Search Results (648)

Illegal mining operations induce cascading ecosystem degradation by causing extensive ground subsidence, necessitating accurate underground goaf localization for effectively induced-hazard mitigation. The conventional locating method applied the synthetic aperture radar interferometry (InSAR) technique to obtain ground deformation to estimate underground goaf parameters, and the locating accuracy was crucially contingent upon the appropriateness of nonlinear deformation function models selection and the precision of geological parameters acquisition. However, conventional model-driven underground goaf locating frameworks often fail to sufficiently integrate prior geological information during the model selection process, potentially leading to increased positioning errors. In order to enhance the operational efficiency and locating accuracy of underground goaf, deformation model selection must be aligned with site-specific geological conditions under varying cases of prior information. To address these challenges, this study categorizes prior geological information into three different hierarchical levels (detailed, moderate, and limited) to systematically investigate the correlations between model selection and prior information. Subsequently, field validation was carried out by applying two different non-linear deformation function models, Probability Integral Model (PIM) and Okada Dislocation Model (ODM), with three different prior geological information conditions. The quantitative performance results indicate that, (1) under a detailed prior information condition, PIM achieves enhanced dimensional parameter estimation accuracy with 6.9% reduction in maximum relative error; (2) in a moderate prior information condition, both models demonstrate comparable estimation performance; and (3) for a limited prior information condition, ODM exhibits superior parameter estimation capability showing 3.4% decrease in maximum relative error. Furthermore, this investigation discusses the influence of deformation spatial resolution, the impacts of azimuth determination methodologies, and performance comparisons between non-hybrid and hybrid optimization algorithms. This study demonstrates that aligning the selection of deformation models with different types of prior geological information significantly improves the accuracy of underground goaf detection. The findings offer practical guidelines for selecting optimal models based on varying information scenarios, thereby enhancing the reliability of disaster evaluation and mitigation strategies related to illegal mining. Full article

Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), cancer stemness, extracellular matrix (ECM) remodelling, and activation of key signalling pathways such as Wingless/Integrated (Wnt) Wnt/β-catenin and PI3K/Akt. Hypoxia also enhances the secretion of extracellular vesicles (EVs), enriched with pro-metastatic cargos, and upregulates bone-homing molecules including CXCR4, integrins, and PIM kinases, fostering pre-metastatic niche formation and skeletal colonisation. In this review, we analysed current evidence on how hypoxia orchestrates PCa dissemination to bone, focusing on the molecular crosstalk between HIF signalling, Wnt activation, EV-mediated communication, and cellular plasticity. We further explore therapeutic strategies targeting hypoxia-related pathways, such as HIF inhibitors, hypoxia-activated prodrugs, and Wnt antagonists, with an emphasis on overcoming therapy resistance in castration-resistant PCa (CRPC). By examining the mechanistic underpinnings of hypoxia-driven bone metastasis, we highlight promising translational avenues for improving patient outcomes in advanced PCa. Full article

(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity via asymmetric cell divisions, sustaining the stem cell pool. Quiescent LSCs are known to be resistant to tyrosine kinase inhibitors (TKIs), potentially through BCR::ABL-independent signaling pathways. We hypothesize that dysregulation of genes governing asymmetric division in LSCs contributes to disease progression, and that their expression pattern may serve as a prognostic marker during the chronic phase of CML. (2) Methods: Genes related to asymmetric cell division in the context of hematopoietic stem cells were extracted from the PubMed database with the keyword “asymmetric hematopoietic stem cell”. The collected relative gene set was tested on two independent bulk transcriptome cohorts and the results were confirmed by single-cell RNA sequencing. (3) Results: The expression of genes involved in asymmetric hematopoietic stem cell division was found to discriminate disease phases during CML progression in the two independent transcriptome cohorts. Concordance between cohorts was observed on asymmetric molecules downregulated during blast crisis (BC) as compared to the chronic phase (CP). This downregulation during the BC phase was confirmed at single-cell level for SELL, CD63, NUMB, HK2, and LAMP2 genes. Single-cell analysis during the CP found that CD63 is associated with a poor prognosis phenotype, with the opposite prediction revealed by HK2 and NUMB expression. The single-cell trajectory reconstitution analysis in CP samples showed CD63 regulation highlighting a trajectory cluster implicating HSPB1, PIM2, ANXA5, LAMTOR1, CFL1, CD52, RAD52, MEIS1, and PDIA3, known to be implicated in hematopoietic malignancies. (4) Conclusion: Regulation of CD63, a tetraspanin involved in the asymmetric division of hematopoietic stem cells, was found to be associated with poor prognosis during CML progression and could be a potential new therapeutic target. Full article

