Response of Three Kinds of Detoxifying Enzymes from Odontotermes formosanus (Shiraki) to the Stress Caused by Serratia marcescens Bizio (SM1)

Subterranean termite Odontotermes formosanus (Shiraki) (Blattodea: Isoptera: Termitidae), is a pest species found in forests and dams. Serratia marcescens Bizio (SM1) has a potential pathogenic effect on O. formosanus. However, the response of detoxifying enzymes to exposure by S. marcescens in O. formosanus has not been studied. In the present work, 20 detoxifying enzyme genes, including 6 glutathione S-transferases (GSTs), 5 UDP glycosyltransferases (UGTs) and 9 Cytochrome P450s (CYPs), were identified from the O. formosanus transcriptome dataset by bioinformatics analysis. Furthermore, the effects of SM1 infection on the transcription levels of detoxifying enzyme genes (GSTs, UGTs and CYPs) in O. formosanus were determined. The results showed that the expression of all detoxifying enzyme gene, except one GST, in O. formosanus were altered in response to the infection by SM1. The response of GSTs, UGTs and CYPs to SM1 in O. formosanus suggested that they may play an important role in the defense against bacterial infection such as SM1, and implies that termites have evolved a complex immune response to potential pathogens

The Tet2–Upf1 complex modulates mRNA stability under stress conditions

Introduction: Environmental stress promotes epigenetic alterations that impact gene expression and subsequently participate in the pathological processes of the disorder. Among epigenetic regulations, ten–eleven Translocation (Tet) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA and RNA and function as critical players in the pathogenesis of diseases. Our previous results showed that chronic stress increases the expression of cytoplasmic Tet2 in the hippocampus of mice exposed to chronic mild stress (CMS). Whether the cytoplasmic Tet2 alters RNA 5hmC modification in chronic stress-related processes remains largely unknown.Methods: To explore the role of cytoplasmic Tet2 under CMS conditions, we established CMS mice model and detected the expression of RNA 5hmC by dot blot. We verified the interaction of Tet2 and its interacting protein by co-immunoprecipitation combined with mass spectrometry and screened downstream target genes by cluster analysis of Tet2 and upstream frameshift 1 (Upf1) interacting RNA. The expression of protein was detected by Western blot and the expression of the screened target genes was detected by qRT-PCR.Results: In this study, we found that increased cytoplasmic Tet2 expression under CMS conditions leads to increase in total RNA 5hmC modification. Tet2 interacted with the key non-sense-mediated mRNA decay (NMD) factor Upf1, regulated the stability of stress-related genes such as Unc5b mRNA, and might thereby affect neurodevelopment.Discussion: In summary, this study revealed that Tet2-mediated RNA 5hmC modification is involved in stress-related mRNA stability regulation and may serve as a potential therapeutic target for chronic stress-related diseases such as depression

Revealing unusual bandgap shifts with temperature and bandgap renormalization effect in phase-stabilized metal halide perovskites

Hybrid organic-inorganic metal halide perovskites are emerging materials in photovoltaics, whose bandgap is one of the most crucial parameters governing their light harvesting performance. Here we present temperature and photocarrier density dependence of the bandgap in two phase-stabilized perovskite thin films (MA0.3FA0.7PbI3 and MA0.3FA0.7Pb0.5Sn0.5I3) using photoluminescence and absorption spectroscopy. Contrasting bandgap shifts with temperature are observed between the two perovskites. By utilizing X-ray diffraction and in situ high pressure photoluminescence spectroscopy, we show that the thermal expansion plays only a minor role on the large bandgap blueshift due to the enhanced structural stability in our samples. Our first-principles calculations further demonstrate the significant impact of thermally induced lattice distortions on the bandgap widening and reveal that the anomalous trends are caused by the competition between the static and dynamic distortions. Additionally, both the bandgap renormalization and band filling effects are directly observed for the first time in fluence-dependent photoluminescence measurements and are employed to estimate the exciton effective mass. Our results provide new insights into the basic understanding of thermal and charge-accumulation effects on the band structure of hybrid perovskites

