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Abstract Introduction The Weight-Adjusted Waist Index (WWI) is a new indicator of obesity that is associated with all-cause mortality in Asian populations. Our study aimed to investigate the linear and non-linear associations between WWI and all-cause mortality in non-Asian populations in the United States, and whether WWI was superior to traditional obesity indicators as a predictor of all-cause mortality. Methods We conducted a cohort study using data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES), involving 18,592 participants. We utilized Cox proportional hazard models to assess the association between WWI, BMI, WC, and the risk of all-cause mortality, and performed subgroup analyses and interaction tests. We also employed a receiver operating characteristics (ROC) curve study to evaluate the effectiveness of WWI, BMI, and WC in predicting all-cause mortality. Results After adjusting for confounders, WWI, BMI, and WC were positively associated with all-cause mortality. The performance of WWI, BMI, and WC in predicting all-cause mortality yielded AUCs of 0.697, 0.524, and 0.562, respectively. The data also revealed a U-shaped relationship between WWI and all-cause mortality. Race and cancer modified the relationship between WWI and all-cause mortality, with the relationship being negatively correlated in African Americans and cancer patients. Conclusions In non-Asian populations in the United States, there is a U-shaped relationship between WWI and all-cause mortality, and WWI outperforms BMI and WC as a predictor of all-cause mortality. These findings may contribute to a better understanding and prediction of the relationship between obesity and mortality, and provide support for effective obesity management strategies.

ABSTRACT: The overuse of antibiotics has resulted in a surge of drug-resistant bacteria, making the pursuit of natural antimicrobials an urgent and significant trend. Encapsulation and nanoparticulation are effective ways to enhance the antibacterial properties of natural drugs. In this study, we encapsulated tannic acid (TA) with chitosan (CS) and poly (lactide-co-glycolide) (PLGA) using the emulsion-solvent evaporation method to enhance the antimicrobial effect of TA. We prepared a bilayer membrane spherical nanoemulsion of TA-PLGA-CS (TPC) with uniform size of 559.87 ± 1.16 nm, and zeta potential of 59.53 ± 1.07 mV. TPC could be stably stored for 90 days at 4°C without affecting the properties of the emulsion, and the minimum bactericidal concentration against four strains of Escherichia coli (E. coli) remained unchanged for 60 d. The results indicated that TPC enhanced the inhibitory effect of TA against E. coli. Scanning electron microscope images revealed that TPC treatment caused damage to the bacterial cell membrane. In addition, in vivo experiments indicated that TPC exhibited a superior therapeutic effect on artificial colibacillosis in chickens infested with Avian pathogenic Escherichia coli, as evidenced by the changes in body weight and a reduction bacterial load in heart. Furthermore, TPC reversed the down-regulation of catalase, glutathione peroxidase1 (GPX1), and GPX7 gene expression levels in intestinal tissues. Compared to the model group, TPC treatment elevated serum glutathione peroxidase activities and lowered myeloperoxidase and lactate dehydrogenase levels, offering antioxidant protection that was slightly better than that of doxycycline hydrochlorid group. In summary, we prepared a novel TA antimicrobial preparation with significant antioxidant potential and inhibitory effect against E. coli both in vitro and in vivo.

To develop an environmentally sustainable and efficient extraction method for flavonoids from Moringa oleifera Lam. (M. oleifera) leaves, natural deep eutectic solvents (NADES) with ultrasound-assisted extraction was utilized in this study. After optimization of extraction parameters of NADES, including ultrasonic power, ultrasonic time, and liquid–solid ratio, the extraction yield of ultrasound-assisted NADES (UAN) composed of betaine and urea (Bet-Urea) reached 54.69 ± 0.19 mg RE/g DW, which made a 1.7-fold increase compared to traditional ultrasound-assisted traditional solvent (UATS). UPLC-Q Exactive/MS analysis revealed that M. oleifera leaves flavonoids (MOLF) was mainly composed of Quercetin 3-β-D-glucoside, Rutin, Kaempferol-3-O-glucoside, Vitexin and Quercetin. Furthermore, the COSMO-RS model was employed to verify the optimal compatibility of solubility and activity coefficient between Bet-Urea and the five primary flavonoids in MOLF. In vitro antioxidant assays verified that MOLF extracted by UAN exhibited superior antioxidant activity compared to MOLF extracted by UATS. Overall, the devised process not only augmented the extraction yield of MOLF but also effectively preserved the bioactive compounds, thus promoting the utilization of green extraction solvents in the food industry.

Bacterial-infected wounds could cause delayed wound healing due to increased inflammation, especially wounds infected by drug-resistant bacteria remain a major clinical problem. However, traditional treatment strategies were gradually losing efficacy, such as the abuse of antibiotics leading to enhanced bacterial resistance. Therefore, there was an urgent need to develop an antibiotic-free multifunctional dressing for bacterially infected wound healing. This study demonstrated the preparation of a multifunctional injectable hydrogel and evaluated its efficacy in treating acute and infected wounds. The hydrogel was prepared by a one-step mixing method, and cross-linked by natural deep eutectic solvent (DES), polyvinyl alcohol (PVA), chitosan (CS), tannic acid (TA), and Cu2+ through non-covalent interactions (hydrogen bonds and metal coordination bonds). PVA/CS/DES/CuTA500 hydrogel has multiple functional properties, including injectability, tissue adhesion, biocompatibility, hemostasis, broad-spectrum antibacterial, anti-inflammatory, and angiogenesis. Most importantly, in the MRSA-infected skin wound model, PVA/CS/DES/CuTA500 hydrogel could ultimately accelerate infected wound healing by killing bacteria, activating M2 polarization, inhibiting inflammation, and promoting angiogenesis. In summary, the PVA/CS/DES/CuTA500 hydrogel showed great potential as a wound dressing for bacterial infected wounds treatment in the clinic.

