Discovery of Dual Targeting GSK-3β/HIV-1 Reverse Transcriptase Inhibitors as Neuroprotective Antiviral Agents.

Glycogen synthase kinase-3 beta (GSK-3β or GSK-3B) is a serine-threonine kinase involved in various pathways and cellular processes. Alteration in GSK-3β activity is associated with several neurological diseases including Alzheimer's disease (AD), bipolar disorder, and rare diseases like Rett syndrome. GSK-3β is also implicated in HIV-associated dementia (HAD), as it is upregulated in HIV-1-infected cells and plays a role in neuronal dysfunction.

Wave Function Localization Reduces the Bandgap of Disordered Double Perovskite CsAgBiBr.

Double perovskite CsAgBiBr is a promising alternative to lead-based perovskites with excellent stability and attractive optoelectronic properties. However, a relatively large bandgap severely limits its performance in many applications such as solar cells and photodetectors. It has been reported that a random distribution of Ag and Bi atoms in CsAgBiBr effectively reduces its bandgap without introducing dopants or impurities, while the mechanism remains unclear.

Comparison of the Results of Modeling Pulmonary Fibrosis in Sprague Dawley Rats by Intratracheal Administration of Bleomycin in the Form of Sulfate and Chloride at a Dose of 3 mg/kg.

: Intratracheal administration of bleomycin (BLM) to laboratory rodents is a standard, widely used technique used to model pulmonary fibrosis (PF). BLM, as a modeling agent, is produced mainly in the form of two salts-sulfate and chloride. We compared the results of modeling PF in SD rats by intratracheal administration of BLM sulfate and BLM chloride.

Dynamic features of virus protein 1 and substitutions in the 3-phenyl ring determine the potency and broad-spectrum activity of capsid-binding pyrazolo[3,4-d]pyrimidines against rhinoviruses.

Pyrazolo[3,4-d]pyrimidines represent one potent class of well tolerated and highly active rhinovirus (RV) inhibitors that act as capsid binders. The lead compound OBR-5-340 inhibits a broad-spectrum of RVs. Aiming to improve lead activity, we evaluated the impact of structural modifications in the 3-phenyl ring of OBR-5-340 on its potency and spectrum of anti-RV activity vitro.

The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.

Aims: The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M.

La(FeCuMnMgTi)O High-Entropy Oxide Nanoparticles as Highly Efficient Catalysts for Solvent-Free Aerobic Oxidation of Benzyl Alcohol.

In this work, a solid-state method for the synthesis of perovskite La(FeCuMnMgTi)O high-entropy oxide (HEO) nanoparticles is detailed. Additionally, the high performance of these nanoparticles as catalysts in the aerobic and solvent-free oxidation of benzyl alcohol is demonstrated. The structural features of HEO nanoparticles are studied by X-ray diffraction and high-resolution transmission electron microscopy.

Origin of the Improved Photoelectrochemical and Photocatalytic Activity in a ZnO-TiO Nanohybrid Revealed by Experimental and Density Functional Theory Studies.

Heterojunctions of metal oxides have attracted a great deal of attention as photo (electro) catalysts owing to their excellent photoactivity. While multiple fundamental studies have been dedicated to heteroaggregation, self-assembly of oppositely charged particles to obtain heterojunctions for energy applications has been underexplored. Herein, we report the synthesis of ZnO-TiO heterojunctions using the electrostatic self-assembly approach.

Mutational spectrum and genotype-phenotype correlation in Mexican patients with infantile-onset and late-onset Pompe disease.

Background: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients.

Methods: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency.

On the utility of ultrafast MS1-only proteomics in drug target discovery studies based on thermal proteome profiling method.

Advances in high-throughput high-resolution mass spectrometry and the development of thermal proteome profiling approach (TPP) have made it possible to accelerate a drug target search. Since its introduction in 2014, TPP quickly became a method of choice in chemical proteomics for identifying drug-to-protein interactions on a proteome-wide scale and mapping the pathways of these interactions, thus further elucidating the unknown mechanisms of action of a drug under study. However, the current TPP implementations based on tandem mass spectrometry (MS/MS), associated with employing lengthy peptide separation protocols and expensive labeling techniques for sample multiplexing, limit the scaling of this approach for the ever growing variety of drug-to-proteomes.

Modulating mycobacterial envelope integrity for antibiotic synergy with benzothiazoles.

Developing effective tuberculosis drugs is hindered by mycobacteria's intrinsic antibiotic resistance because of their impermeable cell envelope. Using benzothiazole compounds, we aimed to increase mycobacterial cell envelope permeability and weaken the defenses of , serving as a model for Initial hit, BT-08, significantly boosted ethidium bromide uptake, indicating enhanced membrane permeability. It also demonstrated efficacy in the -zebrafish embryo infection model and -infected macrophages.

Ferroelectric Polarization and Single-Atom Catalyst Synergistically Promoting CO Photoreduction of CuBiPSe.

Further improving the activity and selectivity of photocatalytic CO reduction remains a challenge. Herein, we propose a new strategy for synergistically promoting photocatalytic CO reduction by combining two-dimensional (2D) ferroelectric polarization and single-atom catalysis. Our calculations showed that the ferroelectric polarization of CuBiPSe provides the internal driving force for the separation and migration of photogenerated carriers, which provides a prerequisite for enhancing the photocatalytic efficiency.

