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Abstract Cloud environment is a virtual, online, and distributed computing environment that provides users with large-scale services. And cloud monitoring plays an integral role in protecting infrastructures in the cloud environment. Cloud monitoring systems need to closely monitor various KPIs of cloud resources, to accurately detect anomalies. However, due to the complexity and highly dynamic nature of the cloud environment, anomaly detection for these KPIs with various patterns and data quality is a huge challenge, especially those massive unlabeled data. Besides, it’s also difficult to improve the accuracy of the existing anomaly detection methods. To solve these problems, we propose a novel Dynamic Graph Transformer based Parallel Framework (DGT-PF) for efficiently detect system anomalies in cloud infrastructures, which utilizes Transformer with anomaly attention mechanism and Graph Neural Network (GNN) to learn the spatio-temporal features of KPIs to improve the accuracy and timeliness of model anomaly detection. Specifically, we propose an effective dynamic relationship embedding strategy to dynamically learn spatio-temporal features and adaptively generate adjacency matrices, and soft cluster each GNN layer through Diffpooling module. In addition, we also use nonlinear neural network model and AR-MLP model in parallel to obtain better detection accuracy and improve detection performance. The experiment shows that the DGT-PF framework have achieved the highest F1-Score on 5 public datasets, with an average improvement of 21.6% compared to 11 anomaly detection models.

ObjectivesPrevious observational epidemiological studies have identified a potential association between inflammatory bowel disease (IBD) and sarcoidosis. Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between IBD with genetic susceptibility to sarcoidosis, as well as to explore the potential mediating role.MethodsThe genetic associations were obtained from publicly available genome-wide association studies (GWASs) of European ancestry. The IBD dataset has 31,665 cases and 33,977 controls, consisting of 13,768 individuals with ulcerative colitis (UC) and 17,897 individuals with Crohn’s disease (CD). The genetic associations of sarcoidosis with 4,854 cases and 446,523 controls. A bidirectional causality between IBD and sarcoidosis was implemented to be determined by a two-sample MR approach. The inverse variance weighted (IVW) method was utilized as the main statistical method, and a series of sensitivity analyses were performed to detect heterogeneity and horizontal pleiotropy. A two-step MR approach was used to investigate whether the mediating pathway from IBD to sarcoidosis was mediated by PBC.ResultsThe forward MR analysis indicated that genetic predisposition to IBD was significantly linked to an increased risk of sarcoidosis (OR = 1.088, 95% CI: 1.023–1.158, pIBD-sar = 7.498e-03). Similar causal associations were observed in CD (OR = 1.082, 95% CI: 1.028–1.138, pCD-sar = 2.397e-03) and UC (OR = 1.079, 95% CI: 1.006–1.158, pUC-sar = 0.034). Reverse MR analysis revealed that genetic susceptibility to sarcoidosis was correlated with an augmented risk of CD (OR = 1.306, 95% CI: 1.110–1.537, psar-CD = 1.290e-03) but not IBD or UC. The mediation analysis via two-step MR showed that the causal influence of IBD and CD on sarcoidosis effects was partly mediated by PBC, and the mediating effect was 0.018 (95% CI: 0.005–0.031, p = 7.596e-03) with a mediated proportion of 21.397% in IBD, and 0.014 (95% CI: 0.004–0.024, p = 7.800e-03) with a mediated proportion of 17.737% in CD.ConclusionsThe MR analysis provided evidence substantiating the causal effect of IBD (CD and UC) on an increased risk of sarcoidosis, with PBC playing a mediating role in IBD and CD. However, sarcoidosis only enhances the risk of developing CD, but not IBD or UC. These findings illuminate the etiology of sarcoidosis and contribute to the management of IBD patients.

