful for athletes to find deficiencies, make full use of their potential, improve skills and adapt basketball tactics. It may also provide more reserve talent for professional basketball. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento deve ser realizado de acordo com as características do basquetebol estabelecendo um sistema de índice de avaliação científica para explorar plenamente o potencial de seus jogadores. Objetivo: Avaliar o sistema de índices de medição do treinamento físico específico para os jogadores de basquetebol. Métodos: Os índices de avaliação do treinamento físico dos atletas foram estudados verificando a literatura científica e estatísticas matemáticas, um índice de avaliação para o treinamento físico de jovens jogadores de basquetebol foi projetado e experimentado. Resultados: A maior proporção da pontuação da aptidão física especial na média atlética foi de 46,25%; a proporção da pontuação da aptidão física geral dos jogadores representou 15% acima e 13,75% abaixo, o nível de aptidão física específica dos jogadores de basquetebol está principalmente no nível mediano. Conclusão: Os efeitos do treinamento podem ser efetivamente avaliados pelo sistema de índice experimentado, sendo útil para que os atletas possam encontrar deficiências, aproveitar plenamente seu próprio potencial, melhorar as habilidades e adaptar as táticas do basquetebol. Também poderá fornecer mais talentos de reserva para o basquetebol profissional. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento debe realizarse de acuerdo con las características del baloncesto estableciendo un sistema de índices de evaluación científica para explotar plenamente el potencial de sus jugadores. Objetivo: Evaluar el sistema de índices de medición del entrenamiento físico específico para jugadores de baloncesto. Métodos: Se estudiaron los índices de evaluación del entrenamiento físico de los deportistas mediante la comprobación de la literatura científica y la estadística matemática, y se diseñó y experimentó un índice de evaluación del entrenamiento físico de los jóvenes jugadores de baloncesto. Resultados: La proporción más alta de la puntuación de la aptitud física especial en la media atlética fue del 46,25%; la proporción de la puntuación de la aptitud física general de los jugadores representó un 15% por encima y un 13,75% por debajo, el nivel de aptitud física específica de los jugadores de baloncesto está principalmente en el nivel medio. Conclusión: Los efectos del entrenamiento pueden evaluarse eficazmente mediante el sistema de índice de experiencia, y es útil para que los deportistas encuentren las deficiencias, aprovechen al máximo su propio potencial, mejoren las habilidades y adapten las tácticas de baloncesto. También puede proporcionar más talentos de reserva para el baloncesto profesional. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

A novel small compound TOIDC suppresses lipogenesis via SREBP1-dependent signaling to curb MAFLD.

BACKGROUND: Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD. METHODS: Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo. RESULTS: We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1). CONCLUSIONS: Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD.

Clinicopathological characteristics of gastrointestinal schwannomas: A retrospective analysis of 78 cases.

Introduction: Schwannomas are tumors arising from Schwan cells of the neural sheath, which rarely occur in the gastrointestinal tract. The aim of the present study was to analyze the clinicopathological features and treatment outcomes of gastrointestinal schwannomas (GISs). Methods: Patients who were diagnosed with GISs in our hospital from January 2010 to December 2021 were selected. Data about demographic characteristics, clinical symptoms, treatment methods and outcomes, pathological results, and follow-up results were retrospectively collected and analyzed. Results: A total of 78 patients with 79 GISs were included, the female-to-male ratio was 55:23, and the average age was 52.12 ± 12.26 years. One-third (26/78) of the patients were asymptomatic. A total of 79 GISs were removed, and the average size was 3.63 ± 2.03 cm (range, 0.3-10 cm). As for tumor location, 54 GISs were located in the stomach, 14 in the esophagus, 2 in the duodenum, 6 in the colorectum (4 in the colon and 2 in the rectum), and the other 3 in the small intestine. A total of 23 and 55 patients underwent endoscopic and surgical resections, respectively. Compared with surgical resection, endoscopic resection is associated with a smaller diameter, lower cost, and shorter hospital stay. Pathological results revealed that S100 was positive in all the GISs. No recurrence was noticed during a median follow-up of 45 months (range, 6-148 months). Conclusion: GISs are rare gastrointestinal tumors with favorable prognoses, which are most commonly seen in the stomach and diagnosed by pathological findings with immunohistochemical staining. Surgical resection remains the standard method for removing GISs, while endoscopic resection may serve as an alternative method for selected patients with GISs and may be attempted in GISs with a diameter of <3 cm and no signs of malignancy.

Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex.

Copper deficiency has emerged to be associated with various lipid metabolism diseases, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms that dictate the association between copper deficiency and metabolic diseases remain obscure. Here, we reveal that copper restoration caused by hepatic ceruloplasmin (Cp) ablation enhances lipid catabolism by promoting the assembly of copper-load SCO1-LKB1-AMPK complex. Overnutrition-mediated Cp elevation results in hepatic copper loss, whereas Cp ablation restores copper content to the normal level without eliciting detectable hepatotoxicity and ameliorates NAFLD in mice. Mechanistically, SCO1 constitutively interacts with LKB1 even in the absence of copper, and copper-loaded SCO1 directly tethers LKB1 to AMPK, thereby activating AMPK and consequently promoting mitochondrial biogenesis and fatty acid oxidation. Therefore, this study reveals a mechanism by which copper, as a signaling molecule, improves hepatic lipid catabolism, and it indicates that targeting copper-SCO1-AMPK signaling pathway ameliorates NAFLD development by modulating AMPK activity.