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To explore the lateral deformation characteristics of prefabricated vertical drains (PVD)-improved soft ground under different preloading loads and provide guidance for the design and construction of relevant structures in soft deposit regions, this study analyzed the lateral deformation characteristics of PVD-improved ground under surcharge preloading and combined vacuum and surcharge preloading using large-scale model tests. The influence of loading rate (LR), surcharge load (ps), and vacuum pressure magnitude (|pv|) on the lateral deformation of PVD-improved ground under combined preloading was systematically studied using finite element analyses. The results show that the preloading under combined vacuum and surcharge could match faster loading rates and larger surcharge loads compared to surcharge preloading alone. In the subsequent consolidation stage after reaching maximum surcharge load, there is aninsignificant increase in the outward lateral deformation of PVD-improved ground under combined preloading; in contrast, the maximum outward lateral deformation of the ground under surcharge preloading could still increase by 10%, and the lateral deformation of localization depths could increase by over 30%. The lateral deformation profile of PVD-improved ground under combined preloading overall moves outward with the increase of ps and LR, and the decrease of the |pv|; meanwhile the lateral deformation rate and the depth of the maximum outward lateral deformation (δom) increase. The outward lateral deformation of PVD-improved presents step growth patterns during the surcharge loading process, and the δom increases approximately linearly with the increase of ps, but increases nonlinearly with the increase of LR and the decrease of |pv|. With the same load change, the variation in |pv| has a more significant impact on the ground lateral deformation compared to the variation in ps. This study can provide basic information for the analysis and design of soft ground improvement under combined vacuum pressure and surcharge load.

Abstract Anesthetics are widely used in electrophysiological tests to assess retinal and visual system functions to avoid experimental errors caused by movement and stress in experimental animals. To determine the most suitable anesthetic for visual electrophysiological tests, excluding ketamine and chloral hydrate due to regulatory and side effect concerns, this study investigated the effects of ethyl carbamate (EC), avertin (AR), and pentobarbital sodium (PS) on visual signal conduction in the retina and primary visual cortex. Assessments included flash electroretinogram (FERG), pattern electroretinogram (PERG), pattern visual evoked potentials (PVEP), and flash visual evoked potentials (FVEP), FERG and FVEP were used to evaluate the responses of the retina and visual cortex to flash stimuli, respectively, while PERG and PVEP assessed responses to pattern stimuli. The research showed that AR demonstrates the least disruption to the visual signal pathway, as evidenced by consistently high characteristic peaks in the AR group across various tests. In contrast, mice given EC exhibited the lowest peak values in both FERG and FVEP, while subjects anesthetized with PS showed suppressed oscillatory potentials and PERG responses. Notably, substantial PVEP characteristic peaks were observed only in mice anesthetized with AR. Consequently, among the three anesthetics tested, AR is the most suitable for visual electrophysiological studies.

Abstract We propose an improved superpixel segmentation algorithm based on visual saliency and color entropy for online color detection in printed products. This method addresses the issues of low accuracy and slow speed in detecting color deviations in print quality control. The improved superpixel segmentation algorithm consists of three main steps: Firstly, simulating human visual perception to obtain visually salient regions of the image, thereby achieving region-based superpixel segmentation. Secondly, adaptively determining the superpixel size within the salient regions using color information entropy. Finally, the superpixel segmentation method is optimized using hue angle distance based on chromaticity, ultimately achieving a region-based adaptive superpixel segmentation algorithm. Color detection of printed products compares the color mean values of post-printing images under the same superpixel labels, outputting labels with color deviations to identify areas of color differences. The experimental results show that the improved superpixel algorithm introduces color phase distance with better segmentation accuracy, and combines it with human visual perception to better reproduce the color information of printed materials. Using the method described in this article for printing color quality inspection can reduce data computation, quickly detect and mark color difference areas, and provide the degree of color deviation.

Abstract Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome. Methods In this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway. Results We observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis. Conclusions Our studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor. Graphical Abstract

To address the challenges posed by inadequate data and data utilization in multiple scenarios of fatigue loading, a Physics-informed Transfer Learning (PITL) model has been developed to predict the fatigue life of IN718 superalloy. Strain-controlled low-cycle fatigue tests were carried out at 400 °C with three distinct strain ratios, which were subsequently segmented for individual transfer learning tests. PITL models with significant engineering value were built by integrating transfer learning methodologies rooted in TrAdaBoost with a physics-based model that hinges on the principles of equivalent strain theory. The findings suggest that PITL models exhibit improved accuracy and greater robustness compared to both transfer learning and physics models.

