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In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation. Immature neutrophils had reduced expression of Slc11a1, a gene that encodes a metal ion transporter generally thought to restrict pathogen growth in macrophages. Adoptive transfer of SLC11A1-proficient neutrophils, but not SLC11A1-deficient neutrophils, reduced systemic Salmonella burden in Slc11a1-/- mice or mice with vitamin A deficiency. Loss of terminal granulopoiesis regulator CCAAT/enhancer-binding protein ϵ (C/EBPϵ) also decreased neutrophil-mediated control of Salmonella, but not that mediated by peritoneal macrophages. Susceptibility to infection increased in Cebpe-/- Slc11a1+/+ mice compared with wild-type controls, in an Slc11a1-expression-dependent manner. These data suggest that SLC11A1 deficiency impairs Salmonella control in part by blunting neutrophil-mediated defence.

BackgroundProgressive age-associated change in frequencies and functional capacities of immune cells is known as immunosenescence. Despite data linking chronic environmental, physiological, and psychosocial stressors with accelerated aging, how stress contributes to immunosenesence is not well characterized.ObjectiveTo help delineate the contribution of cumulative physiological stress on immunosensence we assessed relationships between a composite measurement of cumulative physiological stress, reflecting the functioning of the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, cardiovascular system, and metabolic processes, and lymphocyte changes typically affiliated with aging in a cohort of healthy volunteers ranging from 18 to 66 y.ResultsPhysiological stress load positively correlated with subject age in the study cohort and was significantly higher in adults 50-66 y compared to adults 18-33 y and 34-49 y. Using physiological stress load, we identified a significant age-dependent association between stress load and frequencies of circulating regulatory T lymphocytes (Tregs). Frequencies were higher in younger participants, but only in participants exhibiting low physiological stress load. As stress load increased, frequencies of Tregs decreased in young participants but were unchanged with increasing stress load in middle and older age individuals. Follow-up analysis of stress load components indicated lower circulating DHEA-S and higher urinary norepinephrine as the primary contributors to the effects of total stress load on Tregs. In addition, we identified age-independent inverse associations between stress load and frequencies of naïve Tregs and naïve CD4 T cells and positive associations between stress load and frequencies of memory Tregs and memory CD4 T cells. These associations were primarily driven by stress load components waist circumference, systolic and diastolic blood pressure, CRP, and HbA1c. In summary, our study results suggest that, in younger people, physiological stress load may diminish regulatory T cell frequencies to levels seen in older persons. Furthermore, independent of age, stress load may contribute to contraction of the naïve Treg pool and accumulation of memory Treg cells.Clinical trialRegistered on ClincialTrials.gov (Identifier: NCT02367287).

ObjectiveTo evaluate the effect of a diet pattern based on Dietary Guidelines for Americans (DGA), in a controlled feeding setting, on plasma markers of inflammation and on cytokine production by peripheral blood mononuclear cells (PBMC).DesignWomen (n = 44) with one or more risk factors of metabolic syndrome (and BMI: 25.2-39.8 kg/m2) completed an 8-wk controlled feeding study. They were randomized to either a group following a diet based on DGA 2010 (DGA), or a group given a 'typical American diet' (TAD), based largely on a Western diet pattern. By design, women maintained their body weight. Fasting plasma and PBMC were collected at wk. 0 (baseline) and at wk. 8 (post-intervention). Sixteen plasma markers of inflammation and eight PBMC cytokines were measured at both time points, to evaluate if the diet had a significant effect on concentrations of these inflammatory markers. Data were analyzed using ANCOVA, followed by multiple-comparison adjustment using Benjamini-Hochberg method.ResultsSignificant changes observed in Serum Amyloid A (SAA) and Matrix Metalloproteinase 3 (MMP3) in plasma did not retain significance upon multiple comparison adjustment. SAA: p = 0.044, adj p = 0.450; DGA mean change [95% CI] = - 12.6[- 32.3 to 7.04]; TAD mean change [95% CI] = - 2.24 [- 9.99 to 5.51]. MMP3: p = 0.014, adj p = 0.35; DGA mean change [95% CI] = 2.72[- 4.16 to 9.59]; TAD mean change [95% CI] = - 0.98[- 16.7 to 14.7]). Other inflammation markers were not differently altered by DGA relative to TAD. Effect size of change (Cohens d) indicated a large/medium-large effect of intervention on MMP3 and CRP, and medium effect on IL-6.ConclusionsNo statistically significant changes were observed in the immune markers examined in this study. The biological roles and magnitude of the non-significant differences seen with two variables, CRP and MMP3, suggest that they be examined in future studies.Trial registrationClinicaltrials.gov identifier NCT02298725.

Objective To explore the expression of sirtuin 6 (Sirt6) and lipid metabolism indicators in type 2 diabetic nephropathy (T2DN), and analyze their correlation with renal function indicators and their effectiveness in predicting T2DN. Methods The data of 160 patients with type 2 diabetes admitted to Langfang People's Hospital from January 2019 to November 2020 were retrospectively analyzed. The patients were divided into the observation group (n=80, T2DN) and the control group (n=80, merely type 2 diabetes) according to whether they had nephropathy or not. Sirt6, lipid metabolism indicators ［triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C)］ , and renal function indicators ［blood urea nitrogen (BUN) and blood creatinine (Cr)］ were measured by qRT-PCR, enzyme-linked immunosorbent assay and fully automated biochemical analyzer, respectively. The serum levels of Sirt6, lipid metabolism indicators and renal function indicators between the two groups were compared, the correlation between Sirt6, lipid metabolism indicators, and renal function indicators was analyzed by Pearson correlation. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of Sirt6, lipid metabolism indicators in the diagnosis of T2DN. Results The relative expression level of Sirt6 mRNA in the observation group was lower than that in the control group, and the levels of TG, TC, LDL-C, BUN and Cr were higher than those in the control group (P＜0.05). Pearson correlation analysis showed that Sirt6 was negatively correlated with BUN (r=-0802，P＜0.05) and Cr (r=-0.785，P＜0.05); TG was positively correlated with BUN(r=0.621，P＜0.05) and Cr (r=0.628，P＜0.05); TC was positively correlated with BUN (r=0.768, P＜0.05) and Cr (r=0.759, P＜0.05); LDL-C was positively correlated with BUN (r=0.722, P＜0.05) and Cr (r=0.718, P＜0.05). The area under the ROC curve (AUC) of Sirt6, TG, TC and LDL-C for diagnosis of T2DN was 0.783, 0.588, 0.605 and 0.664, respectively, while the AUC (0.875), sensitivity (92.50%), and specificity (93.75%) of combination of the four indexes were the highest. Conclusion Sirt6 is low expressed in T2DN and negatively correlated with renal function indicators. The lipid metabolism indicators are highly expressed in T2DN and positively correlated with renal function indicators. If the Sirt6 value decreases and the levels of lipid metabolism indicators increase in patients with type 2 diabetes, it reflects that the risk of renal impairment has an increscsing trend, which might lead to renal dysfunction.

BackgroundMonocytes are a heterogenous population of immune cells whose subsets and functions become substantially dysregulated with advanced age. Although much of our current understanding of the age-related changes in monocytes is derived from fasting blood samples, most people are predominately in the postprandial state during waking hours. As hormonal, metabolic, and immunological changes in response to the consumption of a meal are manifested in postprandial blood, it's unclear how age-dependent changes in peripheral monocytes at fasting are impacted by a dietary challenge.ObjectiveWe investigated the impact of age and meal consumption on circulating monocyte frequencies and subsets defined as classical (CD14 + CD16-), intermediate (CD14 + CD16 +), or non-classical (CD14dim CD16 +) in a cohort of 349 healthy adult volunteers grouped into categories based on their age: young adults (18-33 y, n = 123), middle adults (34-49 y, n = 115), and older adults (50-66 y, n = 111).ResultsFollowing 12-h fast total monocyte counts inversely correlated with subject age. Older adults had significantly fewer circulating monocytes along with elevated levels of TGs, cholesterol, glucose, IL-6, IL-8, TNF, neopterin, and CCL2 compared with young adults. Circulating monocyte pools in older adults consisted of smaller proportions of classical but larger proportions of intermediate and non-classical monocytes. Proportions of classical monocytes were inversely correlated with plasma TNF, IL-8, and neopterin while intermediate monocytes were positively correlated with plasma IL-6, TNF, and neopterin. Three hours after consuming a fat-containing meal postprandial monocyte counts increased in all age groups. Despite age-dependent differences in monocyte subsets at fasting, consumption of a meal induced similar changes in the proportions of classical and non-classical monocytes across age groups. Within the circulating postprandial monocyte pool, percentages of classical monocytes decreased while non-classical monocytes increased. However no change in precursory intermediate monocytes were detected. Our study confirms that ageing is associated with changes in monocyte frequencies and subsets and shows that consuming a fat-containing meal induces temporal changes in monocyte frequency and subsets independently of subject age.Clinical trialRegistered on ClincialTrials.gov (Identifier: NCT02367287).

