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BACKGROUND: Despite its widespread use and favored profile, there are extensive variations in the treatment outcome of metformin therapy. Furthermore, studies reported that the inter-individual variability in the occurrence of metformin treatment associated side effects were related to the differences in individual genetic profiles. Thus, this study aimed to evaluate whether the reduced function methionine deletion at codon 420 (M et420del ) variant of SLC22A1 (rs72552763) is associated with metformin induced gastrointestinal intolerance in Ethiopian patients with type 2 diabetes mellitus (T2DM)...

A novel colorimetric-fluorescent dual-mode chemosensor (JT5) based on rhodamine B has been produced for monitoring Sn4+ in the DMSO/H2 O (4:1, v/v) medium. It has high sensitivity, a low detection limit, a short response time (1 s) and high stability, and can still be maintained after two weeks with the red dual fluorescence/ colorimetric response. Enhancement of red fluorescence (591 nm) and red colorimetric (567 nm) response of JT5 by Sn4+ addition. The electrostatic potential of the sensor JT5 molecule was simulated to speculate on the sensing mechanism, and the IR, mass spectrometry and 1 H NMR titration were utilized to further demonstrate that JT5 was coordinated to Sn4+ with a 1:1 type, the rhodamine spironolactam ring of JT5 opens up to form a penta-membered ring with Sn4+ , meanwhile, its system may have chelation enhanced fluorescence (CHEF) effect...

Quantum dots (QDs) with metal fluoride surface ligands were prepared via reaction with anhydrous oleylammonium fluoride. Carboxylate terminated II-VI QDs underwent carboxylate for fluoride exchange, while InP QDs underwent photochemical acidolysis yielding oleylamine, PH3 , and InF3 . The final photoluminescence quantum yield (PLQY) reached 83% for InP and near unity for core-shell QDs. Core-only CdS QDs showed dramatic improvements in PLQY, but only after exposure to air. Following etching, the InP QDs were bound by oleylamine ligands that were characterized by the frequency and breadth of the corresponding ν(N-H) bands in the infrared absorption spectrum...

Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female gender, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers...

UNLABELLED: Computational free energy-based methods have the potential to significantly improve throughput and decrease costs of protein design efforts. Such methods must reach a high level of reliability, accuracy, and automation to be effectively deployed in practical industrial settings in a way that impacts protein design projects. Here, we present a benchmark study for the calculation of relative changes in protein-protein binding affinity for single point mutations across a variety of systems from the literature, using free energy perturbation (FEP+) calculations...

UNLABELLED: Glucocerebrosidase (GCase) is implicated in both a rare, monogenic disorder (Gaucher disease, GD) and a common, multifactorial condition (Parkinson's disease); hence, it is an urgent therapeutic target. To identify correctors of severe protein misfolding and trafficking obstruction manifested by the pathogenic L444P-variant of GCase, we developed a suite of quantitative, high-throughput, cell-based assays. First, we labeled GCase with a small pro-luminescent HiBiT peptide reporter tag, enabling quantitation of protein stabilization in cells while faithfully maintaining target biology...

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial...

BACKGROUND: Garadacimab is a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII. This study evaluated long-term efficacy, health-related quality of life (HRQoL), and safety data for garadacimab in adults with hereditary angioedema. METHODS: This global phase 2 study comprised a treatment period 1 (TP1: 12 weeks, double-blind, placebo-controlled) and a treatment period 2 (TP2: ≥44-week open-label extension). Patients aged 18-65 years with clinically confirmed hereditary angioedema were eligible...

PURPOSE: To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. PATIENTS AND METHODS: Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo...

BACKGROUND: Immune checkpoint inhibitors (ICPis) induce autoimmune diseases, including autoimmune polyendocrine syndrome type 2 (APS-2), which is defined as a combination of at least two of the following endocrinopathies: autoimmune thyroid disease, type 1 diabetes, and Addison's disease. Cases with the full triad are rare. We present a case of an elderly woman who developed APS-2 with the complete triad shortly after starting anti-programmed cell death 1 (anti-PD1) treatment and review the related literature...

Eukaryotic proteins often feature long stretches of amino acids that lack a well-defined three-dimensional structure and are referred to as intrinsically disordered proteins (IDPs) or regions (IDRs). Although these proteins challenge conventional structure-function paradigms, they play vital roles in cellular processes. Recent progress in experimental techniques, such as NMR spectroscopy, single molecule FRET, high speed AFM and SAXS, have provided valuable insights into the biophysical basis of IDP function...