This study seeks to understand the reality and psychological difficulties faced by university graduates in Wuhan after the COVID-19 epidemic was controlled. Methods: A total of 6,417 graduate students were surveyed through an online questionnaire from late May to early June 2020. The questionnaire asked questions on depression, anxiety, insomnia, and suicidal behavior. In addition, self-administered epidemic-related questionnaires consisting of eight items were collected from university graduates. Results: Participants' positive detection rates for depression, anxiety, insomnia, and suicidal behavior are 13.4%, 8.3%, 4.4%, and 12.1%, respectively. The three biggest challenges faced by graduates are future development, economic difficulties, and employment problems. Conclusion: The detectable rate of depression, anxiety, and insomnia is low, and the detectable rate of suicide symptoms should be given more attention. The biggest problem of this group is their future development, and what they want to solve the most is the economic difficulty.

Objectives: This study aimed to establish standard transesophageal echocardiographic (TEE) measurements of left ventricular (LV) morphology, function, and myocardial work parameters in healthy Beagle dogs using pressure-strain loops (PSL). Additionally, it sought to standardize optimal TEE imaging techniques and explore the potiential application of myocardial work analyis in veterinary medicine. Methods: Thirty-seven healthy male Beagle dogs were anesthetized, intubated, and mechanically ventilated for TEE examinations. LV systolic and diastolic function were evaluated, with simultaneous invasive femoral artery pressure measurements. Left ventricular global longitudinal strain (GLS), myocardial work parameters, PSL-derived metrics were analyzed. Results: The mean LV GLS was −16.0 ± 4.0 %, and the LV global myocardial work index (GWI) was 888 ± 298.6 mmHg∗%. Global Myocardial work efficiency (GWE) was 88 ± 3 %, while global myocardial wasted work (GWW) was 152 mmHg∗% (38–431 mmHg∗%). LV ejection fraction (LVEF) averaged 58.7 ± 4.4 %. Left ventricular end-diastolic (LVEDV) and end-systolic volume (LVESV) were 19.3 ± 5.2 ml and 8.0 ± 2.3 ml, respectively. Regional myocardial work analysis revealed significant differences between the interventricular septum and lateral wall. The lateral wall demonstrated reduced segmental work efficiency (SWE), work index (SWI), and constructive work (SCW) but higher wasted work (SWW) compared to the septum (p

Background: Depression commonly co-occurs with inflammatory bowel disease (IBD). Abnormal glutamate levels in the insula and altered plasma inflammatory biomarkers are observed in IBD and depression. However, the changes in glutamate concentrations in insular subregions in IBD and their relationship with depression and inflammatory markers remain unclear. This study aimed to investigate differences in glutamate concentrations in insular subregions between IBD patients and healthy controls (HCs) and their correlation with depression scores and inflammatory markers. Methods: Forty-two IBD patients (19 active, IBD-A; 23 in remission, IBD-R) and 46 HCs underwent glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging. Blood samples from 37 IBD patients were collected for plasma inflammatory biomarker analysis. GluCEST indices in insular subregions were measured. The Hospital Anxiety and Depression Scale (HADS-D) was used to estimate depression symptoms. Whole-brain voxel-based analysis using one-way ANOVA explored between-group differences in GluCEST indices within the insula. FDR-corrected partial correlation analysis evaluated the relationships between GluCEST, depression symptoms, and inflammatory factors. Results: GluCEST indices decreased in IBD patients in the left dorsal dysgranular subregion of the insula (dId) (uncorrected p