Background and objective: Hypertension affects over a billion people worldwide and is often associated with poor prognoses. The neutrophil-to-lymphocyte ratio (NLR) has become a significant marker, showing a connection to adverse outcomes in cardiovascular diseases (CVDs). The objective of this study is to examine the relationship between the NLR and outcomes in patients with hypertension. Methods: The study included hypertensive individuals who were surveyed in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Mortality status was determined using the data from National Death Index (NDI). To investigate the dose-response relationship, restricted cubic spline (RCS) models were used. This study employed adjusted cox proportional hazards regression models to compute hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for all-cause and cardiovascular mortality. The predictive accuracy of the NLR for survival outcomes was assessed utilizing time-dependent receiver operating characteristic (ROC) curve analysis. Results: A total of 13,724 participants were included in the final analysis, including 7073 males and 6651 females. The cohort was stratified into higher (>2.0) and lower (≤2.0) NLR groups according to the median value. Over a median follow-up of 64 months, there were 1619 all-cause deaths and 522 cardiovascular deaths among participants. The RCS analysis indicated a non-linear relationship between NLR and the risk of mortality. The adjusted model showed that the group with a higher NLR had a significantly higher risk of all-cause (HR 1.47, 95% CI 1.22–1.77) and cardiovascular mortality (HR 2.08, 95% CI 1.52–2.86). ROC analysis showed that the area under the curves (AUCs) of 0.692, 0.662, 0.644, and 0.625 for predicting all-cause mortality, and 0.712, 0.692, 0.687, and 0.660 for cardiovascular mortality at 1, 3, 5, and 10 years. Conclusion: Elevated NLR is associated with increased risk of cardiovascular and all-cause mortality, and NLR may independently predict outcomes in individuals with hypertension.

A patient presenting with several basal cell carcinomas, pigmented nevi, and developmental defects was diagnosed with nevoid basal cell carcinoma syndrome. Gene panel sequencing and Sanger sequencing were used to identify a novel heterozygous frameshift mutation, c.1312dupA:p.Ser438Lysfs, in exon 9 of PTCH1. I-Tasser and PyMol analyses indicated that the mutated protein patched homolog 1 (PTCH1) lacked 12 transmembrane domains and the intracellular and extracellular rings of ECD2 compared with the wild-type protein, resulting in a remarkably different structure from that of the wild-type protein. This case extends our knowledge of the mutation spectrum of NBCCS.

Physalis philadelphica, a member of the Solanaceae family, commonly known as Physalis, is a one-year-old herbaceous plant with both medicinal and edible properties, as well as ornamental value. At present, only limited research is available on the flower color of P. philadelphica. This study aimed to elucidate the metabolic characteristics underlying the flower color of P. philadelphica and to identify key genes associated with flower color metabolism. We selected two representative varieties of P. philadelphica with significant differences in flower color, namely, “Tieba” (yellow flower) and “Qingjin” (yellow-purple flower), as the experimental materials. The analysis of related pigment components and the determination of relative content by high-performance liquid chromatography were conducted to investigate the flower color-related metabolic pathways of P. philadelphica. Through next-generation sequencing, these pathways were further investigated for the characteristics and differentially expressed genes (DEGs) associated with flower color formation. The results of the research show that: Anthocyanin is the main component of petal coloring of P. philadelphica var. Qingjin, while malvidin pigment, pelargonidin, delphinidin, and cyanidin are the main components of flower color intensity. Carotenoids are the main components of the petal coloring of P. philadelphica var. Tieba and β-carotene is the main component of flower color intensity. Comparing different developmental stages of these two kinds of Physalis pubescens, we identified two key transcription factors (TFs) (eBP and STAT) that were involved in the inhibition of anthocyanin synthesis and regulate the inhibition of pf05G124640 (dihydroflavonol 4-reductase) and pf09G224140 (anthocyanin synthase) in anthocyanin synthesis. One heat shock transcription factor was found to regulate the flavonoid and flavonol synthesis pathway of pf01G020090 (anthocyanin 3-O-glucosyltransferase); two key TFs (NAC and G2-Like), pf10G255070 (isoricin dehydrogenase) and pf09G237080 (abscisic acid 8′-hydroxylase), played important roles in carotene biosynthesis. This study provides new insights for further exploration of the genetic diversity of petal coloring in P. philadelphica and establishes a foundation for subsequent molecular breeding efforts.

