Holtbanks5347

Initial kinetic experiments with this catalyst revealed a first order in chemical oxidant and a half order in catalyst. This implies a rate-determining oxidation step from a dimeric species that needs to break up to generate the active catalyst. These findings lay the foundation for the rational design of molecular nickel catalysts for water oxidation and highlight that catalyst design rules are not generally applicable for different metals.The aim of the study was to explore the mechanism of mesenchymal stem cell-derived exosomes (MSC-EXO) to protect against experimentally induced pulmonary hypertension (PH). Monocrotaline (MCT)-induced rat model of PH was successfully established by a single intraperitoneal injection of 50 mg/kg MCT, 3 weeks later the animals were treated with MSC-EXO via tail vein injection. Post-operation, our results showed that MSC-EXO could significantly reduce right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index, attenuate pulmonary vascular remodelling and lung fibrosis in vivo. In vitro experiment, the hypoxia models of pulmonary artery endothelial cell (PAEC) and pulmonary vascular smooth muscle cell (PASMC) were used. We found that the expression levels of Wnt5a, Wnt11, BMPR2, BMP4 and BMP9 were increased, but β-catenin, cyclin D1 and TGF-β1 were decreased in MSC-EXO group as compared with MCT or hypoxia group in vivo or vitro. However, these increased could be blocked when cells were transfected with Wnt5a siRNA in vitro. Taken together, these results suggested that the mechanism of MSC-EXO to prevent PH vascular remodelling may be via regulation of Wnt5a/BMP signalling pathway.

Most older Americans use drug therapies for chronic conditions. Several are associated with risk of Alzheimer's disease and related dementias (ADRD).

A scoping review was used to identify drug classes associated with increasing or decreasing ADRD risk. We analyzed size, type, and findings of the evidence.

We identified 29 drug classes across 11 therapeutic areas, and 404 human studies. Most common were studies on drugs for hypertension (93) or hyperlipidemia (81). Fewer than five studies were identified for several anti-diabetic and anti-inflammatory drugs. Evidence was observational only for beta blockers, proton pump inhibitors, benzodiazepines, and disease-modifying anti-rheumatic drugs. #link# For 13 drug classes, 50% or more of the studies reported consistent direction of effect on risk of ADRD.

Future research targeting drug classes with limited/non-robust evidence, examining sex, racial heterogeneity, and separating classes by molecule, will facilitate understanding of associated risk, and inform clinical and policy efforts to alleviate the growing impact of ADRD.

Future research targeting drug classes with limited/non-robust evidence, examining sex, racial heterogeneity, and separating classes by molecule, will facilitate understanding of associated risk, and inform clinical and policy efforts to alleviate the growing impact of ADRD.

Triggering receptor expressed on myeloid cells-2 (TREM2) is an immune receptor expressed on microglia that also can become soluble (sTREM2). How compound library chemical remains poorly understood.

We used comprehensive biolayer interferometry (BLI) analysis to investigate TREM2 and sTREM2 interactions with apolipoprotein E (apoE) and monomeric amyloid beta (Aβ) (mAβ42).

TREM2 engagement of apoE was protein mediated with little effect of lipidation, showing slight affinity differences between isoforms (E4>E3>E2). Another family member, TREML2, did not bind apoE. Disease-linked TREM2 variants within a "basic patch" minimally impact apoE binding. Instead, TREM2 uses a unique hydrophobic surface to bind apoE, which requires the apoE hinge region. TREM2 and sTREM2 directly bind mAβ42 and potently inhibit Aβ42 polymerization, suggesting a potential role for soluble sTREM2 in preventing AD pathogenesis.

These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.

These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.

This study examined the possible associations between frailty and patient-reported outcomes (PROs) in elderly patients with asthma.

Participants completed the Kihon Checklist for frailty screening as well as the following tools for measuring generic- and disease-specific health-related quality of life (HRQOL) and asthma control; the Medical Outcomes Study 36-item short form (SF-36), the Hyland Scale (global scale), the Asthma Quality of Life Questionnaire (AQLQ), the Asthma Control Test (ACT), and the Asthma Control Questionnaire (ACQ).

Of 69 consecutive outpatients with asthma, 38 (55.1%), 21 (30.4%), and 10 (14.5%) were classified as robust, pre-frail, and frail, respectively. Eight out of 52 patients with asthma in the elderly (AIE) (>65 years old) (15.4%) were considered as being frail. The Kihon Checklist total score was significantly correlated with all the scores obtained from the SF-36, Hyland Scale, AQLQ, ACT, and ACQ. All these scores were significantly different between groups with and without frailty. From the viewpoint of correlation coefficient, SF-36 Physical Functioning correlated most strongly with a coefficient of -0.68 (P < .01), and the Hyland Scale score was second (R

= -0.46, P < .01). The correlations between the Kihon Checklist total score and lung function parameters were weak or negative (|R

| < 0.35).

There were significant associations between frailty and PROs, particularly generic perception of HRQOL. Since the Kihon Checklist and PROs such as the HRQOL overlap somewhat in their evaluation of the patients' condition, there might be some similarities in the conceptual frameworks of frailty and quality of life.

There were significant associations between frailty and PROs, particularly generic perception of HRQOL. Since the Kihon Checklist and PROs such as the HRQOL overlap somewhat in their evaluation of the patients' condition, there might be some similarities in the conceptual frameworks of frailty and quality of life.