IntroductionThough COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues to pose a significant threat to human society. Vaccination remains one of the most effective methods for preventing COVID-19. While most of the antigenic regions are found in the receptor binding domain (RBD), the N-terminal domain (NTD) of the S protein is another crucial region for inducing neutralizing antibodies (nAbs) against COVID-19.MethodsIn the two-dose immunization experiment, female BALB/c mice were intramuscularly immunized with different ratios of RBD-Fc and NTD-Fc proteins, with a total protein dose of 8 μg per mouse. Mice were immunized on day 0 and boosted on day 7. In the sequential immunization experiment, groups of female BALB/c mice were immunized with two doses of the inactivated SARS-CoV-2 vaccine (prototype strain) on day 0 and 7. On day 28, mice were boosted with RBD-Fc, NTD-Fc, RBD-Fc/NTD-Fc (9:1), RBD-Fc/NTD-Fc (3:1), inactivated SARS-CoV-2 vaccine (protoype strain), inactivated SARS-CoV-2 vaccine (omicron strain), individually. The IgG antibodies were detected using ELISA, while the neutralizing antibodies were measured through a microneutralization assay utilizing both the prototype and omicron strains. The ELISPOT assays were performed to measure the secretion of IL-4 and IFN-γ, and the concentrations of secreted IL-2 and IL-10 in the supernatants were measured by ELISA.ResultsWe have first developed a two-component recombinant vaccine for COVID-19 based on RBD-Fc and NTD-Fc proteins, with an optimal RBD-Fc/NTD-Fc ratio of 3:1. This novel two-component vaccine demonstrated the ability to induce durable and potent IgG antibodies, as well as the neutralizing antibodies in both the two-dose homologous and sequential vaccinations. Heterologous booster with this two-component vaccine could induce higher neutralizing antibody titers than the homologous group. Additionally, the vaccine elicited relatively balanced Th1- and Th2-cell immune responses.ConclusionThis novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development.

ABSTRACT Purpose This study aims to explore the neuroprotective effect of propofol in improving traumatic brain injury (TBI) by inhibiting ferroptosis through the modulation of the endothelial nitric oxide (NO) synthase (eNOS)/NO signaling pathway. Methods The GSE173975 dataset was used to analyze the differentially expressed genes between TBI and sham surgery control groups in the short and long term. A TBI model was established in 2‐month‐old male SPF C57BL/6 mice by impact exposure of the exposed dura mater. After the establishment of the TBI model, propofol (30 mg/kg) or saline was administered via intraperitoneal injection for intervention. Nissl staining and Perls staining were employed to assess neuronal function and iron deposition, respectively. Western blot technology was employed to detect the expression of proteins related to ferroptosis. Immunofluorescence staining of astrocytes and microglia was utilized to assess the neuroinflammatory response induced by TBI. The Morris water maze (MWM) and novel object recognition (NOR) tests were employed to assess cognitive dysfunction induced by TBI. Findings Bioinformatics analysis revealed aberrant gene expression associated with iron transport, neuronal death, and inflammatory response in the initial stages of TBI. Long‐term abnormalities were predominantly linked to genes involved in inflammatory response. Perls staining and protein expression analysis confirmed the occurrence of iron deposition and ferroptosis following TBI. Propofol treatment significantly reduced iron deposition and ferroptosis induced by TBI. Nissl staining demonstrated enhanced neuronal function, while TUNEL staining indicated reduced neuronal apoptosis. Immunofluorescence analysis demonstrated that propofol significantly reduced the proliferation of astrocytes and activation of microglia induced by TBI in the long term. The results of MWM and NOR tests indicated that propofol significantly improved the long‐term cognitive dysfunction induced by TBI. Propofol exerts neuroprotective effects by increasing the expression of eNOS protein and the content of NO. The neuroprotective effects of propofol can be reversed by the eNOS inhibitor L‐NAME. Conclusion Propofol significantly improves the prognosis of TBI by inhibiting ferroptosis through the modulation of the eNOS/NO signaling pathway. The study results provide a scientific basis for the clinical use of propofol as a neuroprotective agent and offer a new direction for the development of new treatment strategies for TBI.

BackgroundThe association between serum uric acid (UA) and all-cause and cardiovascular-related mortality in hemodialysis (HD) patients is conflicting. We investigated this association and explored the effect modification of underlying nutritional status, as reflected in the lean tissue index (LTI) and the Geriatric Nutritional Risk Index (GNRI), which serve as markers of muscle mass and nutritional risk in HD patients.MethodsA retrospective cohort study was conducted from January 2019 to December 2023. We investigated the association between serum UA and the outcomes using the Cox proportional hazards regression and restricted cubic splines. Subgroup analyses based on the LTI and GNRI were conducted to explore possible effect modification.ResultsDuring a mean follow-up of 32.9 months, 876 patients who underwent HD were included in the analysis. The association between serum UA and all-cause mortality showed a non-linear U-shaped pattern (p = 0.007), with a survival benefit observed for the patients with serum UA levels between 3.4 and 6.8 mg/dL. In the multivariable-adjusted model, the low and high UA groups were associated with a greater risk of all-cause mortality compared to the reference UA group (hazard ratio (HR) =1.24, confidence interval (CI) 1.03–2.12, p = 0.027; HR = 1.09; CI 1.05–2.08. p = 0.012). In the low UA group, a greater risk of mortality was observed in patients with low LTI (

The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366–1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.