Potato scab, a global soil-borne disease caused by Streptomyces, is pivotal in developing resistant cultivars due to its complex resistance mechanisms. This study investigates the transcriptomic responses in potato to common scab using resistant variety CS10 and susceptible CS11 post S. scabie inoculation (0 d and 10 d, 12 cDNA libraries). Differential expression analysis identified 147 key DEGs (Differentially Expressed Genes) essential in disease recognition, signal transduction, and defense. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses revealed several significant metabolic pathways, such as ADP binding, heme binding, chloroplast thylakoid membrane, photosynthesis, glutathione metabolism, and homologous recombination, among others. Notably, the correlation between chloroplast pathways (GO:0019745) and photosynthesis (map00195) highlights photosynthesis’s role in potato scab response, while the oxygen transport (GO:0031408)-related glutathione metabolism pathway (map00480) emphasizes antioxidant defenses. Furthermore, three potential resistance genes were validated: Ethylene Response Factor ERF010 (LOC102589042), Disease Resistance Protein RPP13 (LOC102605863), and Cytochrome P450 83B1 (LOC102604056), demonstrating the linkage between metabolic pathways and pathogen response. These findings offer insights into potato’s molecular resistance mechanisms against potato scab, supporting the breeding of resistant varieties and comprehensive disease management, thus advancing sustainable agriculture.

Abstract Background Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8+ T cell exhaustion. The mechanisms underlying CD8+ T cell responses to IL-7 in melanoma remain not completely elucidated. We previously showed reduced IL-7 level in melanoma patients. Thus, the aim of this study was to investigate the effect of IL-7 regulation on CD127 expression and CD8+ T cell responses in melanoma. Methods Healthy controls and primary cutaneous melanoma patients were enrolled. Membrane-bound CD127 (mCD127) expression on CD8+ T cells was determined by flow cytometry. Soluble CD127 (sCD127) protein level was measured by ELISA. Total CD127 and sCD127 mRNA level was measured by real-time PCR. CD8+ T cells were stimulated with recombinant human IL-7, along with signaling pathway inhibitors. CD8+ T cells were co-cultured with melanoma cell line, and the cytotoxicity of CD8+ T cells was assessed by measurement of lactate dehydrogenase expression. Results Plasma sCD127 was lower in melanoma patients compared with controls. The percentage of CD8+ T cells expressing mCD127 was higher, while sCD127 mRNA level was lower in peripheral and tumor-infiltrating CD8+ T cells from melanoma patients. There was no significant difference of total CD127 mRNA expression in CD8+ T cells between groups. IL-7 stimulation enhanced total CD127 and sCD127 mRNA expression and sCD127 release by CD8+ T cells. However, mCD127 mRNA expression on CD8+ T cells was not affected. This process was mainly mediated by phosphatidylinositol 3-kinase (PI3K) pathway. CD8+ T cells from melanoma patients exhibited decreased cytotoxicity. IL-7 stimulation promoted CD8+ T cell cytotoxicity, while inhibition of PI3K dampened IL-7-induced elevation of CD8+ T cell cytotoxicity. Conclusion The current data suggested that insufficient IL-7 secretion might contribute to CD8+ T cell exhaustion and CD127 dysregulation in patients with primary cutaneous melanoma.

Thirty-eight million people worldwide are living with HIV, PWH, a major public health problem. Antiretroviral therapy (ART) revolutionized HIV treatment and significantly increased the lifespan of PWH. However, approximately 15-50% of PWH develop HIV associated neurocognitive disorders (HIV-NCI), a spectrum of cognitive deficits, that negatively impact quality of life. Many PWH also have opioid use disorder (OUD), and studies in animal models of HIV infection as well as in PWH suggest that OUD can contribute to HIV-NCI. The synthetic opioid agonist, buprenorphine, treats OUD but its effects on HIV-NCI are unclear. We reported that human mature inflammatory monocytes express the opioid receptors MOR and KOR, and that buprenorphine reduces important steps in monocyte transmigration. Monocytes also serve as HIV reservoirs despite effective ART, enter the brain, and contribute to HIV brain disease. Using EcoHIV infected mice, an established model of HIV infection and HIV-NCI, we previously showed that pretreatment of mice prior to EcoHIV infection reduces mouse monocyte entry into the brain and prevents NCI. Here we show that buprenorphine treatment of EcoHIV infected mice with already established chronic NCI completely reverses the disease. Disease reversal was associated with a significant reduction in brain inflammatory monocytes and reversal of dendritic injury in the cortex and hippocampus. These results suggest that HIV-NCI persistence may require a continuing influx of inflammatory monocytes into the brain. Thus, we recommend buprenorphine as a potential therapy for mitigation of HIV brain disease in PWH with or without OUD.

