Search Results (98)

This paper examines the costs associated with installing PIP (Pile-in-Pile) slip joints compared to traditional tubular joints, focusing on investment, installation processes, and long-term benefits. Previous studies have indicated that the structural performance of PIP slip joints is superior to that of traditional joints. By utilizing the frictional interfaces between conventional structural steel components and the simplest installation methods, PIP slip joints maximize structural integrity and ease of maintenance. As a result, they can lead to lower lifecycle costs, provided they are installed correctly. Quantitatively, the PIP slip joint achieved the highest internal rate of return (IRR) at 43.42%, the lowest Levelized Cost of Energy (LCOE) at 0.013589 EUR/kWh, and the shortest payback period at 2.92 years—outperforming grouted and bolted flange joints across all key financial metrics. The analysis also addresses logistical challenges and workforce requirements, highlighting that significant economic benefits can be realized when implemented appropriately. Furthermore, the PIP slip joint promotes sustainability goals by minimizing material usage, which ultimately leads to reduced carbon emissions through more efficient fabrication and installation, as well as enabling faster deployment. A comprehensive financial assessment of these joint systems in offshore wind monopiles reveals that PIP slip joints are the most cost-effective and financially advantageous option, outperforming key metrics like IRR, LCOE, and payback period due to lower initial investments and operational costs. As PIP slip joints yield a higher net present value (NPV), a shorter payback period, and a lower LCOE, they can enhance profitability and reduce financial risk, and are suitable for streamlined implementation. While grouted and bolted flange joints exhibit similar financial performance, PIP slip joints’ minimal expenditure and consistent superiority make them the optimal choice for sustainable and economically viable offshore wind projects. Full article

This study aimed to elucidate the specific role of low NaCl concentrations, particularly 10 and 20 mM, in stimulating cotyledon growth in Chinese white radish (Raphanus sativus L. var. longipinnatus Bailey) seedlings. Chinese white radish seeds were cultivated in sand culture and subjected to daily watering with solutions containing 0, 10, 20, 50, or 100 mM NaCl. Growth, water status, aquaporin gene expression, ion contents, and physiology-related parameters were assessed 4 days after sowing. Applying 10 and 20 mM NaCl significantly promoted the growth of 4-day-old seedlings. Notably, the cotyledons exhibited the most significant growth, achieving a rate of 177% compared with the 125–138% growth observed in the hypocotyl and root parts. This substantial enhancement in cotyledon growth, including biomass, cotyledon area, cotyledon thickness, and mesophyll cell size, was induced by an optimal concentration of 10 mM NaCl. This induction correlated with the increased water content, degree of succulence, and expression of aquaporin genes, specifically within PIP1-1, PIP1-2, PIP2-1, PIP2-2, and TIP1-1, in addition to the maintenance of the Hill reaction, heightened free radical scavenging, and the elevated accumulation of Na⁺, Cl⁻, K⁺, proline, total N, and C. These findings suggest a beneficial role of low NaCl levels in optimising early-stage seedling growth. Full article

To shorten the development cycle of integrated circuit (IC) chips, third-party IP cores (3PIPs) are widely used in the design phase; however, these 3PIPs may be untrusted, creating potential vulnerabilities. Attackers may insert hardware Trojans (HTs) into 3PIPs, resulting in the leakage of critical information, alteration of circuit functions, or even physical damage to circuits. This has attracted considerable attention, leading to increased research efforts focusing on detection methods for HTs. This paper proposes a K-Hypergraph model construction methodology oriented towards the abstraction of HT characteristics, aiming at detecting HTs. This method employs the K-nearest neighbors (K-NN) algorithm to construct a hypergraph model of gate-level netlists based on the extracted features. To ensure data balance, the SMOTE algorithm is employed before constructing the K-Hypergraph model. Then, the K-Hypergraph model is trained, and the weights of the K-Hypergraph are updated to accomplish the classification task of distinguishing between Trojan nodes and normal nodes. The experimental results demonstrate that, when evaluating Trust-Hub benchmark performance indicators, the proposed method has average balanced accuracy of 91.18% in classifying Trojan nodes, with a true positive rate (TPR) of 92.12%. Full article

