A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS

Sepsis, a systemic inflammatory response to infection, is the leading cause of death in the intensive care unit (ICU). Previous studies indicated that mesenchymal stromal cells (MSCs) might have therapeutic potential against sepsis. The current study was designed to investigate the effects of MSCs on sepsis and the underlying mechanisms focusing on inflammasome activation in macrophages. The results demonstrated that the bone marrow-derived mesenchymal stem cells (BMSCs) significantly increased the survival rate and organ function in cecal ligation and puncture (CLP) mice compared with the control-grouped mice. BMSCs significantly restricted NLRP3 inflammasome activation, suppressed the generation of mitochondrial ROS, and decreased caspase-1 and IL-1β activation when cocultured with bone marrow-derived macrophages (BMDMs), the effects of which could be abolished by Mito-TEMPO. Furthermore, the expression levels of caspase-1, IL-1β, and IL-18 in BMDMs were elevated after treatment with mitophagy inhibitor 3-MA. Thus, BMSCs exert beneficial effects on inhibiting NLRP3 inflammasome activation in macrophages primarily via both enhancing mitophagy and decreasing mitochondrial ROS. These findings suggest that restricting inflammasome activation in macrophages by increasing mitophagy and decreasing mitochondrial ROS might be a crucial mechanism for MSCs to combat sepsis

The role of microbiota in the development and treatment of gastric cancer

The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach’s native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer

HSQC of Wortmannilactone M

HSQC of Wortmannilactone

MS data of wortmannilactone M

MS data of wortmannilactone

13 C NMR of Wortmannilactone M

13 C NMR of Wortmannilactone

1H NMR raw data of wortmannilactone M

1H NMR of Wortmannilactone

NOESY of Wortmannilactone M

NOESY of Wortmannilactone

Effect of spin-orbit coupling on the effective-spin correlation in YbMgGaO4

Motivated by the recent experiments on the triangular lattice spin-liquid candidate YbMgGaO4, we explore the effect of spin-orbit coupling on the effective-spin correlation of the Yb local moments. We point out that the anisotropic interaction between the effective spins on the nearest-neighbor bonds is sufficient to reproduce the spin-wave dispersion of the fully polarized state in the presence of strong magnetic field normal to the triangular plane. We further evaluate the effective-spin correlation at zero magnetic field within the mean-field spherical approximation. We explicitly demonstrate that the nearest-neighbor anisotropic effective-spin interaction, originating from the strong spin-orbit coupling, enhances the effective-spin correlation at the M points in the Brillouin zone. We identify these results as strong evidence for the anisotropic interaction and strong spin-orbit coupling in YbMgGaO4

Baicalein, a dietary flavonoid, enhances the insulin‐sensitizing effect of metformin to prevent type 2 diabetes via the regulation of lipid metabolism and gut microenvironment

Abstract Baicalein is a natural flavonoid abundant in various foods and dietary plants, including Tuber aestivum and Oroxylum indicum. In this study, we investigated the role of baicalein in enhancing the insulin‐sensitizing effect of metformin in mice with prediabetes. Baicalein, when combined with 25% of normal‐dose metformin, achieved a diabetes‐reversion rate of 80%, which was 1.86‐fold that of normal‐dose metformin. Mechanistically, baicalein enhanced the insulin‐sensitizing effect of metformin on lipid metabolism by inhibiting de novo lipogenesis through the AMP‐activated protein kinase/SREBP‐1c/FASN pathway and by inducing fatty‐acid β‐oxidation through the upregulation of ACSL1, CPT1A, EHHADH, and acyl‐CoA dehydrogenases (ACADL/ACADM/ACADS). Meanwhile, baicalein enhanced the insulin‐sensitizing effect of metformin via the modulation of the gut microenvironment by enriching probiotics, especially Akkermansia by 53.4‐fold, depleting opportunistic pathogens, and strengthening the intestinal barrier. The improved gut microenvironment led to the alleviation of chronic endotoxemia, as evidenced by decreased levels of lipopolysaccharide and proinflammatory cytokines. Furthermore, baicalein enhanced the effect of metformin on decreasing the circulating level of branched‐chain amino acids (BCAAs), which further improved insulin sensitivity by normalizing the mTORC1/p70S6K/IRS1 signaling pathway and de novo lipogenesis. Moreover, the role of baicalein in enhancing the insulin‐sensitizing effect of metformin was verified by an oleic acid‐induced steatosis model and a BCAA‐induced insulin resistance model in hepatocytes. Our study laid a theoretical foundation for developing baicalein into a dietary supplement for diabetes prevention. The diverse mechanisms of food‐derived flavonoids can be applied in the development of dietary supplements to enhance the efficacy of oral hyperglycemic agents currently used in clinics