A type of phenolic compound, hydroxyacetophenone: tyrosinase inhibition mechanism evaluation by application of biochemical assay and computational molecular dynamics.

Screening and developing tyrosinase inhibitors with novel structures are notable to receive attention in the field of skin pigmentation research due to their application in hyperpigmentation control. Hydroxyacetophenone is a natural antioxidant found in the (Norwegian spruce) needles and is widely used in the cosmetic industry as an antioxidant ingredient. In this study, integrations of virtual molecular dynamics (MD) simulations and biochemical inhibition kinetics were conducted to validate the inhibitory function of hydroxyacetophenone on tyrosinase.

CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published.

Whole-genome sequencing analysis of soybean diversity across different countries and selection signature of Korean soybean accession.

Soybean is an important agricultural crop known for its high protein and oil content, contributing to essential nutritional and health benefits for humans. Domesticated in China over 5,000 years ago, soybean has since adapted to diverse environments and spread worldwide. This study aimed to investigate the genomic characteristics and population structures of 2,317 publicly available soybean whole-genome sequences from diverse geographical regions, including China, Korea, Japan, Europe, North America, and South America.

Development of pluripotent stem cell-derived epidermal organoids that generate effective extracellular vesicles in skin regeneration.

Cellular skin substitutes such as epidermal constructs have been developed for various applications, including wound healing and skin regeneration. These cellular models are mostly derived from primary cells such as keratinocytes and fibroblasts in a two-dimensional (2D) state, and further development of three-dimensional (3D) cultured organoids is needed to provide insight into the in vivo epidermal phenotype and physiology. Here, we report the development of epidermal organoids (EpiOs) generated from induced pluripotent stem cells (iPSCs) as a novel epidermal construct and its application as a source of secreted biomolecules recovered by extracellular vesicles (EVs) that can be utilized for cell-free therapy of regenerative medicine.

Diphenolic boldine, an aporphine alkaloid: inhibitory effect evaluation on α-glucosidase by molecular dynamics integrating enzyme kinetics.

Screening α-glucosidase inhibitors with novel structures is an important field in the development of anti-diabetic drugs due to their application in postprandial hyperglycemia control. Boldine is one of the potent natural antioxidants with a wide range of pharmacological activities. Virtual screening and biochemical inhibition kinetics combined with molecular dynamics simulations were conducted to verify the inactivation function of boldine on α-glucosidase.

Improving Geometric Validation Metrics and Ensuring Consistency with Experimental Data through TrioSA: An NMR Refinement Protocol.

Protein model refinement a the crucial step in improving the quality of a predicted protein model. This study presents an NMR refinement protocol called TrioSA (torsion-angle and implicit-solvation-optimized simulated annealing) that improves the accuracy of backbone/side-chain conformations and the overall structural quality of proteins. TrioSA was applied to a subset of 3752 solution NMR protein structures accompanied by experimental NMR data: distance and dihedral angle restraints.

Potent inhibition of human tyrosinase inhibitor by verproside from the whole plant of var. .

Affinity-based ultrafiltration-mass spectrometry coupled with ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry was utilised for the structural identification of direct tyrosinase ligands from a crude var. extract. False positives were recognised by introducing time-dependent inhibition in the control for comparison.

Human Activity Prediction Based on Forecasted IMU Activity Signals by Sequence-to-Sequence Deep Neural Networks.

Human Activity Recognition (HAR) has gained significant attention due to its broad range of applications, such as healthcare, industrial work safety, activity assistance, and driver monitoring. Most prior HAR systems are based on recorded sensor data (i.e.

Verproside, the Most Active Ingredient in YPL-001 Isolated from var. , Decreases Inflammatory Response by Inhibiting PKCδ Activation in Human Lung Epithelial Cells.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear.

Inhibitory effect of acarbose on tyrosinase: application of molecular dynamics integrating inhibition kinetics.

Due to its clinical and cosmetic applications, investigators have paid attention to tyrosinase (TYR) inhibitor development. In this study, a TYR inhibition study with acarbose was investigated to gain insights into the regulation of the catalytic function. Biochemical assay results indicated that acarbose was turned to be an inhibitor of TYR in a reversible binding manner and probed as a distinctive mixed-type inhibitor via measurement of double-reciprocal kinetic ( = 18.

Identification of New -methyl-piperazine Chalcones as Dual MAO-B/AChE Inhibitors.

Monoamine oxidase-B (MAO-B), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) have been considered target enzymes of depression and neurodegenerative diseases, including Alzheimer's disease (AD). In this study, seventeen -methyl-piperazine chalcones were synthesized, and their inhibitory activities were evaluated against the target enzymes. Compound (3-trifluoromethyl-4-fluorinated derivative) showed the highest selective inhibition against MAO-B with an IC of 0.

BERN2: an advanced neural biomedical named entity recognition and normalization tool.

Unlabelled: In biomedical natural language processing, named entity recognition (NER) and named entity normalization (NEN) are key tasks that enable the automatic extraction of biomedical entities (e.g. diseases and drugs) from the ever-growing biomedical literature.

Application of Computational Simulation Integrating Inhibition Kinetics for Detecting Tyrosinase Inhibitor: Salsalate Is a New Inhibitor.

Background: Tyrosinase inhibitor developments have been widely attended by investigators for their various applications.