VMGuards:A Novel Virtual Machine Based Code Protection System with VM Security as the First Class Design Concern

Process-level virtual machine (PVM) based code obfuscation is a viable means for protecting software against runtime code tampering and unauthorized code reverse engineering. PVM-based approaches rely on a VM to determine how instructions of the protected code region are scheduled and executed. Therefore, it is crucial to protect the VM against runtime code tampering that alters the instructions and behavior of the VM. This paper presents VMGuards, a novel PVM-based code protection system that puts the security of VM as the first class design concern. Our approach advances prior work by promoting security of the VM as the first class design constraint. We achieve this by introducing two new instruction sets to protect the internal implementations of critical code segments and the host runtime environment where the VM runs in. Our new instruction sets not only have an identical code structure as standard virtual instructions, but also provide additional information to allow the VM to check whether the critical internal implementation or the runtime environment is affected. We evaluate our approach by using a set of real-life applications. Experimental results show that our approach provides stronger and more fine-grained protection when compared to the state-of-the-art with little extra overhead

Construction and validation of a risk prediction model for aromatase inhibitor-associated bone loss

PurposeTo establish a high-risk prediction model for aromatase inhibitor-associated bone loss (AIBL) in patients with hormone receptor-positive breast cancer.MethodsThe study included breast cancer patients who received aromatase inhibitor (AI) treatment. Univariate analysis was performed to identify risk factors associated with AIBL. The dataset was randomly divided into a training set (70%) and a test set (30%). The identified risk factors were used to construct a prediction model using the eXtreme gradient boosting (XGBoost) machine learning method. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods were used for comparison. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model in the test dataset.ResultsA total of 113 subjects were included in the study. Duration of breast cancer, duration of aromatase inhibitor therapy, hip fracture index, major osteoporotic fracture index, prolactin (PRL), and osteocalcin (OC) were found to be independent risk factors for AIBL (p < 0.05). The XGBoost model had a higher AUC compared to the logistic model and LASSO model (0.761 vs. 0.716, 0.691).ConclusionThe XGBoost model outperformed the logistic and LASSO models in predicting the occurrence of AIBL in patients with hormone receptor-positive breast cancer receiving aromatase inhibitors

Attenuating effect of Polygala tenuifolia Willd. seed oil on progression of MAFLD

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a common chronic metabolic disease that seriously threatens human health. The pharmacological activity of unsaturated fatty acid-rich vegetable oil interventions in the treatment of MAFLD has been demonstrated. This study evaluated the pharmacological activity of Polygala tenuifolia Willd, which contains high levels of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAGs).Methods: In this study, a mouse model was established by feeding a high-fat diet (HFD, 31% lard oil diet), and the treatment group was fed a P. tenuifolia seed oil (PWSO) treatment diet (17% lard oil and 14% PWSO diet). The pharmacological activity and mechanism of PWSO were investigated by total cho-lesterol (TC) measurement, triglyceride (TG) measurement and histopathological observation, and the sterol regulatory element-binding protein-1 (SREBP1), SREBP2 and NF-κB signaling pathways were evaluated by immunofluorescence and Western blot analyses.Results: PWSO attenuated the increases in plasma TC and TG levels. Furthermore, PWSO reduced the hepatic levels of TC and TG, ameliorating hepatic lipid accumulation. PWSO treatment effectively improves the level of hepatitic inflammation, such as reducing IL-6 levels and TNF-α level.Discussion: PWSO treatment inactivated SREBP1 and SREBP2, which are involved in lipogenesis, to attenuate hepatic lipid accumulation and mitigate the inflammatory response induced via the NF-κB signaling pathway. This study demonstrated that PWSO can be used as a relatively potent dietary supplement to inhibit the occurrence and development of MAFLD

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification