Search Results (239)

Background: Cervical cancer is a major global health concern, causing approximately 350,000 deaths annually. It is also preventable through effective prevention and early detection. To facilitate elimination, the World Health Organization (WHO) set targets for HPV vaccination, screening, and treatment. Achieving these goals requires frameworks to monitor screening program performance. As many regions transition to HPV primary screening, a standardized Cervical Cancer Screening Cascade can track performance, identify gaps in follow-up, and optimize resource allocation. Methods: This paper introduces a structured cascade developed to monitor uptake, retention, and outcomes in HPV-based screening programs. The Cascade was created through collaboration between public health experts, clinicians, and researchers at the University of British Columbia (UBC), the Women’s Health Research Institute, and BC Cancer. Results: The Cascade outlines four phases: screening, triage, detection, and treatment. Each phase includes two substages: “uptake” and “results,” with an additional substage in screening (“invitation”). “Screening” assesses invitation effectiveness and participation. “Triage” tracks follow-up after a positive screen. “Detection” evaluates attendance at diagnostic appointments, and “Treatment” measures the treatment rate for those with precancerous lesions. Conclusions: The Cascade can guide emerging and existing HPV screening programs within Canada and other similarly resourced settings and serve as a benchmark tool for programs to assess their progress towards cervical cancer elimination. Full article

Accurate prediction of ship underwater radiated noise (URN) during navigation is critical for evaluating acoustic stealth performance and analyzing detection risks. However, the labeled data available for the training of URN prediction model is limited. Semi-supervised learning (SSL) can improve the model performance by using unlabeled data in the case of a lack of labeled data. Therefore, this paper proposes an SSL method for URN prediction. First, an anti-perturbation regularization is constructed using unlabeled data to optimize the objective function of EL, which is then used in the Genetic algorithm to adaptively optimize base learner weights, to enhance pseudo-label quality. Second, a semi-supervised ensemble (ESS) framework integrating dynamic pseudo-label screening and uncertainty bias correction (UBC) is established, which can dynamically select pseudo-labels based on local prediction performance improvement and reduce the influence of pseudo-labels’ uncertainty on the model. Experimental results of the cabin model and sea trials of the ship demonstrate that the proposed method reduces prediction errors by up to 65.5% and 62.1% compared to baseline supervised and semi-supervised regression models, significantly improving prediction accuracy. Full article

Background: Rumex patientia (Polygonaceae), a perennial herbaceous species predominantly found in northern temperate regions, has been historically utilized in traditional Chinese medicine for its hematological regulatory properties, including blood cooling, hemostasis, and detoxification. Despite the pharmacological value of this species, unvalidated reference genes compromise precise gene expression profiling. Methods: We initially selected eight candidate genes (ACT, GAPDH, YLS, SKD1, UBQ, UBC, EF-1α, TUA) from R. patientia transcriptomes and then assessed their transcriptional stability using RT-qPCR across root, stem, and leaf tissues under four abiotic stresses: cold, drought, salinity, and heavy metal exposure. Results: ACT emerged as the most stable reference gene in three specific scenarios: root/leaf tissues under cold stress, stems during drought exposure, and roots subjected to salt treatment, revealing distinct tissue–stress response patterns. TUA emerged as the most stable reference in cold- and salt-challenged stems, while SKD1 exhibited superior stability in drought-affected roots/leaves, heavy-metal-stressed tissues, and salt-treated leaves. Validation via the drought-inducible MYB transcription factor confirmed reference gene reliability. Conclusions: This work pioneers a standardized reference gene framework for R. patientia under multi-stress conditions, offering essential methodological foundations for subsequent molecular research in this medicinal plant. Full article