Herein, we demonstrate that soluble factors extracted from the distinct phases of the development of zebrafish embryos (ZFEs) exhibit a specific miRNA profile. We removed proteins and concentrated miRNAs in different phase-related samples, which we investigated further. We observed that ZFEs modulate miRNA expression in both normal and cancerous breast cells, significantly inhibiting the invasiveness and motility of triple-negative breast cancer cells. Namely, ZFEs reactivate the synthesis of miR-218-5p in cancerous cells, leading to the downregulation of PI3K, which consequently alters the distribution of phosphoinositides (such as PIP2/PIP3). Moreover, the silencing of miR-218-5p abolished the ZFE effects. Restoring a proper PIP2/PIP3 ratio is crucial for promoting the regression of the malignant phenotype. Phenotypic reversion follows the extensive cytoskeleton rearrangement and the re-emergence of E-cadherin/β-catenin complexes. In addition, ZFEs antagonize the Epithelial Mesenchymal Transition (EMT) by modulating several pathways, including the TCTP-p53 axis. Overall, these results show that embryo extracts enriched with fish miRNAs reactivate endogenous miR-218-5p in cancerous cells, which in turn downregulates critical pathways involved in tumor progression and metastasis. Full article

Mitochondrial ATP-sensitive K+ channels are closely linked to cardioprotection and are potential therapeutic targets during ischemia reperfusion (IR) injury. The renal outer medullary K+ channel isoform 2 (ROMK2) is an ATP-sensitive K+ channel found in the mitochondria of cardiomyocytes. While the germline knockout of ROMK does not mediate myocardial IR injury, the effect of ROMK loss of function on IR injury in the adult myocardium is unknown. By using a selective small molecule inhibitor of ROMK, we paradoxically found that mouse hearts were protected from IR injury after ROMK inhibition compared to vehicle-treated animals. In addition, we found that ROMK inhibition leads to exaggerated mitochondrial uncoupling and increased ROS production. Phosphatidylinositol 4,5-bisphosphate (PIP₂), an activator of ROMK, increased the effect of ATP to hyperpolarize cardiac mitochondrial membrane potential. ROMK inhibition also increased mitochondrial swelling in the absence of ATP. In conclusion, pharmacologic ROMK inhibition protects the murine heart from IR injury and may promote a phenotype of enhanced mitochondrial matrix K+. ROMK may be more important during conditions that promote mitochondrial matrix K+ efflux than influx. Further research to understand its role in mitochondrial K+ handling and as a therapeutic target in IR injury is needed. Full article

Plasma membrane plays a pivotal role in orchestrating motility and invasive processes, as well as mitosis and genome expression. Indeed, specialized regions of the plasma membrane enriched in phosphoinositides—namely PIP2 and PIP3—can accommodate the requirements of the dynamic interface, which mediates the interplay between cells and their microenvironment. The fine-tuned balance between the two phosphoinositides is instrumental in regulating cytoskeleton organization, motility, ion channel activation, and membrane traffic. The balanced expression of PIP2/PIP3 fulfills these functions by activating pathways through several transporter and receptor proteins. These dynamic interactions modulate the interplay with the extracellular environment by decreasing/increasing their exposure on the cell surface. In this way, lipid structures can rapidly either dismiss or recruit specific proteins, eventually favoring their cooperation with membrane receptors and ion channels. Particularly, exposure of proteins can be managed through the internalization of plasma membrane segments, while receptor signaling can be desensitized by their removal from the cell surface. Notably, the equilibrium between PIP2 and PIP3 is largely dependent on inositol availability, as inositol addition enhances PIP2 content while reducing PIP3 via PI3K inhibition. Pharmacological modulation of PIP2/PIP3 balance promises to be an interesting target in different clinical settings. Full article

During a widespread epidemic, a large portion of the population faces an increased risk of contracting infectious diseases such as COVID-19, monkeypox, and pneumonia. These outbreaks often trigger cascading effects, significantly impacting society and healthcare systems. To contain the spread, the Centers for Disease Control and Prevention (CDC) must monitor infected individuals (targets) and their geographical locations (areas) as a basis for allocating medical resources. This scenario is a Target-to-Area (TTA) problem. Previous research introduced the Point-In-Polygon (PIP) technique to address multi-target and single-area TTA problems. PIP technology relies on an area’s boundary points to determine whether a target is within that region. However, when dealing with multi-target, multi-area TTA problems, PIP alone may have limitations. The K-Nearest Neighbors (KNN) algorithm presents a promising alternative, but its classification accuracy depends on the availability of sufficient samples, i.e., known targets and their corresponding geographical areas. When sample data are limited, the effectiveness of KNN is constrained, potentially delaying the CDC’s ability to track and manage outbreaks. For this problem, this study proposes an improved approach that integrates PIP and KNN technologies while introducing area boundary points as additional samples. This enhancement aims to improve classification accuracy and mitigate the impact of insufficient sample data on epidemic tracking and management. Full article

Long-term geographic isolation and breeding programs both influence population characteristics. Leiqiong cattle, a native breed from the southernmost region of China, are renowned for disease and heat resistance, with two subgroups on Hainan Island and the Leizhou Peninsula. However, the genomic differences between them remain unexplored. In this study, we conducted genomic comparisons using whole-genome sequencing data from the two subgroups of Leiqiong cattle and three commercial breeds to assess their population structures. Leiqiong cattle in Hainan exhibited lower genetic diversity and a pure ancestral content due to their isolation from the mainland. In contrast, the subgroup in Guangdong displayed higher genetic diversity and mixed ancestry, influenced by the intrusion of commercial breeds. The genetic divergence between them was evaluated by estimating a genetic distance of 0.08 and a split time of 3400 to 4250 years ago, highlighting the role of geographical barriers in speciation. Notably, two candidate genes were identified through selection sweeps, including PIP4K2A, potentially related to immunity, and TNFSF4, possibly involved in hair follicle development. Our findings reveal the different genetic structures and genomic characteristics in the two subgroups of Leiqiong cattle, providing valuable insights into their evolutionary history and establishing a foundation for future breeding strategies. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10–20 years), prevention strategies represent an effective means to improve outcomes. One of the risk factors for many cancers and for pancreatic cancer in particular is diet. Hence, our objective is to understand how a diet rich in ω3 and ω6 polyunsaturated fatty acids affects the progression of this disease. Methods: We investigated polyunsaturated fatty acid (PUFA) effects on disease progression employing both in vitro (PDAC cell lines) and in vivo (EL-Kras and KC mice) approaches. Also, we gathered data from the National Health and Nutrition Examination Survey (NHANES) and the National Cancer Institute (NCI) from 1999 to 2017 for a retrospective observational study. Results: The consumption of PUFAs in a patient population correlates with increased PDAC incidence, particularly when the ω3 intake increases to a lesser extent than ω6. Our data demonstrate dietary PUFAs can be incorporated into plasma membrane lipids affecting PI3K/AKT signaling and support the emergence of membrane-targeted therapies. Moreover, we show that the phospholipid composition of a lipid nanoparticle (LNP) can impact the cell membrane integrity and, ultimately, cell viability after administration of these LNPs. Conclusions: Cancer prevention is impactful particularly for those with very poor prognosis, including pancreatic cancer. Our results point to the importance of dietary intervention in this disease when detected early and the potential to improve the antiproliferative effect of drug efficacy when combined with these regimens in later stages of pancreatic cancer. Full article

