Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1 + SiglecF + transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo . Human orthologues of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury.

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The pathological processes of cancer are complex. Current methods used for chemotherapy have various limitations, such as cytotoxicity, multi-drug resistance, stem-like cells growth, and lack of specificity. Several types of nanomaterials are used for cancer treatment. Nanomaterials 1–100 nm in size have special optical, magnetic, and electrical characteristics. Nanomaterials have been fabricated for cancer treatments to overcome cytotoxicity and low specificity, and improve drug capacity and bioavailability. Despite the increasing number of related studies, few nanodrugs have been approved for clinical use. To improve translation of these materials, studies of targeted drug delivery using nanocarriers are needed. Cytotoxicity, enhanced permeability and retention effects, and the protective role of the protein corona remain to be addressed. This mini-review summarizes new nanomaterials manufactured in studies and in clinical use, analyses current barriers preventing their translation to clinical use, and describes the effective application of nanomaterials in cancer treatment.

New Findings What is the central question of the study?Are measures of reduced insulin sensitivity in young, normoglycaemic subjects correlated with near‐infrared spectroscopy‐derived microvascular responsiveness [tissue oxygen saturation reperfusion rate (STO2 upslope)] during postocclusive reactive hyperaemia? What is the main finding and its importance?A sevenfold range of hepatic insulin sensitivity is significantly correlated (r = 0.44, P = 0.02) with STO2 upslope after transient tissue ischaemia. Near‐infrared spectroscopy may be an important tool for determining altered microvascular function before onset of hyperglycaemia. Identification of pre‐type 2 diabetes much earlier than with the present clinical criteria is important for pre‐emptive measures against microvascular deterioration. Abstract Near‐infrared spectroscopy (NIRS) measurement of postocclusive reactive hyperaemia (PORH) tissue oxygen saturation reperfusion rate [STO2 upslope (as a percentage per minute)] has recently been correlated with the percentage of flow‐mediated dilatation (%FMD). Cardiovascular disease is associated with impairments in %FMD. Reduced insulin sensitivity may negatively affect the vascular system for many years before prediabetes/type 2 diabetes states. The aim of this study was to determine whether static and dynamic STO2 parameters during PORH are correlated with reduced insulin sensitivity in young, normoglycaemic subjects. Glucose and insulin were measured during an oral glucose tolerance test in 18‐ to 26‐year‐old, healthy subjects (11 men and 11 women), and STO2 was measured during PORH of antebrachial muscle. Hepatic (ISIHOMA) and whole‐body (ISICOMP) insulin sensitivities were calculated. The STO2 upslope was negatively correlated with minimal STO2 (r = −0.5, P = 0.01). The change of STO2 from minimum to baseline (ΔSTO2) was significantly negatively correlated with fasting insulin (r = −0.5, P = 0.01) and a positively correlated with ISIHOMA (r = 0.65, P = 0.001). The minimum STO2 was significantly negatively correlated with ISIHOMA, and STO2 upslope was significantly positively correlated with ISIHOMA (r = 0.44, P = 0.02). The minimum STO2 (a measure of O2 extraction while the cuff was inflated), ΔSTO2 (a measure of the amount of reperfusion) and STO2 upslope (a measure of responsiveness of the microcirculation to ischaemia) were all positively correlated with ISIHOMA, one of the longest‐used measures of insulin sensitivity. The NIRS‐derived STO2 might be a useful tool for assessing how levels of reduced insulin sensitivity in young, normoglycaemic adults affect the microvasculature.