Osteoarthritis (OA) is a prevalent and debilitating joint disease in older adults with a complex etiology. We investigated the role of SUMOylation, a post-translational modification, in OA pathogenesis, focusing on the mitochondrial chaperone Prohibitin (PHB1) and the cartilage homeostasis transcription factor PITX1. We hypothesized that oxidative stress-induced SUMOylation promotes PHB1 nuclear accumulation, leading to PITX1 downregulation and contributing to OA development. Analysis of cartilage specimens from 27 OA patients and 4 healthy controls revealed an increased nuclear accumulation of PHB1 in OA chondrocytes, accompanied by elevated levels of SUMO-1 and SUMO-2/3. Mechanistically, nuclear PHB1 interacted indirectly with SUMO-1 through a SUMO-interacting motif (SIM), and the deletion of this SIM prevented PHB1 nuclear trapping in OA cells. Furthermore, the SUMO-conjugating enzyme E2 (UBC9) encoded by the UBE2I gene was upregulated in knee OA cartilage, and its overexpression in vitro enhanced PHB1 nuclear accumulation. Consistently, transgenic mice overexpressing the Ube2i gene exhibited increased UBC9 in their knee cartilage, resulting in Pitx1 downregulation and the emergence of an early OA-like phenotype in articular chondrocytes. Our findings uncover a novel role for UBC9-mediated SUMOylation in primary knee and hip OA. This pathway enhances PHB1 nuclear accumulation, contributing to PITX1 repression and subsequent OA development. These results underscore the importance of SUMOylation in OA pathogenesis and suggest potential molecular targets for early diagnosis and therapeutic intervention. Full article

Zinc (Zn) is a crucial trace element in vertebrates, fulfilling a range of physiological functions, whose metabolism and homeostasis are manipulated by Zn transporter proteins. SUMOylation, a reversible post-translational modification (PTM), extensively participates in various biological processes in the body, yet its underlying mechanism in regulating Zn transporters remains unexplored. Our findings indicate that high dietary Zn substantially elevated intestinal Zn content and modulated the expression profiles of Zn transporter-related genes and proteins, including ZIP8 transporter. In addition, high Zn diet tended to inhibit the SUMOylation modification and upregulate deSUMOylation modification in the intestine and intestinal epithelial cells. Furthermore, we found that the ZIP8 protein undergoes SUMOylation modification; UBC9 upregulated but SENP1 and Zn downregulated the SUMOylation level of ZIP8, and the K24 and K222 positions are the primary SUMOylation modification sites of ZIP8 protein in yellow catfish. Mechanistically, SENP1 modulates the deSUMOylation modification of ZIP8 by sensing Zn-induced oxidative stress. In summary, for the first time, we have uncovered a unique regulatory mechanism of ZIP8 mediated by SUMOylation modification in vertebrates and demonstrate that SENP1 is capable of sensing oxidative stress to reduce the SUMOylation modification of ZIP8 at K24 and K222 sites. Full article

Semantic Change Detection (SCD) in remote sensing imagery is a common technique for monitoring surface dynamics. However, geospatial data acquisition increasingly involves the collection of visible and infrared images. SCD in visible and infrared image pairs confronts the challenge of distinguishing genuine semantic change from spectral discrepancies caused by heterogeneous imaging mechanisms. To address this issue, we propose a Modal Feature Analysis Semantic Change Detection Network (MFA-SCDNet), a novel framework that analyzes cross-modal features for change identification. The proposed architecture operates through three principal technical components: An infrared feature enhancement module that transforms infrared inputs into three-channel representations through spectral domain adaptation, enhancing the network’s perception of both high-frequency and low-frequency information in images; an encoder–decoder structure that simultaneously extracts modality-specific features and common features through adversarial learning; and a synergistic information fusion mechanism that integrates semantic recognition with change detection through multi-task optimization. Specific features are employed for semantic recognition, while common features are utilized for change detection, ultimately resulting in a comprehensive understanding of semantic changes. Experiments on public datasets show that MFA-SCDNet has an average improvement of 9.4% in mIoU_bc and 12.9% in mIoU_sc compared with the alternatives. MFA-SCDNet has better performance in heterogeneous images SCD. Full article