Background: Acute myeloid leukemia (AML) is a common and aggressive adults hematological malignancies. This study explored megakaryocyte–erythroid progenitors (MEPs) signature genes and constructed a prognostic model. Methods: Uniform manifold approximation and projection (UMAP) identified distinct cell types, with differential analysis between AML-MEP and normal MEP groups. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression selected biomarkers to build a risk model and nomogram for 1-, 3-, and 5-year survival prediction. Results: Ten differentially expressed genes (DEGs) related to overall survival (OS), six (AHSP, MYB, VCL, PIM1, CDK6, as well as SNHG3) were retained post-LASSO. The model exhibited excellent efficiency (the area under the curve values: 0.788, 0.77, and 0.847). Pseudotime analysis of UMAP-defined subpopulations revealed that MYB and CDK6 exert stage-specific regulatory effects during MEP differentiation, with MYB involved in early commitment and CDK6 in terminal maturation. Finally, although VCL, PIM1, CDK6, and SNHG3 showed significant associations with AML survival and prognosis, they failed to exhibit pathological differential expression in quantitative real-time polymerase chain reaction (qRT-PCR) experimental validations. In contrast, the downregulation of AHSP and upregulation of MYB in AML samples were consistently validated by both qRT-PCR and Western blotting, showing the consistency between the transcriptional level changes and protein expression of these two genes (p < 0.05). Conclusions: In summary, the integration of single-cell/transcriptome analysis with targeted expression validation using clinical samples reveals that the combined AHSP-MYB signature effectively identifies high-risk MEP-AML patients, who may benefit from early intensive therapy or targeted interventions. Full article

Accurate gene expression quantification using reverse transcription quantitative PCR (RT-qPCR) requires stable reference genes (RGs) for reliable normalization. However, few studies have systematically identified RGs suitable for simultaneous high salt, alkaline, and high-temperature conditions. This study addresses this gap by evaluating the stability of eight candidate RGs in the anaerobic halophilic alkalithermophile Natranaerobius thermophilus JW/NM-WN-LF^T under combined salt, alkali, and thermal stresses. The stability of these candidate RGs was assessed using five statistical algorithms: Delta CT, geNorm, NormFinder, BestKeeper, and RefFinder. Results indicated that recA exhibited the highest expression stability across all tested conditions and proved adequate as a single RG for normalization in both RT-qPCR and droplet digital PCR (ddPCR) assays. Furthermore, recA alone or combined with other RGs (sigA, rsmH) effectively normalized the expression of seven stress-response genes (proX, opuAC, mnhE, nhaC, trkH, ducA, and pimT). This work represents the first systematic validation of RGs under polyextreme stress conditions, providing essential guidelines for future gene expression studies in extreme environments and aiding research on microbial adaptation mechanisms in halophilic, alkaliphilic, and thermophilic microorganisms. Full article

