Parahydrogen-induced hyperpolarization of a Zn(II) complex using NMR signal amplification by reversible exchange (SABRE).

Although Zn(II) complexes are critical metallobiomolecules in many biological environments, no parahydrogen-based hyperpolarization technique has been reported for such species. Herein, Zn(II)-tris(2-pyridylmethyl)amine (TPA) was hyperpolarized using NMR signal amplification by reversible exchange (SABRE) as a rapid, low-cost, portable, and repeatable technique for spin hyperpolarization. The hyperpolarization of TPA was not significantly affected by Zn(II) relaxation, whereas the polarization trends with respect to magnetic fields and Zn(II) concentrations differed from those of previous reports.

Combining Multiplexed CRISPR/Cas9-Nickase and PARP Inhibitors Efficiently and Precisely Targets Cancer Cells.

Unlabelled: Triggering cancer cell death by inducing DNA damage is the primary aim of radiotherapy; however, normal cells are also damaged. In this study, we showed that delivery of only four synthetic guide RNAs with Cas9 endonuclease efficiently induced simultaneous DNA double-strand breaks, resulting in efficient cell death in a cell type-specific manner. Off-target effects of Cas9 endonuclease were prevented by using Cas9-nickase to induce DNA single-strand breaks and blocking their repair with PARP inhibitors (PARPi).

Bioprinted Patient-Derived Organoid Arrays Capture Intrinsic and Extrinsic Tumor Features for Advanced Personalized Medicine.

Heterogeneity and the absence of a tumor microenvironment (TME) in traditional patient-derived organoid (PDO) cultures limit their effectiveness for clinical use. Here, Embedded Bioprinting-enabled Arrayed PDOs (Eba-PDOs) featuring uniformly arrayed colorectal cancer (CRC) PDOs within a recreated TME is presented. This model faithfully reproduces critical TME attributes, including elevated matrix stiffness (≈7.

Parahydrogen-Induced Methylated Amino Acid Hyperpolarization and Regression-Based Hyperpolarization Enhancement Factor Prediction.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are powerful analytical tools with diverse applications in research and medicine. However, the inherently poor signal-to-noise ratios induce technical limitations, which suppress their widespread use. Hyperpolarization enhances the NMR signals by inducing highly nonequilibrated population distributions among the nuclear spin states.

Integrative assessment of mixture toxicity of household chemicals using the toxic unit approach and mode of action.

Household chemicals used daily are often combined, leading to inhalation exposure to mixtures. However, methods for assessing their toxic effects are limited. This study proposes an in vitro assay strategy for evaluating household chemical mixtures using benzalkonium chloride (BKC) and didecyldimethylammonium chloride (DDAC), a common disinfectant.

Temperature-Sensitive Magnetic Resonance Probes: Leveraging Hyperpolarized Pyridine-2-Carbaldehyde and SABRE for Real-Time Temperature Sensing.

In this study, we developed a novel approach for real-time, temperature-sensitive nuclear magnetic resonance (NMR) measurements using signal amplification by reversible exchange (SABRE). We discovered that pyridine-2-carbaldehyde (A) exhibits different behavior depending on temperature, showing high hyperpolarization efficiency. In contrast, its reversible reaction product, the hemiacetal form (A'), is not affected by temperature.

Hydramethylnon induces mitochondria-mediated apoptosis in BEAS-2B human bronchial epithelial cells.

Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity.

Oxidation Kinetics of Fluorescent Membrane Lipid Peroxidation Indicators.

The oxidation of the cellular membrane through lipid peroxidation (LPO) is linked to aging and disease. Despite the physiological importance, the chemical mechanisms underlying LPO and oxidative reactions in membranes in general remain incompletely understood, and challenges exist in translating LPO inhibitor efficacies from in vitro to in vivo. The complexity of LPO, including multiple oxidation reactions in complex membrane environments and the difficulty in quantifying reaction kinetics, underlies these difficulties.

Hepatoprotective effects of paeonol by suppressing hepatic stellate cell activation via inhibition of SMAD2/3 and STAT3 pathways.

Unlabelled: Hepatic stellate cell (HSC) activation is a key event in extracellular matrix accumulation, causing hepatic fibrosis. Therefore, identifying chemicals that inhibit HSC activation is an important therapeutic strategy for hepatic fibrosis. The aim of this study was to investigate the therapeutic effects of paeonol on HSC activation.

Melittin-Phospholipase A Synergism Is Mediated by Liquid-Liquid Miscibility Phase Transition in Giant Unilamellar Vesicles.

The primary constituents of honeybee venom, melittin and phospholipase A (PLA), display toxin synergism in which the PLA activity is significantly enhanced by the presence of melittin. It has been shown previously that this is accomplished by the disruption in lipid packing, which allows PLA to become processive on the membrane surface. In this work, we show that melittin is capable of driving miscibility phase transition in giant unilamellar vesicles (GUVs) and that it raises the miscibility transition temperature () in a concentration-dependent manner.

Home-based supportive care in advanced cancer: systematic review.

Objectives: This study systematically reviewed the literature on the effect of home-based supportive care (HbSC) programmes on the quality of life (QoL) of patients with advanced cancer.

Methods: The research question 'Do home-based supportive care programmes for patients with advanced cancer improve their QoL?' was addressed. After registering the plan with PROSPERO (CRD42022341237), literature published from 1 January 1990 to 30 May 2023 was searched on PubMed, Embase, Cochrane database, CINAHL and Web of Science, and reviewed for inclusion based on predefined criteria.

Water-Compatible and Recyclable Heterogeneous SABRE Catalyst for NMR Signal Amplification.

