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Abstract Background This multicenter, double-blinded, randomized controlled trial (RCT) aims to assess the impact of an artificial intelligence (AI)-based model on the efficacy of intracranial aneurysm detection in CT angiography (CTA) and its influence on patients’ short-term and long-term outcomes. Methods Study design: Prospective, multicenter, double-blinded RCT. Settings: The model was designed for the automatic detection of intracranial aneurysms from original CTA images. Participants: Adult inpatients and outpatients who are scheduled for head CTA scanning. Randomization groups: (1) Experimental Group: Head CTA interpreted by radiologists with the assistance of the True-AI-integrated intracranial aneurysm diagnosis strategy (True-AI arm). (2) Control Group: Head CTA interpreted by radiologists with the assistance of the Sham-AI-integrated intracranial aneurysm diagnosis strategy (Sham-AI arm). Randomization: Block randomization, stratified by center, gender, and age group. Primary outcomes: Coprimary outcomes of superiority in patient-level sensitivity and noninferiority in specificity for the True-AI arm to the Sham-AI arm in intracranial aneurysms. Secondary outcomes: Diagnostic performance for other intracranial lesions, detection rates, workload of CTA interpretation, resource utilization, treatment-related clinical events, aneurysm-related events, quality of life, and cost-effectiveness analysis. Blinding: Study participants and participating radiologists will be blinded to the intervention. Sample size: Based on our pilot study, the patient-level sensitivity is assumed to be 0.65 for the Sham-AI arm and 0.75 for the True-AI arm, with specificities of 0.90 and 0.88, respectively. The prevalence of intracranial aneurysms for patients undergoing head CTA in the hospital is approximately 12%. To establish superiority in sensitivity and noninferiority in specificity with a margin of 5% using a one-sided α = 0.025 to ensure that the power of coprimary endpoint testing reached 0.80 and a 5% attrition rate, the sample size was determined to be 6450 in a 1:1 allocation to True-AI or Sham-AI arm. Discussion The study will determine the precise impact of the AI system on the detection performance for intracranial aneurysms in a double-blinded design and following the real-world effects on patients’ short-term and long-term outcomes. Trial registration This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT06118840 . Registered 11 November 2023.

Gemcitabine is a common first-line chemotherapy agent, but gemcitabine resistance is a clinical challenge for pancreatic ductal adenocarcinoma patients. Solute carrier 39A1 (SLCA39A1) as a zinc regulator presents a crucial function in the modulation of malignancy progression. Here, the impact of SLC39A1 on the gemcitabine resistance of pancreatic ductal adenocarcinoma was investigated. Immunohistochemistry demonstrated that the SLC39A1 expression was significantly up-regulated in gemcitabine-resistant pancreatic ductal adenocarcinoma samples compared with gemcitabine-sensitive ones. Gemcitabine dose-dependently inhibited the viability of the cancer cells, and SLC39A1 knockdown aggravated this effect. Both mRNA and protein expression of SLC39A1 were elevated in the gemcitabine-resistant cancer cells. SLC39A1 knockdown also reversed AMP-activated protein kinase (AMPK) phosphorylation and S6K expression of cancer cells regulated by the gemcitabine resistance. SLC39A1 promotes gemcitabine resistance of pancreatic ductal adenocarcinoma by activating AMPK signaling, revealing SLC39A1 may be a potential target in patients with gemcitabine resistance.

To obtain high-quality bovine oocytes, the effects of vitamin C (VC) on the IVM of bovine oocytes and early embryo development were investigated. The results showed the following. (1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate but did not affect the parthenogenetic embryo development. (2) The IVC medium containing 20 µg/mL VC improved the cleavage rate of the IVF embryos and enhanced the mRNA transcriptions of pluripotency gene Oct4, Sox2, Cdx2, and Nanog in the blastocysts but had no effects on the blastocyst rate. (3) Combining supplementation of 50 µg/mL VC in IVM medium + 20 µg/mL VC in IVC medium (named as VC 50/20, similar hereinafter) elevated the cleavage rate of IVF embryos and enhanced the mRNA expressions of Oct4, Sox2, Cdx2, and Nanog in the blastocysts. (4) Combination of VC 0/20 and VC 50/20 enhanced the transcription of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the transcription of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and diminished the Bcl-2/Bax ratio in blastocysts. Together, employing 50 µg/mL VC improves the IVM of bovine oocytes and combination of VC 50/20 potentially changes bovine embryo quality by enhancing the expressions of the pluripotency genes and regulating the expressions of apoptosis-related genes.

Circular RNA (circRNA) has been confirmed to play a vital role in pancreatic ductal adenocarcinoma (PDAC) progression. However, the function and regulatory mechanism of hsa_circ_0012634 in PDAC progression remain unclear. Quantitative real-time PCR was used to measure the expression of hsa_circ_0012634, microRNA (miR)-147b and homeodomain interacting protein kinase 2 (HIPK2). Cell function was assessed by cell counting kit 8 assay, EdU assay, colony formation assay and flow cytometry. Glucose uptake and lactate production were evaluated to determine cell glycolysis ability. Protein expression was examined by western blot analysis. RNA interaction was confirmed by RNA pull-down assay and dual-luciferase reporter assay. Exosomes were isolated from serums and cell culture supernatant using ultracentrifugation and identified by transmission electron microscopy. Animal experiments were conducted using nude mice. Hsa_circ_0012634 was downregulated in PDAC tissues and cells, and its overexpression suppressed PDAC cell proliferation, glycolysis and enhanced apoptosis. MiR-147b was targeted by hsa_circ_0012634, and its inhibitors repressed PDAC cell growth and glycolysis. HIPK2 could be targeted by miR-147b, and hsa_circ_0012634 regulated miR-147b/HIPK2 to suppress PDAC cell progression. Hsa_circ_0012634 was lowly expressed in serum exosomes of PDAC patients. Exosomal hsa_circ_0012634 inhibited PDAC cell growth and glycolysis in vitro, as well as tumorigenesis in vivo. Exosomal hsa_circ_0012634 restrained PDAC progression via the miR-147b/HIPK2 pathway, confirming that hsa_circ_0012634 might serve as a diagnosis and treatment biomarker for PDAC.