Abstract Rheumatoid Arthritis (RA) is an increasingly prevalent inflammatory disorder worldwide. Its complex etiology has recently brought dietary factors, particularly fiber intake, into focus as potential influencers. Our study investigates the intricate relationship between various sources of dietary fiber and RA, emphasizing the mediating role of the Dietary Inflammatory Index (DII). Leveraging data from the National Health and Nutrition Examination Survey spanning 2011 to 2020. We meticulously assessed dietary fiber intake through dual 24 h dietary recall interviews, while RA diagnoses were established based on comprehensive medical surveys. The relationships between fiber intake, RA prevalence, and DII mediation were analyzed using sophisticated multivariate logistic regression and mediation analysis. Among our study cohort, 7% were diagnosed with RA. We observed a notable inverse correlation between increased total fiber intake, particularly 5 g/day increments, and the incidence of RA, with cereal fiber intake emerging as the primary mitigating factor. Intriguingly, the DII played a significant role in mediating this association, especially regarding cereal fiber. Our findings reveal a significant association between higher cereal fiber consumption and a reduced prevalence of RA. Additionally, the DII stands out as a pivotal mediator in this relationship, highlighting dietary management's critical role in preventing and managing RA.

ABSTRACT: The avian influenza virus is infected through the mucosal route, thus mucosal barrier defense is very important. While the inactivated H9N2 vaccine cannot achieve sufficient mucosal immunity, adjuvants are needed to induce mucosal and systemic immunity to prevent poultry from H9N2 influenza virus infection. Our previous study found that polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) had immune-enhancing effects in vitro. This study aimed to evaluate the mucosal immune responses of oral whole-inactivated H9N2 virus (WIV)+AMP-ZnONPs and its impact on the animal challenge protection, and the corresponding changes of pulmonary metabolomics after the second immunization. The results showed that compared to the WIV, the combined treatment of WIV and AMP-ZnONPs significantly enhanced the HI titer, IgG and specific sIgA levels, the number of goblet cells and intestinal epithelial lymphocytes (iIELs) as well as the expression of J-chain, polymeric immunoglobulin receptor (pIgR), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). In viral attack experiments, WIV combing with AMP-ZnONPs effectively reduced lung damage and viral titers in throat swabs. Interestingly, significant changes of both the IgA intestinal immune network and PPAR pathway could also be found in the WIV+AMP-ZnONPs group compared to the non-infected group. Taken together, these findings suggest that AMP-ZnONPs can serve as a potential mucosal vaccine adjuvant, thereby avoiding adverse stress and corresponding costs caused by vaccine injection.

Abstract Background Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers. Methods The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship. Results A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [β = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [β = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD. Conclusions Our findings suggest that apo B is associated with BMD in a site-specific manner.

Abstract Long non-coding RNA (lncRNA) HOXA cluster antisense RNA 3 (HOXA-AS3) regulates the progression of several types of human malignancy. However, the role and potential mechanism of HOXA-AS3 in osteosarcoma (OS) remain unknown. In this study, upregulation of HOXA-AS3 was observed in OS tissues and cell lines and associated with poor clinical outcomes. Silencing of HOXA-AS3 significantly inhibited the proliferation, migration and invasion of OS cells in vitro and suppressed the tumorigenesis of OS cells in vivo. Furthermore, knockdown of HOXA-AS3 inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and epithelial-to-mesenchymal transition (EMT) in OS. Further investigation of this mechanism revealed that HOXA-AS3 could directly upregulate the expression of TEAD1 via its competing endogenous RNA (ceRNA) activity on miR-1286. This study clarified the oncogenic roles of the HOXA-AS3/miR-1286/TEAD1 axis in OS progression, suggesting a novel therapeutic target for OS.

Abstract Introduction Even though cadmium (Cd) exposure and cellular senescence (telomere length) have been linked in previous studies, composite molecular aging biomarkers are more significant and reliable factors to consider when examining the connection between metal exposure and health outcomes. The purpose of this research was to assess the association between urinary cadmium (U-Cd) and whole-body aging (phenotypic age). Methods Phenotypic age was calculated from chronological age and 9 molecular biomarkers. Multivariate linear regression models, subgroup analysis, and smoothing curve fitting were used to explore the linear and nonlinear relationship between U-Cd and phenotypic age. Mediation analysis was performed to explore the mediating effect of U-Cd on the association between smoking and phenotypic age. Results This study included 10,083 participants with a mean chronological age and a mean phenotypic age of 42.24 years and 42.34 years, respectively. In the fully adjusted model, there was a positive relationship between U-Cd and phenotypic age [2.13 years per 1 ng/g U-Cd, (1.67, 2.58)]. This association differed by sex, age, and smoking subgroups (P for interaction

Abstract Background The weight-adjusted waist circumference index (WWI) is a novel obesity indicator that offers improved accuracy in assessing both muscle and fat mass compared to traditional measures. This study aimed to investigate the association between WWI and bone mineral density (BMD) in adults. Methods Weighted multivariate logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) curves were used to explore the relationship between WWI and BMD based on data from the National Health and Nutrition Examination Survey (NHANES). Results This study had 40,568 individuals in total. At all four measurement sites, we detected a negative linear correlation between WWI and BMD. Even when quartile factors for WWI were created, this unfavorable connection maintained. In comparison to those in the lowest quartile, those in the highest percentile of WWI showed declines in lumbar BMD of 0.08 g/cm2 and femoral neck BMD of 0.03 g/cm2, respectively. This adverse correlation, nevertheless, differed among several categories. Conclusions Our findings suggest an adverse correlation between WWI and BMD among US adults. Employing WWI as a tool for osteoporosis prevention in the general population may enhance interventions.