To address the limitations of single-layer nitride coatings, such as poor load adaptability and low long-term durability, MoN/TiN multilayer coatings were prepared via high-power impulse magnetron sputtering (HiPIMS). HiPIMS produces highly ionized plasmas that enable intense ion bombardment, yielding nitride films with enhanced mechanical strength, durability, and thermal stability versus conventional methods. The multilayer coating demonstrated a low coefficient of friction (COF, ~0.4) and wear rate (1.31 × 10⁻⁷ mm³/[N·m]). In contrast, both TiN and MoN coatings failed at 5 N and 10 N loads, respectively. Under increasing loads, the multilayer coating maintained stable wear rates (1.84–3.06 × 10⁻⁷ mm³/[N·m]) below 20 N, and ultimately failed at 25 N. Furthermore, the MoN layer contributes to COF reduction. Grazing-incidence X-ray diffraction analysis confirmed the enhanced crystallographic stability of the multilayer coating, thereby revealing a dominant (111) orientation. The multilayer architecture suppresses crack propagation while effectively balancing hardness and toughness, offering a promising design for extreme-load applications. Full article

The accurate inversion of mining subsidence prediction parameters is key to the precise prediction of deformation during mining. However, the use of traditional genetic algorithms (GA) for inversion prediction has problems such as poor resistance to differences, and the accuracy of inversion parameters is affected when key monitoring points are missing. In response to these issues, a probability integral parameter inversion method is proposed in this study that integrates a selection-weighted iterative robust genetic algorithm. This method combines the selection-weighted iteration method with a genetic algorithm to determine the weights of different observation values, and then a probability integral parameter inversion method is constructed for the fusion selection-weighted iterative robust GA. The results indicate that the fusion selection-weighted iterative robust GA is stronger than the traditional GA, and the parameters obtained have higher accuracy and greater reliability. An experiment using real working face engineering showed that, compared with the GA method, the RMSE (root mean square error) of the proposed method is reduced by 24.4 mm and 37.5 mm, thus verifying the usability of this method. Full article

The intensive use of various sensors in industrial machines has the potential to indicate the real-time health status of critical equipment. This is achieved through the connectivity of their automation systems (PIMS and MES), enabling the optimization of the preventive maintenance interval, a reduction in corrective maintenance and safety-related failures, an increase in productivity and reliability and a reduction in maintenance costs. Through the use of the CRISP-DM data analysis methodology, the fault logs of ceramic plates applied in an iron ore filtration process are coupled with sensor readings of the process variables over the time of operation to create exponential survival models via two techniques: a multiple linear regression model with averaged data and a random forest regression machine learning model with individual instant data. The instantaneous reliability of ceramic plates is then used in the online prediction of the remaining useful life of the components. The model obtained from the instantaneous reading of 12 sensors led to the estimation of the remaining useful life for ceramic plates with up to 5600 h of use, allowing the adoption of a strategy of replacing these components by condition instead of replacing them by a fixed time, leading to increased process reliability and improved stock planning. The linear regression model for reliability prediction had an R² of 78.32%, whereas the random forest regression model had an R² of 63.7%. The final model for predicting the remaining useful life had an R² of 99.6%. Full article

Hybrid materials based on porous organic polymers (POPs) and metal–organic frameworks (MOFs) are increasing attention for advanced separation processes due to the possibility to combine their properties. POPs provide high surface areas, chemical stability, and tunable porosity, while MOFs contribute a high variety of defined crystalline structures and enhanced separation characteristics. The combination (or hybridization) with PIMs gives rise to mixed-matrix membranes (MMMs) with improved permeability, selectivity, and long-term stability. However, interfacial compatibility remains a key limitation, often addressed through polymer functionalization or controlled dispersion of the MOF phase. MOF/COF hybrids are more used as biochemical sensors with elevated sensitivity, catalytic applications, and wastewater remediation. They are also very well known in the gas sorption and separation field, due to their tunable porosity and high electrical conductivity, which also makes them feasible for energy storage applications. Last but not less important, hybrids with other POPs, such as hyper-crosslinked polymers (HCPs), covalent triazine frameworks (CTFs), or conjugated microporous polymers (CMPs), offer enhanced functionality. MOF/HCP hybrids combine ease of synthesis and chemical robustness with tunable porosity. MOF/CTF hybrids provide superior thermal and chemical stability under harsh conditions, while MOF/CMP hybrids introduce π-conjugation for enhanced conductivity and photocatalytic activity. These and other findings confirm the potential of MOF-POP hybrids as next-generation materials for gas separation and carbon capture applications. Full article

