Modeling Infrared Spectroscopy of Nucleic Acids: Integrating Vibrational Non-Condon Effects with Machine Learning Schemes.

Vibrational non-Condon effects, which describe how molecular vibrational transitions are influenced by a system's rotational and translational degrees of freedom, are often overlooked in spectroscopy studies of biological macromolecules. In this work, we explore these effects in the modeling of infrared (IR) spectra for nucleic acids in the 1600-1800 cm region. Through electronic structure calculations, we reveal that the transition dipole moments of the C═O and C═C stretching modes in nucleobases are highly sensitive to solvation, hydrogen bonding, and base stacking conditions.

Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis.

Background: The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0.

Methods: Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe mice among T0 and/or MGF treatment.

The Roles of Long Noncoding RNA in Depression.

Depression is a common psychiatric disorder that brings great pain and burden to patients and their families. However, the pathogenesis underlying the development of depression remains unclear, limiting the development of diagnostic and therapeutic approaches for the disease. Recently, an increasing number of studies have shown that long noncoding RNAs (lncRNAs) play modulatory roles in depression.

Prediction and design of protease enzyme specificity using a structure-aware graph convolutional network.

Site-specific proteolysis by the enzymatic cleavage of small linear sequence motifs is a key posttranslational modification involved in physiology and disease. The ability to robustly and rapidly predict protease-substrate specificity would also enable targeted proteolytic cleavage by designed proteases. Current methods for predicting protease specificity are limited to sequence pattern recognition in experimentally derived cleavage data obtained for libraries of potential substrates and generated separately for each protease variant.

Chemical features and machine learning assisted predictions of protein-ligand short hydrogen bonds.

There are continuous efforts to elucidate the structure and biological functions of short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms reside more than 0.3 Å closer than the sum of their van der Waals radii. In this work, we evaluate 1070 atomic-resolution protein structures and characterize the common chemical features of SHBs formed between the side chains of amino acids and small molecule ligands.

Histologic inflammation and collagen content are not positively correlated in human BPH.

Introduction: Recent clinical studies have implicated prostate inflammation and fibrosis in the development of bladder outlet obstruction and lower urinary tract symptoms (LUTS). Studies utilizing rodent models, including work in our laboratory, have shown prostate fibrosis to occur as a consequence of inflammation. However, the relationship between collagen content and inflammation in human tissue samples obtained from surgical treatment of benign prostatic hypererplasia (BPH)/LUTS has not to our knowledge been previously examined.

Critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages in periodontitis.

Objective: To determine the critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages during periodontitis.

Background: Cathepsin S (CatS) is a cysteine protease and exerts important roles in the immune response.

Chemical Features and Machine Learning Assisted Predictions of Protein-Ligand Short Hydrogen Bonds.

There are continuous efforts to elucidate the structure and biological functions of short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms reside more than 0.3 A closer than the sum of their van der Waals radii. In this work, we evaluate 1070 atomic-resolution protein structures and characterize the common chemical features of SHBs formed between the side chains of amino acids and small molecule ligands.

Genome-wide analysis of R2R3-MYB genes in cultivated peanut ( L.): Gene duplications, functional conservation, and diversification.

The cultivated Peanut ( L.), an important oilseed and edible legume, are widely grown worldwide. The R2R3-MYB transcription factor, one of the largest gene families in plants, is involved in various plant developmental processes and responds to multiple stresses.

Prediction and Design of Protease Enzyme Specificity Using a Structure-Aware Graph Convolutional Network.

Site-specific proteolysis by the enzymatic cleavage of small linear sequence motifs is a key post-translational modification involved in physiology and disease. The ability to robustly and rapidly predict protease substrate specificity would also enable targeted proteolytic cleavage - editing - of a target protein by designed proteases. Current methods for predicting protease specificity are limited to sequence pattern recognition in experimentally-derived cleavage data obtained for libraries of potential substrates and generated separately for each protease variant.

Targeting autophagy in atherosclerosis: Advances and therapeutic potential of natural bioactive compounds from herbal medicines and natural products.

Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS.

Assessing PDB macromolecular crystal structure confidence at the individual amino acid residue level.

Approximately 87% of the more than 190,000 atomic-level three-dimensional (3D) biostructures in the PDB were determined using macromolecular crystallography (MX). Agreement between 3D atomic coordinates and experimental data for >100 million individual amino acid residues occurring within ∼150,000 PDB MX structures was analyzed in detail. The real-space correlation coefficient (RSCC) calculated using the 3D atomic coordinates for each residue and experimental-data-derived electron density enables outlier detection of unreliable atomic coordinates (particularly important for poorly resolved side-chain atoms) and ready evaluation of local structure quality by PDB users.

Global Survey, Expressions and Association Analysis of Genes in Peanut.

Cystathionine γ-synthase (CGS), methionine γ-lyase (MGL), cystathionine β-lyase (CBL) and cystathionine γ-lyase (CGL) share the Cys_Met_Meta_PP domain and play important roles in plant stress response and development. In this study, we defined the genes containing the Cys_Met_Meta_PP domain (PF01053.20) as like genes ().

Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases.

