In this report, we investigated the molecular genetic mechanism underlying the deafness-associated mitochondrial tRNAHis 12201T>C mutation. The destabilization of a highly conserved base-pairing (5A-68U) by the m.12201T>C mutation alters structure and function of tRNAHis. Using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into mtDNA-less (ρo) cells, we showed ∼70% decrease in the steady-state level of tRNAHis in mutant cybrids, compared with control cybrids. The mutation changed the conformation of tRNAHis, as suggested by slower electrophoretic mobility of mutated tRNA with respect to the wild-type molecule. However, ∼60% increase in aminoacylated level of tRNAHis was observed in mutant cells. The failure in tRNAHis metabolism was responsible for the variable reductions in seven mtDNA-encoded polypeptides in mutant cells, ranging from 37 to 81%, with the average of ∼46% reduction, as compared with those of control cells. The impaired mitochondrial translation caused defects in respiratory capacity in mutant cells. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cells. The data provide the evidence for a mitochondrial tRNAHis mutation leading to deafness.

Cannabidiol (CBD) is an abundant non‐psychoactive phytocannabinoid in cannabis extracts which has high affinity on a series of receptors, including Type 1 cannabinoid receptor (CB1), Type 2 cannabinoid receptor (CB2), GPR55, transient receptor potential vanilloid (TRPV) and peroxisome proliferator‐activated receptor gamma (PPARγ). By modulating the activities of these receptors, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti‐inflammatory, analgesic and anticancer properties. CBD could also be applied to treat or prevent COVID‐19 and its complications. Here, we provide a narrative review of CBD's applications in human diseases: from mechanism of action to clinical trials.

The liver is able to regenerate itself in response to partial hepatectomy or liver injury. This is accomplished by a complex network of different cell types and signals both inside and outside the liver. Bile acids (BAs) are recently identified as liver-specific metabolic signals and promote liver regeneration by activating their receptors: Farnesoid X Receptor (FXR) and G-protein-coupled BA receptor 1 (GPBAR1, or TGR5). FXR is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. FXR promotes liver regeneration after 70% partial hepatectomy (PHx) or liver injury. Moreover, activation of FXR is able to alleviate age-related liver regeneration defects. Both liver- and intestine-FXR are activated by BAs after liver resection or injury and promote liver regeneration through distinct mechanism. TGR5 is a membrane-bound BA receptor and it is also activated during liver regeneration. TGR5 regulates BA hydrophobicity and stimulates BA excretion in urine during liver regeneration. BA signaling thus represents a novel metabolic pathway during liver regeneration.

Rhesus D (RhD) is one of the most important immunogenic antigens on red blood cells (RBCs). However, the supply of RhD-negative blood frequently faces critical shortages in clinical practice, and the positive-to-negative transition of the RhD antigen remains a great challenge. Here, we developed an alternative approach for sheltering the epitopes on RhD-positive RBCs using a surface-anchored framework, which is flexible but can achieve an optimal shield effect with minimal physicochemical influence on the cell. The chemical framework completely obstructed the RhD antigens on the cell surface, and the assessments of both blood transfusion in a mouse model and immunostimulation with human RhD-positive RBCs in a rabbit model confirmed the RhD-epitope stealth characteristics of the engineered RBCs. This work provides an efficient methodology for improving the cell surface for universal blood transfusion and generally indicates the potential of rationally designed cell surface engineering for transfusion and transplantation medicine.

The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5′-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.