Hybrid composite pile foundations face critical challenges in terms of optimizing load transfer mechanisms across variable soil densities, particularly in regions like Kano, Nigeria, characterized by loose to dense sandy deposits and fluctuating groundwater levels. This study addresses the need for sustainable, high-performance foundation systems that are adaptable to diverse geotechnical conditions. The research evaluates the mechanical behavior of steel–concrete and timber–concrete hybrid piles, quantifying skin friction dynamics, combining eight (8) classical ultimate bearing capacity (UBC) methods (Vesic, Hansen, Coyle and Castello, etc.) with numerical simulations, and assessing load distribution across sand relative densities (10%, 35%, 50%, 75%, 95%). Laboratory investigations included the geotechnical characterization of Wudil River well-graded sand (SW), direct shear tests, and interface shear tests on composite materials. Relative densities were calibrated using electro-pneumatic compaction. Increasing Dr from 10% to 95% reduced void ratios (0.886–0.476) and permeability (0.01–0.0001 cm/s) while elevating dry unit weight (14.1–18.0 kN/m³). Skin friction angles rose from 12.8° (steel–concrete) to 37.4° (timber–concrete) at Dr = 95%, with timber interfaces outperforming steel by 7.4° at Dr = 10%. UBC for steel–concrete piles spanned from 353.1 kN (Vesic, Dr = 10%) to 14,379 kN (Vesic, Dr = 95%), while timber–concrete systems achieved 9537.5 kN (Hansen, Dr = 95%). PLAXIS simulations aligned closely with Vesic’s predictions (14,202 vs. 14,379 kN). The study underscores the significance of soil density, material interfaces, and method selection in foundation design. Full article

Chinese fir (Cunninghamia lanceolata (Lamb.) Hook) is one of the main afforestation tree species in southern China. Continuous planting for multiple generations has led to a decrease in the content of available phosphorus in the soil. To adapt to low phosphorus stress, plants develop a series of physiological, biochemical, and developmental responses through self-regulation. Recent studies have shown that miRNAs play a regulatory role in plants’ responses to low phosphorus stress. However, the regulatory mechanism of miRNAs in Chinese fir in response to low phosphorus stress is still unclear. Here, we performed small RNA sequencing on the Chinese fir roots treated with normal phosphorus and low phosphorus and identified a total of 321 miRNAs, including 139 known miRNAs and 182 new miRNAs, with 43 differentially expressed miRNAs (DEMs). Integrative analysis combined with degradome sequencing data revealed that 193 miRNAs (98 known and 95 new) targeted 469 genes, among which 23 DEMs targeted 44 genes. Gene enrichment analysis indicated that under low phosphorus stress, transcription and transcriptional regulation, as well as signal transduction, were significantly activated in Chinese fir. Modules in the miRNA–target pathways, such as miR166/HD-ZIP III, miR169/NFYA7, miR529/SPL, and miR399/UBC23, may be the key regulatory factors in the response to low phosphorus stress in Chinese fir. In addition, we found that PC-3p-1033_8666 was significantly downregulated and that PC-5p-3786_2830 was significantly upregulated, which presumably respond to low phosphorus stress by indirectly affecting phosphorus-related hormone signaling or PSR genes. The identified miRNA–target network and significantly activated pathways in this study provide insights into the post-transcriptional regulatory mechanisms of Chinese fir adapting to low phosphorus environments, which can offer theoretical references for the stress resistance and superior variety breeding of Chinese fir. Full article

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, and responding to injury and repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading to imbalances in the brain’s internal milieu that eventually impact neuronal function and lead to neurodegeneration. Until now, most evidence of astrocytic dysfunction in aging has come from experiments done with whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived from animal models or cell lines. In this study, we used postmortem-derived whole cells sorted with anti-GFAP antibodies to compare the unbiased, whole-transcriptomes of human astrocytes from control, older non-impaired individuals and subjects with different neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (ADD), and progressive supranuclear palsy (PSP). We found hundreds of dysregulated genes between disease and control astrocytes. In addition, we identified numerous genes shared between these common neurodegenerative disorders that are similarly dysregulated; in particular, UBC a gene for ubiquitin, which is a protein integral to cellular homeostasis and critically important in regulating function and outcomes of proteins under cellular stress, was upregulated in PSP, PD, and ADD when compared to control. Full article