To study the impact and erosion mechanism of solid particles in centrifugal pumps, the standard k–ε turbulence model and SIMPLE algorithm are adopted in this paper. Based on the discrete phase model (DPM) of the Lagrange method and McLaury erosion model, the flow impact characteristics and erosion mechanism of solid particles impacting the surface of flow passage components in a single-stage centrifugal pump were numerically simulated, and the test data were compared with the numerical simulation results of the external characteristics of the pump in clean water. The results show that the erosion mechanism of the pressure surface of the blade is mostly the impact erosion caused by high-speed particles with large impact angles, and the impact angle and impact velocity are larger near the tail of the pressure surface. The impact angle of solid particles on the shroud and hub is relatively small, but the erosion mechanism is still impact erosion. The erosion mechanism of the volute wall is mostly the cutting friction erosion caused by the low-velocity particles with small impact angles, and it is only impacted by the particles with large angles near the volute tongue, which is impact erosion. Overall, the average impact angle and impact velocity of the particles on the pressure surface of the blade are higher than those on the volute, so the erosion of the pressure surface is more serious than that of the volute in theory. The research results have certain theoretical reference value for improving the wear resistance of a centrifugal pump.

Objectives: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy. However, few studies have investigated the prognosis of familial HCM (FHCM) through clinical data. The purpose of this study was to compare the clinical outcomes of FHCM and non-FHCM through propensity score matching analysis. Methods and results: The cohort study included 1243 patients with HCM between 1996 and 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences, among whom 125 patients had FHCM. During a mean follow-up of 7.6 ± 3.8 years (interquartile range: (IQR) 5.0–10.0 years), 217 (16.57%) of the 1243 patients had died, including 3 patients who underwent cardiac transplantation. Using 30 demographic and clinical variables, a 4:1 propensity score matched cohort for FHCM was established. The stepwise variable selection procedure for the Cox proportional hazards model was performed to identify the factors associated with mortality and competing risk regression analysis was performed to analyze the competitive risk of cardiovascular and non-cardiovascular mortality. The results showed that FHCM patients had a higher risk of cardiovascular mortality/cardiac transplantation (log-rank χ2 = 6.8, P = 0.0084) and an increased tendency of sudden cardiac death (SCD) (log-rank χ2 = 3.2, P = 0.074) compared with non-FHCM patients, but there was no difference in all-cause mortality (log-rank χ2 = 2.7, P = 0.1) between the two groups. Moreover, the Cox model showed that FHCM was an independent prognostic predictor for cardiovascular mortality/cardiac transplantation in HCM patients. Conclusion: FHCM patients had a higher risk of cardiovascular mortality/cardiac transplantation and a higher tendency of SCD than non-FHCM patients, but there was no difference in all-cause mortality. Moreover, FHCM was an independent prognostic predictor for cardiovascular mortality/cardiac transplantation in HCM patients.

Abstract Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro‐inflammatory cytokines secretion, while overwhelmed pyroptosis contributes to organ dysfunction and pathological inflammatory response. Caffeic acid (CA) and ferulic acid (FA) are both well‐known antioxidant and anti‐inflammatory phenolic acids, which resemble in chemical structure. Here we found that CA, but not FA, protects macrophages from both Nigericin‐induced canonical and cytosolic lipopolysaccharide (LPS)‐induced non‐canonical pyroptosis and alleviates LPS‐induced mice sepsis. It significantly improved the survival of pyroptotic cells and LPS‐challenged mice and blocked proinflammatory cytokine secretion. The anti‐pyroptotic effect of CA is independent of its regulations in cellular lipid peroxidation, mitochondrial function, or pyroptosis‐associated gene transcription. Instead, CA arrests pyroptosis by directly associating with gasdermin D (GSDMD) and blocking its processing, resulting in reduced N‐GSDMD pore construction and less cellular content release. In LPS‐induced septic mice, CA inhibits GSDMD activation in peritoneal macrophages and reduces the serum levels of interleukin‐1β and tumor necrosis factor‐α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis‐associated disease.

H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine’s impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT.

Background: Delayed wound healing, a common problem in patients with diabetes mellitus (DM), is associated with impaired keratinocyte autophagy. Epigallocatechin gallate (EGCG), a catechin, has been proven to promote diabetic wound healing. This study aims to explore the therapeutic mechanism of EGCG on diabetic wound healing. Methods: High glucose (HG)-induced keratinocytes and streptozotocin (STZ)-induced DM rats were prepared and intervened with EGCG to examine its therapeutic effects in in vivo and in vitro settings. The AMPK inhibitor, Compound C, was utilized to determine whether EGCG exerted its therapeutic effects through the AMPK/ULK1 pathway. Results: In vitro, EGCG improved HG-induced autophagy impairment in keratinocytes by increasing LC3II/LC3I, Becline1, and ATG5 levels and decreasing p62 level. Mechanically, EGCG activated the AMPK/ULK1 pathway, thereby promoting keratinocyte autophagy through the phosphorylation of AMPK and ULK1. Notably, EGCG promoted the proliferation, migration, synthesis and release of C-C motif chemokine ligand 2 (CCL2) in HG-treated keratinocytes. Furthermore, EGCG indirectly promoted the activation of fibroblasts, as evidenced by increased alpha-smooth muscle actin (α-SMA) and Collagen I levels. In vivo, EGCG promoted wound healing in DM rats, primarily by reducing inflammatory infiltration and increasing granulation tissue to promote wound epithelialization. Besides, EGCG promoted ATG5, KRT10, KRT14, TGF-β1, Collagen I, and α-SMA expressions in the neonatal epithelial tissues of DM rats. However, the use of Compound C reversed the effects of EGCG. Conclusions: These findings indicated that EGCG restored keratinocyte autophagy to promote diabetic wound healing through the AMPK/ULK1 pathway.

