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INTRODUCTION: The P2Y14 receptor (P2Y14R), a member of the G protein-coupled receptor family, is activated by extracellular nucleotides. Due to its involvement in inflammatory, immunological and other associated processes, P2Y14R has emerged as a promising therapeutic target. Despite lacking a determined three-dimensional crystal structure, the homology modeling technique based on closely related P2Y receptors' crystallography has been extensively utilized for developing active compounds targeting P2Y14R. Recent discoveries have unveiled numerous highly effective and subtype-specific P2Y14R inhibitors. This study presents an overview of the latest advancements in P2Y14R inhibitors. AREAS COVERED: This review presents an overview of the advancements in P2Y14R inhibitor research over the past five years, encompassing new patents, journal articles, and highlighting the therapeutic prospects inherent in these compounds. EXPERT OPINION: The recent revelation of the vast potential of P2Y14R inhibitors has led to the development of novel compounds that exhibit promising capabilities for the treatment of sterile inflammation of the kidney, potentially diabetes, and asthma. Despite being a relatively nascent class of compounds, certain members have already exhibited their capacity to surmount specific challenges posed by conventional P2Y14R inhibitors. Targeting P2Y14R through small molecules may present a promising therapeutic strategy for effectively managing diverse inflammatory diseases.

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Contactless fluorescent thermometers are rapidly gaining popularity due to their sensitivity and flexibility. However, the development of sensitive and reliable non-rare-earth-containing fluorescent thermometers remains a significant challenge. Here, a new rare-earth-free, red-emitting phosphor, Li2MgHfO4:Mn4+, was developed for temperature sensing. An experimental analysis combined with density functional theory and crystal field calculations reveals that the sensitive temperature-dependent luminescence arises from nonradiative transitions induced by lattice vibration. Li2MgHfO4:Mn4+ also exhibits reliable recovery performance after 100 heating-cooling cycles due to the elimination of surface defects, which is rare but vital for practical application. This study puts forward a new design strategy for fluorescent thermometers and sheds light on the fundamental structure-property relationships that guide sensitive temperature-dependent luminescence. These considerations are crucial for developing next-generation fluorescence-based thermometers.

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The combination of tetramethylpyrazine phosphate (TMPP) and borneol (BO) protects against cerebral ischemia. However, the mechanism for their synergistic effect is unclear. In this study, an oxygen-glucose deprivation (OGD) injured brain model was induced in microvascular endothelium cells (BMECs). TMPP and BO concentrations were optimized according to an MTT assay. Cells were divided into five groups: control, model, TMPP, BO, and TMPP+BO. Subsequently, oxidative stress was evaluated based on the levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS). Intracellular calcium ([Ca2+]i) was detected using a laser confocal microscope. Cellular apoptosis was examined via Hoechst 33342 staining, flow cytometry, and expression of p53, B-cell lymphoma 2 (BCL-2), BCL-2-like protein 4 (BAX), and caspase-3 mRNA. Angiogenesis was evaluated based on expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), fibroblast growth factor receptor 1 (FGFR1), Vascular endothelial growth factor receptor 1 (VEGFR1), and VEGFR2. Results showed that 5.0 µM TMPP and 0.5 µM BO were optimal. Monotherapy significantly enhanced CAT, BCL-2, and VEGF, and also reduced [Ca2+]i, apoptosis, and BAX. TMPP increased SOD, GSH-Px, and bFGF, and reduced MDA, ROS, p53, and caspase-3 levels. BO reduced VEGFR1 expression. TMPP+BO combination exhibited synergistic effects in decreasing apoptosis, and modulating expression of BCL-2, BAX, and VEGFR1. These results indicate that protection of OGD-injured BMECs by TMPP+BO combination involves anti-oxidation, apoptosis inhibition, and angiogenesis. Moreover, their synergistic mechanism was mainly related to the regulation of apoptosis and angiogenesis.

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Digital flexor tendon repair poses a significant challenge for hand surgeons. Currently, extrasynovial tendon grafts are frequently used in clinical settings to bridge flexor tendon defects. However, the healing process is always accompanied by postoperative adhesion. This is mostly due to the fact that no synovial membrane covers the extrasynovial tendon surface, in contrast to the intrasynovial tendon. In this study, we present an efficient method of developing a functional synovial biomembrane on the surface of the extrasynovial tendon. Synoviocytes were isolated from the knee joint of a Japanese white rabbit. After being infected with lentivirus, the over-expression of synoviolin in these synoviocytes was confirmed by semi-quantitative RT-PCR and western blotting. Cellular proliferation and increased hyaluronic acid secretion were confirmed in the synoviolin over-expressing synoviocytes by MTT-based method, cell cycle assays and ELISA. Furthermore, the synoviolin over-expressing synoviocytes were co-cultured with extrasynovial tendons that were harvested from the hind leg of rabbits. After being co-cultured in vitro for 3 and 7 days, these infected synoviocytes were found to accelerate the formation of a biomembrane on the tendon surface compared to the control group. More importantly, Alcian blue staining confirmed the ability of this cultured biomembrane to produce specific matrices containing acidic carboxyl mucopolysaccharides (mainly hyaluronic acid). All these results demonstrate that the over-expression of synoviolin stimulates the proliferation and HA secretion of synoviocytes and facilitates the formation of a functional synovial biomembrane.