ABSTRACTHuman cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) −6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

Abstract Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.

The existence of defects in the enclosure structure is the primary cause of water and sand leakage in foundation pits, as well as being a significant source of danger in pit construction, but current research lacks an in-depth investigation of the generation mechanism and gestation process. In this paper, which comprehensively considers the microscopic particles and macroscopic level, the development mechanism of a water and sand leakage disaster in a foundation pit with a water-rich sand layer was studied using the principle of computational fluid dynamics and discrete element method coupled analysis (CFD–DEM); moreover, based on the anisotropy of the particle force and fluid energy analysis, the deformation of the stratum and ground stress field were analyzed. The results show that the stress field will produce a plugging effect at a certain distance from the defect, and the strata exhibit a dominant displacement tendency in the vertical direction, resulting in the emergence of a gradually concave stress relaxation zone and an elliptical contour in the strata displacement map near the defect. The fluid energy describes the displacement of the sand layer very well, and it is separated into the sand layer’s centralized loss region and the major loss area based on the high and low levels of the fluid energy class. The impact of fluid at the defect reaches the maximum kinetic energy, which penetrates the structural weakness and causes the loss of sand particles, and the cross-section of the water influx near the defect gradually expands with the loss of particles, indicating that there is a danger of further expansion of the defect under the impact of water flow. These results have technical implications for the management of water and sand leakage disasters in foundation pit engineering.

Abstract Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14+ (K14+) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14+ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140+/ K14+ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14+ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14+ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140+/K14+, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.

To investigate the seismic performance and isolation effect of a high-temperature gas-cooled reactor, a 1/20 scale model including a reactor, a spent-fuel plant, and a nuclear auxiliary plant was fabricated. In addition, 220 mm lead-rubber bearings were designed and produced for use in the shaking table test, which included both isolated and nonisolated conditions. Two historical earthquake records and three artificial earthquake motions were used to input the ground motion in the tests. The results demonstrated that the seismic performance of the plant was better and that the structure was in an elastic state, under a safe shutdown earthquake event. Isolation bearings were found to effectively reduce the dominate frequency of the structure. The acceleration amplification factor of the superstructure was found to be less than 1. The isolation test results showed that the peak of the floor response spectrum at the pressure vessel support was less than 0.1 g. In the nonisolation test, the peak of the floor response spectrum was greater than 1 g. In the isolation test, the relative displacement of the structure was less than 1.1 mm, which was relatively small. The structure maintained a good isolation performance and exhibited improved safety under extreme ground motion.

ObjectivesPressure-strain loop (PSL) is a novel method to quantify myocardial work in many cardiovascular diseases. To investigate the value of myocardial work parameters derived from PSL for evaluating cardiac function and clinical prognosis in patients with pulmonary hypertension (PH).MethodsA total of 52 patients with PH and 27 healthy controls were enrolled in this prospective study. PSLs determined by echocardiography were used to calculate global work index (GWI) of left ventricle (LV) and right ventricle (RV). Global constructive work (GCW) comprised the sum of myocardial work performed during shortening in systole and during lengthening in isovolumic relaxation. Global wasted work (GWW) comprised the sum of myocardial work performed during lengthening in systole and during shortening in isovolumic relaxation. Global work efficiency (GWE) was defined as GCW/(GCW + GWW).ResultsLVGWW, RVGWI, RVGCW and RVGWW were significantly higher in patients than controls (all P < 0.001). LVGWE, LVGWI, LVGCW, and RVGWE were lower in patients than controls (all P < 0.01). Myocardial work parameters correlated well with clinical and other conventional echocardiographic assessments (all P < 0.05). In binary logistic regression analysis, the combination of RVGWE and estimation of pulmonary arterial systolic pressure (ePASP) was the best model to predict clinical outcomes (OR = 0.803, P = 0.002 and OR = 1.052, P = 0.015, respectively). Receiver operating characteristic curv demonstrated the combination of RVGWE and ePASP was the best predictor of adverse events with 100% sensitivity and 76.3% specificity (AUC = 0.910, P < 0.001).ConclusionMyocardial work parameters derived from PSL are emerging markers of cardiac function. And the combination of RVGWE and ePASP is a useful predictor of clinical outcome in PH patients.