BackgroundSkin cutaneous melanoma (SKCM) is a highly malignant skin tumor. DIRAS2 is considered to be a tumor suppressor gene; however, its function in SKCM has not been explored.MethodsThe Gene Expression Profiling Interactive Analysis (GEPIA) was implemented to investigate the expression of DIRAS2 in SKCM, and plot the survival curve to determine the effect of DIRAS2 on the survival rates of SKCM patients. Then, the correlation between DIRAS2 and tumor immune infiltration was also discussed, and the expression of DIRAS2 and immune infiltration level in SKCM immune cells was determined using TIMER. The top 100 genes most associated with DIRAS2 expression were used for functional enrichment analysis. In order to confirm the anti-cancer effects of DIRAS2 in SKCM in the data analysis, in vitro assays as well as in vivo studies of DIRAS2 on SKCM tumor cell proliferation, migration, invasion, and metastasis were conducted. Western blot and immunofluorescence assay were employed to study the relationship between DIRAS2 and Wnt/β-catenin signaling pathway in SKCM.ResultsDIRAS2 expression was shown to be significantly correlated with tumor grade using univariate logistic regression analysis. DIRAS2 was found to be an independent prognostic factor for SKCM in multivariate analysis. Of note, DIRAS2 expression levels were positively correlated with the infiltration levels of B cells, CD4+ T cells, and CD8+ T cells in SKCM. The infiltration of B cells, CD4+ T cells, and CD8+ T cells was positively correlated with the cumulative survival rate of SKCM patients. In vitro experiments suggested that proliferation, migration, invasion, and metastasis of SKCM tumor cells were distinctly enhanced after DIRAS2 knockdown. Furthermore, DIRAS2 depletion promoted melanoma growth and metastasis in vivo. As for the mechanism, silencing DIRAS2 can activate the signal transduction of the Wnt/β-catenin signaling pathway.ConclusionDIRAS2 functions as a tumor suppressor gene in cases of SKCM by inhibiting the Wnt/β-catenin signaling. It is also associated with immune infiltration in SKCM.

