Altered Composition of Ceramides and Sphingomyelin Distinctly Modulates the Organizational Landscape and Microdomain Dynamics of Neuronal Plasma Membrane: A Computational Microscopy of Alzheimer's Brain.

Alzheimer's disease (AD) is one of the leading causes of death in the elderly population. Currently, there is no available therapy that can stop the disease progression. Situations are much worse due to a lack of a clear understanding of disease pathogenesis and the unavailability of an appropriate biomarker for early diagnosis.

Early preclinical development of amino acid biosynthesis pathway inhibitor DRILS-1398 as a potential anti-TB drug.

The search for new anti-tubercular agents is vital for the fight against , particularly given the rise of drug-resistant strains. DRILS-1398, a pyrazolo[4,3-]pyrimidine derivative, was discovered as a potent inhibitor of chorismate mutase (-CM) with an IC = 3.0 ± 0.

A critical appraisal of geroprotective activities of flavonoids in terms of their bio-accessibility and polypharmacology.

Flavonoids, a commonly consumed natural product, elicit health-benefits such as antioxidant, anti-inflammatory, antiviral, anti-allergic, hepatoprotective, anti-carcinogenic and neuroprotective activities. Several studies have reported the beneficial role of flavonoids in improving memory, learning, and cognition in clinical settings. Their mechanism of action is mediated through the modulation of multiple signalling cascades.

Bacterial endosymbionts of a nitrogen-fixing yeast JGTA-S1 - insights into a yet unknown micro-ecosystem.

JGTA-S1 is a yeast strain capable of fixing nitrogen and improving nitrogen nutrition in rice plants because of its nitrogen-fixing endobacteria, namely () and sp. To gain a deeper understanding of yeast endosymbionts, we conducted a whole-genome shotgun metagenomic analysis of JGTA-S1 cells grown under conditions of nitrogen sufficiency and deficiency. Our results showed that the endosymbiont population varied depending on the nitrogen regime.

Targeting next-generation PDE4 inhibitors in search of potential management of rheumatoid arthritis and psoriasis.

Immune-mediated inflammatory diseases (IMIDs) comprise a broad spectrum of conditions characterized by systemic inflammation affecting various organs and tissues, for which there is no known cure. The isoform-specific inhibition of phosphodiesterase-4B (PDE4B) over PDE4D constitutes an effective therapeutic strategy for the treatment of IMIDs that minimizes the adverse effects associated with non-selective PDE4 inhibitors. Thus, we report a new class of isoquinolone derivatives as next-generation PDE4 inhibitors for effective management of rheumatoid arthritis (RA) and psoriasis.

Cholesterol Allosterically Modulates the Structure and Dynamics of the Taurocholate Export Pump (ABCB11).

The BSEP/ABCB11 transmembrane protein translocates taurine- and glycine-conjugated bile salts across the hepatocyte bilayer driven by ATP-hydrolysis. Direct inhibition of BSEP/ABCB11 leads to idiosyncratic drug-induced liver injury. ABCB11 is localized within the cholesterol-enriched lipid raft, and membrane cholesterol depletion leads to impaired taurocholate transport.

Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

Background: Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra.

A multi-tier computational screening framework to effectively search the mutational space of SARS-CoV-2 receptor binding motif to identify mutants with enhanced ACE2 binding abilities.

SARS-CoV-2 gained crucial mutations at the receptor binding domain (RBD) that often changed the course of the pandemic leading to new waves with increased case fatality. Variants are observed with enhanced transmission and immune invasion abilities. Thus, predicting future variants with enhanced transmission ability is a problem of utmost research interest.

Preferential Ordering and Organization of Hydration Water Favor Nucleation of Ice by Ice-Nucleating Proteins over Antifreeze Proteins.

Bacteria containing ice-nucleating proteins (INPs) evolved in nature to nucleate ice at the high sub-zero ambiance. The ability of the INPs to induce order in the hydration layer and their aggregation propensity appear to be key factors of their ice nucleation abilities. However, the mechanism of the process of ice nucleation by INPs is yet to be understood clearly.

Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX.

The 12R-lipoxygenase (12R-LOX), a (non-heme) iron-containing metalloenzyme belonging to the lipoxygenase (LOX) family catalyzes the conversion of arachidonic acid (AA) to its key metabolites. Studies suggested that 12R-LOX plays a critical role in immune modulation for the maintenance of skin homeostasis and therefore can be considered as a potential drug target for psoriasis and other skin related inflammatory diseases. However, unlike 12-LOX (or 12S-LOX) the enzyme 12R-LOX did not receive much attention till date.

Antiviral Flavonoids: A Natural Scaffold with Prospects as Phytomedicines against SARS-CoV2.

Flavonoids are vital candidates to fight against a wide range of pathogenic microbial infections. Due to their therapeutic potential, many flavonoids from the herbs of traditional medicine systems are now being evaluated as lead compounds to develop potential antimicrobial hits. The emergence of SARS-CoV-2 caused one of the deadliest pandemics that has ever been known to mankind.

