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Abstract Background Bisphenol A (BPA) is a common environmental pollutant, and its specific mechanisms in cancer development and its impact on the tumor immune microenvironment are not yet fully understood. Methods Transcriptome data from osteosarcoma (OS) patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. BPA-related genes were identified through the Comparative Toxicogenomics Database (CTD), yielding 177 genes. Differentially expressed genes were analyzed using the GSE162454 dataset from the Tumor Immune Single Cell Hub 2 (TISCH2). We constructed the prognostic model using univariate Cox regression and LASSO analysis. The model was validated using the GSE16091 dataset. GO, KEGG, and GSEA analyses were performed to investigate the mechanisms of BPA-related genes. Results A total of 15 BPA-related genes were identified as differentially expressed in OS. Univariate Cox regression and LASSO analysis identified four key prognostic genes (FOLR1, MYC, ESRRA, VEGFA). The prognostic model exhibited strong predictive performance with area under the curve (AUC) values of 0.89, 0.6, and 0.79 for predicting 1-, 2-, and 3-year survival, respectively. External validation using the GSE16091 dataset confirmed the model's high accuracy with AUC values exceeding 0.88. Our results indicated that the prognosis of the high-risk population is generally poorer, which may be associated with alterations in the tumor immune microenvironment. In the high-risk group, immune cells showed predominantly low expression levels, while immune checkpoint genes were significantly overexpressed, along with markedly elevated tumor purity. These findings revealed a correlation between upregulation of BPA-related genes and formation of an immunosuppressive microenvironment, leading to unfavorable patient outcomes. Conclusion Our study highlighted the significant association of BPA with OS biology, particularly in its potential role in modulating the tumor immune microenvironment. We offered a fresh insight into the influence of BPA on cancer development, thus providing valuable insights for future clinical interventions and treatment strategies.

Abstract Hepatic ischemia‐reperfusion injury (HIRI) is a prevalent issue during liver resection and transplantation, with currently no cure or FDA‐approved therapy. A promising drug, Cyclosporin A (CsA), ameliorates HIRI by maintaining mitochondrial homeostasis but has systemic side effects due to its low bioavailability and high dosage requirements. This study introduces a biomimetic CsA delivery system that directly targets hepatic lesions using mesenchymal stem cell (MSC) membrane‐camouflaged liposomes. These hybrid nanovesicles (NVs), leveraging MSC‐derived proteins, demonstrate efficient inflammatory chemotaxis, transendothelial migration, and drug‐loading capacity. In a HIRI mouse model, the biomimetic NVs accumulated at liver injury sites entered hepatocytes, and significantly reduced liver damage and restore function using only one‐tenth of the CsA dose typically required. Proteomic analysis verifies the protection mechanism, which includes reactive oxygen species inhibition, preservation of mitochondrial integrity, and reduced cellular apoptosis, suggesting potential for this biomimetic strategy in HIRI intervention.

Background: Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition of increasing prevalence, is closely related to various metabolic disorders. Hemoglobin, a protein that transports oxygen in red blood cells, is the focus of this study, which seeks to investigate its potential association with NAFLD. Methods: We selected 6,516 eligible adult participants from the United States using the 2017–2020 National Health and Nutrition Examination Survey database for cross-sectional analyses. We analyzed the association of hemoglobin with NAFLD using weighted logistic regression models. Results: The study performed a weighted logistic regression modeling analysis, which verified that hemoglobin levels were positively associated with NAFLD, especially in the higher hemoglobin quartile groups. Subgroup analyses revealed no significant interactions, demonstrating the robustness of the model. The analysis of mediation effects showed that Gamma-Glutamyl Transferase, Alanine Aminotransferase, and triglycerides were important mediating variables in the relationship between hemoglobin and NAFLD. Conclusion: Increased hemoglobin levels were found to be significantly and independently associated with an increased NAFLD risk. This insight is crucial for the risk assessment and early detection of NAFLD, underscoring the need for heightened vigilance in individuals with higher hemoglobin levels.

Fat is one of the three macronutrients and a significant energy source for piglets. It plays a positive role in maintaining intestinal health and improving production performance. During the weaning period, physiological, stress and diet-related factors influence the absorption of fat in piglets, leading to damage to the intestinal barrier, diarrhea and even death. Signaling pathways, such as fatty acid translocase (CD36), pregnane X receptor (PXR), and AMP-dependent protein kinase (AMPK), are responsible for regulating intestinal fat uptake and maintaining intestinal barrier function. Therefore, this review mainly elaborates on the reasons for diarrhea induced by insufficient fat absorption and related signaling pathways in weaned-piglets, with an emphasis on the intestinal fat absorption disorder. Moreover, we focus on introducing nutritional strategies that can promote intestinal fat absorption in piglets with insufficient fat absorption-related diarrhea, such as lipase, amino acids, and probiotics.

As the interface between frozen and unfrozen soil, the ice front is not only a spatial location concept, but also a potentially dangerous interface where the mechanical properties of soil could change abruptly. Accurately identifying its spatial position is essential for the safe and efficient execution of large-scale frozen soil engineering projects. Electrical capacitance tomography (ECT) is a promising method for the visualization of frozen soil due to its non-invasive nature, low cast, and rapid response. This paper presents the design and optimization of a mobile circular capacitance sensor (MCCS). The MCCS was used to measure frozen soil samples along the depth direction to obtain moisture distribution and three-dimensional images of the ice front. Finally, the experimental results were compared with the simulation results from COMSOL Multiphysics to analyze the deviations. It was found that the fuzzy optimization design based on multi-criteria orthogonal experiments makes the MCCS meet various performance requirements. The average permittivity distribution was proposed to reflect moisture distribution along the depth direction and showed good correlation. Three-dimensional reconstructed images could provide the precise position of the ice front. The simulation results indicate that the MCCS has a low deviation margin in identifying the position of the ice front.

With the rapid development of the e-commerce industry, enterprises need to effectively manage and analyze various operational data to support decision making and optimize business processes. Sensor technology is widely used in e-commerce environment, which can collect a lot of voice data and extract valuable information through data mining technology. The study presents the current background and trends of the e-commerce industry, with a focus on the importance and challenges of operational data analytics. A sensor-based voice data mining framework is proposed. Sensors are first used to collect voice data and turn it into a digital signal that can be used for analysis. Then the data mining algorithm is used to process and analyze the voice data, and a series of results about e-commerce operation are obtained. Analyze voice data to help companies develop effective marketing strategies, improve product quality, and optimize supply chain management. This study proves the role of sensor-based voice data mining in e-commerce operational data analysis. By harnessing the full potential of voice data, businesses can better understand and meet customer needs, improve competitiveness and performance. This research result has practical significance for the development of e-commerce industry, and provides guidance and reference for the research and practice in related fields.

ObjectiveThis study aimed to develop and validate a new nomogram model that can predict new vertebral fractures after surgery for osteoporotic compression fractures to optimize surgical plans and reduce the incidence of new vertebral compression fractures.Methods420 patients with osteoporotic vertebral compression fractures were randomly sampled using a computer at a fixed ratio; 80% of the patients were assigned to the training set, while the remaining 20% were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression method was applied to screen the factors influencing refracture and construct a predictive model using multivariate logistic regression analysis.ResultsThe results of the multivariate logistic regression analysis showed a significant correlation between bone cement leakage, poor cement dispersion, the presence of fractures in the endplate, and refractures. The receiver operating characteristic curve (ROC) results showed that the area under the ROC curve (AUC) of the training set was 0.974 and the AUC of the validation set was 0.965, which proves that this prediction model has a good predictive ability. The brier score for the training set and validation set are 0.043 and 0.070, respectively, indicating that the model has high accuracy. Moreover, the calibration curve showed a good fit with minimal deviation, demonstrating the model’s high discriminant ability and excellent fit. The decision curve indicated that the nomogram had positive predictive ability, indicating its potential as a practical clinical tool.ConclusionCement leakage, poor cement dispersion, and presence of fractures in the endplate are selected through LASSO and multivariate logistic regressions and included in the model development to establish a nomogram. This simple prediction model can support medical decision-making and maybe feasible for clinical practice.

