The increasing utilization of artificial intelligence algorithms in drug development has proven to be highly efficient and effective. One area where deep learning-based approaches have made significant contributions is repositioning, enabling the identification new therapeutic applications for existing drugs. In present study, a trained deep-learning model was employed screen library FDA-approved drugs discover novel inhibitors targeting JAK2. To accomplish this, reference datasets...

3D models of CYP2E1 were constructed for the purpose structure-based prediction 2E1 metabolism diverse substrates based on configuration sampling ligand-atom−oxyferryl center distances and quantum chemical criteria. Models basis sequence alignments with templates known structure, including rabbit CYP2C5 (3LVdH) bacterial CYP450s. Following geometric energetic assessments, utility model was tested in predictions metabolism. Autodock used to dock chlorzoxazone, p-nitrophenol,...

Six new polyacetylenes, gymnasterkoreaynes A−F (1−6), were isolated from the roots of Gymnaster koraiensis, together with 2,9,16-heptadecatrien-4,6-diyn-8-ol (7) and 1,9,16-heptadecatriene-4,6-diyn-3,8-diol (8), by bioassay-guided fractionation using L1210 tumor cell line as a model for cytotoxicity. The structures compounds 1−6 established spectroscopically, which included 2D NMR experiments. Gymnasterkoreaynes (1−6) are linear diacetylenes structurally related to falcarinol, panaxynol,...

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades γ-aminobutyric (GABA) in the brain. GABA an important inhibitory neurotransmitter plays neurological roles Therefore, GABA-AT drug target regulates levels. Novel and potent development to inhibit still very challenging task. In this study, we aimed devise novel inhibitors against using computer-aided design (CADD) tools. Since crystal structure of human was not yet available,...

Plasmodium vivax (P. vivax) is one of the human's most common malaria parasites. P. exceedingly difficult to control and eliminate due existence extravascular reservoirs recurring infections from latent liver stages. Traditionally, licorice compounds have been widely investigated against viral infectious diseases exhibit some promising results combat these diseases. In present study, computational approaches are utilized study effect Duffy binding protein (DBP) inhibit malarial invasion...

Fatty acid synthase (FAS) is a key enzyme involved in de novo lipogenesis that produces lipids are necessary for cell growth and signal transduction, it known to be overexpressed, especially cancer cells. Although lipid metabolism alteration an important metabolic phenotype cells, the development of drugs targeting FAS block synthesis hampered by characteristics cells with flexibility leading rapid adaptation resistance. Therefore, confirm alterations at cellular level during inhibition, we...

Malaria remains a global health challenge, with increasing resistance to frontline antimalarial treatments such as artemisinin (ART) threatening the efficacy of current therapies. In this study, we investigated potential FDA-approved drugs selectively inhibit malarial proteasome, novel target for drug development. By leveraging pharmacophore modeling, molecular docking, dynamics (MD) simulations, and binding free-energy calculations, screened library compounds identify inhibitors selective...

Gamma-aminobutyric acid (GABA) transaminase—also called GABA aminotransferase (GABA-AT)—deficiency is a rare autosomal recessive disorder characterized by severe neonatal-infantile epileptic encephalopathy with symptoms such as seizures, hypotonia, hyperreflexia, developmental delay, and growth acceleration. transaminase deficiency caused mutations in GABA-AT, the enzyme responsible for catabolism of GABA. Mutations multiple locations on GABA-AT have been reported their shown to influence...

The prokaryotic global transcription factor CRP has been considered to be an ideal model for in-depth study of both the allostery protein and differential utilization homologous cyclic nucleotide second messengers cAMP cGMP. Here, atomic details from crystal structures two inactive species, apo form a cGMP-bound form, in comparison with known active conformation, cAMP-CRP complex, provide macroscopic microscopic insights into allostery, which is coupled specific discrimination between...

Alvarezsaurid diversity has been markedly increased by recent discoveries from China. However, the number of alvarezsaurid specimens in Nemegt Formation Mongolia remained low since initial report on Mononykus olecranus 1993. Here we three new this formation, which were associated with each other and also multiple oviraptorid skeletons a small multi-species assemblage. Two represent taxon, Nemegtonykus citus gen. et sp. nov., is mainly distinguished alvarezsaurids first sacral vertebra...

Small Molecular Accurate Recognition Technology (SMART 2.0) has recently been introduced as a NMR-based machine learning tool for the discovery and characterization of natural products. We attempted targeted isolation sesquiterpene lactones from Eupatorium fortunei with aid structural annotation by SMART 2.0 chemical profiling. Eight germacrene-type (1-7 10) two eudesmane-type (8 9) were isolated whole plant fortunei. With guidance results subfractions E. obtained 2.0, their cytotoxic...