A water-compatible and recyclable catalyst for nuclear magnetic resonance (NMR) hyperpolarization via signal amplification by reversible exchange (SABRE) was developed. The [Ir(COD)(IMes)Cl] catalyst was attached to a polymeric resin of bis(2-pyridyl)amine (heterogeneous SABRE catalyst, HET-SABRE catalyst), and it amplified the H NMR signal of pyridine up to (-) 4455-fold (43.2%) at 1.

Organoid-Based Human Stomach Micro-Physiological System to Recapitulate the Dynamic Mucosal Defense Mechanism.

Several stomach diseases are attributed to the dysregulation of physiological function of gastric mucosal barrier by pathogens. Gastric organoids are a promising tool to develop treatment strategies for gastric infections. However, their functional features of in vivo gastric mucosal barrier and host-microbe interactions are limited due to the lack of physiological stimuli.

Real-Time Reaction Monitoring of Azide-Alkyne Cycloadditions Using Benchtop NMR-Based Signal Amplification by Reversible Exchange (SABRE).

Rufinamide, possessing a triazole ring, is a new antiepileptic drug (AED) relatively well-absorbed in the lower dose range (10 mg/kg per day) and is currently being used in antiepileptic medications. Triazole derivatives can interact with various enzymes and receptors in biological systems via diverse non-covalent interactions, thus inducing versatile biological effects. Strain-promoted azide-alkyne cycloaddition (SPAAC) is a significant method for obtaining triazoles, even under physiological conditions, in the absence of a copper catalyst.

IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines.

Unlabelled: Tumor-associated macrophages (TAM) are involved in tumor progression, metastasis, and immunosuppression. Because TAMs are highly plastic and could alter their phenotypes to proinflammatory M1 in response to environmental stimuli, reeducating TAMs has emerged as a promising approach to overcoming the challenges of solid cancer treatment. This study investigated the effect of IL9 on macrophage M1 polarization and verified its antitumor potential to retrain TAMs and promote chemokine secretion.

TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand.

Toll-like Receptor 3 (TLR3) initiates a potent anti-viral immune response by binding to double-stranded RNA ligands. Previous crystallographic studies showed that TLR3 forms a homodimer when bound to a 46-base pair RNA ligand. However, this short RNA fails to initiate a robust immune response.

Association between community-level social trust and the risk of dementia: A retrospective cohort study in the Republic of Korea.

Introduction: It is known that biological risk factors and lifestyle behaviors are important determinants of dementia. However, there has been yet to be sufficient evidence to prove that community-level social capital is one of the determinants of dementia. This retrospective cohort study is a large, long-term, population-based study that investigated the association between community-level social trust and the risk of dementia in the Republic of Korea.

Urate-lowering efficacy and renal safety of febuxostat in patients with hyperuricemia and stage 4-5 chronic kidney disease not yet on dialysis: A meta-analysis of observational studies.

Objective: The efficacy and safety of febuxostat in patients with stage 4-5 chronic kidney disease (CKD) remains unclear. We evaluated the urate-lowering efficacy and renal safety of febuxostat in patients with stage 4-5 CKD not yet on dialysis, through a meta-analysis of observational studies.

Methods: We performed a systematic search in PubMed, Ovid MEDLINE, Embase, and the Cochrane Library databases for observational studies of patients with advanced CKD starting febuxostat.

Hyperpolarization study on remdesivir with its biological reaction monitoring signal amplification by reversible exchange.

Our experiments indicate hyperpolarized proton signals in the entire structure of remdesivir are obtained due to a long-distance polarization transfer by -hydrogen. SABRE-based biological real-time reaction monitoring, by using a protein enzyme under mild conditions is carried out. It represents the first successful -hydrogen based hyperpolarization application in biological reaction monitoring.

J-shaped Relationship Between Chronic Kidney Disease and Serum Uric Acid Levels: A Cross-sectional Study on the Korean Population.

Objective: Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function This study investigated the association between uric acid levels and the risk of reduced renal function in men and women.

Methods: We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study A total of 172,970 participants (58,981 men, 113,989 women) aged 40∼79 years were included A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease.

Results: As the uric acid level increased, the risk of reduced renal function increased Moreover, for uric acid levels ≤20 mg/dL, the risk of reduced renal function was higher than that of the reference group Among the total, man, and woman groups, a statistically significant association was observed in men (OR 171, 95% CI 0945∼3111, OR 5003, 95% CI 1405∼17809, and OR 1377, 95% CI 0696∼2724, respectively).

Protective and Therapeutic Effects of an IL-15:IL-15Rα-Secreting Cell-Based Cancer Vaccine Using a Baculovirus System.

This study reports the use of the BacMam system to deliver and express self-assembling IL-15 and IL-15Rα genes to murine B16F10 melanoma and CT26 colon cancer cells. BacMam-based IL-15 and IL-15Rα were well-expressed and assembled to form the biologically functional IL-15:IL-15Rα complex. Immunization with this IL-15:IL-15Rα cancer vaccine delayed tumor growth in mice by inducing effector memory CD4 and CD8 cells and effector NK cells which are tumor-infiltrating.

Bath Ankylosing Spondylitis Disease Activity Index is Associated With the Quality of Sleep in Ankylosing Spondylitis Patients.

Objective: High disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep.

Methods: A total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates.

Results: Overall, 65% (70/107) of subjects reported poor sleep quality (PSQI>5) There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.

Effects of Alzheimer's and Vascular Pathologies on Structural Connectivity in Early- and Late-Onset Alzheimer's Disease.

Early- and late-onset Alzheimer's disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps.