Search Results (268)

Wilms tumor (WT), the most common pediatric renal malignancy, shares some clinical and pathological features with chronic kidney disease (CKD). Understanding biomarkers of kidney injury among CKD and WT patients is of high interest due to its potential implications for diagnosis, prognosis, and treatment strategies. This study enrolled twenty pediatric patients with WT (stage I–IV), forty with CKD (stage I–V), and twenty healthy volunteers. Urine samples were collected and six urine biomarkers (calbindin, clusterin, GST-π, IL-18, KIM-1, MCP-1) associated with kidney injury were assessed using the Bio-Plex Pro RBM Human Kidney Toxicity Assays kit (Bio-Plex Manager software 4.0). A comparative analysis of biomarker levels across the three groups revealed distinct patterns. Creatinine levels were notably elevated in CKD (1.32 ± 1.9) compared to WT (0.64 ± 0.26) and the control group. Tested biomarkers were calculated per milligram of urine creatinine, and all the differences among the groups were statistically significant. Pearson’s correlation coefficients showed strong interplay among CKD biomarkers. This study identified variations in biomarker patterns among WT and CKD patients. Understanding biomarker interactions may provide future diagnostic approaches for pediatric kidney conditions. Full article

Tumor development is mainly marked by the gradual transformation of cells that acquire capacities such as sustained growth signaling, evasion of growth suppression, resistance to cell death, and induction of angiogenesis, achieving replicative immortality and activating invasion and metastasis. How different epigenetic alterations like m¹A, m⁵C, and m⁶A contribute to tumor development is a field that still needs to be investigated. The immune modulators, CD70, CD80, and TIGIT, mainly regulate T-cell activation and consequently the immune evasion of tumors. Here, we explored the presence and the potential consequences of RNA modifications in these regulators in pan-cancer. Our findings highlight the critical role of the m⁶A, m⁵C, and m¹A in regulating CD70, CD80, and TIGIT across multiple solid tumors. By combining epitranscriptomics data with functional enrichment and survival modeling, we show that RNA modification enzymes not only modulate immune-related gene expression but also serve as potential biomarkers for patient prognosis. By constructing a robust four-gene prognostic signature involving YTHDF3, RBM15B, IGF2BP2, and TRMT61A, we demonstrate that RNA modification profiles can accurately stratify patients into risk groups with distinct overall survival outcomes. The performance of this model across eight cancer types underscores the translational promise of epitranscriptomic markers in both mechanistic understanding and personalized oncology. Altogether, our study bridges the gap between the mechanistic regulation of immune checkpoints and their clinical utility, offering novel insights into how the epitranscriptome can be leveraged to improve cancer prognosis and potentially enhance immunotherapeutic strategies. Full article

Nitrogen is a crucial element that impacts rice yield and its constituent factors. The effects of reduced nitrogen levels on yield constitute is a complex quantitative trait that is controlled by multiple genes, and its genetic basis requires further exploration. In this study, 562 MAGIC line population and 284 germplasm varieties were used for genome-wide association analysis (GWAS) and haplotype analysis, aiming to detect quantitative trait loci (QTL) and candidate genes associated with tolerance to low nitrogen levels. The ratio of effective panicle number per plant (REPN), total number of grains per panicle (RTGN), seed setting rate (RSSR), thousand grain weight (RTGW), biomass (RBM), harvest index (RHI), and grain yield per plant (RGY) of low to normal nitrogen conditions were measured in this study. The RBM and RHI were directly closely related to RGY, while the RSSR indirectly and positively affected RGY through RHI, and the REPN and RTGN mainly indirectly and positively affected RGY through RBM. LOC_Os06g06440 was the most likely gene affecting low-nitrogen-tolerance-related traits in rice within the region, ranging from 2.898 Mb to 3.046 Mb (148 kb) on chromosome 6, and the haplotype AA, with a significantly larger mean RGY of 0.95 and 1.53 in the MAGIC and germplasm varieties, respectively, was the advanced allele of LOC_Os06g06440. Nine xian (indica) varieties (IRIS_313-11624, IRIS_313-10932, CX382, B067, B249, IRIS_313-8215, IRIS_313-10544, B052, and B233) carrying the superior haplotype (AA) of LOC_Os06g06440 and having a higher RGY were selected for the molecular marker-assisted selection of low nitrogen tolerance in rice. These results will enhance our knowledge of the genetic basis of tolerance to low levels of nitrogen and provide valuable information for improving tolerance to low levels of nitrogen in rice-breeding programs. Full article

