Two-way magnetic resonance tuning and enhanced subtraction imaging for non-invasive and quantitative biological imaging.

Distance-dependent magnetic resonance tuning (MRET) technology enables the sensing and quantitative imaging of biological targets in vivo, with the advantage of deep tissue penetration and fewer interactions with the surroundings as compared with those of fluorescence-based Förster resonance energy transfer. However, applications of MRET technology in vivo are currently limited by the moderate contrast enhancement and stability of T1-based MRET probes. Here we report a new two-way magnetic resonance tuning (TMRET) nanoprobe with dually activatable T1 and T2 magnetic resonance signals that is coupled with dual-contrast enhanced subtraction imaging. This integrated platform achieves a substantially improved contrast enhancement with minimal background signal and can be used to quantitatively image molecular targets in tumours and to sensitively detect very small intracranial brain tumours in patient-derived xenograft models. The high tumour-to-normal tissue ratio offered by TMRET in combination with dual-contrast enhanced subtraction imaging provides new opportunities for molecular diagnostics and image-guided biomedical applications

Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection

Abstract Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age–related mosaic chromosomal alterations (mCAs) detected from genotyping of blood–derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15–1.36; P = 1.8 x 10-7), including sepsis (HR 2.68; 95% CI = 2.25–3.19; P = 3.1 x 10-28), pneumonia (HR 1.76; 95% CI = 1.53–2.03; P = 2.3 x 10-15), digestive system infections (HR 1.51; 95% CI = 1.32–1.73; P = 2.2 x 10-9) and genitourinary infections (HR 1.25; 95% CI = 1.11–1.41; P = 3.7 x 10-4). A genome–wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections