Antisense oligonucleotide therapy mitigates autosomal dominant progressive hearing loss in a murine model of human DFNA2.

Hearing loss is the most common sensory disorder, with a substantial proportion caused by genetic mutations. KCNQ4, a voltage-gated potassium channel highly expressed in cochlear outer hair cells, is a common genetic etiology implicated in autosomal dominant progressive hearing loss (DFNA2). The dominant-negative KCNQ4 p.

The Antioxidant and Skin-Brightening Effects of a Novel Caffeic Acid Derivative, Caffeic Acid-3,4-Dihydroxyphenylpropanolester.

Caffeic acid (CA) is a naturally occurring polyphenol antioxidant found in coffee, tea, fruits, and vegetables, known for its strong antioxidant, anti-inflammatory, and anti-aging properties. However, its cosmetic application is limited because of poor dermal absorption due to its high polarity. This study aimed to evaluate the antioxidant and skin-brightening effects of a novel lipophilic CA derivative, CAD (caffeic acid-3,4-dihydroxyphenylpropanolester).

Machine-Learning-Based Design of Metallocene Catalysts for Controlled Olefin Copolymerization.

Polyolefins are versatile materials for various purposes, but their functionality should be fine-tuned for target applications including the mitigation of adverse environmental impacts. Producing such polymers with desired properties requires catalysts that can control polymerization at an atomistic level. However, complex reaction mechanisms and very limited experimental data make it difficult to design new efficient catalysts using conventional computational and data-driven approaches.

One-Pot Gram-Scale Synthesis of Cynandione A and Detailed Mechanistic Insights into its Regioselectivity.

Cynandione A, a natural biaryl product with a bis-acetophenone structure isolated from Cynanchi wilfordii Radix, has garnered considerable attention because of its diverse biological activities, including anti-inflammatory, neuroprotective, antioxidant, and adipogenic effects. However, the limited natural and commercial availability of cynandione A impedes large-scale evaluations, particularly in vivo studies. Herein, we report a one-pot gram-scale synthesis of cynandione A.

Rice OsDof12 enhances tolerance to drought stress by activating the phenylpropanoid pathway.

Drought is a major abiotic stress that severely affects cereal production worldwide. Although several genes have been identified that enhance the ability of rice to withstand drought stress, further research is needed to fully understand the molecular mechanisms underlying the response to drought stress. Our study showed that overexpression of rice DNA binding with one finger 12 (OsDof12) enhances tolerance to drought stress.

High-Pressure Rate Rules for Ether Alkylperoxy Radical Isomerization.

The first isomerization reaction of an alkylperoxy (RO) radical holds significant importance in low-temperature oxidation, as it governs the branching ratios of the hydroperoxyalkyl (QOOH) radicals, which influence the competition between the chain-propagation and chain-branching reactions. In this study, we systematically calculated high-pressure rate rules for the RO isomerization reaction of monoethers, exploring 5-, 6-, 7-, and 8-membered ring transition states. Primary, secondary, and tertiary carbon sites, where both the abstracting peroxy group and the abstracted hydrogen are located, were considered, with particular emphasis on distinguishing between secondary carbons adjacent (alpha) and nonadjacent to the ether functional group.

Unveiling Ru(bpy) -Encapsulated Zeolite Y as Photocatalyst: Harnessing Photocatalytic Singlet Oxygen Generation for Mustard Gas Simulant Detoxification.

This study explores the encapsulation of Ru(bpy) within Zeolite Y (ZY) to improve photocatalytic singlet oxygen generation for the degradation of a mustard gas simulant, namely 2-chloroethyl ethyl sulfide (CEES). Mustard gas simulants are known to disrupt several biological processes; thus, their effective degradation is essential. Zeolite Y, with its hierarchical structure and adjustable Si/Al ratios, is an ideal host for Ru(bpy) , significantly improving its photocatalytic efficiency and stability.

Simple and Efficient Enantioselective α-Deuteration Method of α-Amino Acids without External Chiral Sources.

Deuterium-labeled α-amino acids are useful in research related to drug discovery and biomedical science. However, a high degree of site selectivity and stereoselectivity in the deuterium incorporation process is still difficult to achieve. Herein, we report a new enantioselective deuteration method at the α-position of several amino acids without external chiral sources.

Designing solvent systems using self-evolving solubility databases and graph neural networks.

Designing solvent systems is key to achieving the facile synthesis and separation of desired products from chemical processes, so many machine learning models have been developed to predict solubilities. However, breakthroughs are needed to address deficiencies in the model's predictive accuracy and generalizability; this can be addressed by expanding and integrating experimental and computational solubility databases. To maximize predictive accuracy, these two databases should not be trained separately, and they should not be simply combined without reconciling the discrepancies from different magnitudes of errors and uncertainties.

Drug Discovery Perspectives of Antisense Oligonucleotides.

The era of innovative RNA therapies using antisense oligonucleotides (ASOs), siRNAs, and mRNAs is beginning. Since the emergence of the concept of ASOs in 1978, it took more than 20 years before they were developed into drugs for commercial use. Nine ASO drugs have been approved to date.

Short and scalable synthesis of cynandione A.

A two-step gram-scale synthesis of cynandione A is described. The key to success is the one-pot tandem oxidation/regioselective arylation of 1,4-hydroquinone in the presence of an excess amount of oxidant. Natural bond orbital charge analysis was performed in order to understand the regioselectivity of the arylation step.

Developing CRISPR/Cas9-Mediated Fluorescent Reporter Human Pluripotent Stem-Cell Lines for High-Content Screening.

Application of the CRISPR/Cas9 system to knock in fluorescent proteins to endogenous genes of interest in human pluripotent stem cells (hPSCs) has the potential to facilitate hPSC-based disease modeling, drug screening, and optimization of transplantation therapy. To evaluate the capability of fluorescent reporter hPSC lines for high-content screening approaches, we targeted EGFP to the endogenous OCT4 locus. Resulting hPSC-OCT4-EGFP lines generated expressed EGFP coincident with pluripotency markers and could be adapted to multi-well formats for high-content screening (HCS) campaigns.

Skin barrier dysfunction and filaggrin.

Skin barrier dysfunction caused by endogenous or exogenous factors can lead to various disorders such as xerosis cutis, ichthyoses, and atopic dermatitis. Filaggrin is a pivotal structural protein of the stratum corneum (SC) and provides natural moisturizing factors that play a role in skin barrier functions. Filaggrin aggregates keratin filaments, resulting in the formation of a keratin network, which binds cornified envelopes and collapse keratinocytes to flattened corneocytes.

Acid-treated waste red mud as an efficient catalyst for catalytic fast copyrolysis of lignin and polyproylene and ozone-catalytic conversion of toluene.

In this study, red mud (RM), a highly alkaline waste generated from alumina production industries, was used as a catalytic material for both fast copyrolysis of organosolv lignin (OL) and polypropylene (PP) and toluene removal under ozone at room temperature. The RM was pretreated with HCl to investigate the effect of alkalinity. In the catalytic fast copyrolysis of the OL and PP, the acid-treated RM (HRM) produced more aromatics, phenolics, and light olefins (C to C) but less oxygenates and heavy olefins (C to C) than the RM.

Quantum chemical calculations for over 200,000 organic radical species and 40,000 associated closed-shell molecules.

The stabilities of radicals play a central role in determining the thermodynamics and kinetics of many reactions in organic chemistry. In this data descriptor, we provide consistent and validated quantum chemical calculations for over 200,000 organic radical species and 40,000 associated closed-shell molecules containing C, H, N and O atoms. These data consist of optimized 3D geometries, enthalpies, Gibbs free energy, vibrational frequencies, Mulliken charges and spin densities calculated at the M06-2X/def2-TZVP level of theory, which was previously found to have a favorable trade-off between experimental accuracy and computational efficiency.

A perspective on biomass-derived biofuels: From catalyst design principles to fuel properties.

The hazards to health and the environment associated with the transportation sector include smog, particulate matter, and greenhouse gas emissions. Conversion of lignocellulosic biomass into biofuels has the potential to provide significant amounts of infrastructure-compatible liquid transportation fuels that reduce those hazardous materials. However, the development of these technologies is inefficient, due to: (i) the lack of a priori fuel property consideration, (ii) poor shared vocabulary between process chemists and fuel engineers, and (iii) modern and future engines operating outside the range of traditional autoignition metrics such as octane or cetane numbers.

Publisher Correction: Prediction of organic homolytic bond dissociation enthalpies at near chemical accuracy with sub-second computational cost.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prediction of organic homolytic bond dissociation enthalpies at near chemical accuracy with sub-second computational cost.

Bond dissociation enthalpies (BDEs) of organic molecules play a fundamental role in determining chemical reactivity and selectivity. However, BDE computations at sufficiently high levels of quantum mechanical theory require substantial computing resources. In this paper, we develop a machine learning model capable of accurately predicting BDEs for organic molecules in a fraction of a second.

Graph theory-based reaction pathway searches and DFT calculations for the mechanism studies of free radical-initiated peptide sequencing mass spectrometry (FRIPS MS): a model gas-phase reaction of GGR tri-peptide.

Graph theory-based reaction pathway searches (ACE-Reaction program) and density functional theory calculations were performed to shed light on the mechanisms for the production of [a + H], x, y, z, and [y + 2H] fragments formed in free radical-initiated peptide sequencing (FRIPS) mass spectrometry measurements of a small model system of glycine-glycine-arginine (GGR). In particular, the graph theory-based searches, which are rarely applied to gas-phase reaction studies, allowed us to investigate reaction mechanisms in an exhaustive manner without resorting to chemical intuition. As expected, radical-driven reaction pathways were favorable over charge-driven reaction pathways in terms of kinetics and thermodynamics.

Relationship of sociodemographic and anthropometric characteristics, and nutrient and food intakes with osteoarthritis prevalence in elderly subjects with controlled dyslipidaemia: a cross-sectional study.

Background And Objectives: Several studies have suggested that abnormal levels of serum cholesterol may be a major risk factor for osteoarthritis. However, no studies have been conducted to prevent osteoarthritis under controlled conditions of serum cholesterol. This study aimed to examine the relationship of sociodemographic and anthropometric characteristics, and nutrient and food intakes with osteoarthritis prevalence in Korean elderly subjects with controlled dyslipidaemia.

Common features of F-18 FDG PET/CT findings in Scrub Typhus: prospective study before and after antibiotics therapy.

Scrub typhus is an acute febrile illness caused by obligate intracellular organism Orientia tsutsugamushi. While there have been many reports on the evaluation of disease activity and infectious diseases using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), the clinical value of FDG PET/CT in scrub typhus has not been fully investigated. We enrolled 17 patients who were 18 years of age or older and clinically suspected of having scrub typhus with eschar.

Performance of ACE-Reaction on 26 Organic Reactions for Fully Automated Reaction Network Construction and Microkinetic Analysis.

Accurate analysis of complex chemical reaction networks is necessary for reliable prediction of reaction mechanism. Though quantum chemical methods provide a desirable accuracy, large computational costs are unavoidable as considering numerous reaction pathways on the networks. We proposed a graph-theoretic approach combined with chemical heuristics (named ACE-Reaction) in previous work [ Chem.

Poly(amide-imide) materials for transparent and flexible displays.

The key component currently missing for the next generation of transparent and flexible displays is a high-performance polymer material that is flexible, while showing optical and thermal properties of glass. It must be transparent to visible light and show a low coefficient of thermal expansion (CTE). While specialty plastics such as aromatic polyimides are promising, reducing their CTE and improving transparency simultaneously proved challenging, with increasing coloration the main problem to be resolved.

Efficient prediction of reaction paths through molecular graph and reaction network analysis.

Despite remarkable advances in computational chemistry, prediction of reaction mechanisms is still challenging, because investigating all possible reaction pathways is computationally prohibitive due to the high complexity of chemical space. A feasible strategy for efficient prediction is to utilize chemical heuristics. Here, we propose a novel approach to rapidly search reaction paths in a fully automated fashion by combining chemical theory and heuristics.