Abstract Background Breast cancer (BC) patients tend to suffer from distant metastasis, especially bone metastasis. Methods All the analysis based on open-accessed data was performed in R software, dependent on multiple algorithms and packages. The RNA levels of specific genes were detected using quantitative Real-time PCR as a method of detecting the RNA levels. To assess the ability of BC cells to proliferate, we utilized the CCK8 test, colony formation, and the 5-Ethynyl-20-deoxyuridine assay. BC cells were evaluated for invasion and migration by using Transwell assays and wound healing assays. Results In our study, we identified the molecules involved in BC bone metastasis based on the data from multiple BC cohorts. Then, we comprehensively investigated the effect pattern and underlying biological role of these molecules. We found that in the identified molecules, the EMP1, ACKR3, ITGA10, MMP13, COL11A1, and THY1 were significantly correlated with patient prognosis and mainly expressed in CAFs. Therefore, we explored the CAFs in the BC microenvironment. Results showed that CAFs could activate multiple carcinogenic pathways and most of these pathways play an important role in cancer metastasis. Meanwhile, we noticed the interaction between CAFs and malignant, endothelial, and M2 macrophage cells. Moreover, we found that CAFs could induce the remodeling of the BC microenvironment and promote the malignant behavior of BC cells. Then, we identified MMP13 for further analysis. It was found that MMP13 can enhance the malignant phenotype of BC cells. Meanwhile, biological enrichment and immune infiltration analysis were conducted to present the effect pattern of MMP13 in BC. Conclusions Our result can improve the understanding of researchers on the underlying mechanisms of BC bone metastasis.

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H2O2)-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets.

Abstract Background Early diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF). Methods We recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing

This study aimed to assess the effects of substituting zinc oxide with terminalia chebula extract (TCE) on growth performance, antioxidant capacity, immune function, and intestinal health in weaned pigs. Initially, 72 weaned Duroc × Landrace × Large White piglets, 28 days old with an initial weight of 7.43 ± 0.14 kg, equally divided by gender, were randomly assigned into three groups, with six replicates and four piglets per replicate. They were fed a basal diet (CON group), a diet containing 2 g/kg zinc oxide (ZnO group), or 2 g/kg TCE (TCE group) for a duration of 28 days. Subsequently, to further confirm the most appropriate levels of TCE in piglets, 96 piglets of the same breeds and age, with an initial weight of 7.42 ± 0.12 kg, also equally divided by gender, were randomly assigned into four groups, each with six replicates and four piglets per replicate, and fed a basal diet (CON group), or diets supplemented with 1 g/kg TCE (LTCE group), 2 g/kg TCE (MTCE group), or 4 g/kg TCE (HTCE group) for a duration of 28 days. The results demonstrated that both TCE and ZnO reduced diarrhea rates (p = 0.001) and enhanced average daily gain (ADG) (p = 0.014) compared to the control group. TCE at 1 g/kg and 4 g/kg reduced the feed to gain ratio (p = 0.050). Dietary supplementing with TCE and ZnO increased serum total antioxidant capacity (T-AOC) (p = 0.020). Various doses of TCE also increased jejunal IgA (p = 0.000) levels and IL-10 expression (p = 0.004), and decreased the levels of TNF-α in both serum (p = 0.043) and jejunal mucosa (p = 0.000). Notably, TCE reduced the crypt depth (CD) of the duodenal (p = 0.007) and increased the villus height (VH) of the ileal (p = 0.045), and with increased dosage, there was a rise in the villus height to crypt depth ratio (VH:CD) in the duodenum (p = 0.000) and jejunum (p = 0.001). Higher abundances of Lactobacillaceae (p = 0.000) and lower levels of Streptococcaceae (p = 0.000) and Peptostreptococcaceae (p = 0.035) in cecal contents were fed the ZnO and TCE pigs compared with CON pigs. Therefore, TCE was firstly presented as being able to replace zinc oxide, improve intestinal morphology, and enhance antioxidant and immune functions, thus safeguarding intestinal mucosal health and promoting piglet growth.

Abstract Background Early weaning and shorter breastfeeding duration are applied by a proportion of young mothers, especially in the social spheres of poverty-stricken areas. Early childhood is a critical period for intestinal development, which is driven by intestinal stem cells (ISCs). However, how early weaning practice affects the function of ISCs to mediate intestinal development remains unclear. Methods We established an excellent early weaning mice model that has significant intestinal atrophy and growth arrest symptoms to explore the responses of ISCs to early weaning. The primary and passaged intestinal organoids from the suckling or early weaning mice were cultured to explore the underlying mechanism of early weaning affecting the ISCs. Results Early weaning depressed the self-renewal of ISCs and attenuated the activity of ISCs-driven intestinal epithelial regeneration and crypt expansion in vivo and ex-vivo. Further results showed that early weaning retarded the differentiation of ISCs into transit-amplifying cells and Paneth cells, and accelerated the apoptosis of villous epithelial cells, jointly leading to intestinal epithelial atrophy. Mechanistically, early weaning inhibited Wnt signaling in ISCs, while an exogenous Wnt amplifier restored ISCs’ function in ex-vivo. Conclusion Our findings indicate that early weaning depresses the activity of ISCs via attenuating Wnt/β-catenin signaling and triggers the proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-17 in jejunum, thereby impeding ISCs-driven epithelial regeneration and intestinal growth, which may provide a basal theory for the development of infant nutrients targeting stem cells to alleviate early weaning-induced intestinal problems.

Biodiesel stands at the forefront as a replacement for fossil diesel in compression ignition engines, particularly in the transportation sector where diesel engines are the primary movers. However, biodiesel production is hampered by poor heat and mass transfer during the transesterification reaction, leading to long production times and high costs due to inefficient energy utilisation. This study targets heat and mass transfer issues during the production of biodiesel via a synergic approach that combines microwave-assisted heating and microfluidics via a polyethylene terephthalate glycol (PETG) microchannel reactor. The transesterification reaction of palm oil and methanol was investigated using a full factorial design of experiments (DOE) method. Biodiesel yield was quantified via gas chromatographic analysis, and the results were optimised using statistical analysis. Optical analysis of slug quantification within the microchannel revealed that small slugs, smaller than 1 mm, accelerated the transesterification reaction. The composite-optimised experimental results, aimed at minimising energy costs and environmental impacts while maximising fatty acid methyl ester (FAME) yield, indicate a reaction temperature of 50 °C, a catalyst loading of 1.0 wt.%, and a 3:1 methanol to oil molar ratio. Regression analysis revealed that the reaction temperature was statistically insignificant when utilising the PETG microchannel reactor. This key finding positively impacts biodiesel production as it relates to significantly reduced energy intensity, costs, and emissions. Overall, this research work paves a pathway toward an energy-efficient and sub-minute rapid transesterification reaction, highlighting the effectiveness of microwave heat delivery and effects of microfluidics via the PETG microchannel reactor in overcoming heat and mass transfer barriers in biodiesel production.