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its receptors may influence tumor growth and the tumor microenvironment. This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. The drugs were first tested individually, followed by co-treatment with tyrosine (Tyr), a dopamine precursor, and hydrogen peroxide (H₂O₂), an inducer of oxidative stress. Additionally, drug activity was evaluated in the simultaneous presence of H₂O₂ and Tyr. CLZ exhibited the highest cytotoxicity in both cell lines, suggesting strong anticancer potential and also synergism among the different combinations, particularly in SH-SY5Y. Liquid chromatography of the extracellular medium showed greater Tyr consumption in SH-SY5Y compared to A172 cells, indicating a higher dependence on extracellular Tyr to mitigate drug- and/or stress-induced cytotoxicity. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology. Full article

Oximes have been reported to exhibit useful pharmaceutical properties, including compounds with anticancer, anti-arthritis, antibacterial, and neuroprotective activities. Many oximes are kinase inhibitors and have been shown to inhibit various kinases. Herein, a panel of oxime derivatives of tricyclic isatins was synthesized and evaluated for inhibition of cellular inflammatory responses and binding affinity to several kinases. Compounds 5a and 5d (a.k.a. NS-102), which have an unsubstituted oxime group, inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in human THP-1Blue monocytic cells and interleukin-6 (IL-6) production in human MonoMac-6 monocytic cells, with IC₅₀ values in the micromolar range. These compounds also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Compounds 5a and 5d exhibited nanomolar/submicromolar binding affinity toward several kinase targets. The most potent inhibitor, 5d (3-(hydroxyimino)-5-nitro-1,3,6,7,8,9-hexahydro-2H-benzo[g]indol-2-one), demonstrated high binding affinity for 12 kinases, including DYRK1A, DYRK1B, PIM1, Haspin, HIPK1-3, IRAK1, NEK10, and DAPK1-3. Molecular modeling suggested modes of binding interaction of selected compounds in the DYRK1A and PIM1 catalytic sites that agreed with the experimental binding data. Our results demonstrate that tricyclic isatin oximes could be potential candidates for developing anti-inflammatory drugs with neuroprotective effects for treating neurodegenerative diseases. Full article

Powder injection molding (PIM) has been used to produce nearly net-shaped samples of tungsten-based alloys. These alloys have been previously shown to have favorable characteristics when compared with standard ITER-grade tungsten. Six different alloys were produced with this method: W-1TiC, W-2Y₂O₃, W-3Re-1TiC, W-3Re-2Y₂O₃, W-1HfC and W-1La₂O₃-1TiC. These were tested alongside ITER-grade tungsten in the PSI-2 linear plasma device under ITER-relevant plasma and heat loads to assess their suitability for use in a fusion reactor. All materials showed good behavior when exposed to the lower pulse number tests (≤1000 ELM-like pulses), although standard tungsten performed slightly better, with no observable difference in surface roughness. High-power shots, namely one laser pulse of 1.6 GWm⁻², revealed that samples containing yttria are more prone to melting and droplet ejection. After high pulse number tests (10,000 and 100,000 pulses), with and without plasma, the reference tungsten showed the most cracking and highest surface roughness of all materials, while the PIM samples seemed to have a higher resistance to cracking. This can be attributed to the higher ductility of these alloys, particularly those containing rhenium. This means that tungsten-based alloys, whether produced via PIM or other methods, could potentially be used in certain areas of a fusion reactor. Full article

