Identification and Validation of Inverse Agonists for Nuclear Receptor Subfamily 4 Group A Member 2.

Former studies indicate that nuclear receptor subfamily 4 group A member 2 (Nurr1, NR4A2), a transcription factor, is regarded as a potential therapeutic target for central nervous system diseases, and many studies have focused on the development and optimization of agonists of Nurr1. Recent studies have shown that Nurr1 is upregulated in many other diseases. However, there is still a lack of effective inverse Nurr1 agonists as a therapeutic strategy or as pharmacological tools to counteract the receptor's inherent activity.

Predictable Modulation of a Spontaneous Post-translational Modification in Living Cells.

Glycation is a nonenzymatic posttranslational modification associated with aging and disease. Because it occurs spontaneously, it is extremely difficult to control the extent of glycation at distinct sites within target proteins, especially in cellular systems. Here, we report a chemical approach, referred to as "dialAGE", that enables the site-specific control of protein glycation.

Elucidating the Role and Mechanism of Lycopene β-Cyclase from through Functional Characterization and Targeted Mutagenesis.

Lycopene β-cyclase (LCYb) serves as a pivotal gatekeeper enzyme in carotenoid biosynthesis, catalyzing an enzymatic conversion of lycopene to β-carotene. While phylogenetically widespread across life domains, structural and functional characterization of archaeal LCYbs remains conspicuously understudied. Here, we report biochemical validation and mechanistic dissection of a putative LCYb from the hypersaline-adapted archaeon (Hma-LCYb).

Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer.

Background: Ovarian cancer is a highly prevalent cancer among women with a high risk for relapse and drug resistance. Seventy eight percent of women diagnosed with ovarian cancer live for at least one year after diagnosis. Hyptolide, a natural compound, has been shown to act as an anti-inflammatory and antibacterial agent, and latest research shows that it acts as an anticancer agent.

Predictable modulation of a spontaneous post-translational modification in living cells.

Glycation is a non-enzymatic post-translational modification associated with aging and disease. Because it occurs spontaneously, it is extremely difficult to control the extent of glycation at distinct sites within target proteins, especially in cellular systems. Here we report a chemical approach, referred to as 'dialAGE', that enables the site-specific control of protein glycation.

Computational Design of a Bicyclic Peptide Inhibitor Targeting the ICOS/ICOS-L Protein-Protein Interaction.

The interaction between the inducible T-cell costimulatory molecule (ICOS) and its ligand (ICOS-L) is a critical pathway in T-cell activation and immune regulation. We computationally designed a bicyclic peptide (CP5) that inhibits the ICOS/ICOS-L protein-protein interaction (PPI). Using the structural insights derived from the ICOS/ICOS-L co-crystal structure (PDB: 6X4G) and bias-exchange metadynamics simulations (BE-META), we first designed monocyclic peptide candidates containing the β-strand (residues 51-55 YVYWQ) of ICOS-L that interact with ICOS.

Skull CT metadata for automatic bone age assessment by using three-dimensional deep learning framework.

Bone age assessment (BAA) means challenging tasks in forensic science especially in some extreme situations like only skulls found. This study aimed to develop an accurate three-dimensional deep learning (DL) framework at skull CT metadata for BAA and try to explore new skull markers. In this study, retrospective data of 385,175 Skull CT slices from 1,085 patients ranging from 16.

Bacterial cellulose and keratin reinforced PAM hydrogels for advanced dye removal: Insights from batch and QCM analyses.

Industrial wastewater, particularly from textile industries, contains toxic dyes that require practical and sustainable removal technologies. Hydrogels are potential materials for this purpose due to their high water absorption capacity, but conventional designs suffer from poor mechanical strength and limited dye adsorption efficiency. In this study, we developed a bio-based hydrogel composite by reinforcing polyacrylamide (PAM) with bacterial cellulose (BC) and keratin intermediate filaments (KIF) derived from human hair.

Risk factors for pterygium recurrence based on a retrospective study of 196 patients.

Pterygium is considered as important clinical problem due to its special characteristics such as high incidence, multi-factorial disorder and high recurrence rate. The purpose of this study is to identify the postoperative recurrence rate of pterygium and examine the association between systemic inflammation and the type of pterygium and pterygium recurrence. From January 2017 to January 2018, a total of 196 pterygium patients who received surgery were included in this study.

Molecular Dynamics (MD)-Derived Features for Canonical and Noncanonical Amino Acids.

Machine learning (ML) models have become increasingly popular for predicting and designing structures and properties of peptides and proteins. These ML models typically use peptides and proteins containing only canonical amino acids as the training data. Consequently, these models struggle to make accurate predictions for peptides and proteins containing new amino acids that are absent in the training data set (, noncanonical amino acids).

Frameworks Construction with Rhodium-Organic Cuboctahedra via Rigid Linker Incorporation.

The architectural characteristics of metal-organic frameworks (MOFs) can be examined through their net topology, which consists of nodes and linkers. A node's connectivity and site symmetry are likely the key elements influencing the net topology of MOFs. Metal-organic polyhedra (MOPs) function effectively as nodes when used as supermolecular building blocks (SBBs).

Functional Role and Mutational Analysis of the Phytoene Synthase from the Halophilic Euryarchaeon in Bacterioruberin Biosynthesis.

Phytoene synthase (PSY) is one of key enzymes in carotenogenesis that catalyze two molecules of geranylgeranyl diphosphate to produce phytoene. PSY is widespread in bacteria, archaea, and eukaryotes. Currently, functional role and catalytic mechanism of archaeal PSY homologues have not been fully clarified due to the limited reports.

Verapamil inhibits ferroptosis in septic acute lung injury by blocking L-type calcium channels.

