Structure-Based Virtual Screening Identifying Novel FOXM1 Inhibitors as the Lead Compounds for Glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options and a poor prognosis. Cancer stem cells (CSCs) have emerged as a critical factor in GBM resistance and management, contributing to tumor growth, heterogeneity, and immunosuppression. The transcription factor FOXM1 has been identified as a key player in the progression, spread, and therapy resistance of various cancers, including GBM. OBJECTIVE: In this research, the objective was to perform structure-based in silico screening with the aim of identifying natural compounds proficient in targeting the DNA-binding domain (DBD) of the FOXM1 protein. METHODS: In this study, in silico tools were employed for screening a hundred naturally occurring compounds capable of targeting the FOXM1 protein. Through molecular docking analysis and pharmacokinetic profiling, five compounds were found to be promising candidates for extensive interaction with the FOXM1 protein. Further, these compounds were validated for the stability of the FOXM1-natural compound complex using molecular dynamics (MD) simulations. RESULTS: Four compounds, such as Withaferin A, Bryophyllin A, Silybin B, Sanguinarine and Troglitazone (control compound), emerged as promising candidates with substantial interactions with FOXM1, suggesting their potential as a protein inhibitor based on molecular docking investigations. After MD simulation analysis, the FOXM1- Bryophyllin A complex was found to maintain the highest stability, and the other three ligands had moderate but comparable binding affinities over a period of 100 ns. CONCLUSION: This study provides valuable insights into four promising FOXM1 inhibitors that have the ability to induce senescence in GBM stem cells. These findings contribute to the development of structure-based designing strategies for FOXM1 inhibitors and innovative therapeutic approaches for the treatment of Glioblastoma.

Recent Advances of Transition Metal Dichalcogenides-Based Materials for Energy Storage Devices, in View of Monovalent to Divalent Ions.

The fast growth of electrochemical energy storage (EES) systems necessitates using innovative, high-performance electrode materials. Among the various EES devices, rechargeable batteries (RBs) with potential features like high energy density and extensive lifetime are well suited to meet rapidly increasing energy demands. Layered transition metal dichalcogenides (TMDs), typical two dimensional (2D) nanomaterial, are considered auspicious materials for RBs because of their layered structures and large specific surface areas (SSA) that benefit quick ion transportation. This review summarizes and highlights recent advances in TMDs with improved performance for various RBs. Through novel engineering and functionalization used for high-performance RBs, we briefly discuss the properties, characterizations, and electrochemistry phenomena of TMDs. We summarised that engineering with multiple techniques, like nanocomposites used for TMDs receives special attention. In conclusion, the recent issues and promising upcoming research openings for developing TMDs-based electrodes for RBs are discussed.

Evolution Mechanism of Arsenic Enrichment in Groundwater and Associated Health Risks in Southern Punjab, Pakistan.

Arsenic (As) contamination in groundwater is a worldwide concern for drinking water safety. Environmental changes and anthropogenic activities are making groundwater vulnerable in Pakistan, especially in Southern Punjab. This study explores the distribution, hydrogeochemical behavior, and pathways of As enrichment in groundwater and discusses the corresponding evolution mechanism, mobilization capability, and health risks. In total, 510 groundwater samples were collected from three tehsils in the Punjab province of Pakistan to analyze As and other physiochemical parameters. Arsenic concentration averaged 14.0 µg/L in Vehari, 11.0 µg/L in Burewala, and 13.0 µg/L in Mailsi. Piper-plots indicated the dominance of Na+, SO42-, Ca2+, and Mg2+ ions in the groundwater and the geochemical modeling showed negative saturation indices with calcium carbonate and salt minerals, including aragonite (CaCO3), calcite (CaCO3), dolomite (CaMg(CO3)2), and halite (NaCl). The dissolution process hinted at their potential roles in As mobilization in groundwater. These results were further validated with an inverse model of the dissolution of calcium-bearing mineral, and the exchange of cations between Ca2+ and Na+ in the studied area. Risk assessment suggested potential carcinogenic risks (CR > 10-4) for both children and adults, whereas children had a significant non-carcinogenic risk hazard quotient (HQ > 1). Accordingly, children had higher overall health risks than adults. Groundwater in Vehari and Mailsi was at higher risk than in Burewala. Our findings provide important and baseline information for groundwater As assessment at a provincial level, which is essential for initiating As health risk reduction. The current study also recommends efficient management strategies for As-contaminated groundwater.