BackgroundAs a tumor type with high mortality and poor therapeutic effect, the pathogenesis of pancreatic cancer is still unclear. It is necessary to explore the significance of necroptosis in pancreatic cancer.MethodsPancreatic cancer transcriptome data were obtained from the TCGA database, ICGC database, and GSE85916 in the GEO database. The TCGA cohort was set as a training cohort, while the ICGC and GSE85916 cohort were set as the validation cohorts. Single-cell sequencing data of pancreatic cancer were obtained from GSE154778 in the GEO database. The genes most associated with necroptosis were identified by weighted co-expression network analysis and single-cell sequencing analysis. COX regression and Lasso regression were performed for these genes, and the prognostic model was established. By calculating risk scores, pancreatic cancer patients could be divided into NCPTS_high and NCPTS_low groups, and survival analysis, immune infiltration analysis, and mutation analysis between groups were performed. Cell experiments including gene knockdown, CCK-8 assay, clone formation assay, transwell assay and wound healing assay were conducted to explore the role of the key gene EPS8 in pancreatic cancer. PCR assays on clinical samples were further used to verify EPS8 expression.ResultsWe constructed the necroptosis-related signature in pancreatic cancer using single-cell sequencing analysis and transcriptome analysis. The calculation formula of risk score was as follows: NCPTS = POLR3GL * (-0.404) + COL17A1 * (0.092) + DDIT4 * (0.007) + PDE4C * (0.057) + CLDN1 * 0.075 + HMGA2 * 0.056 + CENPF * 0.198 +EPS8 * 0.219. Through this signature, pancreatic cancer patients with different cohorts can be divided into NCPTS_high and NCPTS_low group, and the NCPTS_high group has a significantly poorer prognosis. Moreover, there were significant differences in immune infiltration level and mutation level between the two groups. Cell assays showed that in CAPAN-1 and PANC-1 cell lines, EPS8 knockdown significantly reduced the viability, clonogenesis, migration and invasion of pancreatic cancer cells. Clinical PCR assay of EPS8 expression showed that EPS8 expression was significantly up-regulated in pancreatic cancer (*P

Due to the complexity of electromechanical equipment and the difficulties in obtaining large-scale health monitoring datasets, as well as the long-tailed distribution of data, existing methods ignore certain characteristics of health monitoring data. In order to solve these problems, this paper proposes a method for the fault diagnosis of rolling bearings in electromechanical equipment based on an improved prototypical network—the weight prototypical networks (WPorNet). The main contributions of this paper are as follows: (1) the prototypical networks, which perform well on small-sample classification tasks, were improved by calculating the different levels of influence of support sample distributions in order to achieve the prototypical calculation. The change in sample influence was calculated using the Kullback–Leibler divergence of the sample distribution. The influence change in a specific sample can be measured by assessing how much the distribution changes in the absence of that sample; and (2) The Gramian Angular Field (GAF) algorithm was used to transform one-dimensional time series into two-dimensional vibration images, which greatly improved the application effect of the 2D convolutional neural network (CNN). Through experiments on MAFAULDA and CWRU bearing datasets, it was shown that this network effectively solves the shortcomings of a small number of valid samples and a long-tail distribution in health monitoring data, it enhances the dependency between the samples and the global data, it improves the model’s feature extraction ability, and it enhances the accuracy of model classification. Compared with the prototypical network, the improved network model increased the performance of the 2-way 10-shot, 2-way 20-shot, and 2-way 50-shot classification tasks by 5.23%, 5.74%, and 4.37%, respectively, and it increased the performance of the 4-way 10-shot, 4-way 20-shot, and 4-way 50-shot classification tasks by 12.02%, 10.47%, and 4.66%, respectively. Experimental results show that the improved prototypical network model has higher sample classification accuracy and stronger anti-interference ability compared with traditional small-sample classification models.

Catalytic upgrading of fast pyrolysis bio-oil from two different types of lignocellulosic biomass was conducted using an H-ZSM-5 catalyst at different temperatures. A fixed-bed pyrolysis reactor has been used to perform in situ catalytic pyrolysis experiments at temperatures of 673, 773, and 873 K, where the catalyst (H-ZSM-5) has been mixed with wood chips or lignin, and the pyrolysis and upgrading processes have been performed simultaneously. The fractionation method has been employed to determine the chemical composition of bio-oil samples after catalytic pyrolysis experiments by gas chromatography with mass spectroscopy (GCMS). Other characterization techniques, e.g., water content, viscosity, elemental analysis, pH, and bomb calorimetry have been used, and the obtained results have been compared with the non-catalytic pyrolysis method. The highest bio-oil yield has been reported for bio-oil obtained from softwood at 873 K for both non-catalytic and catalytic bio-oil samples. The results indicate that the main effect of H-ZSM-5 has been observed on the amount of water and oxygen for all bio-oil samples at three different temperatures, where a significant reduction has been achieved compared to non-catalytic bio-oil samples. In addition, a significant viscosity reduction has been reported compared to non-catalytic bio-oil samples, and less viscous bio-oil samples have been produced by catalytic pyrolysis. Furthermore, the obtained results show that the heating values have been increased for upgraded bio-oil samples compared to non-catalytic bio-oil samples. The GCMS analysis of the catalytic bio-oil samples (H-ZSM-5) indicates that toluene and methanol have shown very similar behavior in extracting bio-oil samples in contrast to non-catalytic experiments. However, methanol performed better for extracting chemicals at a higher temperature.

In recent decades, the increasing incidence of depression has contributed to an increase in the use of serotonergic drugs, such as antidepressants, which predisposes humans to serotonin syndrome. Serotonin syndrome is caused by elevated serotonin levels in the central and peripheral nervous systems. It has been well documented that the development of offspring can be affected by maternal exposure to environmental challenges, such as stress, diseases, or an unhealthy diet during pregnancy. Serotonin, also called 5-hydroxytryptamine (5-HT), is widely expressed in the female reproductive system and plays an important role in the development of follicles and embryos. However, whether the suffering of the mother from serotonin syndrome before pregnancy affects fetal development is still uncertain. In the present study, to explore the effect of maternal prepregnancy 5-HT exposure on the fetus, intraperitoneal injection of 5-HT was used to change maternal prepregnancy 5-HT levels. It was found that maternal prepregnancy 5-HT exposure significantly reduced the body weight and liver weight and the levels of estrogen and progesterone in female mice. Although there was no significant difference in the cleavage rate and blastocyst rate between the 5-HT and control groups, maternal prepregnancy 5-HT exposure increased the percentage of embryo resorption, decreased placental weight, and led to placental inflammation at E13.5. Notably, 5-HT exposure caused weight loss in the offspring at 2 weeks. These results suggested that maternal prepregnancy 5-HT exposure could affect the development of the offspring, which was partly caused by reduced hormonal secretion and placental inflammation.