Blueberry plants are among the most important fruit-bearing shrubs, but they have shallow, hairless roots that are not conducive to water and nutrient uptake, especially under drought conditions. Therefore, the mechanism underlying blueberry root drought tolerance should be clarified. Hence, we established a yeast expression library comprising blueberry genes associated with root responses to drought stress. High-throughput sequencing technology enabled the identification of 1475 genes potentially related to drought tolerance. A subsequent KEGG enrichment analysis revealed 77 key genes associated with six pathways: carbon and energy metabolism, biosynthesis of secondary metabolites, nucleotide and amino acid metabolism, genetic information processing, signal transduction, and material transport and catabolism. Metabolomic profiling of drought-tolerant yeast strains under drought conditions detected 1749 differentially abundant metabolites (DAMs), including several up-regulated metabolites (organic acids, amino acids and derivatives, alkaloids, and phenylpropanoids). An integrative analysis indicated that genes encoding several enzymes, including GALM, PK, PGLS, and PIP5K, modulate key carbon metabolism-related metabolites, including D-glucose 6-phosphate and β-D-fructose 6-phosphate. Additionally, genes encoding FDPS and CCR were implicated in terpenoid and phenylalanine biosynthesis, which affected metabolite contents (e.g., farnesylcysteine and tyrosine). Furthermore, genes for GST and GLT1, along with eight DAMs, including L-γ-glutamylcysteine and L-ornithine, contributed to amino acid metabolism, while genes encoding NDPK and APRT were linked to purine metabolism, thereby affecting certain metabolites (e.g., inosine and 3′,5′-cyclic GMP). Overall, the yeast functional screening system used in this study effectively identified genes and metabolites influencing blueberry root drought tolerance, offering new insights into the associated molecular mechanisms. Full article

Grain weight and grain shape are key traits affecting grain yield and quality in rice. In this research, a quantitative trait locus (QTL), qTGW2, that controls 1000-grain weight (TGW), grain length (GL), and grain width (GW) in rice, was fine-mapped within an 84.7 kb region on chromosome 2 using three sets of near isogenic lines (NILs) originated from the indica rice cross, Teqing (TQ)/IRBB52. In the NIL populations, the TGW, GL, and GW of the IRBB52 homozygous lines increased by 0.22 g, 0.020 mm, and 0.009 mm compared with the TQ homozygous lines. Four annotated genes showed nucleotide polymorphisms between the two parental lines in the qTGW2 region. Only one annotated gene, LOC_Os02g57660, exhibited significant expression differences between NIL^TQ and NIL^IRBB52 in the young panicles performed by RNA sequencing and the quantitative real-time polymerase chain reaction. These results indicated that LOC_Os02g57660, which encodes phosphatidylinositol-4-phosphate 5-kinase (PIP5K), was the candidate gene of qTGW2. Then, one insertion-deletion (InDel) was found in the LOC_Os02g57660 coding region. The haplotype analysis was performed based on the phenotypic data of 4720 rice accessions from RiceVarMap V2.0. Two haplotypes, Hap1 (TQ-type) and Hap2 (IRBB52-type), were classified according to one InDel. Significant differences in grain weight traits were identified between Hap1 and Hap2. Hap2 has greater GL and RLW but lower GW, thus exhibiting potential to simultaneously improve grain yield and quality. Full article

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation and chronic inflammation across various organ systems. While anti-dsDNA and anti-Sm antibodies are commonly associated with SLE, the presence of anti-RNP antibodies is often linked to unique gene expression profiles and immune responses. This study aims to investigate the gene expression profiles in ribonucleoprotein (RNP) autoantibody-positive SLE patients by analyzing publicly available transcriptomic data. Methods: This study analyzed transcriptomic data from the GEO dataset GSE61635, which includes gene expression profiles from 79 anti-RNP-positive SLE patients and 30 healthy controls. Differentially expressed genes (DEGs) were identified using the GEO2R tool with a p-value < 0.05 and |log2fold change| > 1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Tissue-specific and cell-type enrichment analyses highlighted the involvement of immune tissues. Results: A total of 1891 DEGs were identified between anti-RNP-positive SLE patients and healthy controls. Among the identified DEGs, SLC4A1 and EPB42 were notably downregulated, while PIP4K2A was highly upregulated. Enrichment analyses revealed significant dysregulation in antiviral response and immune regulation pathways. PPI network analysis highlighted key hub genes, suggesting a heightened antiviral state in these patients. Tissue-specific enrichment and cell-type enrichment identified the bone marrow and immune tissues as being highly affected by the altered gene expression. Additionally, gene frequency analysis highlighted RASD2 as being recurrently significant across multiple studies. Conclusions: The findings suggest that anti-RNP-positive SLE patients exhibit distinct gene expression and immune dysregulation profiles, particularly in antiviral and immune regulation pathways. These results provide insights into the molecular mechanisms driving SLE in this patient subset and may guide future therapeutic interventions. Full article