Restricted Boltzmann machines (RBMs) have demonstrated considerable success as variational quantum states; however, their representational power remains incompletely understood. In this work, we present an analytical proof that RBMs can exactly and efficiently represent stabilizer code states—a class of highly entangled quantum states that are central to quantum error correction. Given a set of stabilizer generators, we develop an efficient algorithm to determine both the RBM architecture and the exact values of its parameters. Our findings provide new insights into the expressive power of RBMs, highlighting their capability to encode highly entangled states, and may serve as a useful tool for the classical simulation of quantum error-correcting codes. Full article

Background/Objectives: RNA-binding motif protein 3 (RBM3) is a cold-shock protein associated with a favorable prognosis in various malignancies. However, its role in epithelial ovarian cancer (OC) remains unclear. This study aimed to evaluate the prognostic significance of RBM3 expression in OC and its association with clinicopathological features. Methods: We retrospectively analyzed 183 cases of OC. Tissue microarrays were constructed using paired 2 mm tumor cores, and RBM3 expression was assessed by immunohistochemistry. Nuclear staining was semi-quantitatively scored based on intensity and proportion, generating a nuclear score (NS). Cases were classified as high (NS > 1) or low (NS ≤ 1) expression. Associations with clinicopathological parameters and survival outcomes were analyzed using chi-square tests, Kaplan–Meier survival curves, and Cox regression models. Results: High RBM3 expression was observed in 51.4% of cases and was significantly associated with favorable histologic subtypes (mucinous, endometrioid, clear cell), early International Federation of Gynecology and Obstetrics (FIGO) stage, and the absence of distant metastasis. Subgroup survival analyses stratified by histologic subtype revealed no significant differences in survival outcomes. RBM3 expression was correlated with prolonged disease-free and overall survival, although it did not retain significance in multivariate analysis. Conclusions: RBM3 expression is strongly associated with favorable pathological features in epithelial ovarian cancer. Although not an independent prognostic marker, RBM3 may serve as a complementary biomarker for risk stratification and prognosis in clinical practice. Full article

Alternative splicing (AS) is a pivotal post-transcriptional mechanism that expands the functional diversity of the proteome by enabling a single gene to generate multiple mRNA and protein isoforms. This process, which involves the differential inclusion or exclusion of exons and introns, is tightly regulated by splicing factors (SFs), such as serine/arginine-rich proteins (SRs), heterogeneous nuclear ribonucleoproteins (hnRNPs), and RNA-binding motif (RBM) proteins. These factors recognize specific sequences, including 5′ and 3′ splice sites and branch points, to ensure precise splicing. While AS is essential for normal cellular function, its dysregulation is increasingly implicated in cancer pathogenesis. Aberrant splicing can lead to the production of oncogenic isoforms that promote tumorigenesis, metastasis, and resistance to therapy. Furthermore, such abnormalities can cause the loss of tumor-suppressing activity, thereby contributing to cancer development. Importantly, abnormal AS events can generate neoantigens, which are presented on tumor cell surfaces via major histocompatibility complex (MHC) molecules, suggesting novel targets for cancer immunotherapy. Additionally, splice-switching oligonucleotides (SSOs) have shown promise as therapeutic agents because they modulate splicing patterns to restore normal gene function or induce tumor-suppressive isoforms. This review explores the mechanisms of AS dysregulation in cancer, its role in tumor progression, and its potential as a therapeutic target. We also discuss innovative technologies, such as high-throughput sequencing and computational approaches, that are revolutionizing the study of AS in cancer. Finally, we address the challenges and future prospects of targeting AS for personalized cancer therapies, emphasizing its potential in precision medicine. Full article

Maintenance plays a key role in oil and gas enterprises, especially in the process of increasing pressure to improve equipment efficiency, reduce costs, and comply with environmental protection requirements towards sustainable production. This study proposes an optimal maintenance strategy based on the overall equipment effectiveness (OEE) index, using a multi-criteria decision-making method (MCDM) integrating an Analytical Hierarchy Process (AHP) and a Technique for Order of Preference by Similarity to an Ideal Solution (TOPSIS). The study evaluates five maintenance strategies—preventive maintenance (PM), risk-based maintenance (RBM), condition-based maintenance (CBM), reliability-centered maintenance (RCM), and predictive maintenance (PdM)—based on four key criteria: maintenance cost, safety, efficiency, and flexibility. The comparison of each pair of criteria and the maintenance strategy choices was carried out systematically to ensure consistency in the decision-making process. The Evaluation Distance to the Mean Solution (EDAS) method was used as a cross-validation tool to strengthen the reliability of the results. The results showed that RCM is the optimal maintenance strategy, providing superior equipment performance and reliability. The study expands the theoretical basis in industrial maintenance, providing a structured and data-driven decision support tool. The method can be flexibly applied in many industries to optimize maintenance strategies and promote sustainable production. Full article

