Platelet dysfunction caused by differentially expressed genes as key pathogenic mechanisms in COVID-19.

At the end of 2019, the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became prevalent worldwide, which brought a heavy medical burden and tremendous economic losses to the world population. In addition to the common clinical respiratory symptoms such as fever, cough and headache, patients with COVID-19 often have hematological diseases, especially platelet dysfunction. Platelet dysfunction usually leads to multiple organ dysfunction, which is closely related to patient severity or mortality. In addition, studies have confirmed significant changes in the gene expression profile of circulating platelets under SARS-CoV-2 infection, which will further lead to changes in platelet function. At the same time, studies have shown that platelets may absorb SARS-COV-2 mRNA independently of ACE2, which further emphasizes the importance of the stability of platelet function in defense against SARS-CoV-2 infection. This study reviewed the relationship between COVID-19 and platelet and SARS-CoV-2 damage to the circulatory system, and further analyzed the significantly differentially expressed mRNA in platelets after infection with SARS-CoV-2 on the basis of previous studies. The top eight hub genes were identified as NLRP3, MT-CO1, CD86, ICAM1, MT-CYB, CASP8, CXCL8 and CXCR4. Subsequently, the effects of SARS-CoV-2 infection on platelet transcript abnormalities and platelet dysfunction were further explored on the basis of 8 hub genes. Finally, the treatment measures of complications caused by platelet dysfunction in patients with COVID-19 were discussed in detail, so as to provide reference for the prevention, diagnosis and treatment of COVID-19.

The seewo interactive whiteboard (IWB) for ESL teaching: How useful it is?

The perceived usefulness (PU) of a technology is critical for its final adoption; however, what makes an interactive whiteboard (IWB) perceived useful remains unclear. This study aims to investigate how pre-service teachers perceive the usefulness of Seewo interactive whiteboards for ESL (English-as-a-second-language) instruction. We recruited 80 pre-service ESL teachers, divided them into 16 groups, provided five weeks of training, and conducted focus group interviews to gather qualitative feedback. The data were analyzed using grounded theory techniques with the aid of the software Nvivo. Three research questions were addressed: how pre-service ESL teachers perceive the usefulness of Seewo IWB in terms of its functions that enhance the learning process (PU-process), how they perceive the usefulness of Seewo IWB in terms of its functions that improve learning outcomes (PU-outcome), and how they perceive the non-usefulness of Seewo IWB. The findings shed light on the determinants of the perceived usefulness (PU) concept, which is crucial for fostering a higher intention to accept technology.

Epidural esketamine and morphine for postoperative analgesia after caesarean delivery: A pilot study.

Objective: The aim of this study was to determine whether the addition of esketamine to morphine would improve postoperative analgesia after cesarean section. Methods: Parturients who planned for a cesarean delivery using combined spinal-epidural anesthesia with a request for postoperative anesthesia were randomly divided into four groups (A, B, C, and D). When the surgery was completed, the parturients in groups A, B, C, and D were administered 2 mg morphine, 0.25 mg/kg of esketamine, 0.25 mg/kg of esketamine plus 2 mg morphine hydrochloride, and 0.25 mg/kg of esketamine plus 1 mg morphine through the epidural catheters, respectively. The postoperative pain at rest, pain with movement, the number of rescue analgesics, and adverse effects were evaluated for 48 h after cesarean delivery. Results: A total of 119 parturients were included in this study, including 30 cases in group A, 30 cases in group B, 30 cases in group C, and 29 cases in group D. All visual analog scale (VAS) scores at rest and with movement were much lower in group C as compared with those in group A and group B (P < 0.05). Moreover, VAS scores at rest were also lower in Group C than in group D for 24 h (P < 0.05). Corresponding to the low pain scores, parturients in group C also required less rescue analgesia as compared with the other three groups (P = 0.021 for C vs. A, P < 0.001 for C vs. B, and P < 0.001 for C vs. D). There were no statistically significant differences between the four study groups with regard to the incidence of adverse events (P > 0.05). Conclusions: The addition of esketamine to morphine improved postoperative analgesia after cesarean section without increasing the incidence of adverse events.

Preparation and Repeated Repairability Evaluation of Sunflower Oil-Type Microencapsulated Filling Materials.

