Browse Articles

Numerical investigation on damage characteristics of surrounding rocks in the deep underground tunnel subjected to full-face smooth blasting

The effects of LED Spectra on synthesis of antiparasitic bioactive compound in Eurycoma longifolia hairy root culture against Blastocystis Sp

Toward based on concentrated multi-scale linear attention real-time UAV tracking using joint natural language specification

Metabolomic signatures of cognitive function in a type 2 Diabetes-Enriched cohort

A feasibility of computational drug screening for Fuchs endothelial corneal dystrophy

Abstract Fuchs endothelial corneal dystrophy (FECD) remains a leading cause of corneal blindness globally, with corneal transplantation being the primary treatment. FECD is characterized by the formation of guttae, extracellular matrix (ECM) deposits beneath the corneal endothelium, and progressive endothelial cell loss. These pathological changes cause visual deterioration through light scattering by guttae and corneal edema due to endothelial cell loss. However, limitations such as donor shortage and graft failure necessitate alternative therapeutic approaches. We employed computational drug screening using three platforms (L1000FWD, L1000CDS2, and SigCom LINCS) to identify compounds capable of normalizing FECD-associated differentially expressed genes (DEGs). Analysis of transcriptome data from FECD patients with TCF4trinucleotide repeat expansion identified 706 upregulated and 962 downregulated genes. The screening platforms identified 200, 35, and 76 compounds through L1000FWD, L1000CDS2, and SigCom LINCS, respectively, with five compounds commonly predicted across all platforms. Among these, LDN193189 and cercosporin were selected for further evaluation based on availability and lack of cytotoxicity. Both compounds significantly decreased the expression of ECM-related genes (FN1, MATN3, BGN, and LTBP2) in FECD cell models and suppressed TGF-β-induced fibronectin expression. Additionally, both compounds reduced aggresome formation to normal control levels, suggesting protection against endoplasmic reticulum stress-induced cell death. This study demonstrates the feasibility of computational drug screening for identifying therapeutic candidates for FECD, with LDN193189 and cercosporin showing promise in normalizing FECD-associated pathological changes.

Modulation of glucose metabolism and insulin resistance following hepatitis C virus clearance via direct-acting antivirals

A holocene n-alkane stable isotope record from Wonderwerk Cave, South Africa and its implications for the later stone age record

Abstract Sediment biomarkers are important archives of regional, and global climate signatures, particularly in regions which lack continuous terrestrial archives such as the semi-arid deserts of Africa. We measured carbon and hydrogen stable isotopes from plant wax n-alkanes recovered from the Holocene Later Stone Age (LSA) sedimentary sequence at Wonderwerk Cave (South Africa), that comprises several technocomplexes (Kuruman/Oakhurst, Wilton, Ceramic Wilton and Historic). The plant wax n-alkane results were integrated with published palaeoenvironment reconstructions from the cave based on faunal, botanical, geological and sedimentological proxies which provides a robust comparative framework. The findings match well with other proxy records from the same strata and indicate a semi-arid to semi-humid early Holocene, with a mix of woody C3 plants and C4 grasses. In contrast, the mid-late Holocene environment was increasingly arid, open and dominated by C4 grasses. A distinct humid period at 5300–6200 cal. BP is evident, associated with a high density of archaeological material and a change in cultural expression in the Wonderwerk record. This study provides a step forward in using stable isotopes from biomarkers to create terrestrial environmental records in semi-arid regions.

Enhanced photocatalytic performance of non-stoichiometric WO3−x nanocrystals via near-infrared localized surface plasmon resonance

Characterization of transcriptomics during aging and genes required for lifespan in Drosophila intestine

Evaluation and optimization simulation of land suitability for village construction in the urban rural integration zone empirical test based on 49 administrative villages in Chuzhou city China

Unveiling Berberine analogues as potential inhibitors of Escherichia coli FtsZ through machine learning molecular docking and molecular dynamics approach

Abstract The bacterial cell division protein FtsZ, a crucial GTPase, plays a vital role in the formation of the contractile Z-ring, which is essential for bacterial cytokinesis. Consequently, inhibiting FtsZ could prevent the formation of proto-filaments and interfere with the cell division machinery. The remarkable conservation of FtsZ across diverse bacterial species makes it a promising drug target for combating drug resistance. In the present study, 1072 berberine analogues were screened for favorable pharmacokinetic properties. A total of 60 compounds that fulfilled the drug-likeliness criteria and were found to be non-toxic were selected for virtual screening against Escherichia coli FtsZ protein (PDB ID: 8GZY). Molecular docking revealed a strong binding affinity of ZINC000524729297 (− 8.73 kcal/mol) and ZINC000604405393 (and − 8.55 kcal/mol) with FtsZ by strong intermolecular hydrogen bonds and hydrophobic interactions. Subsequently, the docking profiles were validated through a 500 ns MD simulation and MMPBSA analysis of the FtsZ-ligand complexes. The analysis revealed the FtsZ- ZINC524729297 and FtsZ-ZINC000604405393 complexes had the lowest root-mean-square deviation with lowest binding energy and enhanced conformational stability in a dynamic environment. These findings suggest that ZINC524729297 and ZINC000604405393 are the potent lead compound that targets FtsZ and requires further experimental validation.