The depletion of fossil fuels, harmful emissions from their combustion, and the 2022 global energy shock due to geopolitical instabilities have led to the surge in renewable energy development. Within the context of the transportation sector, biodiesel is a sustainable and green source of liquid biofuel that can replace petroleum diesel and simultaneously be part of a solution to the aforementioned global problems. Conventional biodiesel production suffers from poor mass transfer, which leads to slow reaction kinetics, lengthy reaction time and inefficient heating of reaction. This study aims to enhance the mass transfer of biodiesel production through microwave heating in combination with a mesochannel reactor, fabricated using polyethylene terephthalate glycol (PETG). A full factorial experimental study was investigated using palm oil with sodium hydroxide as catalyst, incorporating test parameters of methanol to oil molar ratio (3:1, 6:1, 9:1), catalyst loading (0.6, 0.8, 1.0 wt%) and reaction temperature (50, 60, 70 °C). Biodiesel samples were characterised using gas chromatography to quantify the biodiesel yield. The highest biodiesel yield of 78.0 % was achieved in under 1 minute at a methanol to oil molar ratio, reaction temperature and catalyst loading of 3:1, 70 °C and 1.0 wt%, respectively. It is postulated that greater yield could be achieved by lengthening the reactor channels. Overall, the use of PETG mesochannel reactor in combination with microwave-assisted heating has the prospect of facilitating rapid biodiesel production with enhanced mass transfer between reactants.

Biodiesel is an important renewable fuel derived from bioresources that can help to mitigate climate change by significantly reducing carbon emissions from the transportation sector. The conventional batch reactor transesterification process to produce biodiesel is inefficient due to long production time and high energy consumption. In this study, transesterification of palm oil for biodiesel production is conducted using the combined technologies of tubular reactor and microwave-assisted heating method. Parameters investigated include the effects of microwave power, methanol to oil molar ratio, KOH catalyst concentration, and tube length, on FAME yield. Fatty acid methyl ester (FAME) yield of 96.5 % meeting the EN 14214 standard were obtained within the conditions where methanol to oil molar ratio was 8.5-10.0 and microwave power was.320 to 350 W. It was observed that FAME yield reduces when excess microwave power is provided to the reaction due to overheating of organic molecules and boiling of methanol. An average increase of around 10 % in FAME yield was found when the KOH catalyst concentration increases from 0.8 to 1.2 wt%. The results of this study provide insights into the optimisation of transesterification process for producing biodiesel using the combined microwave-assisted heating in tubular reactor method.

ObjectiveSepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis.MethodsDatasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN).ResultsAnalysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level.ConclusionCYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

Abstract Background Guide extension catheters (GEC) are widely applied to cope with insufficient backup support in complex percutaneous coronary intervention (PCI). In the study, we aim to evaluate the feasibility and safety with a novel 5-4F tapered GEC used in complex lesion. Methods The single-center retrospective study enrolled a total of 615 patients, in whom the 5F or 5-4F Expressman GEC was used to facilitate PCI procedure. Demographic and procedural data were collected. Results 5F GEC was used in 295 patients and 5-4F tapered GEC in 320 patients. The average age was 63.6 ± 11.0 years and 81.6% of the patients were male. Severe calcification and chronic total occlusion (CTO) were the commonest indication for the GEC use. The 5-4F tapered GEC was frequently used in active greeting technique (AGT) during CTO intervention procedure than 5F GEC (6.1% vs. 13.1%, p

The depletion of fossil fuels, along with the environmental damages brought by their usage, calls for the development of a clean, sustainable and renewable source of energy. Biofuel, predominantly liquid biofuel such as biodiesel, is a promising alternative to fossil fuels, due to its compatible direct usage within the context of compression ignition engines. However, the industrial production of biodiesel is far from being energy and time efficient, which contributes to its high production cost. These inefficiencies are attributed to poor heat and mass transfer of the transesterification reaction. The utilisation of microchannel reactors is found to be excellent in escalating heat and mass transfer of the reactants, benefitting from their high surface area-to-volume ratio. The microchannel also intensifies the mixing of reactants via the reactor design, micromixers and the slug flow patterns within the reactor, thus enhancing the contact between reactants. Simulation studies have aided in the identification of mixing regimes within the microchannel reactors, induced by various reactor designs. In addition, microwave irradiation heating is found to enhance biodiesel production by localised superheating delivered directly to the reactants at a molecular level. This enables the reaction to begin much earlier, resulting in rapid biodiesel production. It is postulated that the synergy between microchannel reactors and microwave heating would catapult a pathway towards rapid and energy-efficient biodiesel production by enhancing heat and mass transfer between reactants.

The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased (p < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased (p < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased (p < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased (p < 0.05) Gln concentrations in both the jejunum and ileum, along with β-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased (p < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon-β in the duodenum. In addition, Gln supplementation led to an increase (p < 0.05) in the number of Lactobacillus genus in the colon, but a decrease (p < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced (p < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as MX1, OAS1, IFIT1, IFIT2, IFIT3, and IFIT5 in both the jejunum and ileum, and the numbers of Clostridium coccoides, Enterococcus genus, and Enterobacterium family in the colon. Moreover, Gln supplementation enhanced (p < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.

Background. The pathogenesis of ankylosing spondylitis (AS) is still not clear, and immune-related genes have not been systematically explored in AS. The purpose of this paper was to identify the potential early biomarkers most related to immunity in AS and develop a predictive disease risk model with bioinformatic methods and the Gene Expression Omnibus database (GEO) to improve diagnostic and therapeutic efficiency. Methods. To identify differentially expressed genes and create a gene coexpression network between AS and healthy samples, we downloaded the AS-related datasets GSE25101 and GSE73754 from the GEO database and employed weighted gene coexpression network analysis (WGCNA). We used the GSVA, GSEABase, limma, ggpubr, and reshape2 packages to score immune data and investigated the links between immune cells and immunological functions by using single-sample gene set enrichment analysis (ssGSEA). The value of the core gene set and constructed model for early AS diagnosis was investigated by using receiver operating characteristic (ROC) curve analysis. Results. Biological function and immune score analyses identified central genes related to immunity, key immune cells, key related pathways, gene modules, and the coexpression network in AS. Granulysin (GNLY), Granulysin (GZMK), CX3CR1, IL2RB, dysferlin (DYSF), and S100A12 may participate in AS development through NK cells, CD8+ T cells, Th1 cells, and other immune cells and represent potential biomarkers for the early diagnosis of AS occurrence and progression. Furthermore, the T cell coinhibitory pathway may be involved in AS pathogenesis. Conclusion. The AS disease risk model constructed based on immune-related genes can guide clinical diagnosis and treatment and may help in the development of personalized immunotherapy.

Objective. To explore the influence and potential factors of the bone cement dispersion state on residual pain after vertebral augmentation. Methods. The cases included in this retrospective cohort study were patients treated with vertebral augmentation (VA) for osteoporotic vertebral compression fractures (OVCFs) between July 2018 and June 2021. According to the type of cement diffusion distribution, the patients were divided into a sufficient diffusion group (Group A) and an insufficient diffusion group (Group B). The differences in the baseline data, visual analog scale (VAS), Oswestry disability index score (ODI), injured vertebral height (IVH), and local kyphosis angle (LKA) between the two groups were analyzed. Assessments were performed preoperatively on the 2nd day postoperation and at the last follow-up. The imaging data of injured vertebrae were accurately reconstructed by a GE AW4.7 workstation, and the differences in the vertebral body volume, bone cement volume, and bone cement volume ratio were compared between the groups. Result. After screening, 36 patients were included. (1) The postoperative VAS and ODI scores of the two groups were significantly improved compared with the preoperative scores. (2) On the 2nd day postoperation and the last follow-up, the VAS and ODI scores of Group A were significantly different from those of Group B, and Group A outperformed Group B. (3) The IVH and LKA of the two groups were improved after the operation, and no significant difference was found between the groups. (4) Significant differences were found in the bone cement volume and bone cement volume ratio between the groups, and Group A was larger than Group B. Conclusions. Sufficient bone cement diffusion can reduce residual pain after vertebral augmentation.