In the present study, centrifuge tests for small-scale specimens were performed to investigate dynamic soil pressure of basement buildings subjected seismic ground motions. To effect embedded depth basement, a deep model fixed rock (model 1) and shallow in 2) tested. The pressures acting at front wall (Dynamic pressure, DSP) back (Soil wall, BSP) measured. Under Northridge earthquake (with PGAb = 0.33 g), DSP Model 1 (fixed based model) reached 100 kPa showing an increasing linear...

Deuk-Soo Choia*, Jeong Sun Parkb*, Min Jee Kimb, Jong Seok Su Yeon Jeongb, Jun Seong Jinyoung Parkc & Iksoo Kimb*a Department of Plant Quarantine, Animal and Quarantine Agency, Gimcheon-si, Republic Korea; b College Agriculture Life Sciences, Chonnam National University, Gwangju, c Ecological Monitoring Assessment, Institute Ecology, Seocheon-gun, Chungcheongnam-do, Korea

Abstract Streamlining a body is major adaptation for aquatic animals to move efficiently in the water. Whereas diving birds are well known have streamlined bodies, such shapes not been documented non-avian dinosaurs. It primarily because most theropods terrestrial, barring few exceptions. However, clear evidence of bodies absent even purported semiaquatic groups. Here we report new theropod, Natovenator polydontus gen. et sp. nov., from Upper Cretaceous Mongolia. The specimen includes...

The bacterial toxin-antitoxin (TA) system regulates cell growth under various environmental stresses. Mycobacterium tuberculosis, the causative pathogen of tuberculosis (TB), has three HigBA type II TA systems with reverse gene organization, consisting toxin protein HigB and labile antitoxin HigA. Most modules are transcriptionally autoregulated by itself. In this report, we first present crystal structure M. HigA3 (MtHigA3) MtHigA3 bound to its operator DNA complex. We also investigated...

A new articulated postcranial specimen of an indeterminate ankylosaurid dinosaur from the Upper Cretaceous (middle-upper Campanian) Baruungoyot Formation Hermiin Tsav, southern Gobi Desert, Mongolia includes twelve dorsal vertebrae, ribs, pectoral girdles, forelimbs, pelvic hind limbs, and free osteoderms. The shows that Asian ankylosaurids evolved rigid bodies with a decreased number pedal phalanges. It also implies there were at least two forms flank armor within Ankylosauridae, one...

Abstract A new ankylosaurid dinosaur, Tarchia tumanovae sp. nov., has been recovered from the Upper Cretaceous Nemegt Formation of Mongolia. It includes a well-preserved skull, dorsal, sacral, caudal vertebrae, sixteen dorsal ribs, ilia, partial ischium, free osteoderms, and tail club. The squamosal horns T. are divided into two layers, external dermal layer underlying horn proper. irregular ventral margin base upper may represent resorption surface, suggesting that some ankylosaurids...

The lucanid beetles of the subspecies Cyclommatus metallifer from Indonesia are revised here. Five known Indonesia. Among them, otanii Mizunuma and Nagai was confirmed to be a synonym aenomicans Parry. Moreover, new subspecies, butonensis ssp. nov., is described Buton Island identification key, distributional data, photos adults, genitalia, figures for each provided.

This study was carried out to ascertain regional gene differences in the carabid beetle, Coptolabrus jankowskii, Korea. There are eight subspecies of this species Korea and it is very difficult identify them due morphological similarity. The mitochondrial NADH dehydrogenase subunit 5 (ND5) jankowskii from four regions, Sangju, Daegu, Jumbongsan Mountain, Jejudo Island, compared. results showed base sequence at a total 57 sites amino acid variation 25 sites. neighbor-joining (NJ) tree maximum...

Peppers (Piper nigrum L.) are distinguished by their pungent flavor and aroma. Piperine is a major acid-amide alkaloid with piperidine ring that gives pepper its scent. In plant metabolomics research, the accessibility of chemical standards critical for scientific credibility. We isolated identified 10 novel dimers acid amide alkaloids (9–15 20–22), along 12 known monomers (1–6) (7, 8, 16–19) from black pepper. Subsequently, we found distribution in white peppers twenty-two which obtained...

NF-κB-inducing kinase (NIK) plays a pivotal role in regulating both the canonical and non-canonical NF-κB signaling pathways, driving expression of proteins involved inflammation, immune responses, cell survival. Overactivation NIK is linked to various pathological conditions, including chronic autoimmune diseases, metabolic disorders, cancer progression. As such, represents compelling target for therapeutic intervention these diseases. In this study, we explored inhibitory potential...