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Recently, various second near-infrared window (NIR-II, 1000-1700 nm) fluorophores have been synthesized for in vivo imaging with nonradiation, high resolution, and low autofluorescence. However, most of the NIR-II fluorophores, especially inorganic nanoprobes, are mainly retained in the reticuloendothelial system (RES) such as the liver and spleen, leading to long-term safety concerns. Herein, a type of lanthanide-based excretable NIR-II nanoparticle, RENPs@Lips, which can be quickly cleared out of body after intravenous administration with half-lives of 23.0 h for the liver and 14.9 h for the spleen, is reported. Interestingly, over 90% of RENPs@Lips can be excreted through a hepatobiliary system within 72 h postinjection. The moderate blood half-time (T 1/2 = 17.96 min) allows for multifunctional applications in delineating the hemodynamics of vascular disorders (artery thrombosis, ischemia, and tumor angiogenesis) and monitoring blood perfusion in response to acute ischemia. In addition, RENPs@Lips exhibit high performance in identifying orthotopic tumor vessels intraoperatively and embolization surgery under NIR-II imaging navigation. Moreover, excellent signal-to-background ratio (SBR) is successfully achieved to facilitate sentinel lymph nodes biopsy (SLNB) with tumor-bearing mice. The high biocompatibility, favorable excretability, and outstanding optical properties warrant RENPs@Lips as novel promising NIR-II nanoparticles for future applications and translation into an interdisciplinary amalgamation of research in diverse fields.

Acute venous thrombosis is prevalent and potentially fatal. Accurate diagnosis of early thrombus is needed for patients in timely clinical intervention to prevent life-threatening conditions. Photoacoustic imaging (PAI) with excellent spatial resolution and high optical contrast shows more promise for this purpose. However, its application is dramatically limited by its signal-off effect on thrombus because of the ischemia in thrombus which lacks the endogenous photoacoustic (PA) signal of hemoglobin. To address this dilemma, we herein report the feasibility of using organic semiconducting nanoparticles (NPs) for contrast-enhanced PAI of thrombus in living mice. An organic semiconducting NP, self-assembled by amphiphilic perylene-3,4,9,10-tetracarboxylic diimide (PDI) molecules, is chemically modified with cyclic Arg-Gly-Asp (cRGD) peptides as a PA contrast agent (cRGD-PDI NPs) for selectively lightening early thrombus. cRGD-PDI NPs presents high PA intensity, good stability in light and serum, and sufficient blood-circulating half-life. In living mice, PA intensity of early thrombus significantly increases after tail vein injection of cRGD-PDI NPs, which is 4-fold greater than that of the control, blocking, and old thrombus groups. Pathological and immunohistochemical findings show that glycoprotein IIb/IIIa abundant in early thrombus is a good biomarker targeted by cRGD-PDI NPs for distinguishing early thrombus from old thrombus by PAI. Such a lightening PAI effect by cRGD-PDI NPs successfully provides accurate information including the profile, size and conformation, and spatial distribution of early thrombus, which may timely monitor the obstructive degree of thrombus in blood vessels and the thrombolysis effect.