Astrocytes play an important role in the central nervous system (CNS). Ion channels in these cells not only function in ion transport, and maintain water/ion metabolism homeostasis, but also participate in physiological processes of neurons and glial cells by regulating signaling pathways. Increasing evidence indicates the ion channel proteins of astrocytes, such as aquaporins (AQPs), transient receptor potential (TRP) channels, adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels, and P2X7 receptors (P2X7R), are strongly associated with oxidative stress, neuroinflammation and characteristic proteins in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS).

Simplified quality assessment for small-molecule ligands in the Protein Data Bank.

More than 70% of the experimentally determined macromolecular structures in the Protein Data Bank (PDB) contain small-molecule ligands. Quality indicators of ∼643,000 ligands present in ∼106,000 PDB X-ray crystal structures have been analyzed. Ligand quality varies greatly with regard to goodness of fit between ligand structure and experimental data, deviations in bond lengths and angles from known chemical structures, and inappropriate interatomic clashes between the ligand and its surroundings.

Effective prediction of short hydrogen bonds in proteins via machine learning method.

Short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms lie within 2.7 Å, exhibit prominent quantum mechanical characters and are connected to a wide range of essential biomolecular processes. However, exact determination of the geometry and functional roles of SHBs requires a protein to be at atomic resolution.

Mitochondrial Targeting Therapeutics: Promising Role of Natural Products in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, and its prevalence is still growing rapidly. However, the efficient therapies for this liver disease are still limited. Mitochondrial dysfunction has been proven to be closely associated with NAFLD.

Identification of key factors shaping integrated levels of ACE2 and TMPRSS2 expression in head and neck squamous cell carcinoma.

: To quantify the integrated levels of ACE2 and TMPRSS2, the two well-recognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry-related genes, and to further identify key factors contributing to SARS-CoV-2 susceptibility in head and neck squamous cell carcinoma (HNSC). : We developed a metric of the potential for tissue infected with SARS-CoV-2 ("TPSI") based on ACE2 and TMPRSS2 transcript levels and compared TPSI levels between tumor and matched normal tissues across 11 tumor types. For further analysis of HNSC, weighted gene co-expression network analysis (WGCNA), functional analysis, and single sample gene set enrichment analysis (ssGSEA) were conducted to investigate TPSI-relevant biological processes and their relationship with the immune landscape.

Robust estimation and variable selection for the accelerated failure time model.

This article concerns robust modeling of the survival time for cancer patients. Accurate prediction of patient survival time is crucial to the development of effective therapeutic strategies. To this goal, we propose a unified Expectation-Maximization approach combined with the L -norm penalty to perform variable selection and parameter estimation simultaneously in the accelerated failure time model with right-censored survival data of moderate sizes.

Cluster analysis of men undergoing surgery for BPH/LUTS reveals prominent roles of both bladder outlet obstruction and diminished bladder contractility.

Lower urinary tract symptoms (LUTS) in aging men are commonly attributed to bladder outlet obstruction from benign prostatic hyperplasia (BPH) but BPH/LUTS often reflects a confluence of many factors. We performed a hierarchical cluster analysis using four objective patient characteristics (age, HTN, DM, and BMI), and five pre-operative urodynamic variables (volume at first uninhibited detrusor contraction, number of uninhibited contractions, Bladder Outlet Obstruction Index (BOOI), Bladder Contractility Index (BCI) and Bladder Power at Qmax) to identify meaningful subgroups within a cohort of 94 men undergoing surgery for BPH/LUTS. Two meaningful subgroups (clusters) were identified.

Metabolic Dysregulation Contributes to the Progression of Alzheimer's Disease.

Alzheimer's disease (AD) is an incurable neurodegenerative disease. Numerous studies have demonstrated a critical role for dysregulated glucose metabolism in its pathogenesis. In this review, we summarize metabolic alterations in aging brain and AD-related metabolic deficits associated with glucose metabolism dysregulation, glycolysis dysfunction, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) deficits, and pentose phosphate pathway impairment.

Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats.

Background: Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders.

An Easy-to-Implement Hierarchical Standardization for Variable Selection under Strong Heredity Constraint.

For many practical problems, the regression models follow the strong heredity property (also known as the marginality), which means they include parent main effects when a second-order effect is present. Existing methods rely mostly on special penalty functions or algorithms to enforce the strong heredity in variable selection. We propose a novel hierarchical standardization procedure to maintain strong heredity in variable selection.

Abnormal Mitochondrial Quality Control in Neurodegenerative Diseases.

Neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis, are characterized by a progressive loss of selective neuron subtypes in the central nervous system (CNS). Although various factors account for the initiation and development of these diseases, accumulating evidence shows that impaired mitochondrial function is a prominent and common mechanism. Mitochondria play a critical role in neurons and are involved in energy production, cellular metabolism regulation, intracellular calcium homeostasis, immune responses, and cell fate.

Involvement of Cathepsins in Innate and Adaptive Immune Responses in Periodontitis.

Periodontitis is an infectious disease whereby the chronic inflammatory process of the periodontium stimulated by bacterial products induces specific host cell responses. The activation of the host cell immune system upregulates the production of inflammatory mediators, comprising cytokines and proteolytic enzymes, which contribute to inflammation and bone destruction. It has been well known that periodontitis is related to systemic inflammation which links to numerous systemic diseases, including diabetes and arteriosclerosis.