As the first line of defence against pathogens and endotoxins crossing the intestine-blood barrier, the intestinal epithelial barrier plays a determinant role in pigs' health and growth. 4-Phenylbutyric acid (4-PBA), an aromatic fatty acid, was reported to benefit homeostasis of endoplasmic reticulum and protein synthesis. However, whether 4-PBA affects intestinal epithelial barrier function in pigs is unknown. This study aimed to explore the effects of 4-PBA on the intestinal barrier function, using in vitro models of well-differentiated intestinal porcine epithelial cell (IPEC-J2) monolayers in the transwell plates. Cell monolayers with or without 4-PBA (1.0 mmol/L) treatment were challenged with physical scratch, deoxynivalenol (DON, 2.0 μg/mL, 48 h), and lipopolysaccharide (LPS, 5.0 μg/mL, 48 h), respectively. Transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD-4) permeability were measured to indicate barrier integrity and permeability. Real-time PCR and Western blot were conducted to determine relative gene and protein expressions of tight junction proteins. As expected, physical scratch, DON, and LPS challenges decreased TEER and increased FD-4 permeability. 4-PBA treatment accelerated cell mitigation and rehabilitation of the physical scratch-damaged intestinal epithelial barrier but did not alleviate DON or LPS induced barrier damage. However, once 48-h DON and LPS challenges were removed, rehabilitation of the epithelial barrier function of IPEC-J2 monolayer was accelerated by the 4-PBA treatment. Also, the relative gene and protein expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 were further upregulated by the 4-PBA treatment during the barrier rehabilitation. Taken together, 4-PBA accelerated the IPEC-J2 cell monolayer barrier recovering from physical scratch, DON-, and LPS-induced damage, via enhancing cell mitigation and expressions of tight junction proteins.

In order to investigate the influence of modulus of the base layer on the strain distribution for asphalt pavement, the modulus ratio of the base layer and the AC layer (Rm) is introduced as a controlled variable when keeping modulus of the AC layer as a constant in this paper. Then, a three-layered pavement structure is selected as an analytical model, which consists of an AC layer with the constant modulus and a base layer with the variable modulus covering the subgrade. A three dimensional (3D) finite element model was established to estimate the strains along the horizontal and vertical direction in the AC layer under different Rm. The results show that Rm will change the distribution of the horizontal strains along the depth in the AC layer; the increase of Rm could reduce the maximum tensile strain in the AC layer, but its effect is limited; the maximum tensile strain in the AC layer does not necessarily occur at the bottom, but gradually rises to the middle with the increase of Rm. Rm could significantly decline the bottom strain in the AC layer, and there is a certain difference between the bottom and the maximum strain when Rm is greater than or equal to one, which will enlarge with increasing Rm. Rm could change the depth of the neutral axis in the AC layer, and the second neutral axis will appear at the bottom of the AC layer under a sufficiently large Rm. The average vertical compressive strain in the AC layer will significantly enlarge with the increase of Rm.

Abstract Backgroud Myocardial infarction (MI) is one of the leading causes of global death. Dendritic cell-derived exosomes (DEXs) provide us with the possibility of improving cardiac function after MI but are limited by low retention times and short-lived therapeutic effects. In this study, we developed a novel drug delivery system incorporating alginate hydrogel that continuously releases DEXs and investigated the mechanisms underlying the action of DEXs in the improvement of cardiac function after MI. Results We incorporated DEXs with alginate hydrogel (DEXs-Gel) and investigated controlled released ability and rheology, and found that DEXs-Gel release DEXs in a sustainable mammer and prolonged the retention time of DEXs but had no detrimental effects on the migration in vivo. Then DEXs-Gel was applicated in the MI model mice, we found that DEXs-Gel siginificantly enhanced the therapeutic effects of DEXs with regards to improving cardiac function after MI. Flow cytometry and immunofluorescence staining revealed that DEXs significantly upregulated the infiltration of Treg cells and M2 macrophages into the border zoom after MI, and DEXs activated regulatory T (Treg) cells and shifted macrophages to reparative M2 macrophages, both in vitro and in vivo. Conclusion Our novel delivery method provides an innovative tool for enhancing the therapeutic effects of DEXs after MI. Further analysis revealed that DEXs exert effect by activating Treg cells and by modifying the polarization of macrophages. Graphic Abstract

The purpose of this study was to evaluate the effects of different levels of potassium magnesium sulfateon (PMS) on growth performance, diarrhea rate, intestinal morphology, antioxidant capacity, intestinal immunity, and gut microbiota in weaned piglets. A total of 216 weaned piglets were randomly divided into six dietary groups: the basal diet with 0% (CON), 0.15, 0.3, 0.45, 0.6, and 0.75% PMS. The results showed that the ADFI of 29–42 days and 1–42 days was linearly and quadratically increased by the PMS supplementation (P < 0.05), and significantly reduced the diarrhea rate in weaned piglets (P < 0.05). Moreover, dietary supplementation with PMS significantly reduced the serum adrenaline and noradrenaline levels in weaned piglets (P < 0.05). Furthermore, 0.3% PMS significantly increased the activity of glutathione peroxidase (GSH-Px) in the jejunum (P < 0.05) and tended to increase the activity of superoxide dismutase (SOD) in the jejunal mucosa of piglets (P < 0.1). Additionally, dietary supplementation with PMS significantly reduced the interleukin-1β (IL-1β) level in the jejunal mucosa (P < 0.05), and 0.3% PMS increased the serum IgM content in piglets (P < 0.05). Furthermore, the analysis of colonic microbiota by 16S RNA sequencing showed that the addition of PMS increased the Shannon index (P < 0.05) and Observed Species index (P < 0.05). Based on linear discriminant analysis effect size (LEfSe) and T-test analysis, the addition of PMS increased the relative abundance of Ruminococcaceae and Peptostreptococcaceae in the colonic digesta (P < 0.05). Spearman analysis showed that there was a positive correlation between intestinal GSH-Px activity and the relative abundance of Peptostreptococcaceae. These results showed that dietary supplementation with PMS could improve growth performance, alleviate diarrhea incidence, and modulate the antioxidant capacity and intestinal immunity in weaned piglets, which was partially related to the significant changes in colonic microbiota composition.

Intestinal epithelial barrier injury disrupts immune homeostasis and leads to many intestinal disorders. Lactobacillus reuteri (L. reuteri) strains can influence immune system development and intestinal function. However, the underlying mechanisms of L. reuteri LR1 that regulate inflammatory response and intestinal integrity are still unknown. The present study aimed to determine the effects of LR1 on the ETEC K88-induced intestinal epithelial injury on the inflammatory response, intestinal epithelial barrier function, and the MLCK signal pathway and its underlying mechanism. Here, we showed that the 1 × 109 cfu/ml LR1 treatment for 4 h dramatically decreased interleukin-8 (IL-8) and IL-6 expression. Then, the data indicated that the 1 × 108 cfu/ml ETEC K88 treatment for 4 h dramatically enhanced IL-8, IL-6, and tumor necrosis factor-α (TNF-α) expression. Furthermore, scanning electron microscope (SEM) data indicated that pretreatment with LR1 inhibited the ETEC K88 that adhered on IPEC-J2 and alleviated the scratch injury of IPEC J2 cells. Moreover, LR1 pretreatment significantly reversed the declined transepithelial electrical resistance (TER) and tight junction protein level, and enhanced the induction by ETEC K88 treatment. Additionally, LR1 pretreatment dramatically declined IL-8, IL-17A, IL-6, and TNF-α levels compared with the ETEC K88 group. Then, ETEC K88-treated IPEC-J2 cells had a higher level of myosin light-chain kinase (MLCK), higher MLC levels, and a lower Rho-associated kinase (ROCK) level than the control group, while LR1 pretreatment significantly declined the MLCK and MLC expression and enhanced ROCK level in the ETEC K88-challenged IPEC-J2 cells. Mechanistically, depletion of MLCK significantly declined MLC expression in IPEC-J2 challenged with ETEC K88 compared to the si NC+ETEC K88 group. On the other hand, the TER of the si MLCK+ETEC K88 group was higher and the FD4 flux in the si MLCK+ETEC K88 group was lower compared with the si NC+ETEC K88 group. In addition, depletion of MLCK significantly enhanced Claudin-1 level and declined IL-8 and TNF-α levels in IPEC-J2 pretreated with LR1 followed by challenging with ETEC K88. In conclusion, our work indicated that L. reuteri LR1 can decline inflammatory response and improve intestinal epithelial barrier function through suppressing the MLCK signal pathway in the ETEC K88-challenged IPEC-J2.

Background: Emerging evidence indicates that the worldwide incidence of early-onset coronary artery disease (EOCAD) is increasing. The genetic background has been assumed to harbor pathogenic risk, although the existing findings are mainly restricted to Caucasians. Little is known regarding the clinical profiles of patients with EOCAD and the extent to which genetic factors are related to disease susceptibility and outcomes in Asian people, especially ethnic Chinese. Methods and Results: The Genetic characteristics of coRonary Artery disease (CAD) in ChiNese young aDults (GRAND) study is a multicenter, hospital-based observational clinical study, combined of case-control design and longitudinal prospective cohort. Six thousand nationally representative patients who underwent coronary angiography at 38 centers have been enrolled since May 2017. Clinical data of patients with EOCAD (aged ≤45 years) are collected at the baseline to delineate conventional risk factors, clinical profiles, and therapeutic options of EOCAD and compared with data for patients with late-onset CAD (aged ≥65 years) and age-matched controls without CAD. The patients are followed for 3 years to trace major adverse cardiovascular (CV) events: cardiac death, nonfatal myocardial infarction, and ischemia-driven revascularization. Functional variants contributing to EOCAD risk are identified by high-depth whole-exome sequencing. The genetic profiles are further linked to disease severity and prognosis. A multi-dimensional risk score is established to predict prevalent EOCAD and incident CV events among young Chinese adults. Conclusions: The GRAND study will generate a thorough understanding of the clinical characteristics and genetic basis of EOCAD and may pave the way for genetic screening, early prevention, and future drug discovery for CAD in young Chinese generations.

Objectives: The aim of this study was to identify differentially expressed genes (DEGs) related to myocardial infarction (MI), which may serve as research and therapeutic targets. Methods: MI expression profiles were obtained from the Gene Expression Omnibus (GEO) database. DEGs were screened using GEO2R, and DEGs in multiple datasets were identified using Venn diagrams. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery v6.8. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape 3.7.2. Coexpedia was used for gene coexpression network analysis and functional annotation. Results: We identified 50 DEGs in the four datasets, including 29 with important roles in the PPI network. GO functional enrichment analysis revealed the involvement of DEGs in biological processes such as cytokine activation, peptidase inhibition, and chemokine activation. KEGG analysis revealed enrichment in chemokine signaling and cytokine-cytokine receptor interactions. Gene coexpression network analysis identified nine hub genes involved in the occurrence and development of MI including tissue inhibitor of metalloproteinase 1; CD44 antigen; lysyl oxidase; formyl peptide receptor 2; matrix metallopeptidase 3; formyl peptide receptor 1; serine (or cysteine) peptidase inhibitor, clade E, member 1; prostaglandin-endoperoxide synthase 2; and elastin. Conclusions: The hub genes identified may play important roles in MI-related biological processes and represent potential diagnostic and therapeutic targets. Therefore, this study lays a foundation for further exploration of the molecular mechanisms of MI.

Activity level measurement and fusion rules are the two key factors of image fusion. In the fusion method based on neural networks, the activity level measurements are realized by dividing the image into small blocks and predicting the sharpness of each block; then, the global decision graph guiding fusion is generated according to the predicted results. However, these two tasks are serial in nature, which makes it difficult to complete them simultaneously while achieving satisfactory fusion performance. Therefore, a new multi-focus microscopic image fusion method is proposed in this paper to quickly fuse multiple histological microscopic images from different focusing planes to generate full-focus images. The improved SegNet network was used to detect the unfocused regions. Considering that two or more images are needed for fusion, a parallel fusion strategy is proposed herein to generate clear fusion images based on multiple images instead of pairwise decision graphs. Compared with the convolutional neural network, the proposed network has better representation ability and can extract and fuse the most ideal features to provide a more accurate fusion decision. Compared with the traditional Segnet network, it is lightweight, which greatly improves computing speed and achieves real-time fusion.

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in weaned piglets, and ornithine α-ketoglutarate (OKG) as a food supplement has been shown to improve intestinal immune status in animals and humans. However, it remains unknown whether OKG alleviates inflammation through the regulation of gut microbiota and its metabolites on ETEC-infected piglets. This study was conducted to explore the impact of OKG on growth performance, immunity, and ileal mucosa microbiota and its metabolites in piglets infected with ETEC. On a total of 40 pigs, a 2 × 2 factor design was performed; the major factors were diet (basal diet or 1% OKG diet) and challenge (E. coli or LB Broth). The results showed that ETEC-infection inhibited growth performance, and OKG supplementation alleviated growth performance. Interestingly, ETEC-infection increased the serum TNF-α and IL-6, decreased the serum IL-10, downregulated the mRNA expression of IL-1β, IL-6, MyD88, and improved the mRNA expression of IL-8, IL-18, and TLR4. OKG inhibited serum IL-6, suppressed the phosphorylation of downstream signals of NF-κB/JNK in the ileum, and enhanced serum IL-10 and ileum SIgA in ETEC-challenged piglets. OKG supplementation enhanced the mRNA expression of IL-1β and IL-10 and reduced NF-κB and MyD88 in the ileum. Importantly, OKG reversed intestinal microbiota dysfunction, including the diversity of ileal microbiota, the relative abundances of Actinobacillus, Turicibacter, and [Acetivibrio]_ethanolgignens_group, which significantly affected arachidonic acid metabolism and primary bile acid biosynthesis. Collectively, our results suggest that OKG improves growth performance, regulates immunity, and ileal mucosa microbiota and its metabolites in ETEC-infected piglets.