Objectives: All patients with congenital heart disease (CHD) receive postoperative management in ICUs. Infection prevention and control (IPC) has a significant impact on prognosis. This study provides a preliminary understanding of the fundamental aspects of IPC in ICUs following CHD surgery in China. Methods: From September to October 2023, we initiated a survey on healthcare-associated infection (HAI) management in hospitals that perform CHD surgeries independently. The questionnaires were jointly completed by the ICU physicians and IPC personnel. Duplicate or unqualified questionnaires were excluded from the study. The contents of our questionnaires covered hospital and ICU capacity, performance of the infection control department, HAI surveillance, implementation of IPC measures, and antimicrobial stewardship (AMS). Qualified questionnaires were compared according to the volume of annual CHD surgeries performed in different ICUs. Group 1 was defined as volume more than 300 cases and group 2 was defined as volume less than or equal to 300 cases. Results: Sixty-two of the 118 questionnaires were completed, with a response rate of 53%. The CHD surgical volume in 2022 of the 62 hospitals was 36342, accounting for 52%of the annual CHD surgical volume (69 672) across the country. The postoperative infection rates obtained from the 15 ICUs varied from 1.3 to 15%, with a median rate of 4.5%. A total of 16 ICUs provided data on drug-resistant bacteria, Klebsiella pneumoniae exhibiting the highest frequency. More than 95% of ICUs have established complete HAI management systems. Information-based HAI surveillance was conducted in 89% of ICUs. Approximately 67% of ICUs stopped prophylactic antibiotics within 48 hours after surgery. In complex cases, carbapenems were administered empirically in 89% of ICUs. Group 1 had an advantage over group 2 in preventing multi-drug-resistant organisms (all instruments should be used alone 100% vs. 86%, P=0.047; cleaning and disinfection of environmental surfaces, 100% vs. 81%, P=0.035; antibiotic consumption control 85%vs. 61%, P=0.044) and in preventing surgical site infections (perioperative blood glucose monitoring, 88% vs. 67%, P=0.048). However, Group 1 did not perform well in preventing catheter-related bloodstream infection (delayed catheter removal due to convenience of laboratory tests, 31% vs. 6%, P=0.021) and catheter-associated urinary tract infection (delayed catheter removal due to muscle relaxant administration, 88% vs. 58%, P=0.022). Conclusions: A relatively complete HAI management system has been established throughout the country in ICUs for CHD patients. Information-based surveillance of HAI needs to be promoted, and actions should be taken to facilitate the implementation of IPC measures and AMS bundles. Training and feedback are critical for implementing IPC measures. [ABSTRACT FROM AUTHOR]

Thirty-eight million people worldwide are living with HIV, PWH, a major public health problem. Antiretroviral therapy (ART) revolutionized HIV treatment and significantly increased the lifespan of PWH. However, approximately 15-50% of PWH develop HIV associated neurocognitive disorders (HIV-NCI), a spectrum of cognitive deficits, that negatively impact quality of life. Many PWH also have opioid use disorder (OUD), and studies in animal models of HIV infection as well as in PWH suggest that OUD can contribute to HIV-NCI. The synthetic opioid agonist, buprenorphine, treats OUD but its effects on HIV-NCI are unclear. We reported that human mature inflammatory monocytes express the opioid receptors MOR and KOR, and that buprenorphine reduces important steps in monocyte transmigration. Monocytes also serve as HIV reservoirs despite effective ART, enter the brain, and contribute to HIV brain disease. Using EcoHIV infected mice, an established model of HIV infection and HIV-NCI, we previously showed that pretreatment of mice prior to EcoHIV infection reduces mouse monocyte entry into the brain and prevents NCI. Here we show that buprenorphine treatment of EcoHIV infected mice with already established chronic NCI completely reverses the disease. Disease reversal was associated with a significant reduction in brain inflammatory monocytes and reversal of dendritic injury in the cortex and hippocampus. These results suggest that HIV-NCI persistence may require a continuing influx of inflammatory monocytes into the brain. Thus, we recommend buprenorphine as a potential therapy for mitigation of HIV brain disease in PWH with or without OUD. [ABSTRACT FROM AUTHOR]

Most of existing deep learning-based methods for image splicing forgery detection use convolutional layer for forensics feature extraction.However,convolution kernel conducts the local computation process with the limited reception field.More-over,existing methods mainly apply the location of tampering regions to guide the detection model to train,and it is difficult to learn richer tamper trace features.To overcome above-mentioned limitations,a multitask transformer-based network(MT-Net) is proposed for image splicing detection and localization.The self-attention mechanism of Transformer is leveraged in encoder to learn the pixel correlation,which is able to provide different attention levels for pixels and makes the detection network pay more attention to tampering traces.Meanwhile,MT-Net considers three subtasks simultaneously to guide the detection network expose tampering traces from both local and global information,including tampered edge detection,tampered area detection and the prediction of the tampered area's proportion.Finally,three specific loss functions for their corresponding subtask are designed to better optimize the detection network in the training phase.In experiments,the proposed method(MT-Net) achieves better detection results compared with other state-of-the-art methods on three public available datasets,including CASIA v2.0,Columbia and IDM2020,where F1 scores are 0.808,0.913 and 0.675 respectively.The visualization results also demonstrate that the proposed method has the better capability of localizing the splicing regions.