COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Risk factors affecting the sleep quality of patients on dialysis: A single-center cross-sectional study.

Sleep quality is among the common complication in patients on dialysis and serious affect their health and quality of life; however, other associated risk factors are unclear. This study aimed to investigate the risk factors affecting sleep quality in patients on dialysis. Data were collected from 260 patients who met the inclusion criteria at out hospital from May 2023 to October 2023. Questionnaires were completed by patients, and biochemical indicators were obtained from past medical records. Univariate and multifactor analyses were used to find factors influencing sleep quality in patients on dialysis. Simple linear regression results showed that female, type of kidney primary disease, high systolic blood pressure (SBP), pruritus, pruritus frequency, restless legs syndrome (RLS), anxiety, and depression were associated with poor sleep quality. Blood biochemical parameters showed that low sodium and calcium levels and high ferritin levels were associated with poor sleep quality. Multiple linear regression statistics showed that female, pruritus, RLS, high SBP, depression, and high ferritin levels were associated with poor sleep quality. This study showed that female, chronic nephritis syndrome, high SBP, pruritus, RLS, low mood. and high ferritin levels were associated with poor sleep quality. Future development of individual nursing and targeted therapies is key to improving sleep quality in patients on dialysis.

E3 ubiquitin ligase RNF180 impairs IPO4/SOX2 complex stability and inhibits SOX2-mediated malignancy in ovarian cancer.

RING finger protein 180 (RNF180), an E3 ubiquitin ligase, is thought to be a tumor suppressor gene. However, the detailed mechanism of its effect on ovarian cancer (OV) has not been elucidated. Importin 4 (IPO4) which belongs to transport protein is reported to have cancer-promoting effects on OV. Here, we explored the potential signaling pathways related to RNF180 and IPO4. It was first verified that RNF180 is downregulated and IPO4 is upregulated in OV. By overexpressing or knocking down RNF180 in OV cells, we confirmed that RNF180 inhibited the malignant behaviors of OV cells both in vitro and in vivo. Bioinformatics analysis and proteomics experiments found that RNF180 could interact with IPO4 and promote the degradation of IPO4 through ubiquitination. In addition, overexpression of IPO4 removed the inhibitory effect of RNF180 on OV. We subsequently found that IPO4 could bind to the oncogene Sex determining Region Y-box 2 (SOX2). Knockdown of IPO4 in OV cells decreased SOX2 protein level in nucleus and promoted cyclin-dependent kinase inhibitory protein-1 (p21) expression. Overexpression of RNF180 also inhibited the expression of SOX2 in nucleus. All these results indicated that RNF180 inhibited the nuclear translocation of SOX2 by promoting ubiquitination of IPO4, which ultimately promoted the expression of p21 and then suppressed the progression of OV. This study verified the tumor suppressor effect of RNF180 on OV, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in OV and identified for OV.

Frailty mediated the association between tooth loss and mortality in the oldest old individuals: a cohort study.

Introduction: Tooth loss is associated with increased mortality risk; however, the mechanism underlying this is still not clear. The objective of this study was to explore whether frailty mediates the association between tooth loss and mortality risk among the oldest old individuals. Methods: The participants were followed up from 1998 to 2018 in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Frailty was constructed following a standard procedure. Mortality, frailty, and tooth loss were applied as the outcome, mediator, and independent variables, respectively. The Cox model was fitted, including possible confounders, for causal mediation analysis. A total effect (TE), an average causal mediation effect (ACME), an average direct effect (ADE), and a proportion mediated (PM) effect were calculated. Results: During the 129,936 person-years at risk, 31,899 individuals with a mean age of 91.79 years were included. The TE and ADE of severe tooth loss on mortality were 0.12 (95% CI: 0.08, 0.15) and 0.09 (95% CI: 0.05, 0.13); the ACME of frailty was 0.03 (95% CI: 0.02, 0.03) with 21.56% of the TE being mediated. Discussion: This study illustrated that tooth loss is associated with mortality, and frailty appeared to mediate the relationship. It is recommended that oral health indicators and frailty status be incorporated into routine geriatric assessments to promote optimal oral health and non-frailty status.

Electrochemical degradation of vanillin using lead dioxide electrode: influencing factors and reaction pathways.

In this study, a novel PbO2-CeO2 composite electrode was applied it to the electrocatalytic degradation of vanillin. The operating parameters such as applied current density, initial vanillin concentration, supporting electrolyte concentration and pH value were investigated and optimised. After 120 min, in a 0.10 mol L-1 Na2SO4 solution with a current density of 50 mA cm-2 and a pH value of 5.0 containing 30 mg L-1 vanillin, the vanillin removal efficiency can reach 98.03%, the COD removal efficiency is up to 73.28%. The results indicate that electrochemical degradation has a high ability to remove vanillin in aqueous solution. The reaction follows a pseudo-first-order reaction kinetics model with rate constants of 0.03036 min-1. In the process of electrochemical degradation, up to eight hydroxylated or polyhydroxylated oxidation by-products were identified through hydroxylation, dealkylation and substitution reactions. Furthermore, the degradation pathways were proposed, which eventually mineralised into inorganic water and carbon dioxide.