Two representative programs, MICH-PAVE and KENLAYER, are selected and compared to many key aspects of their analysis algorithms to achieve an in-depth understanding of the features of the Finite Element Method and elastic layered system theory in nonlinear material analysis of the structure of asphalt pavement. Furthermore, by conducting a case study, the impact of using different analysis methods on the calculation results is presented. Moreover, the feasibility of the equivalent resilient modulus obtained by the Finite Element Method is discussed. The results show that the difference among the nonlinear analysis algorithms used by the two software packages is mainly reflected in the determination of the initial resilient modulus, the stress correction, and the convergence condition. Besides, the Finite Element Method could consider the variation of the resilient modulus induced by the change in the stress condition in both the radial and the depth directions simultaneously. In contrast, the theory of the elastic layered system only considers the dependence of the resilient modulus on the stress in the depth direction. Additionally, the use of diverse nonlinear analysis methods has different levels of impact on mechanical responses. Finally, the equivalent resilient modulus obtained by nonlinear analysis can be used to calculate mechanical responses of pavement structure except the surface deflection in a linear analysis.

Abstract Background The management of diagonal branch (D) occlusion is still controversary. The association between the flow loss of D and the prognosis remains unclear. We aim to detect the impact of D flow on cardiac function and clinical outcomes in patients with anterior ST-segment elevation myocardial infarction (STEMI). Methods Patients with anterior STEMI undergoing primary percutaneous coronary intervention (PCI) at our clinic between October 2015 and October 2018were reviewed. Anterior STEMI due to left anterior descending artery (LAD) occlusion with or without loss of the main D flow (TIMI grade 0–1 or 2–3) was enrolled in the analysis. The short- and long-term incidence of major adverse cardiac events (MACEs, a composite of all-cause death, target vessel revascularization and reinfarction) and left ventricular ejection fraction (LVEF) were analyzed. Results A total of 392 patients (mean age of 63.9 years) with anterior STEMI treated with primary PCI was enrolled in the study. They were divided into two groups, loss (TIMI grade 0–1, n = 69) and no loss (TIMI grade2–3, n = 323) of D flow, before primary PCI. Compared with the group without loss of D flow, the group with loss of D flow showed a lower LVEF post PCI (41.0% vs. 48.8%, p = 0.003). Meanwhile, loss of D flow resulted in the higher in-hospital, one-month, and 18-month incidence of MACEs, especially in all-cause mortality (all p

BackgroundCurrent guidewires for transradial coronary angiography had defects of passage difficulty or branch injury. This study sought to investigate the safety and efficiency of a novel method of active knuckle-angle 0.035-inch hydrophilic guidewire in transradial coronary angiography.MethodsPatients undergoing a transradial coronary procedure in our team from August 2015 to June 2020 were retrospectively investigated. We compared the demographic and interventional characteristics of 1,457 patients receiving advancement of unmodified guidewires (Traditional group) and 1,322 patients receiving advancement of the knuckle guidewire (Knuckle group). Afterwards we included 239 patients and randomized them according to a random number table to either the unmodified or the knuckle guidewire to further confirm the efficiency and safety of knuckle guidewire advancement.ResultsIn the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, p < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, p < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group.ConclusionActive knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.

In this paper, dry-mixed recycled cement concrete gravel (CCG) piles and dry-mixed cement macadam gravel (CMG) piles were analyzed. CCG and CMG were prepared by using recycled concrete aggregate (RCA) with different substitution rates, recycled macadam aggregate (RMA) from waste bricks and tiles, and fly ash, respectively. Mechanical properties, hydration heat release performance, and frost resistance were used as evaluation factors. The compressive strength, hydration heat, relative dynamic elastic modulus, and mass loss rate were tested. Based on the requirements of subgrade reinforcement on the material strength, hydration heat release, and frost resistance of dry-mixed CRA piles, TOPSIS analysis method was used to conduct a comprehensive evaluation. The results show that the mechanical properties and frost resistance of CCG and CMG gradually deteriorate with the increase of RCA and RMA replacement rates. At the same time, the hydration heat release of CCG and CMG increases with the increase of the replacement rate. The fly ash instead of cement can improve the compressive strength and frost resistance of CCG and CMG and reduce the hydration heat and material cost. When the CCG replacement rate reaches 20%, the CCG composite score of 20% fly ash is higher than that of traditional dry-mixed cement gravel pile and has better comprehensive performance.

The air-booster vacuum preloading method has been applied to slurry ground improvement. It is based on the conventional vacuum preloading method but with an additional injection of pressurised air into the soil via pre-installed conductors. The drainage effect of air-booster vacuum preloading has been demonstrated by past studies; however, direct observations of the real-time behaviour of slurries subjected to boosted air remain lacking. This study used a combined monitoring technique that included particle image velocimetry, pore water/air pressure gauges, a vortex flowmeter and an electronic balance to conduct a laboratory test of air-booster vacuum consolidation of dredged slurry. The tests allowed analyses of (1) the real-time displacement field of the slurry, (2) the pressure–flux relationship of the pressurised air, and (3) the pore water pressure responses during air boosting. The first aspect allowed direct observation of small-crack initialisation and propagation during pressurisation; while the latter two confirmed the crack initiation based on drops in air and pore water pressures. The measured crack initiation pressure was verified by comparison with theoretical predictions. The results demonstrate that pressurised air induces cracks in soil, which promote the drainage consolidation of dredged slurry.

Phosphorus (P) pollution from modern swine production is a major environmental problem. Dietary interventions to promote bone growth can improve the utilization of dietary P, and thereby reduce its emission. Recent in vitro studies have shown that alpha-ketoglutarate (AKG) exerts a pro-osteogenic effect on osteoblast cells. This study aimed to evaluate the effects of AKG supplementation on bone growth, P and Ca digestion, and the gut microbial profile in piglets. Thirty-two piglets were randomly assigned into two dietary groups. The piglets were fed a basic diet containing 10 g/kg AKG or 10 g/kg maize starch (control) for 28 days. On days 21–28, titanium dioxide was used as an indicator to determine the apparent digestibility of P. AKG supplementation improved the bone mineral density, length, weight, and geometrical and strength properties of the femur and tibia. Furthermore, AKG supplementation increased apparent ileal and total tract digestibility of P. Colonic microbiota analysis results showed that AKG supplementation increased α-diversity and beneficial bacteria, including Lactobacillus and Clostridium butyricum, and decreased nitrogen fixation and chemoheterotrophy. Together, AKG supplementation improves bone growth, the utilization of dietary P, and the colonic microbial profile, which may provide a nutritional strategy for diminishing P pollution originating from the pig industry.

Dendritic cells (DCs) play key roles in promoting wound healing after myocardial infarction (MI). Our previous studies have shown that exosomes derived from DCs (DEXs) could migrate to lymphoid tissue and improve cardiac function post-MI by activating CD4+ T cells; however, the mechanism of DEXs’ migration to lymphoid tissue and the improvement of cardiac function are still unknown. In our study, we found that CCR7 expression significantly increased in MI-DEXs compared with control-DEXs; meanwhile, CCL19 and CCL21, the ligands of CCR7, significantly increased in the serum of MI-model mice. Subsequently, we overexpressed and knocked down CCR7 in MI-DEXs and found that overexpressed CCR7 enhanced the migration of MI-DEXs to the spleen; however, CCR7 knockdown attenuated MI-DEXs’ migration according to near-IR fluorescence imaging. Furthermore, overexpressed CCR7 in MI-DEXs enhanced the MI-DEXs’ improvement of cardiac function after MI; however, CCR7-knockdown MI-DEXs attenuated this improvement. In addition, after DEXs’ migration to the spleen, MI-DEXs activated CD4+ T cells and induced the expression of IL-4 and IL-10, which were significantly increased in the MI-DEX group compared with the control group. In conclusion, CCR7 could mediate DEXs’ migration to the spleen and improve cardiac function after MI, and we found that the mechanism was partly via activation of CD4+ T cells and secretion of IL-4 and IL-10. Our study presented an innovative method for improving cardiac function by enhancing the migration ability of MI-DEXs after MI, while CCR7 could be a potential candidate for MI-DEX bioengineering to enhance migration.