Cracks are the main challenges for asphalt pavement, which should be timely repaired. One of the most commonly used repairing methods is to fill the binding materials into cracks, but the repeated repairing ability is insufficient. The self-healing microcapsule technologies provide the potentials for enhancing the repeated repairing ability of filling materials. Therefore, the microcapsule core material was selected from sunflower oil in this study, and the capsular wall material was selected from melamine-urea-formaldehyde resin, which was used to prepare the microcapsule by using in-situ polymerization method. Three kinds of microcapsules with different particle sizes were prepared by adjusting the emulsifier dosage and core wall ratio. The microstructure, molecular structure, thermal stability, and dispersion features were further studied, and the effects of microcapsules with different particle sizes on the repeated repairability of the filling materials were evaluated via the fatiguerepair-fatigue test. In addition, the traditional regenerative microcapsules were compared to determine the optimal particle size range for sunflower oil microcapsules. According to the experimental research, it was thus concluded that the emulsion droplet size distribution was most concentrated when the emulsifier content was 0.7%; and when the core-wall ratio was 1.3:1, the microcapsules had uniform particle size and good dispersion effect. When the microcapsule emulsification rate was 900 rpm and microcapsule content was 2%, then the repeated repair effect for the microcapsule crack filling materials was optimal. The sunflower oil type microcapsule therefore meets the filling temperature requirement for the filler.

Distinct Changes in the Expression TAZ are Associated with Normal Cervix and Human Cervical Cancer.

The transcriptional coactivator with the PDZ-binding motif (TAZ) has been associated with different types of cancer. In this study, we examined the TAZ protein expression and cellular localization in 194 cases of human cervical squamous cell carcinoma (SCC). We observed that a normal cervix is characterized by higher expression levels of both nuclear and cytosolic TAZ compared to cervical SCC. Lower membranous and cytosolic TAZ expression levels are associated with lymph node involvement. We observed that TAZ expression levels are associated with ß1 integrin and Src in SCC and cell lines derived from human cervical cancers. Of note, knock down of TAZ increased the expression of ß1 integrin and Src in both normal and human cervical cancer cells. Our data indicate that the expression and cellular localization of TAZ are inversely associated with the development and progression of cervical SCC, and TAZ-mediated transcription may be involved in the activation of the integrin-Src signalling pathway.

MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway.

Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays. In this study, miR-21 was strikingly downregulated by metformin in a time- and dose-dependent manner. miR-21 directly targeted the 3'-UTR of PTEN and SMAD7, and negatively regulated their expression. Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-ß-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin's action and revealed significant promotion effects. Our study broadens our understanding of the regulatory mechanism of miR-21 mediating metformin-induced anti-angiogenic effects, providing important implications regarding the design of novel miRNA-based therapeutic strategies against angiogenesis.

Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets.

Type 2 diabetic mellitus (DM2) is associated with accelerated thrombotic complications and is characterized by high levels of plasminogen activator inhibitor-1 (PAI-1). Recent studies show that human platelets have high levels of miR-30c and synthesize considerable active PAI-1. The underlying mechanism of how PAI-1 expression is upregulated in DM2 is poorly understood. We now report that hyperglycaemia-induced repression of miR-30c increases PAI-1 expression and thrombus formation in DM2. Bioinformatic analysis and identification of miRNA targets were assessed using luciferase assays, quantitative real-time PCR and western blots in vitro and in vivo. The changes in miR-30c and PAI-1 levels were identified in platelets from healthy and diabetic individuals. We found that miR-30c directly targeted the 3' UTR of PAI-1 and negatively regulated its expression. miR-30c was negatively correlated with glucose and HbA1c levels in DM2. In HFD-fed diabetic mice, increasing miR-30c expression by lenti-miR-30c significantly decreased the PAI-1 expression and prolonged the time to occlusion in an arterial thrombosis model. Platelet depletion/reinfusion experiments generating mice with selective ablation of PAI-1 demonstrate a major contribution by platelet-derived PAI-1 in the treatment of lenti-miR-30c to thrombus formation. These results provide important implications regarding the regulation of fibrinolysis by platelet miRNA under diabetic mellitus.

Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia.

BACKGROUND: Angiopoietin-2 (Ang-2), a ligand of the Tie-2 receptor, plays an important role in maintaining endothelial cells and in destabilizing blood vessels. Collateral artery growth (arteriogenesis) is a key adaptive response to arterial occlusion. It is unknown whether the destabilization of blood vessels by Ang-2 can affect arteriogenesis and modulate mononuclear cell function. This study aimed to investigate the effects of Ang-2 on collateral artery growth. METHODS: Hindlimb ischaemia model was produced in C57BL/6 mice by femoral artery ligation. Blood flow perfusion was measured using a laser Doppler perfusion imager quantitative RT-PCR analysis was applied to identify the level of angiogenic factors. RESULTS: After the induction of hindlimb ischaemia, blood flow recovery was impaired in mice treated with recombinant Ang-2 protein; this was accompanied by a reduction of peri-collateral macrophage infiltration. In addition, quantitative RT-PCR analysis revealed that Ang-2 treatment decreased monocyte chemotactic protein-1 (MCP-1), platelet-derived growth factor-BB (PDGF-BB) mRNA levels in ischaemic adductor muscles. Ang-2 can lead to macrophage M1/M2 polarization shift inhibition in the ischaemic muscles. Furthermore, Ang-2 reduced the in vitro inflammatory response in macrophages and vascular cells involved in arteriogenesis. CONCLUSIONS: Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration.