Modular coupling MOF nanozyme with natural enzyme on hollow fiber membrane for rapid and reusable detection of H2O2 and glucose.

A novel strategy based on gradient porous hollow fiber membrane (GPF) is proposed for the modular assembly of enzyme-nanozyme cascade systems. The porous structure of GPF provided sufficient specific surface area, while the gradient structure effectively minimized the leaching of enzymes and nanozymes. To enhance stability, we prepared and immobilized metal-organic framework (MOF) nanozymes, resulting in the fabrication of GPF-MOF with excellent stability and reusability for colorimetric H2O2 detection. To improve specificity and expand the detection range, micro-crosslinked natural enzymes were modularly assembled, using glucose oxidase as the model enzyme. The assembled system, GPF-mGOx@MOF, achieved a low detection limit of 0.009 mM and a linear range of 0.2 to 11 mM. The sensor retained 87.2% and 80.7% of initial activity after being stored for 49 days and 9 recycles, respectively. Additionally, the reliability of the biosensor was validated through glucose determination of human blood and urine samples, yielding comparable results to a commercial glucose meter.

[Prognostic risk factors of catheter-related bloodstream infection in patients with maintenance hemodialysis].

OBJECTIVE: To analyze the pathogen distribution and prognostic risk factors of catheter-related bloodstream infection (CRBSI) in patients with maintenance hemodialysis (MHD) during non-hospitalization. METHODS: A retrospective comparative study was conducted. Thirty-four patients of MHD with semi-permanent catheter admitted to the department of nephrology of Gansu Provincial Hospital from January 2020 to May 2023 due to CRBSI during non-hospitalization were enrolled. The distribution characteristics of pathogens causing CRBSI in MHD patients during non-hospital period were analyzed. All patients were actively given anti-infection treatment after admission. The general data, laboratory indicators and prognosis during hospitalization were collected through the electronic medical record system. Patients were divided into poor prognosis group (14 cases) and good prognosis group (20 cases) according to the treatment results during hospitalization. Univariate and binary Logistic regression were used to analyze the risk factors affecting the prognosis of patients, and receiver operator characteristic curve (ROC curve) was drawn to evaluate its predictive value for prognosis. RESULTS: A total of 28 pathogenic bacteria were isolated from 34 patients, of which 25 were Gram-positive, Staphylococcus was the most common pathogen, accounting for 82.15% of the total, and 16 strains of Staphylococcus aureus (57.15%), including 6 methicillin-resistant Staphylococcus aureus (MRSA, 21.43%). There were 7 strains of Staphylococcus epidermidis (25.00%), including 3 strains of methicillin-resistant Staphylococcus epidermidis (MRSE, 10.71%). There were 3 strains of Gram-negative bacteria, 1 strain each of Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii. Univariate analysis showed that the fever duration of MHD patients with CRBSI in the poor prognosis group was significantly longer than that in the good prognosis group [days: 8.50 (3.75, 45.00) vs. 2.50 (1.00, 4.75), P < 0.01], serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and random blood glucose (GLU) were significantly higher than those in the good prognosis group [ESR (mm/1 h): 82.36±24.98 vs. 56.95±35.65, CRP (mg/L): 123.45±74.10 vs. 67.35±55.22, GLU (mmol/L): 8.74±3.66 vs. 6.42±1.95, all P < 0.05]. Binary Logistic regression analysis showed that serum CRP was an independent risk factor for poor prognosis in MHD patients with CRBSI [odds ratio (OR) = 1.020, 95% confidence interval (95%CI) was 1.002-1.038, P = 0.025]. ROC curve analysis showed that the area under the curve (AUC) of serum CRP in predicting poor prognosis of MHD patients with CRBSI was 0.711; when the optimal cut-off value was 104.65 mg/L, the sensitivity was 64.3% and the specificity was 85.0%, indicating that it has good predictive value. CONCLUSIONS: Gram-positive bacteria are the main pathogens of CRBSI in MHD patients during non-hospital period. The poor prognosis is mainly related to the high level of serum CRP. Serum CRP level can effectively screen the high-risk group of MHD patients with CRBSI with poor prognosis.

Coupling metal organic frameworks nanozyme with carbon nanotubes on the gradient porous hollow fiber membrane for nonenzymatic electrochemical H2O2 detection.

In this paper, we present a gradient porous hollow fiber structure integrated the signal transduction within a microspace, serving as a platform for cellular metabolism monitoring. We developed a nonenzymatic electrochemical electrode by coupling carbon nanotubes (CNT) and metal organic frameworks (MOF) nanozyme on three-dimensional (3D) gradient porous hollow fiber membrane (GPF) for in-situ detection of cell released hydrogen peroxide (H2O2). The GPF was used as a substrate for cell culture as well as the supporting matrix of the working electrode. The ultrasonically coupled CNT@MOF composite was immobilized on the outer surface of the GPF by means of pressure filtration. Notably, the MOF, acting as a peroxidase mimic, exhibits superior stability compared to traditional horseradish peroxidase. The incorporation of CNT not only provided sufficient specific surface area to improve the uniform distribution of MOF nanozyme, but also formed 3D conductive network. This network efficiently facilitates the electrons transfer during the catalytic process of the MOF, addressing the inherent poor conductivity of MOFs. The GPF-CNT@MOF nonenzymatic bioelectrode demonstrated excellent electrocatalytic performance including rapid response, satisfactory sensing selectivity, and attractive stability, which enabled the development of a robust in-situ cellular metabolic monitoring platform.

BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10.

Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low-complexity domain (LCD) of BRD4L in cells by using CRISPR-Cas9. In particular, the deletion of exon 14 (BRD4-E14) results in cellular morphological changes towards spindle-shaped and loosely packed. BRD4-E14 deficient cells show increased cell migration and reduced cell adhesion. The expression of S100A10 was significantly increased in cells lacking E14. BRD4L binds with MYC via the E14-encoded region of the LCD to inhibit the expression of S100A10. In cancer tissues, there is a positive correlation between BRD4 and MYC, while both of these proteins are negatively associated with S100A10 expression. Finally, knocking out the BRD4-E14 region or MYC promotes tumor growth in vivo. Together, these data support a tumor-suppressive role of BRD4L and MYC in some contexts. This discovery emphasizes the significance of a discreetly design and precise patient recruitment in clinical trials that testing cancer therapy based BRD4 and MYC.