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BACKGROUND:More than two-thirds of women who undergo surgery for suspected ovarian neoplasm do not have cancer. Our previous results suggest phospholipids as potential biomarkers of ovarian cancer. In this study, we measured the serum levels of multiple phospholipids among women undergoing surgery for suspected ovarian cancer to identify biomarkers that better predict whether an ovarian mass is malignant. METHODOLOGY/PRINCIPAL FINDINGS:We obtained serum samples preoperatively from women with suspected ovarian cancer enrolled through a prospective, population-based rapid ascertainment system. Samples were analyzed from all women in whom a diagnosis of epithelial ovarian cancer (EOC) was confirmed and from benign disease cases randomly selected from the remaining (non-EOC) samples. We measured biologically relevant phospholipids using liquid chromatography/electrospray ionization mass spectrometry. We applied a powerful statistical and machine learning approach, Hybrid huberized support vector machine (HH-SVM) to prioritize phospholipids to enter the biomarker models, and used cross-validation to obtain conservative estimates of classification error rates. RESULTS:The HH-SVM model using the measurements of specific combinations of phospholipids supplements clinical CA125 measurement and improves diagnostic accuracy. Specifically, the measurement of phospholipids improved sensitivity (identification of cases with preoperative CA125 levels below 35) among two types of cases in which CA125 performance is historically poor - early stage cases and those of mucinous histology. Measurement of phospholipids improved the identification of early stage cases from 65% (based on CA125) to 82%, and mucinous cases from 44% to 88%. CONCLUSIONS/SIGNIFICANCE:Levels of specific serum phospholipids differ between women with ovarian cancer and those with benign conditions. If validated by independent studies in the future, these biomarkers may serve as an adjunct at the time of clinical presentation, to distinguish between women with ovarian cancer and those with benign conditions with shared symptoms and features.

The AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. Most studies have focused on its activation by Receptor Tyrosine Kinase (RTK) mediated Phosphatidylinositol-3-OH kinase (PI3K) activation or loss of Phosphatase and Tensin homolog (PTEN). We have uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation. Mice expressing activated Ack1 specifically in the prostate exhibit AKT Tyr176-phosphorylation and develop murine prostatic intraepithelial neoplasia (mPINs). Further, expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast cancer patients. Thus, RTK/Ack1/AKT pathway provides a novel target for drug discovery.

The aim of this study is to analyze whether melatonin administration influenced the nuclear factor-kappa B (NF-κB) activity, proinflammatory cytokines expression, and oxidative response in the basilar artery after SAH. A total of 48 rabbits were randomly divided into four groups: control group, SAH group, SAH + vehicle group, and SAH + melatonin group. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. The melatonin was administered intraperitoneally at a dose of 5 mg/kg/12 h simultaneously with SAH from day 0 to day 5. The basilar arteries were extracted on day 5 after SAH. As a result, we found that vascular inflammation and oxidative stress were induced in all SAH animals. In animals given melatonin, basilar arterial NF-κB and pro-inflammatory cytokines were decreased in comparison to vehicle-treated animals. Measures of oxidative stress also showed significant downregulation after melatonin treatment. Furthermore, administration of melatonin prevented vasospasm on day 5 following SAH. In conclusion, post-SAH melatonin administration may attenuate inflammatory response and oxidative stress in the spasmodic artery, and this may be one mechanism involved in the therapeutic effect of melatonin on the subsequent vasospasm after SAH.

Gastric cancer (GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species (ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC. [ABSTRACT FROM AUTHOR]

Within the increasingly complex and changeable market environment of new energy vehicles, consumers' attention to product safety has increased significantly, and higher, updated requirements are put forward at the level of product safety. Simultaneously, a product harm crisis, which often entails product recalls, can lead to consumer concerns regarding product specifications and security. Based on the heuristic-systematic model, this study verified the effect of information processing on the vehicle purchase intention of consumers during crisis situations and conducted an empirical study through questionnaires and structural equation modelling. The data obtained in this study presents the following relationships: (1) risk perception has a significant and positive influence on information search and systematic processing but a negative influence on heuristic processing; (2) heuristic processing and systematic processing have a significant and positive influence on purchase intention; (3) information search has a significant and positive influence on heuristic processing and systematic processing. The study can offer a relevant basis and suggestions for risk communication of new energy vehicle enterprises, thereby fundamentally improving consumer loyalty. [ABSTRACT FROM AUTHOR]

Irrigation stands as the primary sector of human water consumption and plays a pivotal role in enhancing crop yields and mitigating drought effects. The precise distribution of irrigation is crucial for effective water resource management and the assessment of food security. However, the existing global irrigated cropland map is characterized by a coarse resolution, typically around 10 kilometers, and is often not regularly updated. In our study, we present a robust methodology that leverages irrigation performance during drought stress as an indicator of crop productivity and water consumption to identify global irrigated cropland. Within each irrigation mapping zone (IMZ), we identified the dry months occurring during the growing season from 2017 to 2019 or the driest months from 2010 to 2019. To delineate irrigated cropland, we utilized collected samples to calculate normalized difference vegetation index (NDVI) thresholds for the dry months of 2017 to 2019 and the NDVI deviation from the ten-year average for the driest month. By combining the results with the higher accuracy between these two methods, we generated the Global Maximum Irrigation Extent dataset at 100-meter resolution (GMIE-100), achieving an overall accuracy of 83.6%. GMIE-100 reveals that the maximum extent of irrigated cropland encompasses 403.17 million hectares, accounting for 23.4% of the global cropland. Concentrated in fertile plains and regions adjacent to major rivers, the largest irrigated cropland area is found in India, followed by China, the United States, and Pakistan, ranking 2nd to 4th, respectively. Importantly, the spatial resolution of GMIE-100, at 100 meters, surpasses that of the dominant irrigation map, offering more detailed information essential for supporting estimates of agricultural water use and regional food security assessments. Furthermore, with the help of the DL method, the global central pivot irrigation system (CPIS) was identified using Pivot-Net. We found that there are 11.5 million hectares of CPIS, accounting for about 2.9% of total irrigated cropland. In Namibia, the US, Saudi Arabia, South Africa, Canada, and Zambia, the CPIS proportion was larger than 10%. To our best knowledge, this is the first effort to identify irrigation methods globally. The GMIE-100 dataset containing both or irrigated extent and CPIS distribution is accessible on Harvard Dataverse at: https://doi.org/10.7910/DVN/HKBAQQ (Tian et al., 2023a). [ABSTRACT FROM AUTHOR]