Association between dietary vitamin E intake and constipation: NHANES 2005–2010

BackgroundThis investigation aimed to analyze the association between dietary vitamin E intake and constipation prevalence among United States adults.MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES), this cross-sectional study assessed vitamin E intake through 24-h dietary recall and defined constipation based on the Bristol Stool Form Scale (BSFS). Logistic regression models were employed to evaluate the relationship between vitamin E intake and constipation, with results presented as odds ratios (ORs) and 95% confidence intervals (CIs). Stratified analyses were conducted based on covariates such as age, and restricted cubic spline (RCS) models were generated to explore the potential linear or non-linear association.ResultsIndividuals experiencing constipation exhibited lower vitamin E intake compared to those without constipation. Weighted multivariate logistic regression models demonstrated a negative correlation between vitamin E intake and constipation risk, even after adjusting for potential confounding variables. Further RCS analysis revealed a statistically significant non-linear inverse relationship between vitamin E intake and constipation risk (p-value for non-linearity = 0.0473).ConclusionOur findings suggest an independent inverse association between vitamin E intake and constipation prevalence in United States adults. Prospective research is needed to validate these observations

Establishment of Elymus natans improves soil quality of a heavily degraded alpine meadow in Qinghai-Tibetan Plateau,

Abstract Elymus natans is a dominant native species widely planted to restore the heavily degraded alpine meadows in Qinghai-Tibetan plateau. The objective of this study was to determine how E. natans establishment affected the quality and fertility of a heavily degraded soil. Soil samples (at depths of 0-10, 10-20 and 20-30 cm) were collected from the 3-and 7-year-old E. natans re-vegetated grasslands, and in the heavily degraded alpine meadow (control). The establishment of E. natans promoted plant cover and aboveground biomass. Compared to the non-reseeded meadow, the concentration of total organic C increased by 13% in the soil under 3-year-old reseeded E. natans grassland at 0-10 cm, and by 7-33% in the soil under 7-year-old reseeded E. natans grassland at 0-10, 10-20 and 20-30 cm depths. Rapid increases in total and available N were also observed in two E. natans re-vegetated grasslands, especially in the 0-10 cm soil layer. Across three sampling depths, total P concentration was increased by 17-35% and 18-54% in 3-and 7-year-old reseeded soil respectively, compared to the soil of control. After 3 years of E. natans growth, microbial biomass C increased by 13-58% at 0-10 and 10-20 cm layers; while it increased by 43-87% in 7-year-old reseeded treatment at 0-10, 10-20 and 20-30 cm depths relative to control. A similar increasing trend was observed for microbial biomass N and P generally. Significant increase in neutral phosphatase, urease, catalase and dehydrogenase was also found in 3-and 7-year-old re-vegetated grasslands compared with heavily degraded meadow. Our results suggest a significant positive impact of E. natans establishment on soil quality. Thus, E. natans establishment could be an effective and applicable measure in restoring heavily degraded alpine meadow in the region of Qinghai-Tibetan Plateau

Establishment of Elymus natans improves soil quality of a heavily degraded alpine meadow in Qinghai-Tibetan Plateau,

Abstract Elymus natans is a dominant native species widely planted to restore the heavily degraded alpine meadows in Qinghai-Tibetan plateau. The objective of this study was to determine how E. natans establishment affected the quality and fertility of a heavily degraded soil. Soil samples (at depths of 0-10, 10-20 and 20-30 cm) were collected from the 3-and 7-year-old E. natans re-vegetated grasslands, and in the heavily degraded alpine meadow (control). The establishment of E. natans promoted plant cover and aboveground biomass. Compared to the non-reseeded meadow, the concentration of total organic C increased by 13% in the soil under 3-year-old reseeded E. natans grassland at 0-10 cm, and by 7-33% in the soil under 7-year-old reseeded E. natans grassland at 0-10, 10-20 and 20-30 cm depths. Rapid increases in total and available N were also observed in two E. natans re-vegetated grasslands, especially in the 0-10 cm soil layer. Across three sampling depths, total P concentration was increased by 17-35% and 18-54% in 3-and 7-year-old reseeded soil respectively, compared to the soil of control. After 3 years of E. natans growth, microbial biomass C increased by 13-58% at 0-10 and 10-20 cm layers; while it increased by 43-87% in 7-year-old reseeded treatment at 0-10, 10-20 and 20-30 cm depths relative to control. A similar increasing trend was observed for microbial biomass N and P generally. Significant increase in neutral phosphatase, urease, catalase and dehydrogenase was also found in 3-and 7-year-old re-vegetated grasslands compared with heavily degraded meadow. Our results suggest a significant positive impact of E. natans establishment on soil quality. Thus, E. natans establishment could be an effective and applicable measure in restoring heavily degraded alpine meadow in the region of Qinghai-Tibetan Plateau

Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease

Coronary heart disease (CHD) is top risk factor for health in modern society, causing high mortality rate each year. However, there is no reliable way for early diagnosis and prevention of CHD so far. So study the mechanism of CHD and development of novel biomarkers is urgently needed. In this study, metabolomics and metagenomics technology are applied to discover new biomarkers from plasma and urine of 59 CHD patients and 43 healthy controls and trace their origin. We identify GlcNAc-6-P which has good diagnostic capability and can be used as potential biomarkers for CHD, together with mannitol and 15 plasma cholines. These identified metabolites show significant correlations with clinical biochemical indexes. Meanwhile, GlcNAc-6-P and mannitol are potential metabolites originated from intestinal microbiota. Association analysis on species and function levels between intestinal microbes and metabolites suggest a close correlation between Clostridium sp. HGF2 and GlcNAc-6-P, Clostridium sp. HGF2, Streptococcus sp. M143, Streptococcus sp. M334 and mannitol. These suggest the metabolic abnormality is significant and gut microbiota dysbiosis happens in CHD patients

Expansion of Pathogenic Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1) or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), have revolutionized cancer management but are associated with devastating immune-related adverse events including myocarditis. The main risk factor for ICI myocarditis is the use of combination PD-1 and CTLA4 inhibition. ICI myocarditis is often fulminant and is pathologically characterized by myocardial infiltration of T lymphocytes and macrophages. Although much has been learned about the role of T-cells in ICI myocarditis, little is understood about the identity, transcriptional diversity, and functions of infiltrating macrophages. METHODS: We used an established murine ICI myocarditis model (Ctla4+/-Pdcd1-/- mice) to explore the cardiac immune landscape using single-cell RNA-sequencing, immunostaining, flow cytometry, in situ RNA hybridization, molecular imaging, and antibody neutralization studies. RESULTS: We observed marked increases in CCR2 (C-C chemokine receptor type 2)+ monocyte-derived macrophages and CD8+ T-cells in this model. The macrophage compartment was heterogeneous and displayed marked enrichment in an inflammatory CCR2+ subpopulation highly expressing Cxcl9 (chemokine [C-X-C motif] ligand 9), Cxcl10 (chemokine [C-X-C motif] ligand 10), Gbp2b (interferon-induced guanylate-binding protein 2b), and Fcgr4 (Fc receptor, IgG, low affinity IV) that originated from CCR2+ monocytes. It is important that a similar macrophage population expressing CXCL9, CXCL10, and CD16α (human homologue of mouse FcgR4) was expanded in patients with ICI myocarditis. In silico prediction of cell-cell communication suggested interactions between T-cells and Cxcl9+Cxcl10+ macrophages via IFN-γ (interferon gamma) and CXCR3 (CXC chemokine receptor 3) signaling pathways. Depleting CD8+ T-cells or macrophages and blockade of IFN-γ signaling blunted the expansion of Cxcl9+Cxcl10+ macrophages in the heart and attenuated myocarditis, suggesting that this interaction was necessary for disease pathogenesis. CONCLUSIONS: These data demonstrate that ICI myocarditis is associated with the expansion of a specific population of IFN-γ-induced inflammatory macrophages and suggest the possibility that IFN-γ blockade may be considered as a treatment option for this devastating condition

Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse

BACKGROUND: Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci, such as albumin (Alb). Unfortunately, the precise in vivo integration efficiency of a long insert is very low (~ 0.1%). RESULTS: We report that the use of a double-cut donor leads to a 10- to 20-fold increase in liver editing efficiency, thereby completely reconstituting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb and B domain-deleted (BDD) F8 donor plasmids. We find that the integration of a double-cut donor at the Alb locus in mouse liver is mainly through non-homologous end joining (NHEJ)-mediated knock-in. We then target BDDF8 to multiple sites on introns 11 and 13 and find that NHEJ-mediated insertion of BDDF8 restores hemostasis. Finally, using 3 AAV8 vectors to deliver genome editing components, including Cas9, sgRNA, and BDDF8 donor, we observe the same therapeutic effects. A follow-up of 100 mice over 1 year shows no adverse effects. CONCLUSIONS: These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns after AAV-mediated delivery of editing components

The gut microbiome in atherosclerotic cardiovascular disease

The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs