Exploring the mortality and cardiovascular outcomes with SGLT-2 inhibitors in patients with T2DM at dialysis commencement: a health global federated network analysis.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement. METHODS: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission. RESULTS: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions. CONCLUSIONS: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis.

Graphene-supported platinum nanoparticles prepared by a self-regulated reduction method.

Graphene-supported Pt nanoparticles were prepared by a self-regulated reduction method without using any extra reductive agent. Unassisted reduction of Pt ions by the oxygen-containing functional groups on graphene was demonstrated. X-ray diffraction (XRD) showed a (200) peak of face-centered cubic Pt crystals and energy dispersive X-ray spectroscopy (EDS) further confirmed the presence of Pt. Transmission electron microscopy (TEM) depicted good dispersion of the Pt nanoparticles on graphene. The particle sizes estimated by TEM and XRD ranged from 2 to 6 nm. In comparison, the Pt nanoparticles reduced using ethylene glycol as an extra reducing agent exhibited larger sizes, a wider spread of size distribution, and less uniform dispersion on graphene. The electrocatalytic activity of Pt on graphene was verified by cyclic voltammetry. In addition, Raman scattering spectroscopy showed an increase in D- to G-peak ratio and an effect of surface-enhanced Raman scattering for the graphene decorated with Pt nanoparticles.

One-step chromatographic purification of Helicobacter pylori neutrophil-activating protein expressed in Bacillus subtilis.

Helicobacter pylori neutrophil-activating protein (HP-NAP), a major virulence factor of Helicobacter pylori (H. pylori), is capable of activating human neutrophils to produce reactive oxygen species (ROS) and secrete inammatory mediators. HP-NAP is a vaccine candidate, a possible drug target, and a potential in vitro diagnostic marker for H. pylori infection. HP-NAP has also been shown to be a novel therapeutic agent for the treatment of allergic asthma and bladder cancer. Hence, an efficient way to obtain pure HP-NAP needs to be developed. In this study, one-step anion-exchange chromatography in negative mode was applied to purify the recombinant HP-NAP expressed in Bacillus subtilis (B. subtilis). This purification technique was based on the binding of host cell proteins and/or impurities other than HP-NAP to DEAE Sephadex resins. At pH 8.0, almost no other proteins except HP-NAP passed through the DEAE Sephadex column. More than 60% of the total HP-NAP with purity higher than 91% was recovered in the flow-through fraction from this single-step DEAE Sephadex chromatography. The purified recombinant HP-NAP was further demonstrated to be a multimeric protein with a secondary structure of α-helix and capable of activating human neutrophils to stimulate ROS production. Thus, this one-step negative chromatography using DEAE Sephadex resin can efficiently yield functional HP-NAP from B. subtilis in its native form with high purity. HP-NAP purified by this method could be further utilized for the development of new drugs, vaccines, and diagnostics for H. pylori infection.

Preparation and characterization of polypropylene-graft-thermally reduced graphite oxide with an improved compatibility with polypropylene-based nanocomposite.

Polypropylene was successfully covalently grafted onto the surface of thermally reduced graphite oxide (PP-g-TRGO) by taking advantage of the "residual oxygen-containing functional groups" and the "grafting to" method. The PP-g-TRGO obtained showed an improved compatibility, and interfacial interaction, with an isotactic PP (iPP) matrix. The iPP/PP-g-TRGO nanocomposite exhibited a dramatically improved thermal stability compared to that of neat iPP even at low loadings.

Preparation of covalently functionalized graphene using residual oxygen-containing functional groups.

When fabricated by thermal exfoliation, graphene can be covalently functionalized more easily by applying a direct ring-opening reaction between the residual epoxide functional groups on the graphene and the amine-bearing molecules. Investigation by X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and transmission electron microscopy (TEM) all confirm that these molecules were covalently grafted to the surface of graphene. The resulting dispersion in an organic solvent demonstrated a long-term homogeneous stability of the products. Furthermore, comparison with traditional free radical functionalization shows the extent of the defects characterized by TEM and Raman spectroscopy and reveals that direct functionalization enables graphene to be covalently functionalized on the surface without causing any further damage to the surface structure. Thermogravmetric analysis (TGA) shows that the nondestroyed graphene structure provides greater thermal stability not only for the grafted molecules but also, more importantly, for the graphene itself, compared to the free-radical grafting method.

Helicobacter pylori neutrophil-activating protein promotes myeloperoxidase release from human neutrophils.

Helicobacter pylori infection induces acute and chronic inflammation and plays a key role in gastric mucosal diseases. H. pylori neutrophil-activating protein (HP-NAP), one of its virulence factors, induces not only chemotactic but also oxidative burst responses of neutrophils. Activated neutrophils use myeloperoxidase (MPO) to generate many cytotoxic oxidants, which might result in gastric mucosal injury. In this study, we evaluated whether HP-NAP could promote MPO release from human neutrophils. Recombinant HP-NAP expressed in Escherichia coli was purified by two sequential gel filtration chromatographies and then subjected to syringe filtration for endotoxin removal. The purified recombinant HP-NAP assembles into a multimer with a secondary structure of the typical alpha-helix. In addition to stimulating the production of reactive oxygen species, HP-NAP is able to induce the secretion of MPO in human neutrophils. The increased MPO release from neutrophils induced by HP-NAP may be related to the pathogenesis of H. pylori-associated gastritis.