Harnessing noncanonical trans-cleavage characteristics of Cas12 and Cas13a to enhance CRISPR-based diagnostics.

Cas12 and Cas13 are extensively utilized in molecular diagnostics for their trans-cleavage activities, yet their activation characteristics remain partially understood. Here, we conduct an in-depth investigation of Cas12a, Cas12f1, and Cas13a, uncovering the characteristics of their trans-DNase and trans-RNase activities with noncanonical activators. Our findings reveal that DNA can serve as a direct target for CRISPR-Cas13a, markedly increasing the detection sensitivity for single-base mismatches.

NAD rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis.

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5 (Cdh5) cerebral vascular cells in naturally aging mice and confirmed it in human brain samples.

Chemical screening links disulfiram with cardiac protection after ischemic injury.

Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction, however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited. Here, we report the identification and characterization of the FDA-approved drug disulfiram (DSF) as a cardioprotective compound. By applying high-throughput chemical screening, we found that DSF decreased HO-induced cardiomyocyte death by inhibiting Gasdermin D, but not ALDH1, in cardiomyocytes.

Protocol to identify small molecules promoting rat and mouse cardiomyocyte proliferation based on the FUCCI and MADM reporters.

Discovery of small molecules promoting cardiomyocyte proliferation is important for heart regeneration and related heart disease. Here, we describe a protocol to isolate neonatal rat and mouse cardiomyocytes, infect cardiomyocytes with Tnnt2-mAG-hGeminin (1/110) or Tnnt2-Cre adenovirus, and identify small molecules that promote cardiomyocyte proliferation by high-content microscopy. This protocol can be modified to investigate other pro-proliferation factors in cardiomyocytes and other cell types.

A DUSP6 inhibitor suppresses inflammatory cardiac remodeling and improves heart function after myocardial infarction.

Acute myocardial infarction (MI) results in loss of cardiomyocytes and abnormal cardiac remodeling with severe inflammation and fibrosis. However, how cardiac repair can be achieved by timely resolution of inflammation and cardiac fibrosis remains incompletely understood. Our previous findings have shown that dual-specificity phosphatase 6 (DUSP6) is a regeneration repressor from zebrafish to rats.

Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction.

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction.

A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration.

Zebrafish and mammalian neonates possess robust cardiac regeneration via the induction of endogenous cardiomyocyte (CM) proliferation, but adult mammalian hearts have very limited regenerative potential. Developing small molecules for inducing adult mammalian heart regeneration has had limited success. We report a chemical cocktail of five small molecules (5SM) that promote adult CM proliferation and heart regeneration.

Overview of Metabolomic Analysis and the Integration with Multi-Omics for Economic Traits in Cattle.

Metabolomics has been applied to measure the dynamic metabolic responses, to understand the systematic biological networks, to reveal the potential genetic architecture, etc., for human diseases and livestock traits. For example, the current published results include the detected relevant candidate metabolites, identified metabolic pathways, potential systematic networks, etc.

Lactobionic acid-modified phycocyanin nanoparticles loaded with doxorubicin for synergistic chemo-photodynamic therapy.

Phycocyanin (PC) is considered to be an effective natural photosensitizer, but it has not been well utilized as its inefficient biostability and intracellular accumulation. To overcome these limitations, the nano-sized PC particles (LAPC/DOX) were developed by grafting with lactobionic acid (LA) and loading with doxorubicin (DOX). Compared to the PC solution, the storage-stability and photostability of PC particles were remarkably increased, and the formation of nanoparticles further improved its biostability.

Molecular regulation of myocardial proliferation and regeneration.

Heart regeneration is a fascinating and complex biological process. Decades of intensive studies have revealed a sophisticated molecular network regulating cardiac regeneration in the zebrafish and neonatal mouse heart. Here, we review both the classical and recent literature on the molecular and cellular mechanisms underlying heart regeneration, with a particular focus on how injury triggers the cell-cycle re-entry of quiescent cardiomyocytes to replenish their massive loss after myocardial infarction or ventricular resection.

Mink is a highly susceptible host species to circulating human and avian influenza viruses.

Pandemic influenza, typically caused by the reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remains unclear.

Ablation of protein phosphatase 5 (PP5) leads to enhanced both bone and cartilage development in mice.

This study aimed to investigate the role of protein phosphatase 5 (PP5) on bone and cartilage development using both in vivo and in vitro approaches. Six- to 8-week- old male PP5 knockout mice (KO) and their wild-type (WT) littermate controls were randomly selected for this study, and their body weights and bone (femur) lengths were measured. Micro-computed tomography scanning (Micro-CT) was performed to determine femoral bone density and micro-architecture.