Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.

It has been challenging to determine how a ligand that binds to a receptor activates downstream signaling pathways and to predict the strength of signaling. The challenge is compounded by functional selectivity, in which a single ligand binding to a single receptor can activate multiple signaling pathways at different levels. Spectroscopic studies show that in the largest class of cell surface receptors, 7 transmembrane receptors (7TMRs), activation is associated with ligand-induced shifts in the equilibria of intracellular pocket conformations in the absence of transducer proteins.

Ligand Reorganization for End-Point Binding Free Energy Calculations: Identifying Preferred Poses of Fentanyls in the μ Opioid Receptor.

We have developed a method that uses energy landscapes of unbound and bound ligands to compute reorganization free energies for end-point binding free-energy calculations. The method is applied to our previous simulations of fentanyl derivatives bound to the μ opioid receptor in different orientations. Whereas the mean interaction energy provides an ambiguous ranking of binding poses, interaction entropy and ligand reorganization strongly penalize geometric decoys such that native poses observed in CryoEM structures are best ranked.

Enzyme kinetics model for the coronavirus main protease including dimerization and ligand binding.

The coronavirus main protease (MPro) plays a pivotal role in viral replication and is the target of several antivirals against SARS-CoV-2. In some species, CRCs of MPro enzymatic activity can exhibit biphasic behavior in which low ligand concentrations activate the enzyme whereas higher ones inhibit it. While this behavior has been attributed to ligand-induced dimerization, quantitative enzyme kinetics models have not been fit to it.

The kinetics of a light irradiation enhanced room temperature NO gas sensor using hybrid ZnO/ZnTe nanorod structures.

This study focuses on fabricating a hybrid structure consisting of ZnO nanorods and ZnTe nanoparticles for NO gas detection, particularly exploring the impact of light irradiation at room temperature (RT). The morphology, physical characteristics, and chemical properties of the ZnO/ZnTe hybrid structure are carefully studied under diverse analytical methods such as X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and other measurements. The ZnO/ZnTe composite displayed an improved response toward 500 ppb NO under the blue light radiation effect.

Intracellular pocket conformations determine signaling efficacy through the opioid receptor.

It has been challenging to determine how a ligand that binds to a receptor activates downstream signaling pathways and to predict the strength of signaling. The challenge is compounded by functional selectivity, in which a single ligand binding to a single receptor can activate multiple signaling pathways at different levels. Spectroscopic studies show that in the largest class of cell surface receptors, 7 transmembrane receptors (7TMRs), activation is associated with ligand-induced shifts in the equilibria of intracellular pocket conformations in the absence of transducer proteins.

HPTLC sequentially coupled to UV and SERS: A cost-effective tool for confirmative identification and quantitation of sildenafil in falsified herbal products.

The detection of falsified drugs usually requires multi-disciplinary analysis for confirmative identification. Among hyphenated techniques with high specificity detection, thin-layer chromatography coupled with surface-enhanced Raman spectroscopy (TLC-SERS) is an efficient choice, especially for herbal products with diversified matrix. In this study, HPTLC was coupled to two detection techniques: UV absorption and Raman scattering with silver colloid enhancement for the analysis of sildenafil adulterated in herbal products.

Investigations on corrosion resistance of steel coated with chromium-free ZTM conversion coating.

Chromium-free conversion coatings based on Zr/Ti/Mo (ZTM) compounds via chemical conversion technology were investigated to improve the corrosion performance of SPCC-JISG 31 steels. A preliminary study was carried out to evaluate the influences of critical parameters, including the concentrations of active species Zr, Ti and Mo, and the conversion bath's pH, on the protective efficiency using a Statistical design of experiments (DoE) methodology. Passivation layer with compositional Mo, Ti and Zr elements has been employed on the steels by dipping in mixed solutions containing 17 g/l NaMoO, 1 g/l KTiF and 7 g/l KZrF under pH = 5.

Edible river fish-derived extended-spectrum β-lactamase (ESBL)-producing Enterobacterales harboring transferable plasmids encoding , , and .

Transmission of extended-spectrum β-lactamase (ESBL) genes has increased the global prevalence of ESBL-producing bacteria, especially in developing countries. Human infection with these bacteria may be food-mediated but has not been fully elucidated. Therefore, we aimed to examine ESBL-producing bacteria in edible river fish and elucidate their potential for horizontal gene transfer.

Readiness for interprofessional education among health profession lecturers at a University in Vietnam: A cross-sectional study.

Interprofessional education is acknowledged as an efficacious strategy for fostering collaboration among healthcare professionals, especially in developing countries where interdisciplinarity and cooperation among healthcare practitioners are notably deficient. The present study aimed to investigate the readiness among medical, pharmacy, public health, and nursing faculties for development of an IPE curriculum at a university in Vietnam. Employing a quantitative approach, the revised version of the Readiness for Interprofessional Learning Scale (RIPLS) questionnaire, comprising 19 items, was utilized to gather data from sixty-nine lecturers, including 26 medicine, 23 pharmacy, 11 public health, and 9 nursing faculties.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Evaluating compliance with the care standard of proactively assessing bone health in patients with diabetes: a pilot audit of practice across Asia by the Asia Pacific Consortium on Osteoporosis (APCO).

