Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression.

Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but the effector components enclosed in the vesicles and the mechanisms involved are largely unknown. The plant Artemisia annua is known as an anti-malaria agent that also exhibits a wide range of biological activities including the immunoregulatory and anti-tumor properties with the mechanisms to be further addressed. Here, we isolated and purified the exosome-like particles from A. annua, which were characterized by nano-scaled and membrane-bound shape and hence termed artemisia-derived nanovesicles (ADNVs). Remarkably, the vesicles demonstrated to inhibit tumor growth and boost anti-tumor immunity in a mouse model of lung cancer, primarily through remolding the tumor microenvironment and reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via the vesicles, as a major effector molecule to induce the cGAS-STING pathway driving the shift of pro-tumor macrophages to anti-tumor phenotype. Furthermore, our data showed that administration of ADNVs greatly improved the efficacy of PD-L1 inhibitor, a prototypic immune checkpoint inhibitor, in tumor-bearing mice. Together, the present study, for the first time, to our knowledge, unravels an inter-kingdom interaction wherein the medical plant-derived mtDNA, via the nanovesicles, induces the immunostimulatory signaling in mammalian immune cells for resetting anti-tumor immunity and promoting tumor eradication.

Bcl6 drives stem-like memory macrophages differentiation to foster tumor progression.

Cancer development is a long-lasting process during which macrophages play a pivotal role. However, how macrophages maintain their cellular identity, persistence, expanding and pro-tumor property during malignant progression remains elusive. Inspired by the recent report of the activation of stem cell-like self-renewal mechanism in mature macrophages, we postulate that intra-tumoral macrophages might be trained to assume stem-like properties and memory-like activity favoring cancer development. Herein we demonstrated that tumor infiltrating macrophages rapidly converted into the CD11b+F4/80+Ly6C-Bcl6+ phenotype, and adopted stem cell-like properties involving expression of stemness-related genes, long-term persistence and self-renewing. Importantly, Bcl6+ macrophages stably maintained cell identity, gene signature, metabolic profile, and pro-tumor property even after long-term culture in tumor-free medium, which were hence termed stem cell-like memory macrophages (SMMs). Mechanistically, we showed that transcriptional factor Bcl6 co-opted the demethylase Tet2 and the deacetylase SIRT1 to confer the epigenetic imprinting and mitochondrial metabolic traits to SMMs, bolstering the stability and longevity of trained immunity in tumor-associated macrophages (TAMs). Furthermore, tumor-derived redHMGB1 was identified as the priming signal, which, through TLR4 and mTOR/AKT pathway, induced Bcl6-driven program underpinning SMMs generation. Collectively, our study uncovers a distinct macrophage population with a hybrid of stem cell and memory cell properties, and unveils a regulatory mechanism that integrates transcriptional, epigenetic and metabolic pathways to promote long-lasting pro-tumor immunity.

A study on the development of happiness scale for Chinese young children.

This study was conducted to develop an assessment tool for measuring happiness among Chinese preschoolers, and to verify the reliability and validity of this tool. A total of 269 preschoolers aged 3 to 5 years from kindergartens and childcare centers in Hangzhou, China, were surveyed. The Preschooler Happiness Scale, constructed through literature review and interviews with preschoolers, underwent expert content validity verification and pilot testing to refine items. The validity and reliability of the scale were verified in this study, resulting in the development of the final Preschooler Happiness Scale comprising 6 sub-factors and 25 items. The reliability verification revealed a high overall reliability of 0.91 for the Preschooler Happiness Scale, confirming its trustworthiness as a tool. The academic significance of the findings and the practical utility of the Preschooler Happiness Scale in early childhood education settings in China were discussed based on the results of this study.

Effects of flipped classroom teaching in anaesthesiology residents: a protocol for systematic review and meta-analysis.

INTRODUCTION: The flipped classroom teaching model is widely used in medical education and is indicated to be better than traditional lecture approaches in many medical specialties. Emerging studies have evaluated the effects of the flipped classroom teaching model on anaesthesiology residents. This protocol aims to perform a systematic review and meta-analysis to determine whether the flipped classroom teaching model is superior to traditional teaching methods for anaesthesiology residents. METHODS AND ANALYSIS: Seven databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure, Wanfang Data and the VIP database, will be systematically searched from their inception to 1 June 2024. Randomised controlled trials that compared the effects of flipped classrooms versus traditional teaching methods in anaesthesiology residents will be included. The primary outcome will be the theoretical knowledge score. The secondary outcomes will include skill scores and the proportion of anaesthesiology residents who preferred the flipped classroom model. RevMan V.5.4 software will be used to perform the statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will assess the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval is not applicable to this protocol. The results of this study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42024497935.

Quantitative Analysis of Bioactive Compounds in Commercial Teas: Profiling Catechin Alkaloids, Phenolic Acids, and Flavonols Using Targeted Statistical Approaches.

Tea, an extensively consumed and globally popular beverage, has diverse chemical compositions that ascertain its quality and categorization. In this investigation, we formulated an analytical and quantification approach employing reversed-phase ultra-high-performance liquid chromatography (UHPLC) methodology coupled with diode-array detection (DAD) to precisely quantify 20 principal constituents within 121 tea samples spanning 6 distinct variants. The constituents include alkaloids, catechins, flavonols, and phenolic acids. Our findings delineate that the variances in chemical constitution across dissimilar tea types predominantly hinge upon the intricacies of their processing protocols. Notably, green and yellow teas evinced elevated concentrations of total chemical moieties vis à vis other tea classifications. Remarkably divergent levels of alkaloids, catechins, flavonols, and phenolic acids were ascertained among the disparate tea classifications. By leveraging random forest analysis, we ascertained gallocatechin, epigallocatechin gallate, and epicatechin gallate as pivotal biomarkers for effective tea classification within the principal cadre of tea catechins. Our outcomes distinctly underscore substantial dissimilarities in the specific compounds inherent to varying tea categories, as ascertained via the devised and duly validated approach. The implications of this compositional elucidation serve as a pertinent benchmark for the comprehensive assessment and classification of tea specimens.

Improvement of carotenoid bioaccessibility from spinach by co-ingesting with excipient nanoemulsions: impact of the oil phase composition.

Many of the carotenoids found naturally in fruits and vegetables are beneficial to human health, but they often have low oral bioavailability because of their high hydrophobicity. In this study, the effects of varying the composition of the oil phase of excipient nanoemulsions on carotenoid bioaccessibility from spinach were investigated using a simulated gastrointestinal tract. Nanoemulsions containing different ratios of medium chain triglycerides (MCT) and long chain triglycerides (LCT) were prepared: (i) mixing MCT and LCT oils before homogenization and (ii) mixing MCT droplets with LCT droplets after homogenization. The release of carotenoids from spinach and their solubilization within the mixed micelles formed after lipid digestion depended strongly on the oil phase composition. As expected, carotenoid bioaccessibility was always higher in the presence of excipient nanoemulsions than in their absence. The total free fatty acids released in the small intestine increased as the MCT/LCT ratio increased, which can be attributed to the faster release of shorter chain fatty acids from the oil droplet surfaces during lipid digestion. As the MCT ratio increased, lutein bioaccessibility increased but ß-carotene bioaccessibility decreased. This difference was attributed to the ability of the formed mixed micelles to accommodate the two different kinds of carotenoids in their hydrophobic domains. Interestingly, carotenoid bioaccessibility was significantly lower (P < 0.05) when the oil droplets were mixed after homogenization than when the oils were mixed before homogenization. These results have important implications for the design of excipient foods to improve the bioavailability of hydrophobic nutraceuticals in fruits and vegetables.