Inflammation plays an important role in aortic dissection (AD). Macrophages are critically involved in the inflammation after aortic injury. Neuraminidases (NEUs) are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids, which is emerging as a regulator of macrophage-associated immune responses. However, the role of neuraminidase 1 (NEU1) in pathological vascular remodeling of AD remains largely unknown. This study sought to characterize the role and identify the potential mechanism of NEU1 in pathological aortic degeneration. After β-aminopropionitrile monofumarate (BAPN) administration, NEU1 elevated significantly in the lesion zone of the aorta. Global or macrophage-specific NEU1 knockout (NEU1 CKO) mice had no baseline aortic defects but manifested improved aorta function, and decreased mortality due to aortic rupture. Improved outcomes in NEU1 CKO mice subjected to BAPN treatment were associated with the ameliorated vascular inflammation, lowered apoptosis, decreased reactive oxygen species production, mitigated extracellular matrix degradation, and improved M2 macrophage polarization. Furthermore, macrophages sorted from the aorta of NEU1 CKO mice displayed a significant increase of M2 macrophage markers and a marked decrease of M1 macrophage markers compared with the controls. To summarize, the present study demonstrated that macrophage-derived NEU1 is critical for vascular homeostasis. NEU1 exacerbates BAPN-induced pathological vascular remodeling. NEU1 may therefore represent a potential therapeutic target for the treatment of AD.

Background: Angiography-derived index of microcirculatory resistance (angio-IMR) is an emerging pressure-wire-free index to assess coronary microvascular function, but its diagnostic and prognostic value remains to be elucidated.Methods and Results: The study population consisted of three independent cohorts. The internal diagnostic cohort enrolled 53 patients with available hyperemic microcirculatory resistance (HMR) calculated from myocardial blood flow and pressure. The external diagnostic cohort included 35 ischemia and no obstructive coronary artery disease (INOCA) patients and 45 controls. The prognostic cohort included 138 coronary artery disease (CAD) patients who received PCI. Angio-IMR was calculated after the estimation of angiography-derived fractional flow reserve (angio-FFR) using the equation of angio-IMR = estimated hyperemic Pa × angio-FFR × [vessel length/(K × Vdiastole)]. The primary outcome was a composite of cardiac death or readmission due to heart failure at 28 months after index procedure. Angio-IMR demonstrated a moderate correlation with HMR (R = 0.74, p < 0.001) and its diagnostic accuracy, sensitivity, specificity, and area under the curve to diagnose INOCA were 79.8, 83.1, 78.0, and 0.84, respectively, with a best cut-off of 25.1. Among prognostic cohort, patients with angio-IMR ≥25.1 showed a significantly higher risk of cardiac death or readmission due to heart failure than those with an angio-IMR

Background: Coronary artery disease (CAD) is the leading cause of cardiovascular death. The competitive endogenous RNAs (ceRNAs) hypothesis is a new theory that explains the relationship between lncRNAs and miRNAs. The mechanism of ceRNAs in the pathological process of CAD has not been fully elucidated. The objective of this study was to explore the ceRNA mechanism in CAD using the integrative bioinformatics analysis and provide new research ideas for the occurrence and development of CAD.Methods: The GSE113079 dataset was downloaded, and differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) were identified using the limma package in the R language. Weighted gene correlation network analysis (WGCNA) was performed on DElncRNAs and DEGs to explore lncRNAs and genes associated with CAD. Functional enrichment analysis was performed on hub genes in the significant module identified via WGCNA. Four online databases, including TargetScan, miRDB, miRTarBase, and Starbase, combined with an online tool, miRWalk, were used to construct ceRNA regulatory networks.Results: DEGs were clustered into ten co-expression modules with different colors using WGCNA. The brown module was identified as the key module with the highest correlation coefficient. 188 hub genes were identified in the brown module for functional enrichment analysis. DElncRNAs were clustered into sixteen modules, including seven modules related to CAD with the correlation coefficient more than 0.5. Three ceRNA networks were identified, including OIP5-AS1-miR-204-5p/miR-211-5p-SMOC1, OIP5-AS1-miR-92b-3p-DKK3, and OIP5-AS1-miR-25-3p-TMEM184B.Conclusion: Three ceRNA regulatory networks identified in this study may play crucial roles in the occurrence and development of CAD, which provide novel insights into the ceRNA mechanism in CAD.

Background: Whether the role of plasma heat shock protein 70 (HSP70) in acute myocardial infarction (AMI) is protective or detrimental remains debated, and the relationship between HSP70 and total occlusion remains elusive.Methods: A total of 112 patients with primary diagnosis of AMI and 52 patients with chronic coronary syndrome (CCS) were enrolled into the study. Plasma HSP70 level was determined by ELISA on day 1 and day 7 after the onset of AMI and was examined before angiography in patients with CCS. Peak NT-proBNP, high-sensitivity C-reactive protein (CRP), troponin T (cTnT), and left ventricular ejection fraction were measured.Results: Plasma HSP70 was significantly higher in CCS than AMI (P < 0.0001), and it showed a significant decrease from day 1 to day 7 after AMI (P < 0.01). Elevated HSP70 was associated with decreased levels of LDL-C (P < 0.05), peak cTnT (R = −0.3578, P < 0.0001), peak NT-proBNP (R = −0.3583, P < 0.0001), and peak CRP (R = −0.3539, P < 0.0001) and a lower diagnosis of AMI (R = −0.4016, P < 0.0001) and STEMI (R = −0.3675, P < 0.0001), but a higher diagnosis of total occlusion in target vessels (R = 0.1702, P < 0.05). HSP70 may provide certain predictive value for the diagnosis of AMI, STEMI, and total occlusion in target vessels, and the area under the receiver operating characteristic curves were 0.7660, 0.7152, and 0.5984, respectively. HSP70 was also negatively associated with in-hospital stay (P < 0.001) and positively correlated with left ventricular ejection fraction (LVEF) at 1-year follow-up (P < 0.05), despite no association with in-hospital major adverse cardiovascular events (MACE).Conclusion: Plasma HSP70 level was found to decrease from day 1 to day 7 post-AMI, but the overall level of patients with AMI was lower than that of patients with CCS. However, the ability of HSP70 to identify clinically significant AMI and STEMI was moderate, and the predictive value to total occlusion was slight.

