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Abstract There is limited research on the relationship between Life's Essential 8 (LE8) score and metabolic dysfunction-associated steatotic liver disease (MASLD). Our aim is to investigate the relationship between overall lifestyle assessed by LE-8 score and MASLD in a nationally representative sample. We employed the LE8 score to comprehensively evaluate cardiovascular health, the assessment of MASLD primarily utilized the Fatty Liver Index. The weighted logistic regression models, restrictive cubic splines (RCS), subgroup analyses and the weighted quantile sum (WQS) regression were used to evaluate the relationship between the cardiovascular health and MASLD. Logistic regression models revealed that higher LE8 scores were associated with lower odds of having MASLD. The RCS revealed a significant nonlinear dose–response relationship between LE8 scores and MASLD. The WQS regression model indicated that blood glucose contributed the most to the risk of MASLD. The subgroup analysis indicates that there are significant differences in this association across age, educational level, and poverty income ratio. Our study suggests that an inverse correlation between LE8 and the risk of MASLD. Our findings underscore the utility of the LE8 algorithm in MASLD risk assessment and provide support for MASLD prevention through the promotion of healthy lifestyles.

Abstract The aim of this study is to investigate the correlation between soft drusen and the likelihood of mortality from all causes and specific ailments within a representative United States population. This cohort study encompassed 4497 individuals from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) cycles, and followed for survival to December 31, 2019. Data on soft drusen were obtained from fundus images. Survey-weighted Cox regression models were utilized to evaluate the hazard of soft drusen incidence and mortality. After a median follow-up of 12.33 (11.33, 12.58) years, 1014 (22.5%) patients died from all causes. Overall, individuals with soft drusen exhibited an increased risk for all-cause mortality (HR 1.41; 95% CI 1.22 to 1.64), cardiovascular disease (CVD)-related death (HR 1.53; 95% CI 1.15 to 2.04), and mortality from other causes (HR 1.48; 95% CI 1.20 to 1.83). Further stratified analysis revealed that the mortality rates were heightened in participants who had distinct soft drusen or both types of soft drusen, as well as those with soft drusen measuring 500 μm or more in diameter. The investigation revealed that soft drusen was linked to all-cause mortality, CVD mortality, and mortality resulting from non-cardiovascular and non-cancerous conditions, indicating that soft drusen may symbolize frailty and aging processes.

Abstract The large deformation and strong rheological characteristics of the underground rock body under complex geological conditions have led to the failure of the support system and even the instability of tunnels from time to time. Based on the theory of groundwater seepage, the elastic solution of the mechanical model of the tunnel anchorage support system under seepage is solved, which reveals the influence of seepage on the peripheral rock and the support parameters of the anchorage support system; the viscoelastic solution is solved according to the corresponding principle of elasticity—viscoelasticity, which analyses the influence of seepage on the rheological process of the anchorage support system; and the model is simulated with the help of finite element software, which analyses the agreement and discrepancy of the numerical solution and the theoretical solution. The results show that the analytical and numerical solutions are basically consistent. This study can provide important guidance for controlling long-term stability of water-rich tunnel rocks.

Abstract Hypertrophic scars arise from aberrant wound healing and can lead to functional and aesthetic impairments. One of the common interventions for treating hypertrophic scars is fractional carbon dioxide (CO2) laser, which employs narrow laser beams to stimulate dermal collagen deposition. Recent studies and reports have suggested that combining laser therapy with other interventions such as botulinum toxin type A (BTX-A) and topical growth factors may enhance treatment outcomes. Here, we examine the efficacy and safety of a sequential combination of BTX-A, fractional CO2 laser, and topical growth factors, referred to as combined therapy, for treating hypertrophic scars compared with only using fractional CO2 laser and topical growth factors, referred to as monotherapy. Our retrospective study includes 128 patients with hypertrophic scars (56 underwent monotherapy and 72 underwent combined therapy), which were followed-up for up to 15 months after the initiation of treatment to collect demographic and clinical data. Our analysis showed that the combined therapy significantly outperformed monotherapy in improving Vancouver scar scale scores (P