Skin cancer, particularly melanoma, remains a major public health concern due to its high mortality rate. Current treatment options, including chemotherapy with dacarbazine and doxorubicin, have shown limited efficacy, achieving only a 20% objective response rate over six months, along with severe side effects such as cardiotoxicity. Given these limitations, there is a growing interest in herbal medicine as a source of novel anticancer compounds. Bambusa stenostachya, a bamboo species native to Taiwan, was investigated for its potential anti-melanoma properties using network pharmacology and molecular docking. LC-MS analysis identified seven bioactive compounds, including quinic acid and isovitexin, which satisfied Lipinski’s drug-likeness criteria. Among the seven bioactive compounds identified, five belong to the flavonoid family, while two are classified as phenolic compounds that modulate signaling pathways related to cancer and exhibit antioxidant activity, respectively. Through pathway enrichment analysis, four key melanoma-associated genes (PIM1, MEK1, CDK2, and PDK1) were identified as potential therapeutic targets. Ensemble docking results demonstrated that naringin-7-rhamnoglucoside exhibited the highest binding affinity (−6.30 kcal/mol) with phosphoinositide-dependent kinase-1, surpassing the affinities of standard chemotherapeutic agents. Additionally, the average docking scores for naringin-7-rhamnoglucoside and the remaining three proteins were as follows: PIM1 (−5.92), MEK1 (−6.07), and CDK2 (−5.26). These findings suggest that the bioactive compounds in B. stenostachya may play a crucial role in inhibiting melanoma progression by modulating metabolic and signaling pathways. Further in vitro and in vivo studies are necessary to validate these computational findings and explore the potential of B. stenostachya as a complementary therapeutic agent for melanoma. Full article

In this study, we investigated the frictional properties of TiB₂ films produced by high-power impulse magnetron sputtering and compared them with those of TiN- and CrN-sputtered coatings also made using high-power pulsed discharges. The films were characterised by scanning electron microscopy, Electron Probe Micro-Analysis, nanoindentation and friction tests. Sliding friction analyses were performed against aluminium surfaces at different temperatures, ranging from room temperature to 300 °C. The TiB₂ coatings exhibited hardness values of about 39 GPa, regardless of the bias potential used between −50 V and −100 V, a low modulus of around 300 GPa and a dense compact columnar microstructure with grain sizes between 51 and 68 nm in diameter. The friction behaviour on aluminium produced the transfer of this element to the films, at rates that depended on the test temperature. The TiN and CrN coatings exhibited low–medium adhesion to aluminium at room temperature and severe transfer during the friction tests at 150 °C. In the case of the TiB₂ films, the adhesion of aluminium during friction tests was low for temperatures up to 175 °C. In fact, a clear transition of the mild-to-severe adhesion of aluminium on TiB₂ was observed in the temperature range of 175 °C to 200 °C for the testing conditions evaluated in this study, which was concomitant with the evolution observed for the friction coefficients. Full article

Inhibition of CK2 and/or PIM-1 kinases has been shown to induce apoptosis in a variety of cancer cell lines, underscoring their potential as valuable targets in anti-cancer drug development. In this study, a series of N-substituted derivatives of 4,5,6,7-tetrabromo-1H-benzimidazole, including 2-oxopropyl/2-oxobutyl substituents and their respective hydroxyl analogues, were synthesized and evaluated for anti-cancer activity. The compounds’ ability to inhibit CK2α and PIM-1 kinases was assessed through enzymatic assays, complemented by comprehensive in silico enzyme–substrate docking analyses. Cytotoxicity was evaluated using the MTT assay in human cancer cell lines—including acute lymphoblastic leukemia (CCRF-CEM) and breast cancer (MCF-7, MDA-MB-231)—as well as in normal Vero cells. Apoptosis induction in the two most responsive cell lines (CCRF-CEM and MCF-7) was further examined using flow cytometry-based assays, including annexin V binding, mitochondrial membrane potential disruption, caspase-3 activation, and cell cycle analysis. Intracellular inhibition of CK2 and PIM-1 kinases was confirmed in CCRF-CEM and MCF-7 cells using Western blot and phospho-flow cytometry. Among the synthesized compounds, we identified a novel TBBi derivative exhibiting pronounced pro-apoptotic activity and the ability to inhibit PIM-1 kinase intracellularly. These findings support the hypothesis that PIM-1 kinase represents a promising molecular target for the treatment of leukemia. Full article