Unlabelled: This pilot audit explored how bone health is assessed patients with diabetes in diverse centres across Asia. Only 343 of 1092 (31%) audited patients had a bone health assessment, 27% of whom were diagnosed with osteoporosis. Quality improvement strategies are needed to address gaps in patient care in this area.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

ESBL-producing harboring a plasmid encoding IS up and down stream of ,, and isolated from an edible river fish.

Extended-spectrum β-lactamase-producing was isolated from an edible river fish, , which was sold in a market located in Vietnam. The genome sequence was obtained by using next-generation sequencing, which involved Oxford Nanopore and Illumina technologies. The 92 kb plasmid encodes the gene .

Effectiveness of pulmonary valve-sparing strategy for transatrial-transpulmonary repair of tetralogy of Fallot: a single institution experience.

Objective: We report the midterm results of our strategy utilizing transatrial-transpulmonary repair for tetralogy of Fallot at a single institution in a low-middle income country.

Methods: Medical records were retrospectively reviewed for 532 consecutive patients who underwent definitive repair of tetralogy of Fallot at our institution from 2010 to 2020.

Results: The median age and weight of patients in the study patients were 11.

Small bowel perforation due to ingested frog bone: a case report.

Perforation of the gastrointestinal tract by ingested foreign body is an uncommon surgical emergency, most typically associated with the consumption of fish and chicken bones. We present an unusual case of a gentleman presenting emergently with an acute abdomen following ingestion of a meal containing frog meat. Emergent computed tomography (CT) revealed findings suggestive of jejunal perforation due to a foreign body.

On Inactivation of the Coronavirus Main Protease.

A deeper understanding of the inactive conformations of the coronavirus main protease (MPro) could inform the design of allosteric drugs. Based on extensive molecular dynamics simulations, we built a Markov State Model to investigate structural changes that can inactivate the SARS-CoV-2 MPro. In a subset of structures, one subunit of the homodimer assumes an inactive conformation that resembles an inactive crystal structure.

Symptoms, Mental Health, and Quality of Life Among Patients After COVID-19 Infection: A Cross-sectional Study in Vietnam.

Objectives: This study was conducted to characterize the symptoms, mental health, quality of life (QoL), and associated factors following the coronavirus disease 2019 (COVID-19) infection.

Methods: This cross-sectional study included 394 participants previously infected with COVID-19 in Ho Chi Minh City, Vietnam. Mental health was assessed using the 21-item Depression, Anxiety, and Stress Scale (DASS-21).

Learned mappings for targeted free energy perturbation between peptide conformations.

Targeted free energy perturbation uses an invertible mapping to promote configuration space overlap and the convergence of free energy estimates. However, developing suitable mappings can be challenging. Wirnsberger et al.

Detection of chromosome-mediated bla-carrying Aeromonas spp. in the intestinal contents of fresh water river fish in Ho Chi Minh City, Vietnam.

The spread of antibiotic-resistant bacteria is a global problem that should be addressed through the perspective of the "one health" concept. The purpose of this study was to determine the contamination rate of antibiotic-resistant Aeromonas spp. in fresh water river fish purchased from a fish market in Vietnam.

Bayesian Regression Quantifies Uncertainty of Binding Parameters from Isothermal Titration Calorimetry More Accurately Than Error Propagation.

We compare several different methods to quantify the uncertainty of binding parameters estimated from isothermal titration calorimetry data: the asymptotic standard error from maximum likelihood estimation, error propagation based on a first-order Taylor series expansion, and the Bayesian credible interval. When the methods are applied to simulated experiments and to measurements of Mg(II) binding to EDTA, the asymptotic standard error underestimates the uncertainty in the free energy and enthalpy of binding. Error propagation overestimates the uncertainty for both quantities, except in the simulations, where it underestimates the uncertainty of enthalpy for confidence intervals less than 70%.

Effects of Peripheral Nerve Injury on the Induction of c-Fos and Phosphorylated ERK in the Brainstem Trigeminal Sensory Nuclear Complex.

Background: Sequential changes in brainstem and spinal cord neurons after traumatic injury to peripheral nerves are related to neuropathic pain symptoms.

Purpose: This study was conducted to elucidate the influence of nerve insult on stimulus-induced c-Fos expression and ERK phosphorylation by brainstem neurons.

Methods: The brainstem trigeminal sensory nuclear complex (BTSNC) was examined for neuronal profiles immunolabeled with c-Fos and phosphorylated ERK (p-ERK) antibodies elicited by stimulation of the tongue with capsaicin after lingual or inferior alveolar nerve (IAN) injury.