Staphylococcus aureus is a common pathogen that can cause pneumonia and a variety of skin diseases. Skin injuries have a high risk of colonization by S. aureus, which increases morbidity and mortality. Due to the emergence of multidrug-resistant strains, antimicrobial peptides are considered to be among the best alternatives to antibiotics due to their unique mechanism of action and other characteristics. MPX is an antibacterial peptide extracted from wasp venom that has antibacterial activity against a variety of bacteria. This study revealed that MPX has good bactericidal activity against S. aureus and that its minimum inhibitory concentration (MIC) is 0.08 μM. MPX (4×MIC) can kill 99.9% of bacteria within 1 h, and MPX has good stability. The research on the bactericidal mechanism found that MPX could destroy the membrane integrity, increase the membrane permeability, change the membrane electromotive force, and cause cellular content leakage, resulting in bactericidal activity. Results from a mouse scratch model experiment results show that MPX can inhibit colonization by S. aureus, which reduces the wound size, decreases inflammation, and promotes wound healing. This study reports the activity of MPX against S. aureus and its mechanism and reveals the ability of MPX to treat S. aureus infection in mice, laying the foundation for the development of new drugs for bacterial infections.

Introduction Idiopathic pulmonary arterial hypertension (IPAH) is a rare and sporadic form of pulmonary arterial hypertension (PAH), characterized by elevated pulmonary arterial resistance leading to right heart failure. However, molecular mechanisms of PAH development are still not completely understood. Material and methods In this study, we aimed to uncover key mRNAs and long non-coding RNA (lncRNAs), functional modules and pathways. Moreover, to detect the dysregulated pathway or biological function, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. PPI and co-expression networks were constructed to reveal the potential roles of PAH-related mRNAs and lncRNAs. Results A total of 3,134 genes, including 945 up-regulated and 2,189 down-regulated genes, were identified to be differentially expressed in IPAH by differential expression analysis. We identified T cell differentiation and the T cell receptor signaling pathway as up-regulated in IPAH by using GO and KEGG analysis. Based on the PPI module analysis, we identified that the pro-inflammatory genes, such as OAS1, CXCL10, STAT1 and TLR4, were the hub genes in the PPI modules. To link the lncRNAs to the PPI modules, we calculated the Spearman correlation coefficient for lncRNA-DE-mRNA pairs to identify the modules with high correlation with each lncRNA. Conclusions Notably, 6 of these lncRNAs were associated with modules characterized by the NOD-like receptor signaling pathway and chemokine signaling pathway, suggesting that these lncRNAs may promote the occurrence of IPAH via participating in the pro-inflammatory pathways. In conclusion, our systematic analysis not only improved our understanding of the molecular mechanism, but also provided potential lncRNA biomarkers for further research.

The sandy cobble ground has loose structure, uneven particle size, and random distribution characteristics, which may lead to the local collapse of ground. This paper carried out field tests based on the project of Luoyang urban rail transit. For this, the surface settlement, pore water pressure, and earth pressure in the test section were measured. The excavation disturbance and influence range on the soil layer in each stage of earth pressure balance shield tunneling were studied. Meanwhile, based on the key construction elements in sandy cobble ground, a numerical simulation method was proposed based on shield construction parameters. The disturbance characteristics of deformation, seepage action, and stress state of the sandy cobble ground during shield construction were obtained through numerical calculation. The rationality of the simulation results was verified by the measured tests. The results showed that the measured data were in good agreement with the simulation results. The research results provide a calculation method for predicting the soil disturbance in the earth pressure balance shield construction in a sandy cobble ground.

Critical for the seismic safety of immersed tunnels is the magnitude of deformation and force developing in the segment joints. To investigate the seismic performance of segment joint in immersed tunnel, this paper presents a series of shaking table arrays tests that were performed on a microconcrete tunnel model embedded in the soil. The tests take account of the uniform and wave passage effect in different apparent wave velocity of longitudinal seismic excitation. The result showed that the wave passage effect had a great impact on axial force, bending moment and deformation of joints. The comparison showed that structural response under nonuniform earthquake excitation is larger than that under uniform excitation. The simplified model was established in ABAQUS for numerical analysis. The soil around the tunnel was simplified as spring-damper, the tunnel was simplified as beam element, and the joint was simulated by nonlinear spring. The numerical simulation results were in good agreement with the experimental data. In addition, the model was analyzed by changing input apparent wave velocity, joint stiffness and joint number. The results showed that the deformation of joints was smaller and the deformation of flexible joints was greater under high apparent wave velocity.

Sandy gravel stratum is very common in tunnels and underground engineering projects. The accurate determination of mechanical parameters is crucial for engineering design and construction. The Hardening Soil (HS) Model, which accounts for both shear hardening and compression hardening, has demonstrated advantages in numerical simulations. This study conducts large-scale mechanical experiments, including triaxial drained shear tests, loading-unloading tests, and standard consolidation tests, on sandy gravel specimens. The results reveal that the ratio of the three stiffness parameters in the HS Model, namely Young’s modulus under triaxial loading (E50), oedometric loading (Eoed), and unloading-reloading (Eur) is 1:1:4.3. The validity of the established stiffness ratio relationship is verified through numerical simulations of a foundation pit project and comparison with field monitoring data, demonstrating a consistent agreement between the simulation results and actual monitoring values.

