Browse Articles

Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations

Abstract Expansion of RNA polymerase III (Pol III) activity in cancer can activate the transcription of typically silent small RNA genes, including snaR-A (small NF90-associated RNA isoform A), a hominid-specific noncoding RNA that promotes cell proliferation through unclear mechanisms. Here, we show that snaR-A interacts with mRNA splicing factors, including the U2 small nuclear ribonucleoprotein (snRNP) subunit SF3B2, and localizes near subnuclear foci enriched in splicing machinery. Overexpression of snaR-A increases intron retention, a hallmark of inefficient splicing, whereas its depletion enhances splicing of mRNAs characterized by high U2 snRNP occupancy and nuclear speckle proximity. These improvements in splicing coincide with reduced cell proliferation, consistent with tumor-level patterns linking snaR-A to growth in primary cancers. Together, these findings identify snaR-A as a molecular antagonist of splicing and potential disease driver in cancer. We propose that snaR-A-related splicing perturbation may phenocopy splicing defects attributed to U2 snRNP mutations in cancer, eliciting an alternative, non-mutational mechanism of splicing dysregulation during tumorigenesis.

Midnight darkness and evening melatonin pre-treatment reverse night-light-induced neurobehavioural disruptions in a diurnal corvid

Cost analysis of enhanced software reliability model with Weibull testing effort function using simulated annealing

Remote tuning of single-atom Fe-N5 sites via high-coordination defects for enhanced Fenton-like water decontamination

Abstract Fe-N 5 single-atom catalysts (SACs) hold great promise for water decontamination, however, the fundamental relationship between their high coordination shell environment and catalytic performance in Fenton-like reactions remains poorly understood. Here, we precisely regulate the high coordination shell defects of a model SAC with well-defined axial Fe-N 5 configurations to elucidate the impact of remote interactions on peroxymonosulfate (PMS) activation. Experimental and theoretical studies confirm that remote modulation of Fe-N 5 sites through high coordination shell defects profoundly enhance Fenton-like catalytic activity, enabling FeN 5 -SD 2 to achieve a turnover frequency (TOF) value of 0.338 min⁻ 1 , surpassing state-of-the-art SACs. Our findings reveal a critical volcano-type correlation between defect content and catalytic efficiency, where coordinated modulation of Fe d -band center positioning and PMS adsorption energetics governs reaction dynamics. Only the FeN 5 -SD 2 configuration with an optimal level of defects density and moderate adsorption energy enables sufficient O-O bond elongation in PMS to lower the energy barrier for selective singlet oxygen ( 1 O 2 ) evolution. This study unveils the mechanistic role of higher coordination shell defects in regulating Fe-N 5 active sites and introduces a well-defined model to investigate the structure–property correlations of higher coordination shells in SACs for Fenton-like reactions.

Fine-grained temporal–spatial cues for theft recognition in surveillance videos

Evaluation of attitudes of university students towards artificial intelligence using data mining methods

Abstract This study analyzes university students’ attitudes towards artificial intelligence. Within the scope of the research, the data obtained from 1379 students through scale application were classified into three classes as “Insufficient”, “Sufficient” and “Strongly Sufficient” according to their attitudes towards artificial intelligence. The data was classified by data mining methods. For this purpose, MLP, Decision Tree, KNN, XGBoost, Random Forest, CatBoost and SVM algorithms were used. The performance of the model was evaluated with a 5-fold cross-validation method. For each algorithm, basic metrics such as accuracy, precision, recall and F1 score were calculated and the classification performance was compared. According to the results, the highest F1-Score accuracy rate was 95.52% for the SVM algorithm. This was followed by CatBoost (93.66%), Random Forest (92.56%) and XGBoost (92.36%). The lowest success rates were observed in MLP (81.87%) and Decision Tree (82.72%) models. Confusion matrices revealed a tendency for frequent confusion with other classes, especially in the Strongly Sufficient class. The study concluded that advanced classification algorithms provide powerful and reliable tools for analyzing students’ attitudes towards artificial intelligence. These findings may contribute to the development of educational policies and strategies for AI literacy.

Nivolumab plus ipilimumab induce hyper-progression in renal medullary carcinoma: results of a phase II trial and preclinical evidence

Abstract Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that immune checkpoint therapy (ICT) triggered an interferon-γ response that induced a “myeloid mimicry” program in tumor cells, regulated by the CEBPB / p300 axis and linked to proliferation and hyperprogression. In preclinical experiments using an immunocompetent somatic mosaic genetically engineered mouse model of RMC, combination ICT accelerated tumor growth while activating myeloid-affiliated transcriptional circuits. Selective pharmacologic inhibition of p300 suppressed this program and restored sensitivity to ICT. These findings reveal an adaptive mechanism of resistance to ICT in RMC and support targeting master myeloid regulators to enable therapeutic benefit.

