Search Results (836)

Renal cancer is among the deadliest human malignancies. MCM7, a cell cycle-regulating protein, is frequently overexpressed in cancers and is associated with hyperproliferation and cancer progression. miR-25-3p, miR-93-5p, and miR-106b-5p form the miR-106b-25 cluster, located within the MCM7 gene, and have previously been reported as upregulated in RCC. This study investigates whether miRNAs from the miR-106b-25 cluster regulate common target genes, enhance one another’s effect, and act synergistically with MCM7 to promote tumor progression. Tissue samples from clear cell RCC (ccRCC) and paired controls were analysed to assess MCM7 expression and genes targeted by the miR-106b-25 cluster. Findings were further validated using the TCGA-KIRC dataset. Functional studies in RCC-derived cell lines were conducted to evaluate the effects of miRNAs on target gene expression, as well as MCM7, and the combined contributions of MCM7 and the miR-106b-25 cluster to renal cancer progression. We demonstrate that MCM7 is upregulated at both transcript and protein levels in RCC, contributing to cancer progression by regulating cell proliferation and caspase-3/7 activity. Furthermore, we identified cancer-related genes aberrantly expressed in ccRCC (BRMS1L, CPEB3, DNAJB9, KIF3B, NFIB, PTPRJ, RBL2) and targeted by members of the miR-106b-25 cluster, suggesting that their dysregulation may be driven by these miRNAs. Inhibition of the miR-106b-25 cluster increases caspase-3/7 activity. These findings demonstrate that both MCM7 and the miR-106b-25 cluster contribute to renal cancer progression. Full article

Background: Lung adenocarcinoma (LUAD), the most prevalent and malignant form of lung cancer subtypes, is in urgent need of additional therapeutic targets and prognostic indicators. Antioxidant 1 (ATOX1) copper chaperone and RhoA/Rho kinase 1 (ROCK1) are novel anti-tumour targets in cancers. However, their prognostic value and synergistic inhibitory effect remain unclear in LUAD. Methods: We re-analyzed the open-access proteomic landscape study of LUAD in 2019 and investigated the prognostic value of ATOX1/ROCK1 expression patterns. Then we verified it immunohistochemically using an independent cohort from our hospital enrolling 35 patients with TNM stage III/IV LUAD. In vitro, double fluorescence was used to confirm the co-expression and location of ATOX1/ROCK1. The CCK—8 assay and Transwell assay were carried out to assess the changes in proliferation and migration of Lewis lung carcinoma (LLC) cells following treatment with ATOX1/ROCK1 si-RNA or inhibitory drugs. Western blot was used to confirm protein expression after si-RNA transfection. Moreover, ATOX1/ROCK1-targeted drugs’ therapeutic effects were further investigated in the LLC allogeneic transplantation model and MNU-induced tumour model. Results: Firstly, according to the ATOX1/ROCK1 expression pattern derived from proteomic data, double-low expression of ATOX1/ROCK1 indicated a better Disease Free Survival (DFS) (log-rank test p = 0.01) and Overall Survival (OS) (log-rank test p = 8.2 × 10⁻³), whose expression was also correlated with the lower expression of MCM family proteins. Further, we verified this prognostic correlation in our cohort. The IHC-defined ATOX1/ROCK1 low subtype also had the best OS (log-rank test p = 2.4 × 10⁻³). In vitro, double fluorescence confirmed that ATOX1/ROCK1 was highly expressed together in Lewis cells. Co-inhibition of ATOX1 and ROCK1 either by siRNA transfection or inhibitory drugs could lead to a significant decrease in tumour proliferation. Interestingly, transcriptional inhibition of ATOX1 can lead to the up-regulation of ROCK1, while inhibition of ROCK1 resulted in the promotion of ATOX1. Moreover, in the analysis of migration ability, a similar synergistic effect from the co-inhibition of ATOX1/ROCK1 was also observed. Finally, the Lewis and Mnu-induced allogeneic transplantation model also demonstrated a greatly improved therapeutic effect by combining targeting ATOX1 and ROCK1. Conclusions: Collectively, our results suggest that a low expression pattern of ATOX1/ROCK1 can predict better clinical outcomes in LUAD. Combining the inhibition of these two targets can reach a significantly better therapeutic effect than targeting either alone. Full article

Two nitrogen-modified mesoporous MCM-41-type silicas were synthesized by the sol–gel route and post-grafting surface modification procedure, obtaining an aminopropyl-modified MCM-41 (denoted MCM-41-N) and an aminoethyl-aminopropyl-modified MCM-41 (denoted MCM-41-NN). Hexavalent chromium removal from acidified water by adsorption and reduction to Cr(III) on the solid mesophases was analyzed. The modified silicas were characterized by powder X-ray diffraction (XRD), Fourier transformed infrared spectra (FT-IR), nitrogen adsorption–desorption measurements at −196 °C, X-ray photoelectron spectroscopy (XPS), ²⁹Si solid state Nuclear Magnetic Resonance (²⁹Si-RMN), and thermogravimetric analysis (TGA). Both samples exhibited very high capacities for decreasing Cr(VI) concentrations in water, according to the Langmuir isotherm model: 129.9 mg·g⁻¹ for MCM-41-N and 133.3 mg·g⁻¹ for MCM-41-NN. The chromium speciation in the supernatant after 24 h indicates that MCM-41-N had a higher capacity to reduce Cr(VI) to the less toxic Cr(III) species than MCM-41-NN: 92.9% vs. 72.5% when the initial Cr(VI) concentration was 10 mg·g⁻¹. These differences were related to the different capacity of nitrogen atoms in MCM-41-N and MCM-41-NN to interact with the surrounding surface silanols which are required for the chemical reduction in the hexavalent species to take place, as evidenced by FT-IR and XPS analysis. Also, the Cr(III)/Cr(VI) atomic ratios on the solid’s surfaces were higher for MCM-41-N. These results highlight the characteristics that nitrogen atoms incorporated into silica matrices must possess in order to maximize the transformation of Cr(VI) into the trivalent species, thereby reducing the generation of toxic waste harmful to living organisms. Full article

Background/Objectives: As part of the human adaptation to dairy consumption, the presence of the rs4988235-T variant in the MCM6 gene primarily determines lactase persistence in adult European populations, increasing the expression of the lactase-encoding LCT gene. Carriers of the C/C variant are lactose intolerant, while carriers of the T/T or T/C variant have persistent lactase enzyme activity and are able to digest lactose in adulthood. While the association between lactose intolerance and increased cardiovascular risk (CVR) is well-known, the underlying causes have only been partly explored. The present study aimed to investigate the association of rs4988235 polymorphism with significant lipids affecting cardiovascular health and estimated CVR. Methods: The rs4988235 polymorphism was genotyped in 397 subjects from the general Hungarian population and 368 individuals from the Roma population. To characterize the overall lipid profile, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein AI (ApoAI), and apolipoprotein B100 (ApoB100) levels were measured, and their ratios (TG/HDL-C, LDL-C/HDL-C, and ApoB100/ApoAI) were calculated. Cardiovascular risk was estimated using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCE), Revised Pooled Cohort Equations (RPCE), and the Systematic Coronary Risk Evaluations (SCORE and SCORE2) algorithms. Adjusted linear and logistic regression analyses were performed, with p < 0.05 considered significant. Results: The Roma population had a significantly higher prevalence of the C/C genotype than the general population (65.5% vs. 40.3%, respectively). The results of the adjusted linear regression analysis showed a significant association between the C/C genotype and higher LDL-C level (B = 0.126, p = 0.047) and ApoB100 level (B = 0.046, p = 0.013), as well as a higher LDL-C/HDL-C ratio (B = 0.174, p = 0.021) and a higher ApoB100/ApoAI ratio (B = 0.045, p = 0.002), as well as a lower HDL-C level (B = −0.041, p = 0.049). The C/C genotype was also significantly associated with an increased cardiovascular risk (CVR) as estimated by the SCORE (B = 0.235, p = 0.034), SCORE2 (B = 0.414, p = 0.009), PCE (B = 0.536, p = 0.008), and RPCE (B = 0.289, p = 0.045) but not the FRS. After adjusting the statistical model further for ApoAI and ApoB100 levels, the significant correlation with the risk estimation algorithms disappeared (SCORE: p = 0.099; SCORE2: p = 0.283; PCE: p = 0.255; and RPCE: p = 0.370). Conclusions: Our results suggest that the C/C genotype of rs4988235 is associated with significantly higher ApoB100 and lower ApoAI levels and consequently higher ApoB100/ApoAI ratios, potentially contributing to an increased risk of cardiovascular disease. The results of the statistical analyses suggest that the association between lactose intolerant genotype and cardiovascular risk may be mediated indirectly via modification of the apolipoprotein profile. Full article