IntroductionInequality in socioeconomic status plays an important role in the prevalence of metabolic diseases in adolescents. The purpose of this study was to explore the association between family income and the degree of hepatic steatosis quantified by vibration-controlled transient elastography (VCTE) among U.S. adolescents.MethodsThis cross-sectional study included two cycles of the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Multivariate linear regression and smoothing curve fitting were used to investigate the linear and nonlinear relationship between PIR and hepatic steatosis, respectively. Subgroup analysis and interaction tests were used to test whether this relationship was stable across groups.ResultsOf the 1,574 adolescent participants, 456 lived in poor households and 307 lived in wealthy households. After adjusting for all covariates, PIR (Ratio of family income to poverty) was significantly negatively associated with the degree of hepatic steatosis [-4.78 (-7.39, -2.17)], and this remained stable after converting PIR to a categorical variable. In addition, this significant negative association was more pronounced in women [-7.62 (-11.38, -3.87)], non-Hispanic blacks [-7.19 (-14.43, 0.06)], Mexican Americans [-6.80 (-13.63, 0.03)], and participants with BMI >30 cm2 [-10.83 (-19.70, -1.96)].ConclusionsPIR was significantly and negatively associated with the degree of hepatic steatosis in US adolescents. Additional prospective studies are needed to confirm our findings.

Abstract Background Serum lipids are highly inheritable and play a major role in bone health. However, the relationship between high-density lipoprotein cholesterol (HDL-C) and bone mineral density (BMD) remains uncertain. The goal of this study was to see if there was a link between HDL-C levels and BMD in persons aged 20–59. Methods Multivariate logistic regression models were used to determine the link between HDL-C and lumbar BMD using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018. Generalized additive models and fitted smoothing curves were also used. Results The analysis included a total of 10,635 adults. After controlling for various variables, we discovered that HDL-C was positively linked with lumbar BMD. The favorable connection of HDL-C with lumbar BMD was maintained in subgroup analyses stratified by sex and race in women, but not in men, and in blacks, but not in whites. The relationship between HDL-C and lumbar BMD in men and whites was a U-shaped curve with the same inflection point: 0.98 mmol/L. Conclusions In people aged 20 to 59, our research discovered a positive relationship among HDL-C and lumbar BMD. Among males and whites, this relationship followed a U-shaped curve (inflection point: 0.98 mmol/L). HDL-C measurement might be used as a responsive biomarker for detecting osteoporosis early and guiding therapy.

Centrifugal pumps are frequently utilized in general machinery, but they have issues with low efficiency, unstable operation, and high-power consumption in actual engineering, making performance improvements necessary. In this paper, the particle swarm algorithm is utilized to find the optimal solution among the Pareto front solutions and obtain the most suitable impeller for the centrifugal pump with the lowest entropy generation and highest efficiency as the optimization objectives. Based on the entropy generation theory, the energy losses of the original model and the optimized model are compared and analyzed. The results show that the centrifugal pump impeller and volute are the two areas with the largest entropy generation ratio, the optimized centrifugal pump entropy generation decreases by 5.41%, and the efficiency increases by 3.89%. Turbulent entropy generation and wall entropy generation are the important causes of hydraulic losses. Most of the losses within the impeller occur mainly at leading edge and trailing edge of blade. As the flow rate increases, the closer the distribution of the high entropy generation rate at the front cover of the impeller, the more serious the flow losses. This paper can provide a theoretical reference for the performance optimization of centrifugal pumps.

ABSTRACT: The purpose of this study was to formulate tee tree oil nanoliposomes (TTONL) and evaluate its characterization and antibacterial activity. TTONL was prepared by thin film hydration and sonication technique, and the preparation conditions were optimized by Box-behnken response surface method. The characterization (morphology, size, zeta potential, and stability) and antibacterial activity of TTONL against Escherichia coli (E. coli) in vitro and in vivo were evaluated. The optimal preparation conditions for TTONL: lecithin to cholesterol mass ratio of 3.7:1, TTO concentration of 0.5%, and pH of the hydration medium of 7.4, which resulted in a TTONL encapsulation rate of 80.31 ± 0.56%. TTONL was nearly spherical in shape and uniform in size, and the average particle size was 227.8 ± 25.3 nm with negative charge. The specific disappearance of the TTO peak in the infrared spectrum suggested the successful preparation of TTONL, which showed high stability at 4°C within 35 d. The result of MIC test found that the nanoliposomes improved antibacterial activity of TTO against various E. coli strains. TTONL exposure in vitro caused different degrees of structural damage to the E. coli. TTONL by oral administration alleviated the clinical symptoms and intestinal lesion of chickens induced with E. coli challenge. Furthermore, TTONL treatment remarkably lowered the mRNA expression of NLRP3 and NF-κB (p65) in the duodenum and cecum of E. coli-infected chickens. In conclusion, the prepared TTONL had good stability and slow-release property with dose-dependent inhibition and killing effects on different strains of E. coli, and exerted a preventive role against chicken colibacillosis through inhibition.