Endothelial glycocalyx shedding and oxidative stress in neuronal damage after return of spontaneous circulation in cardiac arrest

A robust solution for power grid management using a hybrid deterministic and probabilistic model for short term load forecasting

Asymmetric bubble-mediated gas transfer enhances global ocean CO2 uptake

Abstract Sea-air carbon dioxide (CO 2 ) flux is typically estimated from the product of the gas transfer velocity ( K ) and the CO 2 fugacity difference between the ocean surface and atmosphere. Total gas exchange comprises interfacial transfer across the unbroken surface and bubble-mediated transfer from wave breaking. While interfacial transfer is symmetric for invasion and evasion, bubble-mediated transfer theoretically favours invasion due to hydrostatic pressure, though field evidence has been lacking. Here we provide direct field evidence of this asymmetry and develop an asymmetric flux equation. Applying the asymmetric equation reduces bias in K , and increases global oceanic CO 2 uptake by 0.3-0.4 Pg C yr -1 (~15% on average from 1991 to 2020) relative to conventional estimates. Further evasion data are needed to better quantify the asymmetry factor. Our study suggests that the ocean may have absorbed more CO 2 than previously thought, and the asymmetric equation should be used for future CO 2 flux assessments.

A multi-model deep learning framework for SEM-based defect detection in $$\textrm{FAPbI}_3$$ Perovskite thin films

Intravenous administration of CpG7909 lipoplex enhances anti-PD1 immunotherapy by modulating the tumor microenvironment and inducing durable tumor regression

Abstract The use of immune checkpoint inhibitors (ICIs) is a potential immunotherapy strategy to prevent immune escape in cancer cells. However, low immune infiltration and low antigen presentation in the tumor microenvironment (TME) have led to ineffective ICI immunotherapy in clinical studies. Although intratumoral injection of Toll-like receptor 9 (TLR9) agonists was shown to improve the efficacy of ICIs by increasing the number of tumor-infiltrating lymphocytes (TILs), it has limited effects on metastatic or deep-seated tumors. To overcome this challenge, we developed CpG7909 (a TLR9 agonist) lipoplex using a cationic lipid formulation, which exhibited preferential accumulation in tumors and spleen following systemic administration, Combination immunotherapy with an anti-PD1 antibody and CpG7909 lipoplex significantly promoted the infiltration of CD8 + T cells (> twofold) into the TME of the CT26 tumor animal model and effectively inhibited both deep-seated colorectal and metastatic lung tumors. Furthermore, the complete response (CR) rate of mice receiving concurrent therapy increased from 0 to 75% compared with that of those receiving anti-PD1 monotherapy. To our knowledge, this study is among the first to evaluate the combination of CpG7909 lipoplexes with anti-PD1 antibodies in the context of cancer immunotherapy. The findings suggest that this approach may convert the TME from an immunologically “cold” to “hot” state, thereby enhancing tumor suppression and potentially improving the response rate to ICIs.

Doctor-blading-assisted interfacial polymerization for green and scalable polyamide membrane fabrication

Adsorptive removal of Cr(VI) from water using silver nanoparticle modified-diatomite nanocomposite

Explainable ensemble learning for Epstein-Barr virus risk prediction in ulcerative colitis and Crohn’s disease using routine biomarkers

Personal, social, and natural co-exposure pattern and plasma proteins in cardiometabolic diseases

Abstract Multiple environmental exposures elevate the risk of cardiometabolic diseases (CMDs), yet the impact of combined co-exposures, and their protein-mediated mechanisms remain underexplored. Among 366,261 UK Biobank participants, this study identified five distinct exposure patterns through clustering analysis: Air and Noise Pollution, Social Deprivation, Blue and Green Space, Health Behaviors and Reference. Notably, the Social Deprivation pattern showed the highest CMDs risk, with hazard ratios ranging from 1.15 to 1.40. Inflammatory and immune proteins were associated with all co-exposure patterns. The Air and Noise Pollution and Social Deprivation patterns demonstrated that the common mediating proteins included CDCP1, CXCL17, FGF21, GDF15 and IGFBP4. CXCL13, CA6, SDC1, and PTN mediated Healthy Behaviors, while MMP12 mediated Blue and Green Space pattern. This study offers etiological insight into the comprehensive human environment, draws attention to the population experiencing health disadvantages as a result of co-exposure to social stressors, and elucidates protein-mediated mechanisms linking environmental exposures to disease.

Intelligent trajectory tracking in autonomous plantation robots using PSO-tuned nonlinear fuzzy PID, fuzzy PID, and conventional PID controllers

Thermally stratified flow of unsteady magnetized nanofluids within squeezing channel with Darcy Forchhimer porous medium

BAF-1–VRK-1 mediated release of meiotic chromosomes from the nuclear periphery is important for genome integrity

Abstract Rapid prophase chromosome movements ensure faithful alignment of the parental homologous chromosomes and successful synapsis formation during meiosis. These movements are driven by cytoplasmic forces transmitted to the nuclear periphery, where chromosome ends are attached through transmembrane proteins. During many developmental stages a specific genome architecture with chromatin nuclear periphery contacts mediates specific gene expression. Whether chromatin is removed from the nuclear periphery as a consequence of chromosome motions or by a specific mechanism is not fully understood. Here, we identify a mechanism to remove chromatin from the nuclear periphery through vaccinia related kinase (VRK-1)–dependent phosphorylation of Barrier to Autointegration Factor 1 (BAF-1) in Caenorhabditis elegans early prophase of meiosis. Interfering with chromatin removal delays chromosome pairing, impairs synapsis, produces oocytes with abnormal chromosomes and elevated apoptosis. Long read sequencing reveals deletions and duplications in offspring lacking VRK-1 underscoring the importance of the BAF-1–VRK-1 module in preserving genome stability in gametes during rapid chromosome movements.

Comparative study of fetal facial shape between Japanese and North American populations using micro-CT