Background/Objectives: Inteins are mobile genetic elements invading highly conserved genes across all domains of life and viruses. Five active intein insertion sites (MCM-a through e) had previously been identified and studied in the archaeal replicative helicase minichromosome maintenance (MCM) subunit gene mcm, making MCM an ideal system for dissecting the dynamics of multi-intein genes. However, work in this system thus far has been limited to particular archaeal groups. To better understand the dynamics and diversity of these inteins, MCM homologs spanning all archaeal groups were extracted from NCBI’s non-redundant protein sequence database, and the distribution and structural architectures of their inteins were characterized. Methods: The amino acid sequences of 4243 archaeal MCM homologs were retrieved from NCBI’s non-redundant protein sequence database. These sequences were systematically assessed for their intein content through within-group multiple sequence alignments. To characterize the inteins present at each site, extensive intein structure predictions and comparisons were performed. Phylogenetic analyses were used to investigate intein relatedness between and within sites, as well as the distribution of different MCM inteins in geographically overlapping populations of archaea. Results: In total, 11 active MCM intein insertion sites were identified, expanding on the previously known five. The insertion sites have varied invasion activity levels across archaeal groups, with Nanobdellati (DPANN) being the only group with all 11 sites active. In all but two (Methanonatronarchaeia and Hadarchaeota) of the archaeal groups studied where inteins were present, at least one MCM homolog was invaded by more than one intein. With respect to intein structure, within-intein insertions bearing semblance to DNA-binding domains were identified, with varied presence between inteins. Additionally, a study of archaeal MCM sequences of samples collected from the Atacama Desert in June 2013 revealed high MCM intein diversity levels. Conclusions: We identified six new active intein insertion sites in archaeal MCM, more than doubling the five previously known sites. All eleven intein insertion sites were either close to the ATP binding site, or the lined the channel through which the single-stranded DNA is pulled during the catalytic cycle of the helicase. Many of the analyzed inteins contained insertions bearing similarity to DNA-binding helix-turn-helix domains suggesting potential involvement in the intein homing process. Additionally, the high levels of MCM intein diversity observed in archaea from the Atacama Desert provide novel and strong support for a co-existence model of intein persistence. Full article

In the rapidly evolving fields of materials science, catalysis, electronics, drug delivery, and environmental remediation, the development of effective substrates for molecular deposition has become increasingly crucial. Ordered mesoporous silica materials have garnered significant attention due to their unique structural properties and exceptional potential as substrates for molecular immobilization across these diverse applications. This study compares three mesoporous silica powders: MCM-41, SBA-15, and SBA-16. A multi-technique characterization approach was employed, utilizing low- and wide-angle X-ray diffraction (XRD), nitrogen physisorption, and transmission electron microscopy (TEM) to elucidate the structure–property relationships of these materials. XRD analysis confirmed the amorphous nature of silica frameworks and revealed distinct pore symmetries: a two-dimensional hexagonal (P6mm) structure for MCM-41 and SBA-15, and three-dimensional cubic (Im$\overline{3}$m) structure for SBA-16. Nitrogen sorption measurements demonstrated significant variations in textural properties, with MCM-41 exhibiting uniform cylindrical mesopores and the highest surface area, SBA-15 displaying hierarchical meso- and microporosity confirmed by NLDFT analysis, and SBA-16 showing a complex 3D interconnected cage-like structure with broad pore size distribution. TEM imaging provided direct visualization of particle morphology and internal pore architecture, enabling estimation of lattice parameters and identification of structural gradients within individual particles. The integration of these complementary techniques proved essential for comprehensive material characterization, particularly for MCM-41, where its small particle size (45–75 nm) contributed to apparent structural inconsistencies between XRD and sorption data. This integrated analytical approach provides valuable insights into the fundamental structure–property relationships governing ordered mesoporous silica materials and demonstrates the necessity of combined characterization strategies for accurate structural determination. Full article