Investigation on Crystal-Structure, Thermal and Electrical Properties of PVDF Nanocomposites with Cobalt Oxide and Functionalized Multi-Wall-Carbon-Nanotubes.

Nanocomposites of polyvinylidene fluoride (PVDF) with dimensional (1D) cobalt oxide (Co3O4) and f-MWCNTs were prepared successfully by the solution casting method. The impact of 1D Co3O4 filler and 1D Co3O4/f-MWCNTs co-fillers on the structural, thermal, and electrical behavior of PVDF were studied. The crystal structural properties of pure PVDF and its nanocomposite films were studied by XRD, which revealed a significant enhancement of ß-phase PVDF in the resulting nanocomposite films. The increase in ß-phase was further revealed by the FTIR spectroscopic analysis of the samples. TG, DTA, and DSC analyses confirmed an increase in thermal stability of PVDF with the addition of nano-fillers as well as their increasing wt.%. From impedance spectroscopic studies, it was found that the DC conductivity of PVDF increases insignificantly initially (up to 0.1 wt.% of nano-fillers addition), but a significant improvement in DC conductivity was found at higher concentrations of the nano-fillers. Furthermore, it was observed that the DC conductivity decreases with frequency. The increase in DC conductivity corresponded to the strong interactions of nano-fillers with PVDF polymer chains.

Metal-organic framework derived ultralow-loading platinum-copper catalyst: a highly active and durable bifunctional electrocatalyst for oxygen-reduction and evolution reactions.

Electrocatalysts with high active oxygen reduction (ORR) and oxygen evolution reaction (OER) activities are key factors in renewable energy technologies. Unlike common strategies for adjusting the proportion of metal centers in a multi-metal organic framework (MOF), herein, we designed and synthesized bifunctional electrocatalysts using cetyltrimethylammonium bromide (CTAB)-capped ultra-low content platinum (Pt) (≤0.5 wt.% Pt) and copper (Cu) nanoparticles and doped on the surface of zinc-based MOF (Zn-MOF-74) and calcinated at 900 °C. According to the electrochemical activity, the Pt/Cu/NPC-900 exhibits superior catalytic activities towards both the ORR with the onset (E0) and half-wave (E1/2) potentials were 1.0 V and 0.89 V versus RHE, respectively, and OER (Eo = 1.48 V versus RHE and overpotential (η) = 0.265 V versus RHE) in an alkaline electrolyte at ambient temperature. Also, Pt/Cu/NPC-900 catalyzes through a 4-electron process and exhibits superior stability. Such insightful findings, as well as a newly developed approach, provides rational design and synthesis of an economical and efficient strategy for bifunctional electrocatalyst development.

Incorporation of Pt-Cr nanoparticles into highly porous MOF-5 as efficient oxygen reduction electrocatalysts.

Developing new materials that can enhance the efficiency of energy conversion and storage systems is critical to meeting the rising energy demand of low-carbon economies. Mesoporous materials have the advantages of large specific surface area and multiple channels, which can increase efficiency and flexibility in terms of energy and power density. An active catalyst for oxygen reduction reaction (ORR) based on Pt-Cr nanoparticles with ultralow Pt content (0.90 wt%) has been studied in this paper. In contrast, electrocatalyst Pt/Cr/NPC-900 exhibited an ORR activity with onset potential (E o) of 1.01 V vs. RHE in an alkaline solution that was superior to commercial Pt/C (20 wt%) (0.96 V vs. RHE). The presence of metal oxides and optimal Pt content enhanced the ORR activity. Therefore, the synergistic effect of the high surface area increased charge transfer, and excellent structural stability can achieve significant ORR efficiency, which is conducive to excellent activity. These findings provide a new perspective for economical and practical ORR electrocatalysts to be designed and synthesized rationally.