BackgroundTryptophan (Trp) metabolites from intestinal bacteria (indole, indole acetic acid [IAA] and indole propionic acid [IPA]), and the Trp metabolite kynurenine (Kyn) from the indoleamine 2,3-dioxygenase (IDO) pathway, are aryl hydrocarbon receptor (AhR) agonists and thus, can regulate immune activity via the AhR pathway. We hypothesized that plasma concentrations of these metabolites would be associated with markers of immune activation in a cohort of healthy adults in a manner consistent with AhR-mediated immune-regulation. We also hypothesized that the plasma Kyn/Trp ratio, a marker of IDO activity, would be associated with immune markers reflecting IDO activation in innate immune cells. Finally, we hypothesized that some intestinal bacteria would be associated with plasma indole, IPA and IAA, and that these bacteria themselves would be associated with immune markers.MethodsA novel set of 88 immune markers, and plasma Trp metabolites, were measured in 362 healthy adults. Bacterial taxa from stool were identified by 16S rRNA gene analysis. Multiple linear regression analysis was used to identify significant associations with immune markers.ResultsThe sum of indole and IAA was positively associated with natural killer T-cells levels. Kyn and Kyn/Trp were positively associated with neopterin and IP-10, markers of type 1 immunity, and TNF-α and C-reactive protein (CRP), markers of the acute phase response, and the regulatory cytokine IL-10. Three bacteria negatively associated with Trp metabolites were associated with markers of immune activation: the family Lachnospiraceae with higher lymphocyte counts but lower level of activated CD4 T-cells, the genus Dorea with higher production of IFN-γ by T-cells in PBMC cultures, and the genus Ruminococcus with higher production IL-6 in PBMC cultures stimulated with bacterial lipopolysaccharide (LPS).ConclusionsIn this cohort of healthy adults bacterial Trp metabolites were not strongly associated with immune markers. Conversely, the Kyn/Trp ratio was strongly associated with markers of systemic inflammation and the acute phase response, consistent with IDO activation in innate immune cells. Finally, commensal bacteria associated with lower plasma (and perhaps intestinal) levels of bacterial Trp metabolites were associated with greater immune activation, possibly reflecting decreased regulatory immune activity related to lower intestinal levels of bacterial indole metabolites.