Rapid building block-economic synthesis of long, multi--GalNAcylated MUC5AC tandem repeat peptides.

The study of mucin function requires access to highly -glycosylated peptides with multiple tandem repeats. Solid-phase synthesis would be a suitable method, however, the central problem in the synthesis of mucin glycopeptides is the need to use precious and potentially vulnerable glycoamino acid building blocks in excess. In this article, we report the development of a method based on SPPS and native chemical ligation/desulfurization chemistry that allows the rapid, reliable, and glyco-economical synthesis of long multi--GalNAcylated peptides.

Radiation Hormesis in Barley Manifests as Changes in Growth Dynamics Coordinated with the Expression of , , and .

The stimulation of growth and development of crops using ionising radiation (radiation hormesis) has been reported by many research groups. However, specific genes contributing to the radiation stimulation of plant growth are largely unknown. In this work, we studied the impact of the low-dose γ-irradiation of barley seeds on the growth dynamics and gene expression of eight barley cultivars in a greenhouse experiment.

Molecular mechanism of rhinovirus escape from the Pyrazolo[3,4-d]pyrimidine capsid-binding inhibitor OBR-5-340 via mutations distant from the binding pocket: Derivatives that brake resistance.

Rhinoviruses (RVs) cause the common cold. Attempts at discovering small molecule inhibitors have mainly concentrated on compounds supplanting the medium chain fatty acids residing in the sixty icosahedral symmetry-related hydrophobic pockets of the viral capsid of the Rhinovirus-A and -B species. High-affinity binding to these pockets stabilizes the capsid against structural changes necessary for the release of the ss(+) RNA genome into the cytosol of the host cell.

Determination of alkaloid-inspired molecule vindeburnol in rabbit plasma by UPLC-HRMS and its application to pharmacokinetic studies and preliminary metabolite identification.

The eburnamine-vincamine alkaloids exhibit a range of pharmacological activities. There is a limited understanding of the pharmacokinetics and pharmacodynamics of vindeburnol, a synthetic derivative of this chemical class of alkaloids. A fast and reliable UPLC-HRMS method was developed and validated to quantify vindeburnol in Soviet Chinchilla rabbit plasma from pharmacokinetics studies.

[On the study of postmortem tissue changes' dynamics according to impedance metrics data].

Objective: To find a way and form of presenting impedance metrics data to clarify prescription of death coming in a comprehensive assessment.

Material And Methods: The impedance of biological objects was measured depending on prescription of death coming in standardized conditions (air temperature +4 °C, humidity 45%). The main examined postmortem period was 1 months.

1-Sulfonyl-3-amino-1-1,2,4-triazoles as Yellow Fever Virus Inhibitors: Synthesis and Structure-Activity Relationship.

Yellow fever virus (YFV) transmitted by infected mosquitoes causes an acute viral disease for which there are no approved small-molecule therapeutics. Our recently developed machine learning models for YFV inhibitors led to the selection of a new pyrazolesulfonamide derivative with acceptable activity. We report that the -phenyl-1-(phenylsulfonyl)-1-1,2,4-triazol-3-amine class, which was recently identified as active non-nucleoside reverse transcriptase inhibitors against HIV-1, can also be repositioned as inhibitors of yellow fever virus replication.

Ultra-Fast Mass Spectrometry in Plant Biochemistry: Response of Winter Wheat Proteomics to Pre-Sowing Treatment with Iron Compounds.

In recent years, ultrafast liquid chromatography/mass spectrometry methods have been extensively developed for the use in proteome profiling in biochemical studies. These methods are intended for express monitoring of cell response to biotic stimuli and elucidation of correlation of molecular changes with biological processes and phenotypical changes. New technologies, including the use of nanomaterials, are actively introduced to increase agricultural production.

Uterus a novel phenotype associated with new genetic variants. A case report.

Objectives: To report the first Mexican case with two novel mutations causing primary ovarian failure, uterus , and early-onset dementia secondary to leukoencephalopathy.

Methods: Detailed clinical, clinimetric, neuroimaging features, muscle biopsy with biochemical assays of the main oxidative phosphorylation complexes activities, and molecular studies were performed on samples from a Mexican female.

Results: We present a 41-year-old female patient with learning difficulties since childhood and primary amenorrhea who developed severe cognitive, motor, and behavioral impairment in early adulthood.

Multi-Omics Analysis of Responses to Chronic Radiation Exposure in the Chernobyl Exclusion Zone.

Our understanding of the long-term consequences of chronic ionising radiation for living organisms remains scarce. Modern molecular biology techniques are helpful tools for researching pollutant effects on biota. To reveal the molecular phenotype of plants growing under chronic radiation exposure, we sampled L.

Pyrrolo[2,3-]indazole as a novel chemotype for both influenza A virus and pneumococcal neuraminidase inhibitors.

Influenza infections are often exacerbated by secondary bacterial infections, primarily caused by . Both respiratory pathogens have neuraminidases that support infection. Therefore, we hypothesized that dual inhibitors of viral and bacterial neuraminidases might be an advantageous strategy for treating seasonal and pandemic influenza pneumonia complicated by bacterial infections.