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Sweroside, a natural secoiridoid glycoside derived from various medicinal plants, is known for its anti‐tumor, anti‐inflammatory, and hepatoprotective properties. However, its pharmacological significance is not fully supported by its low systemic exposure. In this study, a de novo strategy was proposed to investigate the metabolism of sweroside in rats, including drug administration, sample pretreatment, ultra‐high‐performance liquid chromatography/Quadrupole‐Exactive mass spectrometry data acquisition, data processing, and semi‐quantitative analysis. First, following oral administration of sweroside to rats, plasma, urine, and feces were collected, and respectively mixed using the area‐under‐the‐curve pooling method. Secondly, data‐dependent, dynamic exclusion, and parallel reaction monitoring scan modes were employed to build a tandem mass spectra database. Using a neutral loss fragment‐based method, target metabolites were effectively filtered. As a result, sweroside was demonstrated to be extensively metabolized, while 18 metabolites were identified and nine of them were newly reported. Sweroside predominantly underwent phase II metabolism, including glycosylation, sulfonation, glucuronidation, and deglycosylation, and were primarily excreted via the kidney. Notably, N‐heterocyclization (M7 and M10) was likely catalyzed by intestinal bacteria. This study not only elucidates the in vivo drug elimination of sweroside but also offers an efficient approach for profiling the metabolism of specific molecules. [ABSTRACT FROM AUTHOR]

Thermoplastic polyurethane (TPU) has good elasticity and tear resistance, and is often applied in the field of flexible puncture resistance although the puncture resistance of pure TPU is limited. In this paper, silica powder (SiO2) and styrene butadiene rubber powder (SBR) with different concentrations were used as fillers to reinforce the TPU matrix respectively. To overcome the problem of poor interfacial compatibility between filler and matrix, the silane coupling agent r‐Aminopropyltrieth oxysilanee (KH550) was selected to modify the particles. The compatibility of particles and matrix, the puncture properties and tensile properties of composites were assessed by FTIR, TEM, SEM, tensile testing, and needle puncture testing. Further, the tensile and puncture properties of composites with different types and concentrations of particles were systematically compared and analyzed to find optimal parameters. The results show that the best modification effect is gained when the mass ratio of KH550 and nanoparticles is 0.85:1 and the specific puncture strength of TPU membranes incorporated modified SiO2 or SBR nanoparticles can be increased by up to 106.4% and 85% respectively compared to pure TPU membrane. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Inward-rectifier [K.sup.+] current ([I.sub.K1]) is believed to be an important regulator of reentrant-spiral dynamics and a major [...]

What is known and objective: We present two cases of severe coagulation disorders induced by latamoxef, thereby revealing risk factors of coagulation disorder in latamoxef‐treated patients. Case summary: Two very elderly patients developed haemorrhage, and coagulation tests showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). Latamoxef was thought to be responsible for the coagulopathy in these patients, and coagulation disorder was relieved after vitamin‐K intake. What is new and conclusion: We report on two cases of coagulopathy in patients given latamoxef. Advanced age, deficiency in vitamin‐K intake, poor nutritional status, abnormal coagulation history, ongoing anti‐coagulation/anti‐aggregation therapy, renal dysfunction and polypharmacy are possible contributory factors, and should be looked out for when prescribing latamoxef. [ABSTRACT FROM AUTHOR]

As a member of miR‑17‑92 miRNA clusters, miR‑19a has been considered to regulate hepatic glycogenesis by mediating the PI3K/AKT signaling pathway. However, whether miR‑19a serves an important role in gluconeogenesis in hepatocytes remains unknown. In the present study, the impact of miR‑19a on gluconeogenesis in HEP1‑6 cells and its mechanisms of action were investigated. It was observed that overexpression of miR‑19a led to decreased glucose production, accompanied by increased activation of the AKT/FOXO1 signaling pathway and downregulated expression of gluconeogenesis‑associated genes, including peroxisome proliferator‑activated receptor γ coactivator 1α, phosphoenolpyruvate carboxykinase and glucose 6‑phosphatase in the HEP1‑6 cells transfected with the miR‑19a mimic. In contrast, suppression of miR‑19a impaired the activation of the AKT/FOXO1 signaling pathway and increased the expression of gluconeogenesis‑associated genes, accompanied by an elevated glucose production. Additionally, phosphatase and tensin homolog (PTEN) was identified as a target of miR‑19a and participated in the miR‑19a‑mediated gluconeogenesis in hepatocytes. These findings provide mechanistic insight into the effects of miR‑19a on the regulation of the AKT/FOXO1 signaling pathway and the expression of gluconeogenesis‑associated genes. MiR‑19a may mediate gluconeogenesis in hepatocytes by downregulating PTEN expression. [ABSTRACT FROM AUTHOR]

Chronic stress is closely associated with gastrointestinal disorders. However, the impact of stress-related neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) on the intestines under chronic stress conditions remains poorly understood. This study aims to elucidate the mechanisms by which 5-HT affects mitochondrial biogenesis and intestinal barrier integrity during chronic stress. Employing a chronic restraint stress (CRS) mouse model, we observed elevated intestinal 5-HT levels, altered colonic mucosal structure, and disrupted tight junctions. The increase in 5-HT was associated with up-regulated serotonin synthesis enzymes and downregulated serotonin reuptake transporters, indicating an imbalance in serotonin homeostasis imbalance caused by chronic stress. Furthermore, serotonin exacerbated oxidative stress and impaired tight junction protein expression, highlighting its role in promoting intestinal barrier dysfunction. Experiments with cells in vitro demonstrated that 5-HT impairs mitochondrial biogenesis by inhibiting the AMPK-PGC-1α axis via 5-HT 7 receptors and the cAMP-PKA pathway. Pharmacological inhibition of serotonin synthesis or 5-HT 7 receptors alleviated the intestinal barrier damage caused by 5-HT and chronic stress, restoring mitochondrial biogenesis. These findings provide compelling evidence that serotonin exacerbates chronic stress-induced intestinal barrier disruption by inhibiting the AMPK-PGC-1α axis, paving the way for novel therapeutic interventions targeting the detrimental effects of serotonin on the intestine, particularly under chronic stress conditions., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Increasing evidence has shown that microRNAs are involved in apoptosis in different cells. However, the role of miR-31 in atherosclerosis (AS) has never been elucidated. In the present study, we identified the impact of miR-31 on atherosclerosis in macrophages., Methods: The level of miR-31 in macrophages was examined in apoE-/- mice. Cell viability and apoptosis were examined in macrophage cells transfected with miR-31 mimics, inhibitors or negative control. In addition, the impact of NOX4 on cell apoptosis was tested with a specific siRNA targeting NADPH oxidase 4 (NOX4)., Results: An enhanced level of miR-31 was found in macrophage cells of apoE-/- mice, suggesting that miR-31 might contribute to abnormal cell proliferation of macrophage cells. Upregulation of miR-31 decreased cell viability and induced macrophage cell apoptosis. Moreover, knockdown of NOX4 reduced cell migration capacity and enhanced cell apoptosis., Conclusions: The current data suggested that miR-31 contributed to macrophage apoptosis by regulating the expression of NOX4.