The landscape of CDC20 gene expression and its biological impacts across different types of cancers remains largely unknown. Here, a pan-cancer analysis was performed to analyze the role of Cdc20 in various human cancers. Our results indicated that the expression levels of the CDC20 gene were significantly elevated in bladder cancer, breast cancer, colon cancer, rectum cancer, stomach cancer, esophageal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer, and uterine cancer. In addition, the expression of CDC20 was significantly and positively correlated with the increase of clinical stages in multiple cancer types, including breast cancer, kidney cancer, and lung cancer, et al. Among 33 cancer subtypes in the TCGA dataset, the high expression of CDC20 was correlated with poor prognosis in 10 cancer types. Furthermore, the abundance of phosphorylated Cdc20 in the primary tumor was elevated and correlated with increased tumor grade. Next, we sought to elucidate the oncogenic role by analyzing its association with immune infiltration. For most cancer types, the CDC20 expression was positively correlated with the infiltration of cancer-associated fibroblasts and myeloid-derived suppressor cells. To further understand its functional activity, we explored the classic Cdc20 downstream substrates, which were found to be mutually exclusive with the expression of Cdc20. Moreover, the pan-cancer analysis of the molecular function of Cdc20 indicated that BUB1, CCNA2, CCNB1, CDK1, MAD2L1, and PLK1 might play a critical role in interaction with Cdc20. The abundance of Cdc20 was further validated at transcriptional and translational levels with a publicly available dataset and clinical tumor tissues. The knockdown of Cdc20 dramatically inhibited tumor growth both in vivo and in vitro. Therefore, our studies delineated the oncogenic role of CDC20 and its prognostic significance at the pan-cancer level and proved its functional activity in Cdc20 high expression cancer types. Our studies will merits further molecular assays to understand the potential role of Cdc20 in tumorigenesis and provide the rationale for developing novel therapeutic strategies.

Objective: We aimed to assess the association of erectile dysfunction (ED) with the extent of coronary atherosclerosis, and to examine whether revascularization and medication use have an impact on ED status in patients with early onset of coronary artery disease (EOCAD).Methods: International Index of Erectile Function (IIEF-5) was used to evaluate sexual function in 296 male patients with EOCAD (age, 39.9 ± 4.8 years), and 354 male controls (age, 40.6 ± 4.4 years). The extent of coronary atherosclerosis was measured by Gensini score. Endothelial function was evaluated by two vasomotor indexes including endothelin-1 (ET-1) and nitric oxide (NO) by ELISA.Results: ED was more frequent (57.8 vs. 31.1%, P < 0.001) and serious (IIEF-5 score:17.7 ± 6.0 vs. 21.6 ± 5.0, P < 0.001) among EOCAD patients than that among controls. IIEF-5 score was negatively correlated with Gensini score (r = −0.383, P < 0.001). The adjusted odds ratio (OR) for the presence of ED (EOCAD vs. controls) was 1.88 [95% confidential interval (CI), 1.12-3.18]. However, ET-1 and NO attenuated the association between ED and EOCAD (adjusted OR: 1.54, 95% CI: 0.84-2.80). IIEF-5 score increased after coronary revascularization in patients not on beta-blockers (18.71 ± 4.84 vs. 17.59 ± 6.05, P < 0.001) as compared with baseline, while stayed unchanged in the subgroup using beta-blockers (17.82 ± 5.12 vs. 17.70 ± 5.98, P = 0.09).Conclusions: ED was common in patients with EOCAD, and associated with the severity of coronary atherosclerosis. Endothelial dysfunction may be a pathophysiologic mechanism underlying both ED and EOCAD. Coronary revascularization confers a benefit in ED amelioration, while this effect did not appear in patients using beta-blocker.

Type, quality, and origin of cereals in diets of poultry and pigs could influence gut microbes and affect their diversity and function, thereby impacting the intestinal function of the monogastric animal. In this review, we focus on the major carbohydrates in cereals that interact directly with gut microbes and lead to the production of key metabolites such as short-chain fatty acids (SCFA), and discuss how cereal fiber impact intestinal health of poultry and pigs. An overview of how the cereals and cereals-derived carbohydrates such as beta-glucans, resistant starch, cellulose, and arabinoxylans could promote intestinal health and reduce the use of in-feed antibiotics in animal production are presented. The metabolic pathway utilized by microbes and the mechanism of action underlying the produced SCFA on intestinal health of monogastric animals is also discussed. Keywords: Arabinoxylans, Beta-glucans, Resistant starch, Cellulose, SCFA, Intestinal health

The growth performance, nutrient digestibility, hematology, serum chemistry, and lipoprotein concentrations of turkey (Meleagris gallopavo) poults fed diets supplemented with high or recommended concentrations of niacin were investigated in this study. A total of 120 four-week-old turkey poults were randomly divided into three treatment groups with five replicates of eight birds in each group. The poult diets were supplemented with 0.0, 60, and 180 mg/kg niacin in the three treatments, termed control, recommended niacin supplementation (RNS), and high niacin supplementation (HNS), respectively. The study lasted for four weeks. The results showed that the HNS treatment reduced the feed intake and increased the body weight gain of poults. The apparent, nitrogen-corrected, and true metabolizable energy contents were the highest in the HNS-group turkey poults (P

Objective: The aim of the study is to assess the predictors of failure of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions using a retrograde approach. Methods: The present study retrospectively enrolled all 211 patients who underwent retrograde CTO PCI from January 2009 to December 2015 at Shanghai Institute of Cardiovascular Disease. Multivariate Cox regression analysis was used to assess potential predictors of retrograde CTO PCI failure including sex, vascular access site, sheath size, prior PCI, prior coronary artery bypass grafting, history of myocardial infarction, target vessel of CTO, J-CTO score, retrograde wire crossing collaterals, and reverse controlled antegrade and retrograde subintimal tracking (CART) use. Results: Of the 211 patients studied, retrograde CTO PCI was successful in 115 (54.5%) patients, and in an additional 46 (21.8%) with an antegrade approach after retrograde failure. For the 50 (23.7%) patients who failed both retrograde and antegrade approaches, the most common (50% [25/50]) reason was inability to cross collaterals with the retrograde wire. This group of patients had fewer instances of a prior PCI (P < 0.05). Retrograde CTO PCI failure rate was lower with increasing sheath size and with either radial-only or one radial and one femoral access versus femoral-only access (P < 0.05). A multivariate Cox regression analysis showed that the inability to cross collaterals with the retrograde wire (hazard ratio, 5.52 [95% confidence interval, 2.08–12.81];P < 0.001), no prior PCI (3.27 [1.24–8.58];P = 0.01), and no reverse CART use (4.19 [1.33–13.19];P = 0.03) were an independent predictors of retrograde CTO PCI failure. Conclusion: Independent predictors of retrograde CTO PCI failure were the inability to cross collaterals with the retrograde wire, no prior PCI, and no reverse CART use. Vascular access site and sheath size do not have effect on the success of the retrograde approach.

This study was conducted to investigate the effects of Macleaya cordata extract (MCE) on growth performance, immune responses, antioxidant capacity, intestinal morphology and microbiota in weaned piglets. A total of 36 weaned piglets [Duroc× (Large White × Landrace)] with an average body weight of 6.55 ± 0.32 kg at weaning were used in a 21-day experiment. Pigs were divided into three treatments (n = 12). Control (basal diet); MCE (basal diet plus MCE) and ABO (basal diet plus 20 mg/kg falvomycin & 100 mg/kg aureomycin). Compared with the control group, piglets in the MCE and ABO groups had higher average daily gain, lower feed efficiency and diarrhea rates (P < 0.05). Serum IgG level in MCE -fed piglets was higher (P < 0.05) than that of control -fed piglets. A higher (P < 0.05) serum the activity of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) was observed in MCE-fed piglets than those in the control and ABO groups. The addition of MCE increased the amount of Lactobacillus spp. (P < 0.05), while decreased the amount of Salmonella spp. (P < 0.05) and tended to reduce the E. coli population (P < 0.10). Dietary MCE increased villus height and the villus height to crypt depth ratio in the duodenum, jejunum and ileum, and decreased the crypt depth in the jejunum of piglets (P < 0.05). In conclusion, dietary MCE supplementation would exert beneficial effects on growth performance, immune status, antioxidant capacity and the intestinal health and may be used as a potential alternative to antibiotics in weaned piglets.