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Introduction The gut microbiome plays an important role in maintaining both cognitive and physical functions in older adults, and gut dysbiosis is an important pathophysiological mechanism of mild cognitive impairment (MCI) in older adults. As a typical traditional Chinese mind-body exercise, regular Baduanjin training has been shown to improve cognitive function and modulate the gut microbiome in community-dwelling older adults. However, the potential role of the gut microbiome in the benefits of Baduanjin on cognitive function remains unclear. The aim of this study is to investigate the mediating effect of gut microbiome between regular Baduanjin training and improvement in cognitive function in community-dwelling older adults with MCI.Methods and analysis This is a two-arm, randomised, parallel-controlled, single-blinded trial. Four residential communities (clusters) with a total of 64 eligible participants (16 participants in each residential community) will be randomised 1:1 to either the 24-week Baduanjin exercise intervention group (60 min per session, four sessions per week) or the no specific exercise intervention control group. Global cognitive function and the subdimensions of cognition including executive function, visuospatial function, language function and memory function will be assessed using the Montreal Cognitive Assessment Scale, Trail Making Test, Auditory Verbal Learning Test, Boston Naming Test-30 and Clock-Drawing Test, while the gut microbiome and its metabolomics will be detected using 16S rRNA and ultra-high-performance liquid chromatography–tandem mass spectrometry at baseline and at the end of 24-week intervention. The intervention effect of Baduanjin exercise and mediating role of gut microbiota will be analysed using linear mixed models and the bootstrapping method in the Hayes process.Ethics and dissemination This study conforms to Declaration of Helsinki principles and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of the Shanghai University of Medicine and Health Sciences (approval number: 2023-GZR-011). Written informed consent will be obtained from all participants. Results will be disseminated to relevant groups in peer-reviewed journal(s), and at relevant international or national scientific conferences. Key findings will also be shared with social media, healthcare providers, participants or community-dwelling older adults to support access for non-research audiences.Trial registration number ChiCTR2300078147.

BackgroundOxidative stress and chronic inflammation play an important role in the pathogenesis process of cognitive frailty (CF). Regular Baduanjin exercise could improve cognitive frailty in older adults, but it is unclear whether the effect of Baduanjin exercise on improving CF is mediated by modulating circulating oxidative stress and inflammatory process.MethodA total of 102 community-dwelling older adults with CF were recruited and randomly allocated into a 24-week Baduanjin exercise training group or no specific exercise intervention control group at an equal rate. Cognitive function and physical frailty index were assessed using the Montreal Cognitive Assessment (MoCA) and the Edmonton Frail Scale (EFS), as well as the oxidative stress and inflammatory cytokines were measured at baseline and after intervention.ResultAfter 24 weeks of intervention, the increased MoCA score (2.51 ± 0.32 points, p

This study examined the fourth quarters in the close games in the regular NBA games in the last decade, ranging from the 2013–14 season to the 2022–2023 season. A close game is categorically defined by a scenario where the point differential is confined within a 10-point margin at the onset of the fourth quarter and narrows further to a 5-point disparity by the end of the game. In total, 2,295 close games were identified in this study. Advanced game statistics, including offensive rate, defensive rate, assistance ratio, pace of game, and true shooting percentage, etc., are obtained from the NBA box scores using a python script. Understanding key factors that determine the outcome of the basketball games is critical, as such can be used to develop predictive models for coaches to design game strategies. This study developed a Bayesian Logistic Modeling approach to estimate the winning probability of a basketball team in the fourth quarter, using the pace of the last quarter and a team’s shooting percentage. The accuracy of the model is used to evaluate if the model can correctly classify game outcome based on the identified game statistics in the fourth quarter of a game. The binary outcome of the close game is modeled as a Bernoulli distribution. Results reveal that the True Positive Rate and False Positive Rate is 0.93 and 0.07, respectively. Insights from this study can be used to help design coaching strategies in basketball games, illuminating potential tactical pivots that could tilt the game in their favor.

Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.

Dysregulated de novo lipogenesis (DNL) is an essential characteristic of nonalcoholic fatty liver disease (NAFLD). Cucurbitacin B (CuB) is a triterpenoid found in the edible plants of Cucurbitaceae with a broad spectrum of beneficial effects. Here, we investigate the in vivo anti-steatotic efficacy of CuB in an AKT-driven NAFLD mouse model established using hydrodynamic injection. Hepatocyte lines with artificial activation of AKT were used for in vitro experiments. The results demonstrate that CuB effectively attenuates the content of triglyceride and total cholesterol (P

Polygonum cuspidatum (PC) extract has been listed in the “Catalog of Used Cosmetic Ingredients (2021 Edition)”, which can inhibit melanogenesis, thus exerting a whitening effect, and has been widely used in cosmetics. However, there are currently no quality standards for PC extract used in cosmetics, and the bioactive components associated with anti-melanogenesis remain unclear. In view of this, the present study was the first to investigate the spectrum-effect relationship between fingerprints of PC extract and melanogenesis inhibition. Ten batches of PC extract fingerprints were established by HPLC. Pearson’s correlation analysis, gray correlation analysis (GRA) and orthogonal partial least squares regression analysis (OPLSR) were used to screen out resveratrol, emodin and physcion as the main whitening active ingredients using the inhibition of tyrosinase in B16F10 cells as the pharmacological index. Then, the melanogenesis inhibitory effects of the above three components were verified by tyrosinase inhibition and a melanin content assay in B16F10 cells. The interaction between small molecules and proteins was investigated by the molecular docking method, and it was confirmed by quantitative real-time PCR (qRT-PCR) that resveratrol, emodin and physcion significantly down-regulated the transcript levels of melanogenesis-related factors. In conclusion, this study established a general model combining HPLC fingerprinting and melanogenesis inhibition and also analyzed the spectrum–effect relationship of PC extract, which provided theoretical support for the quality control of PC extract in whitening cosmetics.