Number of Hydrogen Bonds per Unit Solvent Accessible Surface Area: A Descriptor of Functional States of Proteins.

Proteins function close to native and near-native conformations. These states are evolutionarily selected to ensure the effect of mutations is minimized. The structural organization of a protein is hierarchical and modular, which reduces the dimensionality of the configurational space of the native states.

investigation of the role of vitamins in cancer therapy through inhibition of MCM7 oncoprotein.

An overabundance of MCM7 protein, a component of the minichromosome maintenance complex that normally initiates DNA replication, has been reported to cause different types of cancers with aggressive malignancy. Inhibition of MCM7 may lead to a significant reduction in cancer-associated cell proliferation. Despite such significance of MCM7 in cancer, the protein structure is yet to be resolved experimentally.

Decoding the effects of spike receptor binding domain mutations on antibody escape abilities of omicron variants.

Recent times witnessed an upsurge in the number of COVID19 cases which is primarily attributed to the emergence of several omicron variants, although there is substantial population vaccination coverage across the globe. Currently, many therapeutic antibodies have been approved for emergency usage. The present study critically evaluates the effect of mutations observed in several omicron variants on the binding affinities of different classes of RBD-specific antibodies using a combined approach of immunoinformatics and binding free energy calculations.

In-Hospital Outcome In Patients With Acyanotic Congenital Heart Disease Undergoing Transcatheter Aortic Valve Replacement.

The purpose of the study was to determine the in-hospital outcome and resource utilization in patients with acyanotic congenital heart disease (ACHD) undergoing transcatheter aortic valve replacement (TAVR). Current guidelines from professional societies do not support TAVR in patients with ACHD, likely from a lack of supportive evidence. Temporal trends in patients with ACHD undergoing TAVR were determined using the 2016-2018 National Inpatient Sample database appropriate ICS-10-PCS code.

Decoding molecular factors shaping human angiotensin converting enzyme 2 receptor usage by spike glycoprotein in lineage B beta-coronaviruses.

Acquiring the human ACE2 receptor usage trait enables the coronaviruses to spill over to humans. However, the origin of the ACE2 usage trait in coronaviruses is poorly understood. Using a multi-disciplinary approach combining evolutionary bioinformatics and molecular dynamics simulation, we decode the principal driving force behind human ACE2 receptor recognition in coronaviruses.

Predictors and mortality risk of venous thromboembolism in patients with COVID-19: systematic review and meta-analysis of observational studies.

Introduction: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 disease is associated with widespread inflammation and a prothrombotic state, resulting in frequent venous thromboembolic (VTE) events. It is currently unknown whether anticoagulation is protective for VTE events. Therefore, we conducted a systematic review to identify predictors of VTE in COVID-19.

The 30-Day Readmission Rate of Same-Day Discharge Following Transcatheter Aortic Valve Implantation (from National Readmission Database 2015 to 2019).

The length of hospital stay after transcatheter aortic valve implantation (TAVI) has decreased over the years, and next-day discharge is being increasingly adopted in clinical practice. Whether further expediting discharge after TAVI by allowing same-day discharge (SDD) in selected patients is safe or derives additional benefits remains unanswered. Using the United States Nationwide Readmission Database 2015 to 2019, we identified 196,618 patients who received TAVI (mean age 79.

Impact of Pulmonary Hypertension in Patients With Hypertrophic Cardiomyopathy Presented With Cardiogenic Shock/Acute Decompensated Heart Failure.

There have been no studies focusing on how pulmonary hypertension (PH) affects inpatient outcomes in patients with hypertrophic cardiomyopathy (HCM) hospitalized for acute decompensated heart failure or cardiogenic shock. This study explores inpatient outcomes of patients with HCM, and concomitant PH compared to patients with HCM. Based on the National Inpatient Sample (NIS) 2016-2018, patients admitted with a primary diagnosis of acute decompensated heart failure or cardiogenic shock were selected.

Outcomes of rotational atherectomy followed by cutting balloon versus plain balloon before drug-eluting stent implantation for calcified coronary lesions: A meta-analysis.

Objective: The aim of this study is to compare outcomes of rotational atherectomy and cutting balloon (RACB) versus rotational atherectomy and plain balloon (RAPB) before drug-eluting stent (DES) implantation in calcified coronary lesions.

Methods: Randomized controlled trials (RCT) and observational studies comparing RACB with RAPB were identified through a systematic search of published literature across multiple databases. Random effect meta-analysis was performed to compare the outcome between the two groups.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment.

Gender-specific outcomes after percutaneous left atrial appendage closure: A nationwide readmission database analysis.

Introduction: Thromboembolism-associated stroke is the most feared complication of atrial fibrillation (AF). Percutaneous left atrial appendage closure (pLAAC) is indicated for stroke prevention in patients with AF who can not tolerate long-term anticoagulation. We aim to study gender differences in peri-procedural and readmissions outcomes in pLAAC patients.

E484K and N501Y SARS-CoV 2 spike mutants Increase ACE2 recognition but reduce affinity for neutralizing antibody.

SARS-CoV2 mutants B.1.1.