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Learning-induced changes of synaptic ultrastructure have long been proposed as a mechanism that may contribute to support memory formation. Although recent studies have demonstrated that the interpositus nuclei (IN) play critical role in acquisition and retention of trace conditioned eyeblink responses (CRs), there is now limited evidence associating trace eyeblink conditioning with changes of synaptic ultrastructure in the IN. Here, we investigated this issue using a transmission electron microscope. Adult guinea pigs were randomly allocated to either a trace-paired, delay-paired, unpaired or exposure-only condition. The IN tissue was taken for morphological analysis 1h after the completion of the tenth training session. Serial section analysis of synaptic ultrastructure revealed that trace eyeblink conditioning induced increases in the thickness of excitatory PSD. Classification of the synapses into shape subtypes indicated that the increased thickness of excitatory PSD was mainly attributable to increase in the concave- and convex-shaped synapses. On the contrary, trace eyeblink conditioning resulted in decreases in the thickness of inhibitory PSD. Specifically, these significant changes of PSD thickness were limited to occur in the animals with good behavioral performance. Further analysis of correlations between the trace CR performance and synaptic ultrastructural modifications showed that the thickness of excitatory PSD within the IN correlated with the peak amplitude of trace CRs, whereas the thickness of inhibitory PSD correlated with the onset latency. The present findings suggest that trace eyeblink conditioning induces structural plasticity in the IN, which may play a crucial role in acquiring and executing adaptive eyeblink movements.

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Objective　To investigate the occurrence of postural hypotension (PH) in patients suffering from type 2 diabetes mellitus with or without hypertension (DMH or DM), and the relationship of PH and diabetic neuropathy, hyperinsulinemia and insulin resistance. Methods　A total of 30 cases of type 2 DM and 30 cases of DMH were included in this study. The blood pressure of all subjects were measured in supine and standing body positions respectively and PH was defined as a decline from supine to standing was ≥20 mmHg in systolic blood pressures (SBP). The concentrations of blood glucose and plasma insulin were measured to calculate the insulin sensitive index (ISI). Autonomic and peripheral function was determined by measuring the postural heart rates and the conduction speeds of superficial peroneal and communicating branch of peroneal nerves etc respectively. Results　Significant difference (P<0.01) was found in the occurrence of PH in the patients with DM (40%) and those with DMH (67%). The changes of postural blood pressure were more obvious in those with DM+PH and DMH+PH than in those with simple DM (P<0.01). The conduction speeds of newes were significantly lower in those with DMH+PH than with simple DM (P<0.05), but the occurrence of autonomic neuropathy had no difference between the 2 groups. There was no difference in postural heart rate, body mass index and blood glucose levels in fasting and 2 h after meal among the DM, DM+PH and DMH+PH groups. The concentrations of plasma insulin of those with DMH+PH were significantly higher, but their ISI significantly lower than those of the patients with DM respectively (P<0.01). The decline of postural SBP in patients with DMH+PH had a significantly positive correlation with their plasma insulin levels in fasting condition (r=0.689, P<0.01). Conclusion　The patients with DMH are more prone to PH compared with those only with DM and PH damages their peripheral nerves. Most of diabetic patients with PH suffer from obvious IR and hyperinsulinemia, and if with hypertension, the above metabolic disturbances are more severe.

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Objective　To investigate the occurrence of postural hypotension (PH) in patients suffering from type 2 diabetes mellitus with or without hypertension (DMH or DM), and the relationship of PH and diabetic neuropathy, hyperinsulinemia and insulin resistance. Methods　A total of 30 cases of type 2 DM and 30 cases of DMH were included in this study. The blood pressure of all subjects were measured in supine and standing body positions respectively and PH was defined as a decline from supine to standing was ≥20 mmHg in systolic blood pressures (SBP). The concentrations of blood glucose and plasma insulin were measured to calculate the insulin sensitive index (ISI). Autonomic and peripheral function was determined by measuring the postural heart rates and the conduction speeds of superficial peroneal and communicating branch of peroneal nerves etc respectively. Results　Significant difference (P<0.01) was found in the occurrence of PH in the patients with DM (40%) and those with DMH (67%). The changes of postural blood pressure were more obvious in those with DM+PH and DMH+PH than in those with simple DM (P<0.01). The conduction speeds of newes were significantly lower in those with DMH+PH than with simple DM (P<0.05), but the occurrence of autonomic neuropathy had no difference between the 2 groups. There was no difference in postural heart rate, body mass index and blood glucose levels in fasting and 2 h after meal among the DM, DM+PH and DMH+PH groups. The concentrations of plasma insulin of those with DMH+PH were significantly higher, but their ISI significantly lower than those of the patients with DM respectively (P<0.01). The decline of postural SBP in patients with DMH+PH had a significantly positive correlation with their plasma insulin levels in fasting condition (r=0.689, P<0.01). Conclusion　The patients with DMH are more prone to PH compared with those only with DM and PH damages their peripheral nerves. Most of diabetic patients with PH suffer from obvious IR and hyperinsulinemia, and if with hypertension, the above metabolic disturbances are more severe.