In response to the demand for precise measurement of illuminance distribution in the quality control of LED monitoring fill light products and the iterative direction of secondary optical design, distributed photometric sensors have shown advantages, but their measurement uncertainty assessment faces challenges. This paper addresses the problem of uncertainty evaluation in photometric parameter measurement with a two-dimensional horizontal distributed photometric sensor and proposes an uncertainty evaluation framework for this task. We have established an uncertainty analysis model for the measurement system and provided two uncertainty synthesis methods, The Guide to the Expression of Uncertainty in Measurement and the Monte Carlo method. This study designed illuminance measurement experiments to validate the feasibility of the proposed uncertainty evaluation method. The results demonstrate that the actual probability distribution of the measurement data follows a trapezoidal distribution. Furthermore, the expanded uncertainty calculated using the GUM method was 21.1% higher than that obtained by the MCM. This work effectively addresses the uncertainty evaluation challenge for illuminance measurement tasks using a two-dimensional horizontal distributed photometric sensor. The findings offer valuable reference for the uncertainty assessment of other high-precision optical instruments and possess significant engineering value in enhancing the reliability of optical metrology systems. Full article

Leveraging the ability of Vision Transformers (ViTs) to model contextual information across spatial patches, Masked Image Modeling (MIM) has emerged as a successful pre-training paradigm for visual representation learning by masking parts of the input and reconstructing the original image. However, this characteristic of ViTs has led many existing MIM methods to focus primarily on spatial patch reconstruction, overlooking the importance of semantic continuity in the channel dimension. Therefore, we propose a novel Masked Channel Modeling (MCM) pre-training paradigm, which reconstructs masked channel features using the contextual information from unmasked channels, thereby enhancing the model’s understanding of images from the perspective of channel semantic continuity. Considering that traditional RGB reconstruction targets lack sufficient semantic attributes in the channel dimension, MCM introduces advanced features extracted by the CLIP image encoder as reconstruction targets. This guides the model to better capture semantic continuity across feature channels. Extensive experiments on downstream tasks, including image classification, object detection, and semantic segmentation, demonstrate the effectiveness and superiority of MCM. Our code will be available later. Full article

In this research, a single composite-type stretchable triboelectric nanogenerator (TENG) is proposed for efficient energy harvesting and handwriting recognition. The composite TENGs were fabricated by blending dielectric barium titanate (BT) and conductive carbon nanotubes (CNTs) in varying amounts into a styrene–butadiene rubber matrix. The energy harvesting efficiency depends on the type and amount of fillers, as well as their dispersion within the matrix. Stearic acid modification of BT enables near-nanoscale filler distribution, resulting in high energy conversion efficiencies. The composite achieved power efficiency, power density, charge efficiency, and charge density values of 1.127 nW/N, 8.258 mW/m³, 0.146 nC/N, and 1.072 mC/m³, respectively, under only 2% cyclic compressive strain at 0.85 Hz. The material performs better at low stress–strain ranges, exhibiting higher charge efficiency. The generated charge in the TENG composite is well correlated with the compressive stress, which provides a minimum activation pressure of 0.144 kPa, making it suitable for low-pressure sensing applications. A flat composite with dimensions of 0.02 × 6 × 5 cm³ can produce a power density of 26.04 W/m³, a charge density of 0.205 mC/m³, and an output voltage of 10 V from a single hand pat. The rubber composite also demonstrates high accuracy in handwriting recognition across different individuals, with clear differences in sensitivity curves. Repeated attempts by the same person show minimal deviation (<5%) in writing time. Additionally, the presence of reinforcing fillers enhances mechanical strength and durability, making the composite suitable for long-term cyclic energy harvesting and wearable sensor applications. Full article