Production of quality fruits in the dry and low humid October-May period has been a challenge in the tropics and sub-tropics having wide weather fluctuations throughout the year. Henceforth, the research aimed at investigating the seasonal variations in vegetative developments as well as flowering, fruiting, yield, and fruit quality of guava emphasizing the off-seasonality by pruning 0 cm (control), 15 cm, 30 cm, and 45 cm from shoot-tip, once a year at spring (early March), monsoon (early June) and autumn (early September) under such atmospheric implications...

Pediatric patients with pulmonary arterial hypertension (PAH) are commonly treated with the prostacyclin analog treprostinil in IV, SQ, inhaled or oral form, or the prostacyclin receptor agonist selexipag. Patients who transition between these medications often follow recommendations for gradual up- and down-titrations that take place over several days in the hospital or several weeks as an outpatient. However, hospital resources are limited, and long transitions are inconvenient for patients and families. We report a case series of eight pediatric patients with PAH transitioned directly between prostacyclins with no overlapping doses...

Continuous peripheral nerve block catheters are simple in concept: percutaneously inserting a catheter adjacent to a peripheral nerve. This procedure is followed by local anesthetic infusion via the catheter that can be titrated to effect for extended anesthesia or analgesia in the perioperative period. The reported benefits of peripheral nerve catheters used in the surgical population include improved pain scores, decreased narcotic use, decreased nausea/vomiting, decreased pruritus, decreased sedation, improved sleep, and improved patient satisfaction...

This study investigates unexpected competitive host-guest interactions of β-cyclodextrin which can occur with polymers in aqueous solution, using the examples of the two polymers poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) and poly(glycerol mono methacrylate) (PGMA). Systematic structural modifications of the polymer provide insight into the host-guest interaction with β-cyclodextrin and the competition between side chains and end groups such as hydrophobic end groups remaining from reversible addition fragmentation chain transfer (RAFT) polymerization or intentionally implemented molecular recognition units such as arylazopyrazole (AAP) photoswitches...

Pincer type coumarin based N-substituted semicarbazone ligands HL1-4 and their corresponding ruthenium(II) complexes (1-4) were synthesized, analyzed and confirmed by various spectro analytical techniques. The molecular structure of the ligand HL3 and complex 3 was confirmed by single crystal X-ray diffraction analysis. The stoichiometry of complexes 1, 2 and 4 was confirmed by high resolution mass spectroscopy (HRMS). The binding affinity of the compounds with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was established by absorption and emission titration methods...

A Schiff-base Ethyl (E)-2-(3-((2-carbamothioylhydrazono)methyl)-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (TZTS) dual functional colorimetric and photoluminescent chemosensor which includes thiazole and thiosemicarbazide has been synthesized to detect arsenic (As3+ ) ions selectively in DMSO: H2 O (7:3, v/v) solvent system. The molecular structure of the probe was characterized via FT-IR, 1 H, and 13 C NMR & HRMS analysis. Interestingly, the probe exhibits a remarkable and specific colorimetric and photoluminescence response to As3+ ions when exposed to various metal cations...

Selective recognition of fructosyl amino acids in water by arylboronic acid-based receptors is a central field of modern supramolecular chemistry that impacts biological and medicinal chemistry. Fructosyl valine (FV) and fructosyl glycyl histidine (FGH) occur as N-terminal moieties of human glycated hemoglobin; therefore, the molecular design of biomimetic receptors is an attractive, but very challenging goal. Herein, we report three novel cationic Zn-terpyridine complexes bearing a fluorescent N -quinolinium nucleus covalently linked to three different isomers of strongly acidified phenylboronic acids ( ortho -, 2Zn; meta -, 3Zn and para -, 4Zn) for the optical recognition of FV, FGH and comparative analytes (D-fructose, Gly, Val and His) in pure water at physiological pH...

UNLABELLED: Reduced susceptibility to ART, the first-line treatment against malaria, is common in South East Asia (SEA). It is associated with point mutations, mostly in kelch13 ( k13 ) but also in other genes, like ubp1 . K13 and its compartment neighbors (KICs), including UBP1, are involved in endocytosis of host cell cytosol. We tested 135 mutations in KICs but none conferred ART resistance. Double mutations of k13 C580Y with k13 R539T or k13 C580Y with ubp1 R3138H, did also not increase resistance...