PAM-flexible Engineered FnCas9 variants for robust and ultra-precise genome editing and diagnostics.

The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a negligible affinity for mismatched substrates, but its low cellular targeting efficiency limits therapeutic use. Here, we rationally engineer the protein to develop enhanced FnCas9 (enFnCas9) variants and broaden their accessibility across human genomic sites by ~3.

Depression predicts emergency care use in people with chronic obstructive pulmonary disease: a large cohort study in primary care.

Depression is common in people with chronic obstructive pulmonary disease (COPD) and has been associated with a variety of poor outcomes. A large proportion of health care costs in the UK are spent on emergency care. This study examined the prospective relationship between depression and use of emergency care in patients with COPD managed in primary care.

Protective effect of 3H-1, 2-dithiole-3-thione on cellular model of Alzheimer's disease involves Nrf2/ARE signaling pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator for a battery of genes encoding detoxifying and antioxidative enzymes. 3H-1, 2-dithiole-3-thione (D3T), a potent free radical scavenger, is able to activate Nrf2 signaling pathway. In the present study, N2a/APPswe cells were used as the Alzheimer's disease (AD) cellular model and we investigated the protective effect of D3T on N2a/APPswe cells and the potential mechanisms.

Depression predicts future emergency hospital admissions in primary care patients with chronic physical illness.

Objective: More than 15 million people currently suffer from a chronic physical illness in England. The objective of this study was to determine whether depression is independently associated with prospective emergency hospital admission in patients with chronic physical illness.

Method: 1860 primary care patients in socially deprived areas of Manchester with at least one of four exemplar chronic physical conditions completed a questionnaire about physical and mental health, including a measure of depression.