The characteristic of ulcerative colitis (UC) is extensive colonic mucosal inflammation. Moringa oleifera (M. oleifera) is a medicine food homology plant, and the polysaccharide from M. oleifera leaves (MOLP) exhibits antioxidant and anti-inflammatory activity. The aim of this study to investigate the potential effect of MOLP on UC in a mouse model as well as the underlying mechanism. Dextran sulfate sodium (DSS) 4% in drinking water was given for 7 days to mice with UC, at the same time, MOLP (25, 50, and 100 mg/kg/day) was intragastric administered once daily during the experiment. Structural analysis revealed that MOLP had an average molecular weight (Mw) of 182,989 kDa and consisted of fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galactose uronic acid, glucuronic acid, glucose uronic acid and mannose uronic acid, with a percentage ratio of 1.64, 18.81, 12.04, 25.90, 17.57, 12.01, 3.51, 5.28, 0.55, 1.27, and 1.43%, respectively. In addition, the features of MOLP were identified by Fourier-transform infrared (FT-IR) and spectra, X-ray diffraction (XRD). The results showed that MOLP exhibited protective efficacy against UC by alleviating colonic pathological alterations, decreasing goblet cells, crypt destruction, and infiltration of inflammatory cells caused by DSS. Furthermore, MOLP notably repressed the loss of zonula occludens-1 (ZO-1) and occludin proteins in mucosal layer, as well as up-regulating the mRNA expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-γ (PPAR-γ), whereas down-regulating the activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB) signaling pathway and the production of pro-inflammatory cytokines. Therefore, these results will help understand the protective action procedure of MOLP against UC, thereby providing significance for the development of MOLP.

BackgroundThe systemic immune-inflammation index (SII) is a novel marker of inflammation, and hepatic steatosis and fibrosis are associated with inflammation. This study aimed to investigate the possible relationship between SII and hepatic steatosis and fibrosis.MethodsThe datasets from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between SII and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship.ResultsThis population-based study included a total of 6,792 adults aged 18–80 years. In a multivariate linear regression analysis, a significant positive association between SII and CAP was shown [0.006 (0.001, 0.010)]. This positive association in a subgroup analysis was maintained in men [0.011 (0.004, 0.018)] but not in women. Furthermore, the association between SII and CAP was nonlinear; using a two-segment linear regression model, we found an inverted U-shaped relationship between SII and CAP with an inflection point of 687.059 (1,000 cells/µl). The results of the multiple regression analysis showed that the relationship between SII and LSM was not significant (P = 0.263).ConclusionsOur findings imply that increased SII levels are linked to hepatic steatosis, but SII is not linked to liver fibrosis. To confirm our findings, more large-scale prospective investigations are needed.

Atractylodes macrocephala Koidz (A. macrocephala) has been used both as a traditional medicine and functional food for hundreds of years in Asia. And it has a variety of biological activities, such as enhancing the ability of immunity and modulating effect on gastrointestinal motility. In this study, a water-soluble polysaccharide with molecular weight of 2.743 × 103 Da was isolated from the root of A. macrocephala. Polysaccharide from A. macrocephala (AMP) consisted of arabinose, galactose, glucose, xylose, mannose, ribose, galactose uronic acid, glucose uronic acid, with a percentage ratio of 21.86, 12.28, 34.19, 0.43, 0.92, 0.85, 28.79, and 0.67%, respectively. Zinc plays an important role in immune system. Therefore, we supposed that AMP binding with zinc oxide (ZnO) nanoparticles (AMP-ZnONPs) might be an effective immunostimulator. AMP-ZnONPs was prepared by Borch reduction, and its structural features were characterized by Scanning Electron Microscope (SEM), Transmission electron microscope (TEM), TEM-energy dispersive spectroscopy mapping (TEM-EDS mapping), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), X-ray diffraction (XRD), particle size and zeta-potential distribution analysis. Then, its immunostimulatory activity and the underlying mechanism were evaluated using RAW264.7 cells. The results showed that AMP-ZnONPs remarkably promoted cell proliferation, enhanced phagocytosis, the release of nitric oxide (NO), cytokines (IL-6 and IL-1β) and the expression of co-stimulatory molecules (CD80, CD86 and MHCII). Moreover, AMP-ZnONPs could promote the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), TNF receptor associated factor 6 (TRAF6), phospho-IκBα (P-IκBα) and phospho-p65 (P-p65), and TLR4 inhibitor (TAK242) inhibited the expression of these proteins induced by AMP-ZnONPs. Therefore, AMP-ZnONPs activated macrophages by TLR4/MyD88/NF-κB signaling pathway, indicating that AMP-ZnONPs could act as a potential immunostimulator in medicine and functional food.