Abstract Burnout, depression, anxiety, and stress negatively impact the well-being and retention of healthcare professionals. The interplay of these symptoms is understudied. Utilizing network analysis, this study examined the interrelationships among these symptom clusters in clinical therapists in China. An anonymous survey was conducted among clinical therapists from 41 tertiary psychiatric hospitals in China. Burnout was assessed using the Maslach Burnout Inventory-Human Service Survey (MBI-HSS), while symptoms of depression, anxiety, and stress were assessed via the Depression, Anxiety, and Stress Scale-21 (DASS-21). Analyses were performed to identify central symptoms and bridge symptoms of this network. A total of 419 participants were included in this survey. The prevalence rate for burnout, depression, anxiety, and stress was 19.8%, 22.2%, 17.9%, and 8.6%, respectively. Network analysis indicated that stress symptoms had the highest expected influence values, closely followed by emotional exhaustion from MBI-HSS. Notably, emotional exhaustion emerged as the strongest bridge of expected influence. The stability of the expected influence and bridge expected influence was robust, with coefficients at 0.75. The study’s findings underscore the importance of recognizing the central symptoms and bridge symptoms, which could lead to more effective early detection and intervention for burnout, depression, anxiety, and stress among clinical therapists.

Abstract Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs–mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.

Abstract The study aims to explore the central genes that Kawasaki disease (KD) and Obesity (OB) may jointly contribute to coronary artery disease. Investigating single-cell datasets (GSE168732 and GSE163830) from a comprehensive gene expression database, we identified characteristic immune cell subpopulations in KD and OB. B cells emerged as the common immune cell characteristic subgroup in both conditions. Subsequently, we analyzed RNA sequencing datasets (GSE18606 and GSE87493) to identify genes associated with B-cell subpopulations in KD and OB. Lastly, a genome-wide association study and Mendelian randomization were conducted to substantiate the causal impact of these core genes on myocardial infarction. Quantitative real-time PCR (qRT-PCR) to validate the expression levels of hub genes in KD and OB. The overlapping characteristic genes of B cell clusters in both KD and OB yielded 70 shared characteristic genes. PPI analysis led to the discovery of eleven key genes that significantly contribute to the crosstalk. Employing receiver operating characteristic analysis, we evaluated the specificity and sensitivity of these core genes and scored them using Cytoscape software. The inverse variance weighting analysis suggested an association between TNFRSF17 and myocardial infarction risk, with an odds ratio of 0.9995 (95% CI = 0.9990–1.0000, p = 0.049). By employing a single-cell combined transcriptome data analysis, we successfully pinpointed central genes associated with both KD and OB. The implications of these findings extend to shedding light on the increased risk of coronary artery disease resulting from the co-occurrence of OB and KD.

Abstract Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001–1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1–1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.

Abstract The joints are existing throughout the underground rock mass. It is of great significance to investigate the shear performance of the rock mass to maintain the stability of the underground structure. In this study, we conducted orthogonal tests to determine the proportion of rock-like materials, and used JRC curves to make specimen molds and then prepare the specimens. We conducted straight shear tests and uniaxial compression tests to determine the various mechanical parameters of the rock-like materials. Next, we carried out the compression and shear tests to investigate the shear characteristics of the specimens, and study the damage pattern and shear strength of the jointed rock mass under different confining pressures and roughness levels. The mesoscopic displacements in the shear process of joints were analyzed by using ABAQUS. The test results show that the effect of the confining pressure on the shear strength of the joint plane is relatively obvious, and a larger confining pressure indicates a larger shear strength. The effects of different joint plane roughness and shear rated on the shear characteristics of the joint plane are also significant. The mesoscopic displacement difference inside the joint plane with higher roughness is relatively large, and the stress concentration phenomenon is obvious and lasts longer, which leads to the faster destruction of the specimen with higher roughness and the higher destruction degree. Therefore, we suggest that the priority should be given to the reinforcement of jointed rock mass with high roughness during the construction to prevent sudden destabilization and failure.