Abstract Understanding the reinforcement effect of the newly developed prestressed reinforcement components (PRCs) (a system composed of prestressed steel bars (PSBs), protective sleeves, lateral pressure plates (LPPs), and anchoring elements) is technically significant for the rational design of prestressed subgrade. A three-dimensional finite element model was established and verified based on a novel static model test and utilized to systematically analyze the influence of prestress levels and reinforcement modes on the reinforcement effect of the subgrade. The results show that the PRCs provide additional confining pressure to the subgrade through the diffusion effect of the prestress, which can therefore effectively improve the service performance of the subgrade. Compared to the unreinforced conventional subgrades, the settlements of prestress-reinforced subgrades are reduced. The settlement attenuation rate (R s) near the LPPs is larger than that at the subgrade center, and increasing the prestress positively contributes to the stability of the subgrade structure. In the multi-row reinforcement mode, the reinforcement effect of PRCs can extend from the reinforced area to the unreinforced area. In addition, as the horizontal distance from the LPPs increases, the additional confining pressure converted by the PSBs and LPPs gradually diminishes when spreading to the core load bearing area of the subgrade, resulting in a decrease in the R s. Under the single-row reinforcement mode, PRCs can be strategically arranged according to the local areas where subgrade defects readily occurred or observed, to obtain the desired reinforcement effect. Moreover, excessive prestress should not be applied near the subgrade shoulder line to avoid the shear failure of the subgrade shoulder. PRCs can be flexibly used for preventing and treating various subgrade defects of newly constructed or existing railway lines, achieving targeted and classified prevention, and effectively improving the bearing performance and deformation resistance of the subgrade. The research results are instructive for further elucidating the prestress reinforcement effect of PRCs on railway subgrades.

Abstract Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Abstract Background Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. Methods Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. Results A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74–12.70], 2.84 [2.38–3.39], 3.02 [2.02–4.51], and 9.53 [7.79–11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42–1.53; P

Abstract Background Expanding the number of biomarkers is imperative for studying the etiology and improving venous thromboembolism prediction. In this study, we aimed to identify promising biomarkers or targeted therapies to improve the detection accuracy of early-stage deep vein thrombosis (DVT) or reduce complications. Methods Quantibody Human Cytokine Antibody Array 440 (QAH-CAA-440) was used to screen novel serum-based biomarkers for DVT/non-lower extremity DVT (NDVT). Differentially expressed proteins in DVT were analyzed using bioinformatics methods and validated using a customized array. Diagnostic accuracy was calculated using receiver operating characteristics, and machine learning was applied to establish a biomarker model for evaluating the identified targets. Twelve targets were selected for validation. Results Cytokine profiling was conducted using a QAH-CAA-440 (RayBiotech, USA) quantimeter array. Cross-tabulation analysis with Venn diagrams identified common differential factors, leading to the selection of 12 cytokines for validation based on their clinical significance. These 12 biomarkers were consistent with the results of previous array analysis: FGF-6 (AUC = 0.956), Galectin-3 (AUC = 0.942), EDA-A2 (AUC = 0.933), CHI3L1 (AUC = 0.911), IL-1 F9 (AUC = 0.898), Dkk-4 (AUC = 0.88), IG-H3 (AUC = 0.876), IGFBP (AUC = 0.858), Gas-1 (AUC = 0.858), Layilin (AUC = 0.849), ULBP-2 (AUC = 0.813)and FGF-9 (AUC = 0.773). These cytokines are expected to serve as biomarkers, targets, or therapeutic targets to differentiate DVT from NDVT. Conclusions EDA-A2, FGF-6, Dkk-4, IL-1 F9, Galentin-3, Layilin, Big-h3, CHI3L1, ULBP-2, Gas-1, IGFBP-5, and FGF-9 are promising targets for DVT diagnosis and treatment.