Abstract In bovine mammary epithelial cells (BMECs), a cascade of inflammatory reactions induced by lipopolysaccharide (LPS) has been shown to result in cell injury and apoptosis. The present study aims to reveal the protective effect of ferulic acid (FA) on LPS-induced BMEC apoptosis and explore its potential molecular mechanisms. First, we showed that FA had low cytotoxicity to BMECs and significantly decreased cell apoptosis and the proinflammatory response induced by LPS. Next, FA blocked LPS-induced oxidative stress by restoring the balance of the redox state and inhibiting mitochondrial dysfunction, the main contributor to LPS-induced apoptosis and ROS generation. Furthermore, the relief of inflammation and redox disturbance in the FA preconditioning group were accompanied by weaker NF-κB activation, enhanced Nrf2 activation and maintained cell viability compared to the LPS group. When BMECs were treated with FA alone, we observed that Nrf2 activation was induced before the inhibition of NF-κB activation and that the Keap1–Nrf2 relationship was disturbed. We concluded that FA prevented LPS-induced BMEC apoptosis by reversing the dominant relationship between NF-κB and Nrf2.

Severe influenza A virus infection leads to overwhelming inflammatory responses and cellular apoptosis, which causes lung injury and contributes to high mortality and morbidity. The gut microbiome altered in response to the infection might influence the disease progression and the treatment outcome. Cangma Huadu (CMHD) granules, an in-hospital preparation of traditional Chinese medicine, have been shown to be favorable in the clinical treatment of influenza. However, the effects and mechanisms of CMHD granules on severe influenza pneumonia and its mechanisms are not well-known. In this study, a lethal influenza A (H1N1) A/Puerto Rico/8/34 virus (PR8)-infected mice model was established, and the 16S ribosomal RNA (16S rRNA) V3–V4 region sequencing of the intestinal microbiome was conducted. We revealed that the oral administration of CMHD granules protects mice against higher mortality, enhanced weight loss, overwhelmed interferon-γ concentration, lung viral titers, and severe lung pathological injury in PR8-infected mice. CMHD granules’ administration downregulated the levels of interleukin (IL)-1β, tumor necrosis factor-α, and malondialdehyde, while it upregulated the levels of IL-10, superoxide dismutase, and glutathione peroxidase. Subsequently, it decreased the protein ratio of B-cell lymphoma-2/Bcl-2-associated X and the expression of cleaved caspase-3. The diversity and compositions of the gut microbes were altered profoundly after the administration of CMHD granules in PR8-infected mice. A higher abundance of Bifidobacterium, Parasutterella, Bacteroides, and Faecalibaculum was observed in the CMHD group, and a higher abundance of Lactobacillus and Turicibacter was observed in the positive drug Ribavirin group. The linear discriminant analysis effect size also revealed a higher proportion of Bacteroides and Bifidobacterium_pseudolongum characterized in the CMHD group. These results demonstrated that CMHD granules are a promising strategy for managing severe influenza and attenuating severe lung damage via reducing viral titer, inflammatory responses, and oxidative stress. The mechanisms are involved in repressed Bcl-2-regulated apoptosis and altered composition and diversity of the gut microbiome.

BackgroundAtrioventricular nodal reentrant tachycardia (AVNRT) is a common arrhythmia. Growing evidence suggests that family aggregation and genetic factors are involved in AVNRT. However, in families with a history of AVNRT, disease-causing genes have not been reported.ObjectiveTo investigate the genetic contribution of familial AVNRT using a whole-exome sequencing (WES) approach.MethodsBlood samples were collected from 20 patients from nine families with a history of AVNRT and 100 control participants, and we systematically analyzed mutation profiles using WES. Gene-based burden analysis, integration of previous sporadic AVNRT data, pedigree-based co-segregation, protein-protein interaction network analysis, single-cell RNA sequencing, and confirmation of animal phenotype were performed.ResultsAmong 95 related reference genes, seven candidate pathogenic genes have been identified both in sporadic and familial AVNRT, including CASQ2, AGXT, ANK2, SYNE2, ZFHX3, GJD3, and SCN4A. Among the 37 reference genes from sporadic AVNRT, five candidate pathogenic genes were identified in patients with both familial and sporadic AVNRT: LAMC1, ryanodine receptor 2 (RYR2), COL4A3, NOS1, and ATP2C2. To identify the common pathogenic mechanisms in all AVNRT cases, five pathogenic genes were identified in patients with both familial and sporadic AVNRT: LAMC1, RYR2, COL4A3, NOS1, and ATP2C2. Considering the unique internal candidate pathogenic gene within pedigrees, three genes, TRDN, CASQ2, and WNK1, were likely to be the pathogenic genes in familial AVNRT. Notably, the core calcium-signaling pathway may be closely associated with the occurrence of AVNRT, including CASQ2, RYR2, TRDN, NOS1, ANK2, and ATP2C2.ConclusionOur pedigree-based studies demonstrate that RYR2 and related calcium signaling pathway play a critical role in the pathogenesis of familial AVNRT using the WES approach.

ABSTRACT: Salmonella enterica serovar Typhimurium (S. Typhimurium) continues to be a serious concern to the poultry industry as a bacterial foodborne zoonosis, which generally results in intestinal inflammation and barrier dysfunction or even death. Eugenol is a phenolic compound with various pharmacological activities involved antioxidant, anti-inflammatory, and antibacterial effects, which is expected to be an effective nonantibiotic therapy. The purpose of this study was to explore the protective effects of eugenol in the cellular and broiler models of S. Typhimurium infection and the possible underlying mechanisms. The results of animal infection showed that eugenol treatments enhanced the relative weight gains and survival rates of broilers with a reduction of the organ bacterial load and intestinal ultrastructural injury. Moreover, eugenol significantly inhibited the mRNA levels of myeloid differentiation factor 88 (MyD88) and toll-like receptor-4 (TLR4), then declined the phosphorylation of p65 and IκBα of NF-κB pathway and the expressions of inflammatory factors (TNF-α, IL-1β, IL-2, and IL-18) in duodenum tissues, while maintained the expressions of intestinal tight junction proteins (ZO-1, claudin-1, occludin). Further experiments in vitro revealed that eugenol markedly inhibited the adhesion and invasion of S. Typhimurium to RAW264.7 or IEC-6 cells, then reduce bacterial multiplication in IEC-6 or DF-1 cells. In conclusion, eugenol could defend broilers from S. Typhimurium infection by stabilizing the intestinal mucosal barrier and relieving inflammatory response, as well as inhibiting bacterial adhesion and invasion to cells.