Background/Objectives: The UbcH10 protein plays an important role in a variety of human malignancies, including thyroid, breast, ovarian, and colorectal carcinomas. It has been previously reported that UbcH10 is overexpressed in non-small cell lung cancer (NSCLC) compared to normal lungs and that its expression is directly and inversely correlated with the mutational status of p53 and EGFR, respectively. Methods: We transfected lung cancer cells with wild-type and mutant forms of EGFR, modulated the expression of UbcH10 and p53, and treated these cells with tyrosine kinase inhibitor (TKI) erlotinib. Using Western blotting, we evaluated the expression of UbcH10 induced by EGFR and p53. Finally, we employed immunohistochemistry to assess the levels of UbcH10 expression in a subset of NSCLC patients receiving TKI therapy. Results: We reported a possible modulation of UbcH10 expression by the overexpression of wild-type and mutant EGFR in H460 lung cancer cells, potentially through p53. The enforced expression of UbcH10 in cells transfected with mutant EGFR suggested a potential increase in resistance to erlotinib treatment. Finally, immunohistochemical analysis of samples from NSCLC patients with mutant EGFR indicated a possible connection between UbcH10 expression levels and progression-free survival. Conclusions: In NSCLC, UbcH10 may play a role in the regulation of TKI response via a molecular pathway potentially involving p53 and EGFR. However, further research is needed to fully understand this mechanism. Full article

Drought stress caused a significant threat to apple growth and production. Although there is an increasing studies concerning the molecular mechanism in apple response to drought, most of these studies focus on the leaves. However, the roots is the first organism to sense the drought signal and play important role in drought response. The molecular mechanisms underlying the apple roots in response to drought needs to be further explored. In this study, we conducted a comparative transcriptomic analysis of roots from drought-resistant (Malus prunifolia) and drought-susceptible (Malus hupehensis) apple genotypes under different soil water contents with 60% (control), 30% (mild drought), 10% (moderate drought), and 5% (severe drought). The further Mapman pathways analysis showed that Malus prunifolia exhibited more rapid activation of abscisic acid (ABA) biosynthesis (NCED, PYL) and signaling pathway, as well as the induction of transcription factors (NAC, WRKY, MYB) compare to Malus prunifolia under mild and moderate drought treatments. This might be one of the reasons why Malus prunifolia exhibits greater drought resistance. Furthermore, weighted gene co-expression network analysis (WGCNA) was adopted for the identification of core drought-responsive genes. Notably, three hub genes, ubiquitin-conjugating enzyme 32 (UBC32), basic leucine-zipper 4 (bZIP4), and highly ABA-induced PP2C gene 2 (HAI2), were selected from the different modules, suggesting their vital roles in drought response. Taken together, our results gain insights into the global expression alterations in drought-resistance and susceptible germplasms under different drought conditions and identify some key genes involved in drought response, which is helpful for drought-resistant apple breeding in future. Full article

Selecting the right reference genes for data normalization is the only way to ensure the precision and reproducibility of gene expression measurement using qRT-PCR. Ottelia cordata is a member of the Hydrocharitaceae family in aquatic plants that exhibits both floating and submerged leaf forms. It has recently drawn interest as a possible model plant for research into non-KRANZ C₄ photosynthesis and heteroblastic leaves. Our earlier research has demonstrated bias in gene expression analysis when actin or GAPDH, two common reference genes, are used for normalization. Furthermore, there has been no study on the Hydrocharitaceae family reference gene selection published to date. To standardize qRT-PCR in O. cordata, seven genes were chosen from a transcriptome database: ACT7, EF1_α, GAPDH, BRCC36, PP2A, UBC7, and UBQ. We conducted qRT-PCR experiments in various tissues, leaves in different developmental stages, leaves in high/low carbon treatment, and leaves in high/low temperature treatment. After analyzing the stability using five statistical methods (geNorm, normFinder, comparative ΔCt, bestKeeper, and comprehensive analysis), PP2A and UBQ were identified as the most stable genes. BRCC36 was identified as a new reference gene in plants. Finally, by contrasting the expression patterns of pepc2, a crucial gene connected to C₄ photosynthesis, in floating and submerged leaves, PP2A, UBQ, and UBC7 were verified. Of these, PP2A and UBQ were shown to be the superior gene for the precise qRT-PCR data normalization. The results of this study offer the initial information concerning reference gene identification for O. cordata as well as the first data in Hydrocharitaceae plants. It will make it easier to do more gene function and molecular biology research on O. cordata and other closely related species. Full article