An efficient method using multiwalled carbon nanotubes (MWCNTs) as dispersive solid-phase extraction sorbent was established for determining chlorantraniliprole residues in fresh tea leaves, which are known to be a troublesome matrix containing abundant pigments, via gas chromatography with an electron capture detector. Acetonitrile was used as the extraction solvent, with sodium chloride enhancing the analyte partition in the organic phase. The optimal mixture of MWCNTs and primary secondary amine (PSA) was based on the distribution of the target analyte recovery and on the clean-up efficiency; while matrix-matched calibration was recommended to combat the matrix effect. Mean recoveries of 95.2%–108.8% were obtained with intraday and interday precisions of less than 7.9% and 10.3%, respectively. Good linearity was observed for concentrations of 0.02–1.0 mg/kg with a correlation coefficient of 0.9984. The limits of detection and quantification were 0.005 mg/kg and 0.02 mg/kg, respectively. The method was employed to investigate the dissipation dynamics of chlorantraniliprole in fresh tea leaves with real field samples. Consequently, the dissipation rates of chlorantraniliprole in fresh tea leaves followed pseudo-first-order kinetics with a half-life of 1.9 d, and the average chlorantraniliprole residue content was below 0.02 mg/kg with a harvest withholding period of 14 d. Keywords: Multiwalled carbon nanotubes, Fresh tea leaves, Chlorantraniliprole, Dispersive solid-phase extraction, Gas chromatography

Cardiovascular failure is one of the most relevant causes of death in pulmonary hypertension (PH). With progressive increases of right ventricular (RV) afterload in PH patients, both RV and left ventricular (LV) function impair and RV–LV dyssynchrony develop in parallel. We aimed to analyze the balance between the left and right ventricular deformation to assess the outcome of patients with pulmonary hypertension by means of speckle tracking echocardiography. In this prospective study, 54 patients with invasively diagnosed pulmonary hypertension, and 26 healthy volunteers were included and underwent a broad panel of noninvasive assessment including 2D-echocardiography, 2D speckle tracking, 6-minute walking test and BNP. Patients were followed up for 338.7 ± 131.1 (range 60 to 572) days. There were significant differences in |LVGLS/RVFLS-1| and |LASc/RASc-1| between PH patients and the control group. During the follow up, 13 patients experienced MACEs, which included 7 patients with cardiac death and 6 patients with re-admitted hospital due to right ventricular dysfunction. In the multivariate Cox model analysis, |LVGLS/RVFLS-1| remained independent prognosis of markers (HR = 4.03). Our study findings show that |LVGLS/RVFLS-1| is of high clinical and prognostic relevance in pulmonary hypertension patients and reveal the importance of the balance between the left and right ventricular deformation.

Objectives. To observe the characteristics of sacral reflex and sympathetic skin reflex in patients with Parkinson’s disease (PD) and multiple system atrophy P-type (MSA-P) and to analyze their value as a differential diagnostic method. Methods. The data of 30 healthy people, 58 PD patients, and 52 MSA-P patients from the First Affiliated Hospital of Wenzhou Medical University were collected. Electrophysiological bulbocavernosus reflex (BCR) and sympathetic skin response (SSR) were evaluated using the Keypoint EMG/EP system. The latency period, amplitude, and extraction rate of BCR and SSR were compared between the control, PD, and MSA-P groups. Results. The incidence of the related autonomic damage in the PD group was lower than that of the MSA-P group. For BCR, the latency period was shorter and the amplitude and elicitation rates were lower in the PD group than in the MSA-P group. For SSR, the latency period was longer in the MSA-P and PD groups than in the control group, but the difference was not statistically significant. Conclusion. SSR cannot be used to assess autonomic nerve function. PD patients can have clinical symptoms similar to those of MSA-P patients, but the incidence is lower. Both MSA-P and PD patients have a damage to the BCR arc, but the MSA-P patients have a more severe damage.

Objectives. To observe and analyze the parameters of the sacral reflex and pudendal nerve somatosensory evoked potential (SSEP) in patients with multiple system atrophy (MSA) with respect to factors such as age, disease course, and subtype and provide evidence for the clinical diagnosis of MSA. Materials and Methods. A total of 51 MSA patients and 30 healthy controls were selected from the First Affiliated Hospital of Wenzhou Medical University from May 2013 to November 2015. Electrophysiological sacral reflex detection and SSEP detection were performed using the Keypoint EMG/EP system. The extraction rate, latency, and amplitude of the sacral reflex and SSEP in the MSA group and control group were compared. Results. The sacral reflex latency and amplitude in patients with MSA were statistically different from those of the healthy controls. The latency of sacral reflex increases with the prolongation of the disease course, and the amplitude and initiation rate decrease with the prolongation of the disease course. There was no significant difference in sacral reflex latency and amplitude between MSA patients of different ages and subtypes. There was no significant difference in the latency or amplitude of SSEP between the MSA group and healthy control group. Conclusions. The latency of sacral reflex increases with the prolongation of the disease course, and the amplitude and extraction rate decrease with the prolongation of the disease course. There was no significant difference in the parameters of sacral reflex between young MSA patients and elderly patients. And there was no statistically significant difference between MSA-P subtypes and MSA-C subtypes. This trial is registered with ISRCTNCR2009041.

Pulmonary hypertension: Alleviating the pressure A study in rats suggests that the small RNA molecule miR-125a-5p is a promising therapeutic target for treating pulmonary arterial hypertension (PAH). This type of high blood pressure is due to the narrowing of arteries that carry blood from the heart to the lungs and at present has no cure. Jieyan Shen at Shanghai Jiao Tong University, China, and colleagues found that PAH lowers the levels of miR-125a-5p in rat pulmonary arteries and that administration of miR-125a-5p as an early preventative treatment reduced disease progression. miR-125a-5p slowed the proliferation of pulmonary artery smooth muscle cells and triggered cell death by directly interacting with a gene expression regulator and reducing the production of certain pro-inflammatory signaling molecules. Targeting miR-125a-5p’s mechanism of action could represent a new treatment approach for this chronic, life-changing disease.

Correlation filter (CF) based trackers have gained significant attention in the field of visual single-object tracking, owing to their favorable performance and high efficiency; however, existing trackers still suffer from model drift caused by boundary effects and filter degradation. In visual tracking, long-term occlusion and large appearance variations easily cause model degradation. To remedy these drawbacks, we propose a sparse adaptive spatial-temporal context-aware method that effectively avoids model drift. Specifically, a global context is explicitly incorporated into the correlation filter to mitigate boundary effects. Subsequently, an adaptive temporal regularization constraint is adopted in the filter training stage to avoid model degradation. Meanwhile, a sparse response constraint is introduced to reduce the risk of further model drift. Furthermore, we apply the alternating direction multiplier method (ADMM) to derive a closed-solution of the object function with a low computational cost. In addition, an updating scheme based on the APCE-pool and Peak-pool is proposed to reveal the tracking condition and ensure updates of the target’s appearance model with high-confidence. The Kalam filter is adopted to track the target when the appearance model is persistently unreliable and abnormality occurs. Finally, extensive experimental results on OTB-2013, OTB-2015 and VOT2018 datasets show that our proposed tracker performs favorably against several state-of-the-art trackers.

A simple, rapid, and reliable method based on dispersive solid-phase extraction (d-SPE) and gas chromatography-mass spectrometry (GC-MS) was developed for quantitating polychlorinated biphenyls (PCBs) in vegetable samples. Parameters affecting both the extraction yields and cleanup efficiency, including the type and volume of extraction solvent, extraction time, type and volume of cleanup sorbent, and cleanup time, were optimized. Matrix effects were evaluated, and matrix-matched calibration was recommended. Under the optimized conditions, carboxylated multiwalled carbon nanotubes (MWCNTs-COOH), which exhibit excellent adsorption capabilities due to large surface area and unique structure, were employed as d-SPE sorbent to remove interfering substances, rather than the analytes, from vegetable samples. Satisfactory linear relationship was observed for all PCBs across a concentration range of 5–500 μg/kg with correlation coefficients no less than 0.9993. Four representative vegetables (cucumber, tomato, lettuce, and cabbage) were selected as matrices for method validation. Each matrix was spiked at concentrations of 5, 10, and 100 μg/kg to evaluate recoveries, which ranged from 84.5% to 116.5% with relative standard deviations (n=6) between 0.6% and 17.6%. The limits of detection and the limits of quantification ranged from 0.3 to 1.4 μg/kg and 0.8 to 4.5 μg/kg, respectively. Twelve real vegetable samples were analyzed using the proposed method. Three of the target PCBs were detected in one lettuce sample with the total concentration of 17.9 μg/kg.

Background. Pulmonary hypertension due to left ventricular heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly medical problem. The aim of the study was to evaluate the clinical efficacy of fasudil on PH-HFpEF elderly patients and to figure out the subtype of PH-HFpEF which may be the therapeutic object of fasudil. Method. 58 PH-HFpEF elderly patients were enrolled. Patients were diagnosed with passive pulmonary hypertension (PPH) or reactive pulmonary hypertension (RPH) by right heart catheterization and all receiving Rho kinase inhibitor fasudil for 2 weeks. The endpoint includes changes in SpO2, NT-pro BNP, cardiac functional classification, and echocardiography measurements after 2 weeks treatment. Results. The course of disease in the RPH group was longer than the PPH group (p

Objective. To investigate the prevalence and prognosis of portopulmonary hypertension (PoPH) in liver transplant recipients. Methods. Patients with advanced liver disease who underwent orthotopic liver transplantation (OLT) were included in this retrospective study from January 2012 to June 2015. According to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis of pulmonary hypertension (PH), patients with tricuspid regurgitation velocity (TRV) >3.4 m/s or 2.9 m/s ≤ TRV ≤ 3.4 m/s coexisting with other echocardiographic PH signs were judged as PH. PH patients with portal hypertension and without other known causes of PH were diagnosed as PoPH. Results. A total of 223 (170 males and 53 females) middle-aged (50.9 ± 9 years old) liver transplant recipients were included in this study. Fourteen patients (6.3%) were diagnosed with PoPH, and none of the patients were treated with vasodilators before or after OLT. After OLT, patients were followed up for 26 ± 13.5 months. In total, 8 of 14 (57%) PoPH patients died, and the main cause of death was pulmonary infection. Kaplan–Meier survival curves revealed a significant difference in survival between PoPH and non-PoPH patients (p

To obtain an accurate uniform hazard spectrum (UHS), this paper proposes combining a stochastic simulation with probabilistic seismic hazard analysis. The stochastic method fully accounts for the effect of the source mechanism, path, and site effect. Historical ground motions in the site specific to the nuclear power plant (NPP) are simulated, and a UHS with an equal exceeding probability is proposed. To compare the seismic performance of the NPP under different ground motions generated by the existing site spectrum (SL-2), the UHS generated by the safety evaluation report, and the US RG1.60 spectrum, respectively, a three-dimensional finite element model is established, and dynamic analysis is performed. Results show that the structural responses to different spectra varied; the UHS response was slightly larger than that of RG1.60. This finding is relatively more reasonable than prior research results. The UHS generated using the stochastic simulation method can provide a reference for the seismic design of NPPs.

DNA demethylation catalysed by the ten-eleven translocation (TET) protein is an important step during extensive global epigenetic reprogramming in mammals. However, whether TET proteins play a key role in DNA demethylation during the development of bovine pre-implanted embryos is still unclear. In this study, we utilized dimethyloxallyl glycine (DMOG), a small-molecule inhibitor of the TET protein, to impede the enzymatic activity of TET and explore subsequent effects on bovine parthenogenetic embryo development. We first detected the expression of the TET family, consisting of TET1, TET2 and TET3, in bovine MII stage oocytes and found that TET3 is more highly expressed than TET1 and TET2. Treatment with 1 mM DMOG increased 5mC levels (30.4% vs 79.8% at the 8-cell stage for satellite I, 25.3% vs 40.6% at the 8-cell stage for α-satellite, 20.5% vs 73.5% at the blastocyst stage for satellite I and 16.6% vs 30.0% at the blastocyst stage for α-satellite) at every bovine parthenogenetic embryo developmental stage. At the same time, DNA methylation level of satellite DNA and pluripotency gene promoters increased significantly. Real-time PCR analysis results indicated that the transcription levels of NANOG and OCT-4 decreased in the DMOG-treated group. Furthermore, TET inhibition negatively affected blastocyst formation, resulting in a decline in the blastocyst rate (17.1 ± 1.3% vs 24.1 ± 0.6%); however, the percentage of apoptotic cells was significantly increased according to the results of a TUNEL assay. Additionally, expression levels of the apoptosis-related gene BAX were up-regulated, while the expression of BCL-2 was down-regulated. In conclusion, these results support that TET plays important roles in bovine parthenogenetic embryo development by influencing DNA methylation reprogramming, gene expression and apoptosis.

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including "immune response" as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.

The principal extracellular lesions of age-related maculopathy (ARM), the leading cause of vision loss in the elderly, involve Bruch's membrane (BrM), a thin vascular intima between the retinal pigment epithelium (RPE) and its blood supply. With age, 80–100 nm solid particles containing esterified cholesterol (EC) accumulate in normal BrM, and apolipoprotein B (apoB) immunoreactivity is detectable in BrM- and ARM-associated lesions. Yet little evidence indicates that increased plasma cholesterol is a risk factor for ARM. To determine if RPE is capable of assembling its own apoB-containing lipoprotein, we examined RPE for the expression of microsomal triglyceride transfer protein (MTP), which is required for this process. Consistent with previous evidence for apoB expression, MTP is expressed in RPE, the ARPE-19 cell line, and, unexpectedly, retinal ganglion cells, which are neurons of the central nervous system. De novo synthesis and secretion of neutral lipid by ARPE-19 was supported by high levels of radiolabeled EC and triglyceride in medium after supplementation with oleate. Lipoprotein assembly and secretion is implicated as a constitutive retinal function and a plausible candidate mechanism involved in forming extracellular cholesterol-containing lesions in ARM.The pigmentary retinopathy and neuropathy of abetalipoproteinemia (Mendelian Inheritance of Man 200100; Bassen-Kornzwieg disease), which is caused by mutations in the MTP gene, may involve loss of function at the retina.

A facile access to polysubstituted 3-(isoxazol-5-yl)pyrroles was developed through [3+2] cycloaddition of tosylmethyl isocyanide (TosMIC) and styrylisoxazoles. In the presence of KOH, various styrylisoxazoles reacted smoothly with tosylmethyl isocyanide and analogs to deliver a wide range of 3-(isoxazol-5-yl)pyrroles at ambient temperature. This transformation is operationally simple, high-yielding, and displays broad substrate scope.

Lignocellulosic biomass is an abundant renewable resource that has the potential to displace petroleum in the production of biomaterials and biofuels. In the present study, the fractionation of different lignin biopolymers from hybrid poplar based on organosolv pretreatments using 80% aqueous methanol, ethanol, 1-propanol, and 1-butanol at 220°C for 30 min was investigated. The isolated lignin fractions were characterized by Fourier transform infrared spectroscopy (FT-IR), high-performance anion exchange chromatography (HPAEC), 2D nuclear magnetic resonance (2D NMR), and thermogravimetric analysis (TGA). The results showed that the lignin fraction obtained with aqueous ethanol (EOL) possessed the highest yield and the strongest thermal stability compared with other lignin fractions. In addition, other lignin fractions were almost absent of neutral sugars (1.16–1.46%) though lignin preparation extracted with 1-butanol (BOL) was incongruent (7.53%). 2D HSQC spectra analysis revealed that the four lignin fractions mainly consisted of β-O-4′ linkages combined with small amounts of β-β′ and β-5′ linkages. Furthermore, substitution of Cα in β-O-4′ substructures had occurred due to the effects of dissolvent during the autocatalyzed alcohol organosolv pretreatments. Therefore, aqueous ethanol was found to be the most promising alcoholic organic solvent compared with other alcohols to be used in noncatalyzed processes for the pretreatment of lignocellulosic biomass in biorefinery.