BackgroundThe liver and bones are both active endocrine organs that carry out several metabolic functions. However, the link between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) is still controversial. The goal of this study was to discover if there was a link between non-alcoholic fatty liver disease and bone mineral density in US persons aged 20 to 59 years of different genders and races.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018, multivariate logistic regression models were utilized to investigate the association between NAFLD and lumbar BMD. Fitted smoothing curves and generalized additive models were also used.ResultsThe analysis included a total of 1980 adults. After controlling for various variables, we discovered that NAFLD was negatively linked with lumbar BMD. The favorable connection of NAFLD with lumbar BMD was maintained in subgroup analyses stratified by sex, race and age in men, other race and aged 20-29 years. The relationship between NAFLD and lumbar BMD in blacks and people aged 40-49 years was a U-shaped curve with the inflection point: at 236dB/m and 262dB/m. Furthermore, we discovered that liver advanced fibrosis and liver cirrhosis were independently connected with higher BMD, while no significant differences were detected in severe liver steatosis and BMD.ConclusionsOur study found an independently unfavorable relationship between NAFLD and BMD in persons aged 20 to 59. We also discovered a positive link between BMD and advanced fibrosis and cirrhosis. More research is needed to back up the findings of this study and to look into the underlying issues.

ObjectivesThis study aims to explore the associations between serum and red blood cell (RBC) folate as indicators of short- and long-term folate status, respectively, and all-cause as well as CVD mortality among hypertensive patients with elevated homocysteine.MethodsA prospective cohort study of the National Health and Nutrition Examination Survey (1999–2006) and 2015 Linked Mortality File was performed. All-cause and CVD mortality risk estimated using Cox proportional hazards models with adjusting for multiple potential covariates.ResultsA total of 1,753 hypertensive patients with elevated homocysteine [mean (SD) age, 68.5 (13.1)] were included in the analysis. During a median follow-up of 10.0 years, a total of 899 all-cause and 257 CVD deaths occurred. Compared the highest with the lowest quartile of RBC folate, the multivariable adjusted hazard ratios and 95% confidence intervals for all-cause and CVD death were 1.13 (0.92–1.39) and 1.47 (1.01–2.16) respectively. There was a significant and positive trend between RBC folate and the risk of CVD death (p for trend = 0.0196). No significant association was found between serum folate and mortality risk among the study sample.ConclusionsHigh level of RBC folate is associated with an increased risk of cardiovascular mortality among hypertensive patients with elevated homocysteine while serum folate has no such effects.

Endoplasmic reticulum (ER) stress may contribute to the pathogenesis and perpetuation of ulcerative colitis (UC). Previous studies have shown artesuante (ARS) has the protective effect on experimental UC. Therefore, it can be assumed that ARS can regulate ER stress and its related reactions. Dextran sulfate sodium (DSS) induced UC model in mice was used to testify this hypothesis. The results clearly showed that DSS exposure caused excessive ER stress evidenced by a markedly increase of GRP78 and CHOP expression, and then activated the ER stress sensors PERK, IRE1, ATF6 and their respective signaling pathways, followed by upregulated caspases12 and lowered Bcl-2/Bax ratio. However, ARS treatment significantly inhibited the occurrence of ER stress via preventing the activation of PERK-eIF2α-ATF4-CHOP and IRE1α-XBP1 signaling pathways, concurrently ER-stress-associated apoptosis in colon tissues. Moreover, ARS treatment remarkably inhibited the activation of NF-κB and the expression levels of pro-inflammatory cytokines, improved the clinical and histopathological alterations as well as maintained the expression of claudin-1 and Muc2 in mucosal layer of colon. Notably, the classic ER stress inhibitor 4-phenyhlbutyric acid enhanced the beneficial effects of ARS; in contrast, the ER stress inducer 2-deoxy-d-glucose substantially abrogated the above-mentioned effects, uncovering the involvement of ER stress in the response. These findings indicated the protection of ARS on UC is associated with its suppressing excessive ER stress mediated intestinal barrier damage and inflammatory response. This study provides a novel aspect to understand the mechanism of ARS against UC.

Faciogenital Dysplasia 1 (FGD1) has been involved in a variety of biological processes, including cytoskeleton restructuring, cell morphology, cell cycle progression, and cell polarity. Abnormal expression of FGD1 was also identified in several types of cancers, indicating its critical role in the development of cancers. However, little is known about the role of FGD1 in hepatocellular carcinoma (HCC). In this study, the expression of FGD1 in HCC was mined with the RNA sequencing data from the cancer genome atlas. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. We find that FGD1 is up-regulated in HCC and correlated with the development and prognosis of HCC. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. Knockdown of FGD1 remarkably inhibits the malignant behaviors and causes morphological disorder of pseudopodia, autophagy inhibition and mitochondrial dyfunction in HCC cells. Further investigation shows that Cdc42, a Rho GTPase, plays a role in these processes. Overexpression of FGD1 significantly promotes the oncogenic properties of HCC cells. Collectively, these findings reveal that FGD1 exhibits oncogenic properties in HCC through regulating cell morphology, autophagy and mitochondrial function, suggesting that FGD1 may serve as a potential therapeutic target for HCC.