After it has metastasized, bladder cancer, the malignant transformation of the bladder urothelium, continues to be a common cause of death after maximal use of all currently available standard treatments. To address this problem in 2025, the drug repurposing movement within oncology aims to identify medicines in common general medical care use that have data indicating that they can interfere or inhibit a growth driving element that has been identified in bladder cancer. This paper now outlines extensive preclinical data showing that four drugs from general medical practice meet these criteria—the melatonergic drug ramelteon, the antidepressant fluoxetine, the antibiotic dapsone, and the analgesic drug celecoxib. This is the UBC4 regimen, meant as a possible adjunct added to standard treatments of metastatic bladder cancer. Three factors justify a clinical pilot trial of UBC4: (1) the UBC4 drugs are usually well tolerated and carry a low risk of harm, (2) the commonly fatal outcome of bladder cancer once it has widely metastasized, plus (3) the strong preclinical database showing UBC growth inhibition by each of the individual UBC4 drugs as outlined in this paper. Full article

Clinacanthus nutans is a valuable traditional medicinal plant that contains enriched active compounds such as triterpenoids and flavonoids. Understanding the accuulation process of these secondary metabolites in C. nutans requires exploring gene expression regulation under abiotic stresses and hormonal stimuli. qRT-PCR is a powerful method for gene expression analysis, with the selection of suitable reference genes being paramount. However, reports on stably expressed reference genes in C. nutans and even across the entire family Acanthaceae are limited. In this study, we evaluated the expression stability of 12 candidate reference genes (CnUBQ, CnRPL, CnRPS, CnPTB1, CnTIP41, CnACT, CnUBC, CnGAPDH, Cn18S, CnCYP, CnEF1α, and CnTUB) in C. nutans across different tissues and under abiotic stresses and MeJA treatment using three programs (geNorm, NormFinder, and BestKeeper). The integrated ranking results indicated that CnUBC, CnRPL, and CnCYP were the most stably expressed genes across different tissues. Under abiotic stress conditions, CnUBC, CnRPL, and CnEF1α were the most stable, while under MeJA treatment, CnRPL, CnEF1α, and CnGAPDH exhibited the highest stability. Additionally, CnRPL, CnUBC, and CnEF1α were the most stable reference genes across all tested samples, whereas CnGAPDH was the least stable. CnRPL, consistently ranking among the top three most stable genes, may therefore serve as an ideal reference gene for qRT-PCR analysis in C. nutans. To further validate the selected reference genes, we assessed the expression of two key biosynthetic genes, CnPAL and CnHMGR. The results confirmed that using the most stable reference genes yielded expression patterns consistent with biological expectations, while using unstable reference genes led to significant deviations. These findings offer valuable insights for accurately quantifying target genes via qRT-PCR in C. nutans, facilitating investigations into the mechanisms underlying active compound accumulation. Full article

Background/Objectives: UBC demonstrates a relatively low prevalence in patients under 50 years old. Our study aimed to compare the pathological characteristics of UBC in young and elderly patients and to assess the age-related variations in these characteristics. Methods: This retrospective study from January 2018 to December 2022 encompassed 762 patients with an initial diagnosis of UBC. To evaluate the pathological characteristics of UBC in young patients, compared to elderly patients, we divided our cohort using a cut-off age of 50 years. Additionally, to evaluate the age-dependent variations in these characteristics, we further stratified our patients into three age groups (≤50, 51–70, and >70 years old). Results: Of the 762 patients included in our study, 37 (4.86%) were young (≤50 years old), with a median age of 44 and a M:F ratio of 3.11:1. Conventional UC was the most common histology (86.5%). Regarding tumour grade, we noticed a higher prevalence of PUNLMP (10.8% versus 2.3%) and LGPUC (45.9% versus 37.1%) and a lower prevalence of HGPUC (43.2% versus 60%) and CIS (0% versus 0.6%) in young patients (p = 0.008). In this group, the pTa stage revealed a higher prevalence (64.9% versus 46.8%), while pT1 and pT2 showed a lower prevalence (32.1% versus 18.9% and 20.6% versus 16.2%) (p = 0.179). All results remained consistent when the cohort was stratified into three age groups, showing age-related variations (p = 0.001 and p = 0.089, respectively). Conclusions: In young patients, UBC tends to be of a lower grade and stage compared to elderly patients, and these characteristics demonstrate a gradual age-related stratification. Full article