This paper presents a hybrid fast charging strategy for static wireless power transfer (WPT) systems that synergistically combines pulsed current and multi-stage current (MCM) modes to enable rapid yet battery-health-conscious electric vehicle (EV) charging, thereby promoting sustainable transportation. The proposed approach employs a memetic algorithm (MA) to dynamically optimize the charging parameters, achieving an optimal balance between speed and battery longevity while maintaining 90.78% system efficiency at the SAE J2954-standard 85 kHz operating frequency. A neural-network-based state of charge (SOC) estimator provides accurate real-time monitoring, complemented by MA-tuned PI control for enhanced resonance stability and adaptive pulsed current–MCM profiles for the optimal energy transfer. Simulations and experimental validation demonstrate faster charging compared to that using the conventional constant current–constant voltage (CC-CV) methods while effectively preserving the battery’s state of health (SOH)—a critical advantage that reduces the environmental impact of frequent battery replacements and minimizes the carbon footprint associated with raw material extraction and battery manufacturing. By addressing both the technical challenges of high-power WPT systems and the ecological imperative of battery preservation, this research bridges the gap between fast charging requirements and sustainable EV adoption, offering a practical solution that aligns with global decarbonization goals through optimized resource utilization and an extended battery service life. Full article

Calpain-5/CAPN5 is a calcium-activated, non-lysosomal cysteine (thiol) protease. The substrate repertoire of CAPN5 is not known. Calpains catalyze limited proteolysis of their substrates, generating neo-N-termini that correspond to internal residues of their nascent substrate proteins. To identify such neo-N-termini generated by CAPN5, we employed an N-terminomics approach called TAILS (Terminal amine isotopic labeling of substrates) to quantitatively compare the N-terminal peptides detected in parental and CAPN5-deficient SH-SY5Y neuroblastoma cells. Thirty neo-N-termini corresponding to 29 protein groups and 24 unique proteins were detected to be depleted in the CAPN5^−/− cells. A subset of the identified putative substrates was further studied with CAPN5 co-immunoprecipitation, in vitro calcium-induced CAPN5 proteolysis assay, and their cellular fragmentation patterns were compared in parental and CAPN5-deficient SH-SY5Y cells. Here, we provide evidence for CAPN5-mediated proteolysis of the synaptic proteins DLGAP4, IQSEC1 and MPDZ, the neurodegeneration-related EWS, hnRNPU, TFG and UGP2, the DNA replication regulator MCM3, and the neuronal differentiation regulator LMTK1. Our data provide new relevance for neovascular inflammatory vitreoretinopathy (NIV), a progressive eye disease caused by pathogenic mutations in CAPN5. Data are available via ProteomeXchange with identifier PXD064313. Full article

Axial flux motors have attracted significant attention in recent years due to their advantages such as shorter axial length and high torque density. However, the optimization of axial flux motors is an extremely time-consuming process. To reduce the computational time required for motor optimization, this study employed a magnetic charge model to establish a coreless axial flux motor model and analyzed the advantages of this approach. This method is applicable to coreless axial flux motor optimizations with surface-mounted rotors and concentrated windings. Parameter optimization was subsequently performed based on the theoretical model. In terms of seeking optimal solutions, the torque obtained through the magnetic charge method (MCM) reached 99.67% of the finite element method (FEM) results. Finally, a prototype was fabricated, and a test platform was constructed based on the optimization results. The experimental torque showed a 4% deviation from simulations, validating the accuracy of the optimization. Full article