Abstract Falls constitute a leading cause of unintentional injury deaths among older adults. This study aimed to examine the comprehensive characteristics of fatal falls among older individuals in Yunnan Province, China, to highlight the challenges faced in elderly care. A total of 22,798 accidental fall-related deaths were extracted from China's National Disease Surveillance Points System aged 60 and above between 2015 and 2019. Quantitative and textual data were analyzed to assess the incidence rates of initiating factors, locations, symptoms, and overall survival (OS) outcomes after falling. Hypertension emerged as the most significant intrinsic factor, especially among individuals aged between 70 and 79, female older adults, and urban residents (P

Abstract To quickly determine the blasting block degree and conduct an accurate and objective analysis of the tunnel blasting effect, this study has enhanced and improved upon the traditional genetic algorithm and Otsu algorithm. It has combined it with the marking watershed method and utilized ground digital acquisition to capture images of blasting debris. These images are then used in our custom-developed blasting analysis software to calculate the blasting block degree distribution and provide a quantitative analysis of blasting block degree. The research results show that the optimized image segmentation algorithm effectively improves the traditional threshold segmentation method on the poor effect of segmentation of the edge of the adherent block or the direct application of the watershed segmentation of the over-segmentation problem, to improve the segmentation accuracy based on the new segmentation technology is close to the traditional technology in terms of time. Through the self-developed software, the construction personnel in the project site to quickly obtain the blasting block degree histogram, block degree cumulative curve and other important indicators of the evaluation of the effect of blasting block degree, to provide data support for on-site construction, to assist in the modification of the blasting program, and to improve the efficiency of construction. This study realizes the rapid detection and block identification of blasting blocks, provides data support for the optimization of blasting parameters, and has good application and promotion value.

Abstract Earth pressure shields are widely used in tunnel construction due to their low environmental impact and mechanized operations. However, ensuring the stability of the excavation surface during the construction process is crucial. Any instability in the excavation surface can lead to soil destruction, such as body collapse or surface uplift. Additionally, the tunneling process can cause deformation disturbances to nearby buildings. In the case of Beijing Metro Line 17, detailed survey data and construction monitoring data were collected through field surveys and tests. The study combined theoretical analysis and numerical simulations to investigate the impact of shield tunneling in clay layers on neighboring buildings. The focus was on analyzing the physical deformation and the response law of influencing factors, such as stratum parameters and engineering effects on surface settlement, building inclination, and distortion. Furthermore, sensitivity analysis of the deformation impact was conducted, and corresponding measures for deformation control were proposed.

Abstract HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor used for treating hyperuricemia. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of HP501 in male Chinese patients. Patients with hyperuricemia were sequentially assigned to receive oral doses of HP501 (30, 50, 60, 90, and 120 mg) as a single dose on Day 1 and as once-daily doses from Days 4 to 13. Safety, pharmacokinetic, and pharmacodynamic data were collected. Multiple oral doses of HP501 were well-tolerated in all the cohorts. The most common adverse events (≥ 10% of patients) of any grade regardless of drug relationship were gout flare (14 patients, 25.93%), diarrhea (12 patients, 22.22%), elevated ALT (8 patients, 14.81%), hypertriglyceridemia (7 patients, 12.96%), dry mouth (7 patients, 12.96%) and oral ulcer (7 patients, 12.96%). All adverse events were mild or moderate. The Cmax and exposure (AUC) of HP501 was approximately dose-proportional between 30 and 120 mg. A dose-dependent serum uric acid (UA)-lowering effect was observed in the dose range of 30 to 60 mg and the serum UA lowering effect was similar between 90 and 120 mg on day 13, indicating that the maximal serum UA lowering effect of HP501 was achieved at 90 mg in the patients with hyperuricemia. In conclusion, the tolerability, pharmacokinetics, and pharmacodynamics supported 90 mg HP501 for subsequent clinical studies of this highly selective URAT1 inhibitor. Clinical Trial registration: No. CTR20212259 ( http://www.chinadrugtrials.org.cn/ ) was registered in September 2021, and No. CTR20222257 was registered in September 2022.