TRAF-interacting protein (TRAIP) is a RING-type E3 ubiquitin ligase which has been implicated in various cellular processes, including NF-κB activation, DNA damage response, mitosis, and tumorigenesis. It is considered as a tumor suppressor in basal cell carcinomas and breast cancer in previous studies. However, in our current study, we found that TRAIP exhibited oncogenic properties in liver cancer. In order to determine its effect on tumor biology and the potential mechanism, a variety of advanced experimental technology was used, such as bioinformatic analysis, isobaric tags for relative and absolute quantification (iTRAQ) analysis, tissue microarray detection, and other in vitro cell biology experiments. The results showed that TRAIP was up-regulated in liver cancer and negatively correlated with prognosis. When TRAIP was knocked-down with lentivirus containing specific targeting short hairpin RNAs, the malignant behaviors of Bel7404 cells were significantly inhibited. Meanwhile, overexpression of TRAIP exerted oncogenic effects in SNU449 cells. More importantly, the iTRAQ analysis indicated that TRAIP was significantly related to centriole, centromere, and histone deacetylation, which are critical for mitosis. These findings are in line with previous reports that TRAIP contributes to proper mitosis. Additionally, the iTRAQ analysis also supported that TRAIP may affect G1/S transition by regulating the expression of certain cell cycle related proteins. In summary, our study firstly revealed that TRAIP was up-regulated and negatively correlated with prognosis in liver cancer patients and exhibited oncogenic properties in liver cancer cells, making it a potential target for treatment of liver cancer.

This paper presents the matching characteristics of impellers and guide vanes of high capacity and pressure seawater desalination pumps by using computational fluid dynamics (CFD). The single-stage pump is numerically calculated, and its external characteristics are consistent with the test results of model pump. Taking this scheme as a prototype, the research is carried out from three aspects: (i) the impeller blade outlet width; (ii) the number of impeller and guide vane blades; and (iii) the area ratio of impeller outlet to guide vane inlet. The results indicate that the blade outlet width significantly affects the pump head and efficiency. Appropriately increasing the number of guide vane blades or changing the number of impeller blades can improve efficiency and expand the high-efficiency area. Additionally, increasing the throat area of the guide vane has the opposite effect on the large flow and small flow area of the pump. An optimized hydraulic model design scheme is obtained.

In our previous study, lipopolysaccharide (LPS) significantly reduced the cell viability of primary bovine mammary epithelial cells (bMEC) leading to cell apoptosis, which were prevented by caffeic acid (CA) through inhibiting NF-κB activation and reducing proinflammatory cytokine expression. While the underlying mechanism remains unclear, here, we determined that LPS induced the extensive microstructural damage of bMEC, especially the mitochondria and endoplasmic reticulum. Then, the obvious reduction of mitochondrial membrane potential and expression changes of apoptosis-associated proteins (Bcl-2, Bax, and casepase-3) indicated that apoptosis signaling through the mitochondria should be responsible for the cell viability decrease. Next, the high-throughput cDNA sequencing (RNA-Seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were employed to verify that the MAPK and JAK-STAT signaling pathways also were the principal targets of LPS. Following, the critical proteins (ERK, JNK, p38, and c-jun) of the MAPK signaling pathways were activated, and the release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) regulated by NF-κB and MAPKs was significantly increased, which can promote a cascade of inflammation that induces cell injury and apoptosis. Meanwhile, CA significantly inhibited the activation of MAPKs and the release of proinflammatory cytokines in a dose-dependent manner, which were similar to its effects on the NF-κB activation that we previously published. So we concluded that CA regulates the proteins located in the upstream of multiple cell signal pathways which can reduce the LPS-induced activation of NF-κB and MAPKs, thus weakening the inflammatory response and maintaining cell structure and function, which accordingly inhibit apoptosis.

Reactive oxygen species (ROS) and oxidative stress are thought to play a central role in potentiating macrophage activation, causing excessive inflammation, tissue damage, and sepsis. Recently, we have shown that punicalagin (PUN) exhibits anti-inflammatory activity in LPS-stimulated macrophages. However, the potential antioxidant effects of PUN in macrophages remain unclear. Revealing these effects will help understand the mechanism underlying its ability to inhibit excessive macrophage activation. Hemeoxygenase-1 (HO-1) exhibits antioxidant activity in macrophages. Therefore, we hypothesized that HO-1 is a potential target of PUN and tried to reveal its antioxidant mechanism. Here, PUN treatment increased HO-1 expression together with its upstream mediator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). However, specific inhibition of Nrf2 by brusatol (a specific Nrf2 inhibitor) dramatically blocked PUN-induced HO-1 expression. Previous research has demonstrated that the PI3K/Akt pathway plays a critical role in modulating Nrf2/HO-1 protein expression as an upstream signaling molecule. Here, LY294002, a specific PI3K/Akt inhibitor, suppressed PUN-induced HO-1 expression and led to ROS accumulation in macrophages. Furthermore, PUN inhibited LPS-induced oxidative stress in macrophages by reducing ROS and NO generation and increasing superoxide dismutase (SOD) 1 mRNA expression. These findings provide new perspectives for novel therapeutic approaches using antioxidant medicines and compounds against oxidative stress and excessive inflammatory diseases including tissue damage, sepsis, and endotoxemic shock.

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2- polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization. [ABSTRACT FROM AUTHOR]