Emerging evidence supports that the gut microbiome, reconsidered as a new organ in the human body, can not only affect the local gut, but also communicate with the brain via multiple pathways related to neuroendocrine, immune, and neural pathways, thereby proposing the new concept of the microbiome-gut-brain (MGB) axis. Recently, the role of short-chain fatty acids (SCFAs), which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis, has garnered significant attention. SCFAs are involved in a broad range of central neurological diseases, including neurodegenerative diseases, cerebral vascular diseases, epilepsy, neuroimmune inflammatory diseases, and mood disorders. However, the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated. Herein, we summarize current knowledge regarding interactions between SCFAs and the MGB axis, as well as their protective effects against central neurological diseases.

γ-glutamylcysteine activates SIRT1 by activating AMPK, promoting the nuclear translocation of GAPDH, while inhibiting that of DBC1. SIRT1 activation causes the deacetylation of p53 in the nucleus and inhibits the protein levels of p21 and p16.

Polynucleotide kinase (PNK) is a key enzyme that is necessary for ligation-based DNA repair. The activity assay and inhibitor screening for PNK may contribute to the prediction and improvement of tumor treatment sensitivity, respectively. Herein, we developed a simple, low-background, and label-free method for both T4 PNK activity detection and inhibitor screening by combining a designed ligation-triggered T7 transcriptional amplification system and a crafty light-up malachite green aptamer. Moreover, this method successfully detected PNK activity in the complex biological matrix with satisfactory outcomes, indicating its great potential in clinical practice.

Calprotectin (CP) is an established biomarker that allows the noninvasive evaluation of inflammation levels in the gastrointestinal tract of patients with inflammatory bowel disease and is helpful for the diagnosis and management of the disease. Herein, we demonstrate that CP can effectively suppress the activity of 17E DNAzyme (17E) by chelating Zn(Ⅱ), which is the cofactor of 17E. As the inhibition efficiency of CP on the DNAzyme is proportional to the concentration of CP, the detection of CP can be readily achieved by assessing the activity of 17E.

Background: Lipotoxicity, driven by dysregulated lipid metabolism, is a key initiator of hepatocyte injury in metabolic dysfunction–associated steatotic liver disease (MASLD). β-1,4-galactosyltransferase 1 (B4GALT1), which primarily mediates galactosylation of glycoproteins and glycolipids, is involved in the regulation of plasma lipid composition. Previous studies have implicated aberrant glycosylation in MASLD progression. However, the role and underlying molecular mechanisms of B4GALT1 in MASLD progression remain unclear. Methods and Results: The protein levels of B4GALT1 were elevated in patients with MASLD as well as in a murine model of MASLD induced by choline-deficient, L–amino acid–defined, high-fat diet (CDAHFD), with a more pronounced increase observed in MASH. Hepatocyte-specific B4galt1 -knockout mice exhibited significantly attenuated hepatic steatosis and inflammation, but not fibrosis. In addition, hepatic B4GALT1 deficiency suppressed the expression of lipogenic genes, reduced lipid accumulation, and inhibited ferroptosis mediated by lipid peroxidation. Mechanistically, B4GALT1 deficiency impaired the N-glycosylation of peroxisome proliferator-activated receptor gamma (PPARγ), leading to its stabilization. Increased PPARγ protein, in turn, transcriptionally repressed acyl-CoA synthetase long chain family member 4 (ACSL4), thereby mitigating lipid peroxidation. Conversely, PPARγ overexpression in steatotic hepatocytes rescued the pro-ferroptotic phenotype driven by B4GALT1. Conclusions: Our findings suggest that B4GALT1 plays a crucial role in MASLD progression by targeting lipid peroxidation in hepatocytes via the PPARγ/ACSL4 axis, thus highlighting a potential therapeutic target for MASLD.