BackgroundMicroRNAs (miRNAs) regulate various biological processes in plants. Considerable data are available on miRNAs involved in the development of rice, maize and barley. In contrast, little is known about miRNAs and their functions in the development of wheat. In this study, five small RNA (sRNA) libraries from wheat seedlings, flag leaves, and developing seeds were developed and sequenced to identify miRNAs and understand their functions in wheat development.ResultsTwenty-four known miRNAs belonging to 15 miRNA families were identified from 18 MIRNA loci in wheat in the present study, including 15 miRNAs (9 MIRNA loci) first identified in wheat, 13 miRNA families (16 MIRNA loci) being highly conserved and 2 (2 MIRNA loci) moderately conserved. In addition, fifty-five novel miRNAs were also identified. The potential target genes for 15 known miRNAs and 37 novel miRNAs were predicted using strict criteria, and these target genes are involved in a wide range of biological functions. Four of the 15 known miRNA families and 22 of the 55 novel miRNAs were preferentially expressed in the developing seeds with logarithm (log2) of the fold change of 1.0 ~ 7.6, and half of them were seed-specific, suggesting that they participate in regulating wheat seed development and metabolism. From 5 days post-anthesis to 20 days post-anthesis, miR164 and miR160 increased in abundance in the developing seeds, whereas miR169 decreased, suggesting their coordinating functions in the different developmental stages of wheat seed. Moreover, 8 known miRNA families and 28 novel miRNAs exhibited tissue-biased expression in wheat flag leaves, with the logarithm of the fold changes of 0.1 ~ 5.2. The putative targets of these tissue-preferential miRNAs were involved in various metabolism and biological processes, suggesting complexity of the regulatory networks in different tissues. Our data also suggested that wheat flag leaves have more complicated regulatory networks of miRNAs than developing seeds.ConclusionsOur work identified and characterised wheat miRNAs, their targets and expression patterns. This study is the first to elucidate the regulatory networks of miRNAs involved in wheat flag leaves and developing seeds, and provided a foundation for future studies on specific functions of these miRNAs.

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Background Patients with diabetes have an increased risk of nonunion and delayed union of fractures. Macrophages have been shown as a key player in diabetic complications. However, it remains obscure how diabetic milieu affects macrophage-derived exosomes and its implications on osteogenic differentiation of BMSCs. In this study, we aim to define the impact of diabetic milieu on macrophage-derived exosomes, role of extracellular vesicles in intercellular communication with BMSCs, and subsequent effects on osteogenic differentiation and fracture repair. Results The osteogenic potential and the ability of fracture repair of exosomes derived from diabetic bone marrow-derived macrophages (dBMDM-exos) were revealed to be lower, as compared with non-diabetic bone marrow-derived macrophages (nBMDM-exos) in vitro and in vivo. Interestingly, miR-144-5p levels were sharply elevated in dBMDM-exos and it could be transferred into BMSCs to regulate bone regeneration by targeting Smad1. In addition, the adverse effects of dBMDM-exos on the osteogenic potential and the ability of fracture repair were reversed through the suppression of miR-144-5p inhibition in vitro and vivo. Conclusions The results demonstrated an important role of exosomal miR-144-5p in bone regeneration, offering insight into developing new strategy for the improvement of fracture healing in patients with diabetes mellitus. Graphic Abstract

Negative pressure wound therapy (NPWT) has been demonstrated to accelerate wound healing by promoting angiogenesis. However, whether blood flow perfusion is regulated by microvessel maturation and pericytes following NPWT remains unclear, as well as the exact association between pericytes and collagen type IV. The aim of this study was to investigate the relevant association between blood flow perfusion and microvessel maturation and pericytes following NPWT, and to further explore the underlying molecular mechanisms. We also aimed to investigate the association between pericytes and collagen type IV. For this purpose, we created a rat model of diabetic wounds and microvascular blood flow perfusion was detected using a laser Doppler blood perfusion imager. The expression levels of angiogenin-1, tyrosine phosphorylation of tyrosine kinase receptor-2 (Tie-2), α-smooth muscle actin (α-SMA) and collagen type IV were detected and analyzed through immunohistochemistry, immunofluorescence, RT-qPCR and western blot analysis. The results revealed that NPWT promoted the overexpression of angiogenin-1, Tie-2, α-SMA and collagen type IV, and significantly increased blood flow perfusion coupled with microvessel maturation in the NPWT group at the later stages (7–10 days) of wound healing. Our results suggested that NPWT can preferentially enhance vessel maturation and increase the number of pericytes, thus regulating blood flow perfusion. On the other hand, pericytes and collagen type IV had a mutual interaction, promoting microvessel maturation.

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