Structural health monitoring (SHM) plays a critical role in ensuring the safety and longevity of civil infrastructure by enabling the early detection of structural changes and supporting preventive maintenance strategies. In recent years, deep learning techniques have emerged as powerful tools for analyzing the complex data generated by SHM systems. This study investigates the use of deep belief networks (DBNs) for classifying structural conditions before and after retrofitting, using both ambient and train-induced acceleration data. Dimensionality reduction techniques such as principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) enabled a clear separation between structural states, emphasizing the DBN’s ability to capture relevant classification features. The DBN architecture, based on stacked restricted Boltzmann machines (RBMs) and supervised fine-tuning, was optimized via grid search and cross-validation. Compared to traditional unsupervised methods like K-means and PCA, DBNs demonstrated a superior performance in feature representation and classification accuracy. Experimental results showed median cross-validation accuracies of $98.04\%$ for ambient data and $96.96\%$ for train-induced data, with low variability. Although random forests slightly outperformed DBNs in classifying ambient data ($99.19\%$), DBNs achieved better results with more complex train-induced signals ($95.91\%$). Robustness analysis under Gaussian noise further demonstrated the DBN’s resilience, maintaining over $90\%$ accuracy for ambient data at noise levels up to ${\sigma }_{\mathrm{noise}}=0.5$. These findings confirm that DBNs are a reliable and effective approach for data-driven structural condition assessment in SHM systems. Full article

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global issue since 2019. The prominent characteristic of SARS-CoV-2 is the presence of the spike (S) protein protruding from the virus particle envelope. The S protein is a major drug and vaccine target because it initiates the key step in infection. Medicinal herbs are a potential treatment option to enhance immunity to fight viral infections. Caesalpinia sappan L. has been reported to display promising anti-viral activities. Specifically, brazilin (BRA), a major bioactive compound in C. sappan, was reported to play a role in inhibiting viral infection. Thus, the ability of BRA as a COVID-19 treatment was tested. The S protein was used as the BRA target of this work. Understanding the binding mechanism of BRA to the S protein is crucial for future utilisation of C. sappan as a COVID-19 treatment or other coronavirus-caused pandemics. Here, we performed molecular docking of BRA onto the S protein receptor binding domain (RBD) and multimerisation (MM) pockets. Molecular dynamics (MD) simulations were conducted to study the stability of binding to glycosylated and non-glycosylated S protein constructs. BRA can bind to the Receptor-binding motif (RBM) on an RBD surface stably; however, it is too large to fit into the MM pocket, resulting in dissociation. Nonetheless, BRA is bound by residues near the S1/S2 interface. We found that glycosylation has no effect on BRA binding, as the proposed binding site is far from any glycans. Our results thus indicate that C. sappan may act as a promising preventive and therapeutic alternative for COVID-19 treatment. Full article

The SARS-CoV-2 spike receptor-binding motif is crucial for viral entry via interaction with the human ACE2 receptor. Mutations N501Y and E484K, found in several variants of concern, impact viral transmissibility and immune escape, but experimental data on their binding effects remain inconsistent. Using isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulations, we analyzed the thermodynamic and structural effects of these mutations. ITC confirmed that N501Y increases ACE2 affinity by 2.2-fold, while E484K enhances binding by 5.8-fold. The Beta/Gamma variant (carrying both mutations) showed the strongest affinity, with a 15-fold increase. E484K was enthalpy-driven, while N501Y introduced entropy-driven effects, suggesting hydrophobic interactions and conformational changes. MD simulations revealed distinct binding poses, with Beta/Gamma peptides interacting with a secondary ACE2 site. A strong correlation was found between entropy contributions and hydrophobic contacts. Additionally, a convolutional neural network was used to estimate the free binding energy of these complexes. Our findings confirm that N501Y and E484K enhance ACE2 binding, with the greatest effect when combined, providing insights into SARS-CoV-2 variant evolution and potential therapeutic strategies. Full article