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), result from pulmonary edema and alveolar-capillary barrier disruption due to inflammation, often triggered by conditions like sepsis. Sepsis-induced ALI (SALI) involves extensive damage to vascular endothelium and alveolar epithelium, leading to respiratory failure. Our study explores ferroptosis, an iron-dependent cell death pathway, and calcium dysregulation in SALI.

Dominant-negative mutations potentiated by the HSF1-regulated proteostasis network.

Protein mutational landscapes are sculpted by the impacts of the resulting amino acid substitutions on the protein's stability and folding or aggregation kinetics. These properties can, in turn, be modulated by the composition and activities of the cellular proteostasis network. Heat shock factor 1 (HSF1) is the master regulator of the cytosolic and nuclear proteostasis networks, dynamically tuning the expression of cytosolic and nuclear chaperones and quality control factors to meet demand.

Identification of a PANoptosis-related prognostic model in triple-negative breast cancer, from risk assessment, immunotherapy, to personalized treatment.

Background: Triple-negative breast cancer is a breast cancer subtype characterized by its challenging prognosis, and establishing prognostic models aids its clinical treatment. PANoptosis, a recently identified type of programmed cell death, influences tumor growth and patient outcomes. Nonetheless, the precise impact of PANoptosis-related genes on the prognosis of triple-negative breast cancer has yet to be determined.

β,β-Dimethylacrylalkannin, a Natural Naphthoquinone, Inhibits the Growth of Hepatocellular Carcinoma Cells by Modulating Tumor-Associated Macrophages.

Tumor-associated macrophages (TAMs) are pivotal in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), influencing various stages from initiation to metastasis. Understanding the role of TAMs in HCC is crucial for developing novel therapeutic strategies. Macrophages exhibit plasticity, resulting in M1 and M2 phenotypes, with M1 macrophages displaying antitumor properties and M2 macrophages promoting tumor progression.

β,β-Dimethylacrylalkannin, a key component of Zicao, induces cell cycle arrest and necrosis in hepatocellular carcinoma cells.

Background: β,β-Dimethylacrylalkannin (DMAKN), a natural naphthoquinone found in Zicao, a traditional Chinese medicine (TCM), serves as the designated quantitative marker in the Chinese Pharmacopoeia. Despite its established role in assessing Zicao quality, DMAKN's biological potential remains underexplored in research.

Methods: We investigated DMAKN's involvement in Zicao's anti-hepatocellular carcinoma (HCC) properties using a combination of HPLC content analysis and comprehensive bioinformatics.

Potent and Protease Resistant Azapeptide Agonists of the GLP-1 and GIP Receptors.

The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important physiological roles including glucose homeostasis and appetite suppression. Stabilized agonists of the GLP-1 receptor (GLP-1R) and dual agonists of GLP-1R and GIP receptor (GIPR) for the management of type 2 diabetes and obesity have generated widespread enthusiasm and have become blockbuster drugs. These therapeutics are refractory to the action of dipeptidyl peptidase-4 (DPP4), that catalyzes rapid removal of the two N-terminal residues of the native peptides, in turn severely diminishing their activity profiles.

New insights into thermostable iron-containing/activated alcohol dehydrogenases from hyperthermophiles.

Alcohol dehydrogenase (ADH) is an important enzyme that catalyzes alcohol oxidation and/or aldehyde reduction. As one of NAD-dependent ADH types, iron-containing/activated ADH (Fe-ADH) is ubiquitous in Bacteria, Archaea, and Eukaryotes, possessing a similar "tunnel-like" structure that is composed of a domain A in its N-terminus and a domain B in its C-terminus. A conserved "GGGS" sequence in the domain A of Fe-ADH associates with NAD, and one conserved Asp residue and three conserved His residues in the domain B are its catalytic active sites by surrounding with Fe atom, suggesting that it might employ similar catalytic mechanism.

Investigations of InO Added SiC Semiconductive Thin Films and Manufacture of a Heterojunction Diode.

This study involved direct doping of InO into silicon carbide (SiC) powder, resulting in 8.0 at% In-doped SiC powder. Subsequently, heating at 500 °C was performed to form a target, followed by the utilization of electron beam (e-beam) technology to deposit the In-doped SiC thin films with the thickness of approximately 189.

Assessing the Performance of Peptide Force Fields for Modeling the Solution Structural Ensembles of Cyclic Peptides.

Molecular dynamics simulation is a powerful tool for characterizing the solution structural ensembles of cyclic peptides. However, the ability of simulation to recapitulate experimental results and make accurate predictions largely depends on the force fields used. In our work here, we evaluate the performance of seven state-of-the-art force fields in recapitulating the experimental NMR results in water of 12 benchmark cyclic peptides, consisting of 6 cyclic pentapeptides, 4 cyclic hexapeptides, and 2 cyclic heptapeptides.

Use of antiviral drugs and incidence of Parkinson's disease in Taiwan.

Patients infected with herpes zoster might be at risk for Parkinson's disease (PD). However, antiviral drugs may impede viral deoxyribonucleic acid (DNA) synthesis. This study aimed to determine whether the currently observed association between herpes zoster and PD is consistent with previous findings, and whether antiviral drug use is associated with PD.

Arnicolide D induces endoplasmic reticulum stress-mediated oncosis via ATF4 and CHOP in hepatocellular carcinoma cells.

Endoplasmic reticulum (ER) stress can trigger various cell death mechanisms beyond apoptosis, providing promise in cancer treatment. Oncosis, characterized by cellular swelling and increased membrane permeability, represents a non-apoptotic form of cell death. In our study, we discovered that Arnicolide D (AD), a natural sesquiterpene lactone compound, induces ER stress-mediated oncosis in hepatocellular carcinoma (HCC) cells, and this process is reactive oxygen species (ROS)-dependent.