Indole-3-carbinol (I3C), a hydrolysis product of indole-3-methylglucosinolate, is toxic to herbivorous insects and pathogens. In mammals, I3C is extensively studied for its properties in cancer prevention and treatment. Produced in Brassicaceae, I3C reversibly inhibits root elongation in a concentration-dependent manner. This inhibition is partially explained by the antagonistic action of I3C on auxin signaling through TIR1. To further elucidate the mode of action of I3C in plants, we have employed a forward-genetic amiRNA screen that circumvents functional redundancy. We identified and characterized two amiRNA lines with impaired I3C response. The first line, ICT2, targets the phosphatidylinositol 4-phosphate 5-kinase family (PIP5K), exhibiting tolerance to I3C, while the second line, ICS1, targets the Wall-Associated Kinases (WAK1–3) family, showing susceptibility to I3C. Both lines maintain I3C-induced antagonism of auxin signaling, indicating that their phenotypes are due to auxin-independent mechanisms. Transcript profiling experiments reveal that both lines are transcriptionally primed to respond to I3C treatment. Physiological, metabolomic, and transcriptomic analysis reveal that these kinases mediate numerous developmental processes and are involved in abiotic and biotic stress responses. Full article

Expression of major histocompatibility complex I (MHC-I) on tumor cells is extremely important for the antitumor immune response for its essential role in activating various immune cells, including tumor-specific CD8+ T cells. Cancers of lower MHC-I expression commonly exhibit less immune cell infiltration and worse prognosis in clinic. In this study, we conducted bioinformatic-experimental screening to identify potential gene targets to enhance MHC-I expression in breast cancer (BRCA). Through a combination of MHC-I scoring, gene expression correlation analysis, survival prognostication, and Cibersort tumor-infiltrated lymphocytes (TILs) scoring, we identify 144 genes negatively correlated with both MHC-I expression and TILs in breast cancer. Furthermore, we verified partially according to KEGG functional enrichment or gene-dependency analysis and figured out multiple genes, including PIP5K1A, NCKAP1, CYFIP1, DIS3, TBP, and EXOC1, as effective gene targets for increasing MHC-I expression in breast cancer. Mechanistically, knockout of each of these genes activated the intrinsic interferon response in breast cancer cells, which not only promoted MHC-I expression but also caused immunogenic cell death of breast cancer. Finally, the scRNA-seq confirmed the negative correlation of PIP5K1A et al. with TILs in breast cancer patients. Collectively, we identified multiple gene targets for an increase in MHC-I expression in breast cancer in this study. Full article

Spider mite infestation has a severe impact on tea growth and quality. In this study, we conducted a deep exploration of the functions and regulations of the CsPIP5K gene family using chromosomal localization and collinearity analysis. Additionally, we carefully examined the cis elements within these genes. To fully understand the metabolic response of CsPIP5K under spider mite infection, we integrated previously published metabolomic and transcriptomic data. Our analysis revealed that multiple CsPIP5K genes are associated with phospholipid metabolism, with CsPIP5K06 showing the strongest correlation. Therefore, we employed qPCR and subcellular localization techniques to determine the expression pattern of this gene and its functional location within the cell. Overall, this study not only comprehensively elucidated the characteristics, structure, and evolution of the CsPIP5K gene family but also identified several candidate CsPIP5K genes related to phospholipid biosynthesis and associated with spider mites based on previously published data. This research makes a significant contribution to enhancing the resistance of tea to spider mite and maintaining optimal tea quality. Full article