Abstract In view of the breakage of the rotary shaft of the traction motor of the locomotive, in order to ensure the reliability and safety of the equipment, this paper studies the magnetic field containing rich information in the space around the rotary shaft, so that the crack defect can be detected and the crack size can be judged in time. In order to study the influence of defect geometric parameters (width, depth and hidden depth) on the spatial magnetic field distribution around the defect in the process of eddy current testing of metal shafts, based on the principle of eddy current testing, a metal rotary shaft detection model with different defect parameters was established by COMSOL software for simulation. The horizontal magnetic induction intensity, vertical magnetic induction intensity and their respective phases are used to analyze the magnetic field distribution around the defect under different parameters. The results show that the magnetic field related parameters can qualitatively and quantitatively evaluate the crack width, qualitatively evaluate the relative size of the crack depth, and qualitatively judge whether there are hidden cracks.

Abstract Touch is the primary way people communicate intimacy in romantic relationships, and affectionate touch behaviors such as stroking, hugging and kissing are universally observed in partnerships all over the world. Here, we explored the association of love and affectionate touch behaviors in romantic partnerships in two studies comprising 7880 participants. In the first study, we used a cross-cultural survey conducted in 37 countries to test whether love was universally associated with affectionate touch behaviors. In the second study, using a more fine-tuned touch behavior scale, we tested whether the frequency of affectionate touch behaviors was related to love in romantic partnerships. As hypothesized, love was significantly and positively associated with affectionate touch behaviors in both studies and this result was replicated regardless of the inclusion of potentially relevant factors as controls. Altogether, our data strongly suggest that affectionate touch is a relatively stable characteristic of human romantic relationships that is robustly and reliably related to the degree of reported love between partners.

Abstract Recent cross-cultural and neuro-hormonal investigations have suggested that love is a near universal phenomenon that has a biological background. Therefore, the remaining important question is not whether love exists worldwide but which cultural, social, or environmental factors influence experiences and expressions of love. In the present study, we explored whether countries’ modernization indexes are related to love experiences measured by three subscales (passion, intimacy, commitment) of the Triangular Love Scale. Analyzing data from 9474 individuals from 45 countries, we tested for relationships with country-level predictors, namely, modernization proxies (i.e., Human Development Index, World Modernization Index, Gender Inequality Index), collectivism, and average annual temperatures. We found that mean levels of love (especially intimacy) were higher in countries with higher modernization proxies, collectivism, and average annual temperatures. In conclusion, our results grant some support to the hypothesis that modernization processes might influence love experiences.

Abstract Fruit leaf diseases have a significant impact on the later development and maturity of fruits, so rapid and accurate identification of fruit leaf diseases plays an important role in the development of fruit production. In this paper, the leaf disease data set of 6 kinds of fruits is divided into 25 categories according to the species—the type of the disease—the severity, and we propose an improved model based on ResNet101 to identify woody fruit plant leaf diseases, in which a global average pooling layer is used to reduce model training parameters, layer normalization, dropout and L2 regularization are used to prevent model overfitting, SENet attention mechanism is used to improve the model's ability to extract features. At the same time, transfer learning is used to reduce training time and training parameters. Experimental results show that the overall accuracy of woody fruit plant leaf recognition based on this model can reach 85.90%. Compared with the classic ResNet network, the accuracy is increased by 1.20%, and the model parameters are reduced by 98.14%. Therefore, the model proposed in this paper provides a better solution for the identification of leaf diseases of woody fruit plants and has a higher accuracy rate.

