Skin interstitial fluid (ISF) is an emerging source of biomarkers for disease diagnosis and prognosis. Microneedle (MN) patch has been identified as an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administrated properties. However, long sampling time is still a serious problem which impedes timely metabolic analysis. In this study, a swellable MN patch that can rapidly extract ISF is developed. The MN patch is made of methacrylated hyaluronic acid (MeHA) and further crosslinked through UV irradiation. Owing to the supreme water affinity of MeHA, this MN patch can extract sufficient ISF in a short time without the assistance of extra devices, which remarkably facilitates timely metabolic analysis. Due to covalent crosslinked network, the MN patch maintains the structure integrity in the swelling hydrated state without leaving residues in skin after usage. More importantly, the extracted ISF metabolites can be efficiently recovered from MN patch by centrifugation for the subsequent offline analysis of metabolites such as glucose and cholesterol. Given the recent trend of easy-to-use point-of-care devices for personal healthcare monitoring, this study opens a new avenue for the development of MN-based microdevices for sampling ISF and minimally invasive metabolic detection.

Graphene quantum dots (GQDs) hold great promise as a new class of fluorophores for bioimaging, owing to their remarkable physicochemical properties including tunable photoluminescence, excellent photostability, and biocompatibility. Despite their highly anticipated potentials, GQDs have yet to be used to specifically label and track molecular targets involved in dynamic cellular processes in live cells. Here, we demonstrate that GQDs can serve as universal fluorophores for bioimaging because they can be readily conjugated with a wide range of biomolecules while preserving their functionalities. As a proof-of-concept demonstration, insulin-conjugated GQDs have been synthesized and utilized for specific labeling and dynamic tracking of insulin receptors in 3T3-L1 adipocytes. Our experiments reveal, for the first time, that the internalization and recycling of insulin receptors in adipocytes are oppositely regulated by apelin and TNFα, which may contribute to the regulations of these two cytokines in insulin sensitivity.

Eye diseases and injuries impose a significant clinical problem worldwide. Safe and effective ocular drug delivery is, however, challenging due to the presence of ocular barriers. Here we report a strategy using an eye patch equipped with an array of detachable microneedles. These microneedles can penetrate the ocular surface tissue, and serve as implanted micro-reservoirs for controlled drug delivery. The biphasic drug release kinetics enabled by the double-layered micro-reservoirs largely enhances therapeutic efficacy. Using corneal neovascularization as the disease model, we show that delivery of an anti-angiogenic monoclonal antibody (DC101) by such eye patch produces ~90% reduction of neovascular area. Furthermore, quick release of an anti-inflammatory compound (diclofenac) followed by a sustained release of DC101 provides synergistic therapeutic outcome. The eye patch application is easy and minimally invasive to ensure good patient compliance. Such intraocular drug delivery strategy promises effective home-based treatment of many eye diseases.

Graphene quantum dots (GQDs) are emerging zero-dimensional materials promising a wide spectrum of applications, particularly, as superior fluorescent reporters for bio-imaging and optical sensing. Heteroatom doping can endow GQDs with new or improved photoluminescence properties. Here, we demonstrate a simple strategy for the synthesis of nitrogen and phosphorus co-doped GQDs from a single biomolecule precursor (adenosine triphosphate - ATP). Such ATP-GQDs exhibit high fluorescence quantum yield, strong two-photon upconversion, small molecular weight, high photostability, and good biocompatibility. Furthermore, transferrin conjugated ATP-GQDs have been used for imaging and real-time tracking of transferrin receptors in live cells.

Background:The autocrine regulatory effects of apelin on self-remodeling of adipose tissue are not known. Results: Apelin enhances not only the differentiation and metabolic activity of brown adipocytes but also the browning of white adipocytes. Conclusion: Apelin-APJ signaling promotes adipose tissue browning. Significance: Apelin signaling may serve as a potential therapeutic target for obesity and associated metabolic diseases.

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Graphene quantum dots (GQDs) are emerging fluorescence reporters attractive for optical sensing, owing to their high photostability, highly tunable photoluminescence, molecular size, atomically thin structure, biocompatibility, and ease of functionalization. Herein, we present a fluorometric sensing platform based on tyramine-functionalized GQDs, which is able to detect a spectrum of metabolites with high sensitivity and specificity. Furthermore, multiparametric blood analysis (glucose, cholesterol, L-lactate, and xanthine) is demonstrated. This convenient metabolite profiling technique could be instrumental for diagnosis, study, and management of metabolic disorders and associated diseases, such as diabetes, obesity, lactic acidosis, gout, and hypertension.