International Normalized Ratio Predicts Recurrence and Bleeding in Patients With Acute Venous Thromboembolism Who Undergo Direct Oral Anticoagulants.

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Inhibition of Fungal Growth and Aflatoxin B1 Synthesis in Aspergillus flavus by Plasma-Activated Water.

The gaseous reactive oxygen/nitrogen species (RONS) generated by cold atmospheric plasma (CAP) can effectively inactivate Aspergillus flavus (A. flavus) and prolong the shelf-life of food. Plasma-activated water (PAW) is the extension of cold plasma sterilization technology. Without the limitation of a plasma device, PAW can be applied to more scenarios of food decontamination. However, the efficacy of PAW as a carrier of RONS for eradicating A. flavus or inhibiting its growth remains unclear. In this study, the immediate fungicidal effect and long-term inhibitory effect of PAW on A. flavus were investigated. The results demonstrated that 60-min instant-prepared PAW could achieve a 3.22 log reduction CFU/mL of A. flavus and the fungicidal efficacy of PAW gradually declined with the extension of storage time. Peroxynitrite (ONOO-/ONOOH) played a crucial role in this inactivation process, which could damage the cell wall and membrane structure, disrupt intracellular redox homeostasis, and impair mitochondrial function, ultimately leading to fungal inactivation. In addition to the fungicidal effect, PAW also exhibited fungistatic properties and inhibited the synthesis of aflatoxin B1 (AFB1) in A. flavus. By analyzing the cellular antioxidant capacity, energy metabolism, and key gene expression in the AFB1 synthesis pathway, it was discovered that PAW can significantly reduce ATP levels, while increasing SOD and CAT activity during 5-d cultivation. Meanwhile, PAW effectively suppressed the expression of genes related to AFB1 synthesis.

Cinnamic acid inhibits cell viability, invasion, and glycolysis in primary endometrial stromal cells by suppressing NF-κB-induced transcription of PKM2.

BACKGROUND:   Endometriosis is a painful disorder characterized by the growth of endometrial tissue outside the uterine cavity. Here, we investigated the effects of the cinnamic acid isolated from the Chinese medicinal plant Cinnamomum cassia Presl on primary endometrial stromal cells. METHODS:   Immunohistochemistry was used to examine protein expression and cell purity. Quantitative RT-PCR was conducted to assess mRNA expression, and Western blot was performed to determine protein level. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Glycolysis and mitochondrial function were evaluated by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) of cells, respectively. Lastly, plasmid transfection and inhibitor treatment were used for overexpression and inhibition studies. RESULTS: Cinnamic acid inhibited cell viability and cell invasion, as well as decreased ECAR and OCR, in primary endometrial stromal cells. Cinnamic acid suppressed the effects of PKM2 overexpression, and inhibition of PKM2 using Compound 3k mimicked the effects of cinnamic acid. Treatment with Compound 3k and cinnamic acid did not lead to additive effects, but rather displayed effects similar to those of Compound 3k alone, suggesting that cinnamic acid elicits its effects on primary endometrial stromal cells by targeting PKM2. CONCLUSIONS:   Our study identified cinnamic acid as a novel compound from Cinnamomum cassia Presl that displays potent effects on primary endometrial stromal cell viability, invasion, and glycolysis, suggesting its potential use for endometriosis treatment.