Abstract The nanoporous (NP) GaN distributed Bragg reflector (DBR) was prepared by using electrochemical etching. Then the NP-GaN DBR was pretreated by using ozone treatment. Atomic force microscopy and X-ray diffraction (XRD) were used to investigate the influence of ozone treatment on the structure of the substrates. The hybrid organic–inorganic CH3NH3PbI3 perovskite films were grown on the NP-GaN DBR and reference substrates by using a one-step solution method. The XRD and field emission scanning electron microscopy test results indicate the high quality of the prepared CH3NH3PbI3 perovskite films. The photoluminescence intensity of the prepared CH3NH3PbI3 perovskite film on the NP-GaN DBR substrate is ~ 3.5 times higher than that of the film on the reference substrate, with a 3.6 nm spectral blue-shift. The enhancement should be contributable to amplify spontaneous emission by resonant cavity, while the blue-shift could be contributable to stoichiometric difference of the films on different substrates.

Abstract The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on the gut microbiota and intestinal barrier in dextran sulfate sodium (DSS)-induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administered TFA (62.5 mg/kg, 125 mg/kg) or prednisone acetate (PAT, 2.5 mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammatory cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125 mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar to that of PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated the colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results revealed for the first time that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly by modulating the gut microflora profile to maintain colonic integrity and inhibit the inflammatory response.

Abstract Acute myeloid leukemia (AML) is the most prevalent form of acute leukemia. Patients with AML often have poor clinical prognoses. Hypoxia can activate a series of immunosuppressive processes in tumors, resulting in diseases and poor clinical prognoses. However, how to evaluate the severity of hypoxia in tumor immune microenvironment remains unknown. In this study, we downloaded the profiles of RNA sequence and clinicopathological data of pediatric AML patients from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, as well as those of AML patients from Gene Expression Omnibus (GEO). In order to explore the immune microenvironment in AML, we established a risk signature to predict clinical prognosis. Our data showed that patients with high hypoxia risk score had shorter overall survival, indicating that higher hypoxia risk scores was significantly linked to immunosuppressive microenvironment in AML. Further analysis showed that the hypoxia could be used to serve as an independent prognostic indicator for AML patients. Moreover, we found gene sets enriched in high-risk AML group participated in the carcinogenesis. In summary, the established hypoxia-related risk model could act as an independent predictor for the clinical prognosis of AML, and also reflect the response intensity of the immune microenvironment in AML.

Abstract One of the most frequently identified tumors and a contributing cause of death in women is breast cancer (BC). Many biomarkers associated with survival and prognosis were identified in previous studies through database mining. Nevertheless, the predictive capabilities of single-gene biomarkers are not accurate enough. Genetic signatures can be an enhanced prediction method. This research analyzed data from The Cancer Genome Atlas (TCGA) for the detection of a new genetic signature to predict BC prognosis. Profiling of mRNA expression was carried out in samples of patients with TCGA BC (n = 1222). Gene set enrichment research has been undertaken to classify gene sets that vary greatly between BC tissues and normal tissues. Cox models for additive hazards regression were used to classify genes that were strongly linked to overall survival. A subsequent Cox regression multivariate analysis was used to construct a predictive risk parameter model. Kaplan–Meier survival predictions and log-rank validation have been used to verify the value of risk prediction parameters. Seven genes (PGK1, CACNA1H, IL13RA1, SDC1, AK3, NUP43, SDC3) correlated with glycolysis were shown to be strongly linked to overall survival. Depending on the 7-gene-signature, 1222 BC patients were classified into subgroups of high/low-risk. Certain variables have not impaired the prognostic potential of the seven-gene signature. A seven-gene signature correlated with cellular glycolysis was developed to predict the survival of BC patients. The results include insight into cellular glycolysis mechanisms and the detection of patients with poor BC prognosis.

