Despite advances in treatment, recurrence and mortality rates from breast cancer (BrCa) continue to rise, clinical effectiveness is limited, and prognosis remains disappointing, especially for ...patients with HER2-positive, triple-negative, or advanced breast cancer. Based on cuproptosis-related long noncoding RNAs (CRLs), this study aims to create a predictive signature to assess the prognosis in patients with BrCa.
The related CRLs RNA-seq data clinicopathological data were collected from The Cancer Genome Atlas (TCGA) database, and the predictive model was constructed after correlation analysis. Subsequently, we examined and validated connections and changes in the CRLs model with prognostic features (including risk curves, ROC curves and nomograms), pathway and functional enrichment, tumor mutation (TMB), tumor immune dysfunction and exclusion (TIDE) and treatment sensitivity.
A prediction model formula composed of 5 CRLs was obtained, and divided breast cancer patients into high and low risk subgroups according to the obtained risk scores. The results showed that the overall survival (OS) of patients in the high-risk group was lower than that in the low-risk group, and the AUC of all samples at 1, 3 and 5 years were 0.704, 0.668 and 0.647, respectively. It was indicated that CRLs prognostic model could independently predict prognostic indicators of BrCa patients. In addition, analysis of gene set enrichment, immune function, TMB, and TIDE showed that these differentially expressed CRLs had a wealth of related pathways and functions, and might be closely related to immune response and immune microenvironment. Additionally, TP53 was found to have the highest mutation frequency in high-risk group (40%), while PIK3CA was found to have the highest mutation frequency in low-risk group (42%), which might become new targets for targeted therapy. Finally, we compared susceptibility to anticancer agents to identify potential treatment options for breast cancer. Lapatinib, Sunitinib, Phenformin, Idelalisib, Ruxolitinib, Cabozantinib were more sensitive to patients in the low-risk group, while Sorafenib, Vinorelbine, Pyrimethamine were more sensitive to patients in high-risk group, namely, these drugs could potentially be used in the future to treat breast cancer patients grouped according to the risk model.
This study identified CRLs associated with breast cancer and provided a tailored tool for predicting prognosis, immune response, and drug sensitivity in patients with BrCa.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in most parts of the world. Although there is no first-line drug approved for the treatment of NAFLD, polyene ...phosphatidylcholine (PPC) is used by clinicians to treat NAFLD patients. This study aimed to evaluate the efficacy of PPC on a mice model of NAFLD, and to study the PPC's mechanism of action. The mice were fed a choline-deficient, L-amino acid-defined (CDAA) diet to induce NAFLD and were subsequently treated with PPC. The treatment effects were evaluated by the liver index, histopathological examination, and routine blood chemistry analyses. Lipidomics and metabolomics analyses of 54 samples were carried out using ultraperformance liquid chromatography (UPLC) coupled to a mass spectrometer to select for changes in metabolites associated with CDAA diet-induced NAFLD and the effects of PPC treatment. The intestinal flora of mice were extracted for gene sequencing to find differences before and after the induction of NAFLD and PPC treatment. PPC significantly improved the CDAA diet-induced NAFLD condition in mice. A total of 19 metabolites including 5 polar metabolites and 14 lipids showed marked changes. In addition, significant differences in the abundance of
were associated with NAFLD. We inferred that the protective therapeutic effect of PPC on the liver was related to the supplement of phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin (PC, LPC, and SM, resectively) and acylcarnitine metabolism. This study developed a methodology for exploring the pathogenesis of NAFLD and can be extended to other therapeutic agents for treating NAFLD.
Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further ...elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD.
Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60–0.92, P = 0.007, 0.007. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) OR: 1.05, 95 % CI: 1.01–1.08, P = 0.009, Interleukin-12p70 (IL-12) OR: 1.04, 95 % CI: 1.00–1.08, P = 0.047, Interleukin-17 (IL-17) OR: 1.04, 95 % CI: 1.00–1.07, P = 0.038, Interleukin-7 (IL-7) OR: 1.07, 95 % CI: 1.02–1.12, P = 0.009, Interferon gamma (IFN-γ) OR: 1.03, 95 % CI: 1.00–1.07, P = 0.046, Granulocyte-colony stimulating factor (GCSF) OR: 1.06, 95 % CI: 1.02–1.09, P = 0.001, Fibroblast growth factor (FGF) P = 0.001, and Fibroblast growth factor (FGF) P = 0.001. Fibroblast growth factor basic (FGF-Basic) OR: 1.04, 95 % CI: 1.01–1.08, P = 0.02 were positively correlated.
Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD.
Software-Defined Networking (SDN) is an innovational network architecture which gives network administrators the ability to directly control the whole network by programming on a centralized ...controller. Due to network complexity, networks are unlikely to be bug-free. The ability to verify data plane properties will make network management easier for network administrators in SDN. In this paper, we present a novel atomic predicates based data plane properties verification method for SDN using Spark which is a big data processing framework. First, we verify packet reachability which is a fundamental data plane property. Then, we verify other data plane properties such as loop-freedom and nonexistence of black holes. In addition, the proposed method can detect a security threat existing in SDN called firewall bypass threat with packet reachability verification. By adopting atomic predicates, we achieve less computational and storage overhead. We implement the methods and study the performance. The results of experiments show that we can efficiently and accurately detect loops, black holes and firewall bypass threats.