Resolvin D1 (RvD1) is a lipid-derived mediator generated during the resolution inflammation. While the immunoresolvent effects of Resolvins have been extensively studied in leukocytes, actions of Resolvins on intrinsic kidney cells have received little attention. The podocyte plays a central role in glomerular function, and podocyte damage can lead to proteinuria and glomerulosclerosis. This study examined whether RvD1 has renoprotective effects upon podocytes. We investigated a mouse model of adriamycin (ADR) nephropathy featuring rapid induction of podocyte damage and proteinuria followed by glomerulosclerosis. We identified a progressive loss of synaptopodin expression over a 28 day time-course of ADR nephropathy which was associated with increased acetylation of 14-3-3β and reduced synaptopodin phosphorylation. Groups of mice were given once daily RvD1 treatment (4 ng/g body weight/day) starting either 30 min (early treatment) or 14 days (late treatment) after ADR injection and continued until mice were killed on day 28. Early, but not late, RvD1 treatment attenuated ADR-induced proteinuria, glomerulosclerosis and tubulointerstitial fibrosis, modified macrophages from an M1 to M2 phenotype. Early RvD1 treatment prevented the down-regulation of synaptopodin expression and changes in 14-3-3β acetylation and synaptopodin phosphorylation. In a podocyte cell line, RvD1 was shown to prevent rapid TNF-α-induced down-regulation of synaptopodin expression. In transfection studies, TNF-α-induced a decrease in synaptopodin phosphorylation and an increase in acetylation of 14-3-3β, resulting in disassociation between 14-3-3β and synaptopodin. RvD1 prevented TNF-α induced post-translational modification of synaptopodin and 14-3-3β proteins, and maintained the synaptopodin/14-3-3β interaction. Furthermore, replacement of lysine K51, or K117+K122 in 14-3-3β with glutamine, to mimic lysine acetylation, significantly reduced the interaction between 14-3-3β and synaptopodin. In conclusion, our studies provide the first evidence that RvD1 can protect against podocyte damage by preventing down-regulation of synaptopodin through inhibition of 14-3-3β/synaptopodin dissociation. RvD1 treatment may have potential application in the treatment of chronic kidney disease.

The role of podocytes in the development and progression of glomerular disease has been extensively investigated in the past decade. However, the importance of glomerular endothelial cells in the pathogenesis of proteinuria and glomerulosclerosis has been largely ignored. Recent studies have demonstrated that endothelial nitric oxide synthatase (eNOS) deficiency exacerbates renal injury in anti-GBM and remnant kidney models and accelerates diabetic kidney damage. Increasing evidence also demonstrates the importance of the glomerular endothelium in preventing proteinuria. We hypothesize that endothelial dysfunction can initiate and promote the development and progression of glomerulopathy. Administration of adriamycin (ADR) to C57BL/6 mice, normally an ADR resistant strain, with an eNOS deficiency induced overt proteinuria, severe glomerulosclerosis, interstitial fibrosis and inflammation. We also examined glomerular endothelial cell and podocyte injury in ADR-induced nephropathy in Balb/c mice, an ADR susceptible strain, by immunostaining, TUNEL and Western blotting. Interestingly, down-regulation of eNOS and the appearance of apoptotic glomerular endothelial cells occurred as early as 24 hours after ADR injection, whilst synaptopodin, a functional podocyte marker, was reduced 7 days after ADR injection and coincided with a significant increase in the number of apoptotic podocytes. Furthermore, conditioned media from mouse microvascular endothelial cells over-expressing GFP-eNOS protected podocytes from TNF-α-induced loss of synaptopodin. In conclusion, our study demonstrated that endothelial dysfunction and damage precedes podocyte injury in ADR-induced nephropathy. Glomerular endothelial cells may protect podocytes from inflammatory insult. Understanding the role of glomerular endothelial dysfunction in the development of kidney disease will facilitate in the design of novel strategies to treat kidney disease.

Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is a rare and sporadic form of pulmonary arterial hypertension (PAH), characterized by elevated pulmonary arterial resistance leading to right heart failure. However, molecular mechanisms of PAH development are still not completely understood. Material and methods: In this study, we aimed to uncover key mRNAs and long non-coding RNA (lncRNAs), functional modules and pathways. Moreover, to detect the dysregulated pathway or biological function, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. PPI and co-expression networks were constructed to reveal the potential roles of PAH-related mRNAs and lncRNAs. Results: A total of 3,134 genes, including 945 up-regulated and 2,189 down-regulated genes, were identified to be differentially expressed in IPAH by differential expression analysis. We identified T cell differentiation and the T cell receptor signaling pathway as up-regulated in IPAH by using GO and KEGG analysis. Based on the PPI module analysis, we identified that the pro-inflammatory genes, such as OAS1, CXCL10, STAT1 and TLR4, were the hub genes in the PPI modules. To link the lncRNAs to the PPI modules, we calculated the Spearman correlation coefficient for lncRNA-DE-mRNA pairs to identify the modules with high correlation with each lncRNA. Conclusions: Notably, 6 of these lncRNAs were associated with modules characterized by the NOD-like receptor signaling pathway and chemokine signaling pathway, suggesting that these lncRNAs may promote the occurrence of IPAH via participating in the pro-inflammatory pathways. In conclusion, our systematic analysis not only improved our understanding of the molecular mechanism, but also provided potential lncRNA biomarkers for further research. [ABSTRACT FROM AUTHOR]