Abstract Diabetic retinopathy (DR) is a major microvascular complication of diabetes. Susceptibility genes for type 2 diabetes may also impact the susceptibility of DR. This case-control study investigated the effects of 88 type 2 diabetes susceptibility loci on DR in a Chinese population with type 2 diabetes performed in two stages. In stage 1, 88 SNPs were genotyped in 1,251 patients with type 2 diabetes, and we found that ADAMTS9-AS2 rs4607103, WFS1 rs10010131, CDKAL1 rs7756992, VPS26A rs1802295 and IDE-KIF11-HHEX rs1111875 were significantly associated with DR. The association between CDKAL1 rs7756992 and DR remained significant after Bonferroni correction for multiple comparisons (corrected P = 0.0492). Then, the effect of rs7756992 on DR were analysed in two independent cohorts for replication in stage 2. Cohort (1) consisted of 380 patients with DR and 613 patients with diabetes for ≥5 years but without DR. Cohort (2) consisted of 545 patients with DR and 929 patients with diabetes for ≥5 years but without DR. A meta-analysis combining the results of stage 1 and 2 revealed a significant association between rs7756992 and DR, with the minor allele A conferring a lower risk of DR (OR 0.824, 95% CI 0.743–0.914, P = 2.46 × 10−4).

Abstract Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are important pathogens of salmon and trout. An active bivalent DNA vaccine was constructed with the glycoprotein gene of Chinese IHNV isolate Sn1203 and VP2–VP3 gene of Chinese IPNV isolate ChRtm213. Rainbow trout (5 g) were vaccinated by intramuscular injection with 1.0 µg of the bivalent DNA vaccine and then challenged with an intraperitoneal injection of IHNV, IPNV, or both, at 30 and 60 days post-vaccination (d.p.v.). High protection rates against IHNV were observed, with 6% and 10% cumulative mortality, respectively, compared with 90–94% in the mock-vaccinated groups. IPNV loads (531-fold and 135-fold, respectively) were significantly reduced in the anterior kidneys of the vaccinated trout. Significant protection against co-infection with IHNV and IPNV was observed, with cumulative mortality rates of 6.67% and 3.33%, respectively, compared with 50.0% and 43.3%, respectively, in the mock-vaccinated groups. No detectable infective IHNV or IPNV was recovered from vaccinated trout co-infected with IHNV and IPNV. The bivalent DNA vaccine increased the expression of Mx-1 and IFN-γ at 4, 7, and 15 d.p.v, and IgM at 21 d.p.v., and induced high titres (≥160) of IHNV and IPNV neutralizing antibodies at 30 and 60 d.p.v.

Abstract Cyclooxygenase-2 (COX-2) was stated to be overexpression in various human malignancies associating with angiogenesis, metastasis and chemoresistence. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease displaying many of these characteristics. A common abnormality of PDAC is overexpression of specificity protein-1 (Sp1), which was said to correlate with malignant phenotypes of human cancers. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we found that Sp1 expression was positively correlated with that of COX-2 in PDAC, and that the inhibition or overexpression of Sp1 in PDAC cells leads to decreased or elevated COX-2 expression. Luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays revealed that elevated transcription of COX-2 requires Sp1 binding to sequence positions around −245/−240 of COX-2 promoter. Activated epidermal growth factor receptor (EGFR) and downstream p38 mitogen-activated protein kinase (p38-MAPK) were also profoundly altered in PDAC. The inhibition of EGFR/p38-MAPK signaling resulted in reduced Sp1 activation, decreased COX-2 and vascular endothelial growth factor (VEGF) expression. Thus, Sp1 could transcriptionally activate COX-2 expression in a process relies on activated EGFR/p38-MAPK signaling. Finally, we found that the inhibition of COX-2 leads to decreased angiogenesis in a process dependent on VEGF, which link COX-2 to angiogenesis in PDAC.