The ongoing miniaturization of semiconductor devices necessitates continuous advancements in lithographic processes, which are critical for high-precision circuit formation. To prevent substrate damage during the etching step, a spin-on hardmask (SOH) layer is often introduced between the photoresist (PR) and the substrate. However, residual metal ions in SOH solutions can adversely affect integrated circuit performance, underscoring the need for efficient and chemically compatible removal strategies. This study investigates the adsorption of metal ions (Al³⁺, Cr³⁺, Cu²⁺, Fe³⁺, Ni²⁺, and Ti⁴⁺) from SOH solutions using mesoporous silica materials—MCM-41 and SBA-15—functionalized with various groups (–OH, –NH₂, –SH, and –CH₃). Adsorption performance was evaluated under solvent-only, monomer-containing, and polymer-containing conditions. Among the tested materials, amine-functionalized mesoporous silica exhibited the highest adsorption efficiency, with SBA-15-NH₂ showing relatively effective and uniform performance in polymer-containing systems. Isotherm analysis supported a monolayer chemical adsorption mechanism, suggesting the significance of surface functional groups in the adsorption process. These findings demonstrate the potential of functionalized mesoporous silica as a promising candidate for trace metal ion removal in semiconductor manufacturing, offering enhanced yield and improved process reliability. Full article

Use of measures of effectiveness (MOE) analysis in exploring candidate systems or alternatives has been the subject of much debate in the systems engineering discipline, as some authors have noted. In this work, methods for MOE analysis are revisited as they pertain to an advanced air mobility platform, first by using the traditional approach, which involves the application of the Pugh matrix, and second by proposing an approach that involves a combination of two (2) methods, namely the Monte Carlo method (MCM) and the analytical hierarchy process (AHP), in order to evaluate and rank the preferred alternative from a selection of candidate systems. The latter method is termed the Monte Carlo–analytical hierarchical hybrid process (MC–AHHP). The results obtained from the application of both approaches demonstrate that the MC–AHHP is a less subjective, more objective, data-driven, and quantitative measure for MOE analysis compared to the erstwhile Pugh matrix method. While the Pugh matrix ranked the SAR AAM as first overall among seven (7) alternatives, the MC–AHHP ranked the same second among three (3) alternatives. The subsequent verification and validation process showed that the MC–AHHP approach resulted in a degree of consistency value of $0.083$, where $CI/RI<0.10$ represents an acceptable level of consistency. Thus, the MC–AHHP approach is recommended as a viable decision-making tool for adoption by systems engineering practitioners. Full article

Wildfire detection in power transmission corridors is essential for providing timely warnings and ensuring the safe and stable operation of power lines. However, this task faces significant challenges due to the large number of smoke-like samples in the background, the complex and diverse target morphologies, and the difficulty of detecting small-scale smoke and flame objects. To address these issues, this paper proposed an improved Oriented R-CNN model enhanced with metric learning for wildfire detection in power transmission corridors. Specifically, a multi-center metric loss (MCM-Loss) module based on metric learning was introduced to enhance the model’s ability to differentiate features of similar targets, thereby improving the recognition accuracy in the presence of interference. Experimental results showed that the introduction of the MCM-Loss module increased the average precision (AP) for smoke targets by 2.7%. In addition, the group convolution-based network ResNeXt was adopted to replace the original backbone network ResNet, broadening the channel dimensions of the feature extraction network and enhancing the model’s capability to detect flame and smoke targets with diverse morphologies. This substitution led to a 0.6% improvement in mean average precision (mAP). Furthermore, an FPN-CARAFE module was designed by incorporating the content-aware up-sampling operator CARAFE, which improved multi-scale feature representation and significantly boosted performance in detecting small targets. In particular, the proposed FPN-CARAFE module improved the AP for fire targets by 8.1%. Experimental results demonstrated that the proposed model achieved superior performance in wildfire detection within power transmission corridors, achieving a mAP of 90.4% on the test dataset—an improvement of 6.4% over the baseline model. Compared with other commonly used object detection algorithms, the model developed in this study exhibited improved detection performance on the test dataset, offering research support for wildfire monitoring in power transmission corridors. Full article