Metabolic syndrome (MetS) has become a major public health challenge in recent years. Nuclear magnetic resonance, as a nondestructive measurement, has been widely used in medical diagnosis and screening. Compared to conventional magnetic resonance imaging and nuclear magnetic spectroscopy, low-field nuclear magnetic resonance is superior in portability, simplicity, and low-cost. In this study, a novel approach based on low-field magnetic resonance analysis is proposed to detect metabolic syndrome. T1–T2 correlation relaxometry is employed to measure human serum. Combining with a classification model based on partial least squares discriminant analysis (PLS-DA), the detection of metabolic syndrome is realized. The classification models based on both T1–T2 relaxation correlation data and spectrum are compared. Additionally, classification model based on convolutional neural networks (CNNs) is also evaluated for comparison. The experimental results indicate that the PLS-DA model based on the T1–T2 spectrum achieves a better performance. Specifically, the area under curve, accuracy, F1 score, recall and precision of the classification model evaluated on testing group are 0.784, 70.91%, 75.00%, 77.42%, and 72.73%, respectively. On the other hand, the testing results of CNN model trained using T1–T2 spectrum are 0.774, 65.45%, 61.22%, 48.39%, and 83.33% for AUC, accuracy, F1 score, recall, and precision. The experimental results reveal the limitation of CNN models on small datasets. In this study, T1–T2 correlation relaxometry is employed for the analysis of MetS for the first time, and the feasibility of proposed method has been demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a nutritional and metabolic disease with a high prevalence today. Artemisia capillaris has anti-inflammatory, antioxidant, and other effects. However, the mechanism of A. capillaris in treating NAFLD is still poorly understood. Methods: This study explored the mechanism of A. capillaris in the treatment of NAFLD through network pharmacology and molecular docking, and verified the results through in vivo experiments using a high-fat diet-induced mouse model and in vitro experiments using an oleic acid-induced HepG2 cell model. Key findings: Aqueous extract of A. capillaris (AEAC) can reduce blood lipids, reduce liver lipid accumulation and liver inflammation in NAFLD mice, and improve NAFLD. Network pharmacology analysis revealed that 51 drug ingredients in A. capillaris correspond to 370 targets that act on NAFLD. GEO data mining obtained 93 liver differentially expressed genes related to NAFLD. In the UHPLC-MS detection results, 36 components were characterized and molecular docked with JNK. Verified in vitro and in vivo, the results show that JNK and the phosphorylation levels of IL-6, IL-1β, c-Jun, c-Fos, and CCL2 are key targets and pathways. Conclusions: This study confirmed that AEAC reduces lipid accumulation and inflammation in the liver of NAFLD mice by inhibiting the JNK/AP-1 pathway. [ABSTRACT FROM AUTHOR]

The increasing attention towards environmental quality, food safety, public security and medical diagnosis demands high requirements and standards for chemical sensors with merits of rapid response, high precision, long-term stability and reusability. In this case, a prominent innovation in sensory materials holds potential to realize new generations of chemical sensor technologies. Specifically, photonic crystals (PCs) as structured dielectric materials with spatially periodic ordered arrangements offer unique advantages in improving the sensing performance of chemical sensors. Consequently, the promising properties of PCs promote research on their implementation as an integral part of chemical sensors. This review highlights the integration of PCs into chemical sensors including a range of building blocks for the construction of PCs with versatile opal or opal inverse structural architectures and a delicate choice of surface functionality with associated sensing interfaces for target recognition and signal transduction. Subsequently, based on their synthesis and functionality, we focus on introducing the sensing principles of recent advances in PC-based chemical sensors, such as reflection spectra-based sensing, visual colorimetric sensing, fluorescence sensing, surface-enhanced Raman spectroscopy (SERS)-based sensing and other integrated sensing. Finally, the future prospects and challenges are discussed for the further improvement of PC-based chemical sensors. [ABSTRACT FROM AUTHOR]

As a colossal developing economy, irrational, and inefficient trades broadly exist in China's stock market and are intensified by the once-in-a-century COVID-19 pandemic. This atypical but prominent event enhances systemic risk and requires a more effective analysis tool that adapts to the investors' sentiment and behavior. Based on the behavioral asset pricing model, this paper verifies the existence of noise traders in China's stock market, measures the intensity of the noise with the NTR indicator, and examines the market noise with IANM. Furthermore, the mechanism of how COVID-19 influences the market noise through investors' behaviors is analyzed with the event study method. The findings show that, based on 92 Chinese companies, the market noise significantly exists, and the noise is associated with psychological biases including over-confidence, herding effects and regret aversion. These biases are affected to varying degrees by COVID-19-related events, leading to notable implications for market stability and investor behavior during crises. Our study provides critical insights for policymakers and investors on managing market risks and understanding behavioral impacts during unprecedented events. [ABSTRACT FROM AUTHOR]