Abstract Coal is one of the most important fossil energy sources and is ensuring global energy security. Annual maximum NDVI (Normalized Difference Vegetation Index) data is an important indicator ...for the research in balancing coal mining and vegetation conservation. However, the existing annual maximum NDVI data displayed lower values with temporally inconsistent and a noticeable mosaic line. Here we propose an algorithm for automatically generating the annual maximum NDVI of China’s coal bases in Google Earth Engine called: Auto-NDVI cb . The accuracy of the Auto-NDVI cb algorithm has been verified with an average RMSE of 0.087 for the 14 coal bases from 2013 to 2022. Based on the proposed Auto-NDVI cb algorithm, an annual maximum NDVI dataset for all 14 coal bases in China from 2013 to 2022 was publicly released. This dataset can be fast and automatically updated online. Hence, the public dataset will continuously serve to monitor the vegetation change induced by coal mining, exploring the mechanism of vegetation degradation, and providing scientific data for developing vegetation protection policies in coal mines.
Mining has caused considerable damage to vegetation coverage, especially in grasslands. It is of great significance to investigate the specific contributions of various factors to vegetation cover ...change. In this study, fractional vegetation coverage (FVC) is used as a proxy indicator for vegetation coverage. We constructed 50 sets of geographically weighted artificial neural network models for FVC and its driving factors in the Shengli Coalfield. Based on the idea of differentiation, we proposed the geographically weighted differential factors-artificial neural network (GWDF-ANN) to quantify the contributions of different driving factors on FVC changes in mining areas. The highlights of the study are as follows: (1) For the 50 models, the average RMSE was 0.052. The lowest RMSE was 0.007, and the highest was 0.112. For the MRE, the average value was 0.007, the lowest was 0.001, and the highest was 0.023. The GWDF-ANN model is suitable for quantifying FVC changes in mining areas. (2) Precipitation and temperature were the main driving factors for FVC change. The contributions were 32.45% for precipitation, 24.80% for temperature, 22.44% for mining, 14.44% for urban expansion, and 5.87% for topography. (3) Over time, the contributions of precipitation and temperature exhibited downward trends, while mining and urban expansion showed positive trajectories. For topography, its contribution remains generally unchanged. (4) As the distance from the mining area increases, the contribution of mining gradually decreases. At 200 m away, the contribution of mining was 26.69%; at 2000 m away, the value drops to 17.8%. (5) Mining has a cumulative effect on vegetation coverage both interannually and spatially. This study provides important support for understanding the mechanism of vegetation coverage change in mining areas.
Wall-associated kinases (WAKs) are important receptor-like proteins that play major roles in plant defense against pathogens. Fusarium head blight (FHB), one of the most widespread and devastating ...crop diseases, reduces wheat yield and leads to quality deterioration. Although WAK gene families have been studied in many plants, systematic research on bread wheat (Triticum aestivum) and its role in FHB resistance, in particular, is lacking. In this study, we identified and characterized 320 genes of the TaWAK family in wheat distributed across all chromosomes except 4B and divided them into three phylogenetic groups. Duplication and synteny analyses provided valuable information on the evolutionary characteristics of the TaWAK genes. The gene expression pattern analysis suggested that TaWAK genes play diverse roles in plant biological processes and that at least 30 genes may be involved in the response to Fusarium infection in wheat spikes, with most of the genes contributing to pectin- and chitin-induced defense pathways. Furthermore, 45 TaWAK genes were identified within 17 hcmQTLs that are related to wheat FHB resistance. Our findings provide potential candidate genes for improving FHB resistance and insights into the future functional analysis of TaWAK genes in wheat.
In the context of global change, the frequency of precipitation pulses is expected to decrease while nitrogen (N) addition is expected to increase, which will have a crucial effect on soil C cycling ...processes as well as methane (CH
) fluxes. The interactive effects of precipitation pulses and N addition on ecosystem CH
fluxes, however, remain largely unknown in grassland. In this study, a series of precipitation pulses (0, 5, 10, 20, and 50 mm) and long-term N addition (0 and 10 g N m
yr
, 10 years) was simulated to investigate their effects on CH
fluxes in a semi-arid grassland. The results showed that large precipitation pulses (10 mm, 20 mm, and 50 mm) had a negative pulsing effect on CH
fluxes and relatively decreased the peak CH
fluxes by 203-362% compared with 0 mm precipitation pulse. The large precipitation pulses significantly inhibited CH
absorption and decreased the cumulative CH
fluxes by 68-88%, but small precipitation pulses (5 mm) did not significantly alter it. For the first time, we found that precipitation pulse size increased cumulative CH
fluxes quadratically in both control and N addition treatments. The increased soil moisture caused by precipitation pulses inhibited CH
absorption by suppressing CH
uptake and promoting CH
release. Nitrogen addition significantly decreased the absorption of CH
by increasing NH
-N content and NO
-N content and increased the production of CH
by increasing aboveground biomass, ultimately suppressing CH
uptake. Surprisingly, precipitation pulses and N addition did not interact to affect CH
uptake because precipitation pulses and N addition had an offset effect on pH and affected CH
fluxes through different pathways. In summary, precipitation pulses and N addition were able to suppress the absorption of CH
from the atmosphere by soil, reducing the CH
sink capacity of grassland ecosystems.
Brand-to-brand help on social media is an unexplored branding strategy and a novel corporate social responsibility (CSR) behavior. The research is based on the framework of communion and agency, ...which has been used to interpret person-to-person help in the context of social psychology and has also been applied to the domain of brands. Across a qualitative study and four experiments the authors demonstrate that compared with conventional self-promoting advertising, such brand-to-brand help conveys signals of high communion and agency, which in turn lead to enhanced brand outcomes. In considering the agentic nature of a for-profit brand that might cause consumer skepticism toward advertising and CSR, the research identifies consumer skepticism as a theoretically relevant moderator, showing that the helping behavior has a stronger positive impact on consumers with higher skepticism. In contrast to the prior work limited to the consequences of perceived communion and agency, the research investigates their drivers for brands. Meanwhile, the authors find that the helping strategy is effective irrespective of the situation and the size of the recipient brand.