Objective: A combination of virtual screening of docking simulations and biochemical inhibition kinetics was performed to find a new inhibitor of tyrosinase for the clinical application of an antipigment agent.

Methods: We conducted docking simulations to detect tyrosinase key binding residues and used the detected binding residues to screen the NCBI PubChem database for probing tyrosinase binding compounds.

Structural resemblance of the DNAJA-family protein, Tid1, to the DNAJB-family Hsp40.

The specific pair of heat shock protein 70 (Hsp70) and Hsp40 constitutes an essential molecular chaperone system involved in numerous cellular processes, including the proper folding/refolding and transport of proteins. Hsp40 family members are characterized by the presence of a conserved J-domain (JD) that functions as a co-chaperone of Hsp70. Tumorous imaginal disc 1 (Tid1) is a tumor suppressor protein belonging to the DNAJA3 subfamily of Hsp40 and functions as a co-chaperone of the mitochondrial Hsp70, mortalin.

Characterization and activity-folding relationship of serine protease from Antarctic krill ().

(Antarctic krill) serine protease (ESP) was investigated to gain insights into the activity-structural relationship, folding behavior, and regulation of the catalytic function. We purified ESP from the krill muscle and characterized biochemical distinctions via enzyme kinetics. Studies of inhibition kinetics and unfolding in the presence of a serine residue modifier, such as phenylmethanesulfonyl fluoride, were conducted.

A comprehensive evaluation of regression-based drug responsiveness prediction models, using cell viability inhibitory concentrations (IC50 values).

Motivation: Predicting drug response is critical for precision medicine. Diverse methods have predicted drug responsiveness, as measured by the half-maximal drug inhibitory concentration (IC50), in cultured cells. Although IC50s are continuous, traditional prediction models have dealt mainly with binary classification of responsiveness.

Pandemics are catalysts of scientific novelty: Evidence from COVID-19.

Scientific novelty drives the efforts to invent new vaccines and solutions during the pandemic. First-time collaboration and international collaboration are two pivotal channels to expand teams' search activities for a broader scope of resources required to address the global challenge, which might facilitate the generation of novel ideas. Our analysis of 98,981 coronavirus papers suggests that scientific novelty measured by the BioBERT model that is pretrained on 29 million PubMed articles, and first-time collaboration increased after the outbreak of COVID-19, and international collaboration witnessed a sudden decrease.

Second-Generation JK-206 Targets the Oncogenic Signal Mediator RHOA in Gastric Cancer.

Ras homologous A (RHOA), a signal mediator and a GTPase, is known to be associated with the progression of gastric cancer (GC), which is the fourth most common cause of death in the world. Previously, we designed pharmacologically optimized inhibitors against RHOA, including JK-136 and JK-139. Based on this previous work, we performed lead optimization and designed novel RHOA inhibitors for greater anti-GC potency.

Characterization and tissue expression analysis of mitochondrial creatine kinases (types I and II) from .

The aim of this study was to characterize the functions of the mitochondrial creatine kinases in the Chinese soft-shelled turtle (PSCK-MT1 and PSCK-MT2) to characterize function in relation to hibernation. Computational prediction via molecular dynamics simulations showed that PSCK-MT1 had stronger kinase- and creatine-binding affinity than PSCK-MT2. We measured PSCK-MT1 and PSCK-MT2 levels in the myocardium, liver, spleen, lung, kidney, and ovary of before and after hibernation and found that the expression of these enzymes was the most significantly upregulated in the ovary.

Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.

An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains. cST3Gal-I was localized to the Golgi membrane when expressed in Saccharomyces cerevisiae. Enzymatic characterization for substrate specificity and kinetic property indicate that cST3Gal-I prefers O-glycans, rather than N-glycan, of asialoglycoproteins as substrates.

Detection of Melanogenesis and Anti-Apoptosis-Associated Melanoma Factors: Array CGH and PPI Mapping Integrating Study.

Background: We investigated melanogenesis- and anti-apoptosis-related melanoma factors in melanoma cells (TXM1, TXM18, A375P, and A375SM).

Objective: To find melanoma associated hub factor, high-throughput screening-based techniques integrating with bioinformatics were investigated.

Methods: Array CGH analysis was conducted with a commercial system.

Crowdsourced identification of multi-target kinase inhibitors for RET- and TAU- based disease: The Multi-Targeting Drug DREAM Challenge.

A continuing challenge in modern medicine is the identification of safer and more efficacious drugs. Precision therapeutics, which have one molecular target, have been long promised to be safer and more effective than traditional therapies. This approach has proven to be challenging for multiple reasons including lack of efficacy, rapidly acquired drug resistance, and narrow patient eligibility criteria.

PATHOME-Drug: a subpathway-based polypharmacology drug-repositioning method.

Motivation: Drug repositioning reveals novel indications for existing drugs and in particular, diseases with no available drugs. Diverse computational drug repositioning methods have been proposed by measuring either drug-treated gene expression signatures or the proximity of drug targets and disease proteins found in prior networks. However, these methods do not explain which signaling subparts allow potential drugs to be selected, and do not consider polypharmacology, i.

Uranium In Situ Electrolytic Deposition with a Reusable Functional Graphene-Foam Electrode.

Nuclear fission produces 400 GWe which represents 11% of the global electricity output. Uranium is the essential element as both fission fuel and radioactive waste. Therefore, the recovery of uranium is of great importance.