The entry and infection of the Severe Acute Respiratory Syndrome Coronavirus 2 virus (SARS-CoV-2) involve recognition and binding of the receptor-binding domain (RBD) of the virus surface spike protein to the peptidase domain (PD) of the host cellular Angiotensin-Converting Enzyme-2 (ACE2) receptor. ACE2 is also involved in normal blood pressure control. An association between hypertension and COVID-19 severity and fatality is evident, but how hypertension predisposes patients diagnosed with COVID-19 to unfavorable outcomes remains unclear. High temperature early during SARS-CoV-2 infection impairs binding to human cells and retards viral progression. Low body temperature can prelude poor prognosis. In this study, all-atom molecular dynamics simulations were performed to examine the effects of high pressure and temperature on RBD/PD binding. A high blood pressure of 940 mmHg enhanced RBD/PD binding. A high temperature above 315 K significantly weakened RBD/PD binding, while a low temperature of 305 K enhanced binding. The curvature of the PD α1-helix and proximity of the PD β3β4-hairpin tip to the RBM motif affected the compactness of the binding interface and, hence, binding affinity. These findings provide novel insights into the underlying mechanisms by which hypertension predisposes patients to unfavorable outcomes in COVID-19 and how an initial high temperature retards viral progression. Full article

Continuous-wave (CW) radar sensors can remotely measure respiration and heartbeat by detecting the periodic movements of internal organs. However, external disturbances, such as random body motion (RBM) or environmental interference, significantly degrade the signal-to-noise ratio (SNR) and reduce the accuracy of vital sign detection. The various motion cancellation techniques that have been proposed to enhance robustness against RBMs include improvements in radar architecture, advanced signal processing algorithms, and studies on electromagnetic propagation characteristics. This paper provides a comprehensive review of recent advancements in motion cancellation techniques for CW radar-based vital sign detectors and discusses future research directions to improve detection performance in dynamic environments. Full article

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer in the head and neck region. In advanced stages of OSCC, chemotherapy is commonly used for treatment, despite some cancer cells having low sensitivity to anticancer drugs. We focused on RBM17/SPF45 as an essential drug-sensitizing factor in the context of malignant cells acquiring chemoresistance. Here, we demonstrate how RBM17 affects anticancer drug resistance in OSCC and we suggest the possible mechanism underlying its effects. After exposing oral cancer cell lines to fluorouracil (5-FU) and cisplatin, but not paclitaxel, the gene and protein expression of RBM17 increased. We found that siRNA-mediated RBM17-knockdown of the cell lines gained a significantly higher sensitivity to 5-FU, which was remarkably followed by a decrease in the expression of checkpoint kinase 1 (CHEK1) protein, whereas treatment with a CHEK1 inhibitor did not affect RBM17 protein expression in the oral cancer cell lines. These results indicate that RBM17 is a factor involved in the development of resistance to cytotoxic chemotherapy. We propose the underlying mechanism that RBM17 promotes CHEK1 protein expression in the ATM/ATR pathway, triggering the development of chemoresistance in cancer cells. Full article

Background/Objectives: HPV+ head and neck squamous cell carcinoma has been shown to have a unique genomic background, requiring researchers to study it as its own distinct type of cancer. HPV+ tumors have been shown to exhibit fewer genetic mutations in cancer drivers as opposed to their HPV− counterparts. In this paper, we explored how targeting post-transcriptional changes, specifically alternative splicing events, could serve as a potential mechanism to treat HPV+ cancer. Methods: Using indisulam, a drug that targets alternative splicing through the degradation of RBM39, we treated various HPV+ and HPV− cell lines and assessed tumor cell viability. We also tested indisulam in vivo to evaluate its effect on tumor volume. Additionally, we analyzed gene expression differences between indisulam-treated subjects and their non-treated counterparts. Results: Indisulam treatment led to a reduction in tumor cell viability in both HPV+ and HPV− cell lines. In vivo experiments showed a reduction in tumor volume following indisulam treatment. Gene expression analysis revealed that indisulam induces consistent differential gene expression changes and highly enriches interferon pathways in treated HPV+ cell lines. Conclusions: These findings suggest that targeting alternative splicing via indisulam may be a promising therapeutic approach for HPV+ cancers. Further research is required to establish indisulam as a viable anti-cancer treatment in clinical settings. Full article

RNA-binding motif 22 (RBM22) is an RNA-binding protein involved in gene regulation, with the capacity to bind DNA and function as a transcription factor for various target genes. Recent studies demonstrated that RBM22 depletion affects cell viability and proliferation of glioblastoma and breast cancer cells. However, the role of RBM22 in colon cancer and the molecular mechanisms underlying its tumor-suppressive function remain largely unclear. In this study, we demonstrate that RBM22 induces apoptosis and suppresses colon cancer cell viability and proliferation by modulating c-Myc expression. Furthermore, RBM22 knockdown reduces c-Myc stability. Therefore, our findings suggest that RBM22 depletion regulates cancer cell proliferation and induces apoptosis via the c-Myc pathway. Full article