Characterisation of the Gillenia S-locus provides insight into evolution of the nonself-recognition self-incompatibility system in apple

Abstract Self-incompatibility (SI) in plants has evolved independently multiple times and S-RNase-based gametophytic self-incompatibility (GSI) is most common. The Rosaceae family possesses both self-recognition (Prunus) and nonself-recognition (Malus) GSI systems, and the latter is widespread in flowering plants. Gillenia trifoliata is a Rosaceae species related to Prunus and Malus, providing utility for understanding SI evolution. Gillenia is sister taxon to Malus, but unlike Malus, has not undergone polyploidisation. In addition, the common ancestor of Gillenia and Prunus is close to the origin of the subfamily. Using a highly contiguous Gillenia genome, orthologous regions to both Malus and Prunus S-loci were identified. Only the Prunus-like S-locus was highly polymorphic and had signatures of a functional S-locus including positive selection of the S-RNase. This suggests a self-recognition system controls SI in Gillenia, and the common ancestors of Gillenia and Prunus, and Gillenia and the apple tribe, likely had a self-recognition SI system. Comparative genomics between Gillenia and Malus suggest apple lost the self-recognition mechanism, and a nonself-recognition mechanism evolved independently from a rudimentary locus with at least one male S-determinant. Repetitive sequences in the Malus-like S-locus in Gillenia may facilitate illegitimate recombination, suggesting putative mechanisms of evolution of nonself-recognition S-loci.

Exploring differences in signaling pathways of the circadian clock and neuromodulators in obstructive sleep apnea

PKM2 modulates chemotherapy sensitivity by regulating autophagy and predicts the prognosis and immunity in pancancer

Control of three-level quadratic DC-DC boost converters for energy systems using various technique-based MPPT methods

Machine learning-based prediction of heating values in municipal solid waste

Global burden of hypertensive heart disease and attributable risk factors, 1990–2021: insights from the global burden of disease study 2021

A deep learning-based multimodal medical imaging model for breast cancer screening

Multiscale deformed attention networks for white blood cell detection

Substituents introduction of methyl and methoxy functional groups on resveratrol stabilizes mTOR binding for autophagic cell death induction

Abstract The regulation of the mammalian target of rapamycin (mTOR) protein by cancer cells can lead to uncontrol of cancer cell growth and cancer therapy resistance. The drug discovery of the anticancer agent 5-(3-hydroxy-4-methoxyphenethyl)-2-methoxy-3-methylphenol (SM-3), a derivative of resveratrol by substituting a methyl group at the hydroxy group of ring A and adding a methoxy group at the para position of ring B, shows promising potential for targeting autophagy to induce cell death and suppress cancer stem cells (CSCs) through the inhibition of the mTOR protein. In human lung cancer cells, SM-3 showed greater efficacy, with lower IC50 values of 72.74 ± 0.13, 67.66 ± 0.10, and 43.24 ± 0.11 µM in A549, H292, and H460 cells, respectively, compared to the parent compound, Resveratrol (Res). Moreover, the selectivity index (SI) values for BEAS2B cells compared to tumor cells treated with SM-3 were 10.99, 11.81, and 18.49 for A549, H292, and H460 cell lines, respectively. Therefore, SM-3 treatment led to reduced proliferation rates and colony formation in lung cancer cells. In our study, spheroids treated with SM-3 showed a higher proportion of dead spheroids compared to those treated with Res. Additionally, SM-3 treatment resulted in decreased expression of stem cell markers (CD133, CD44, and ALDH1A1) and transcription factors (OCT4, NANOG, and SOX2) in spheroids and organoids from human lung cancer cells by inhibiting the mTOR/pAkt pathway. SM-3 was also found to induce autophagic cell death, as indicated by Monodansylcadaverine staining, acidic vesicle formation, and the conversion of LC3BI to LC3BII. Using MM/GBSA calculations, SM-3 exhibited a stronger binding affinity (-25.09 kcal/mol) compared to Res (-18.85 kcal/mol). SM-3 also displayed greater stability during the entire simulation, maintaining lower RMSD values of 2–3 Å even after 80 ns. In summary, the introduction of methyl and methoxy functional groups on Res to create SM-3 effectively suppressed cancer spheroids and organoids formation in lung cancer cells by targeting the upstream mTOR/pAkt pathway.