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Deletion of DRA results in severely reduced colonic HCO3 (-) secretory rate, a loss of colonic fluid absorption, a lack of a firmly adherent mucus layer and a severely reduced colonic mucosal resistance to DSS damage. These data provide potential pathophysiological explanations for the increased susceptibility of CLD patients to intestinal inflammation.

High-mobility group box 1 (HMGB1) proteins are substantially up-regulated in acute and chronic hepatitis. However, the immunopathogenic role of HMGB1 in patients with chronic hepatitis B (CHB) has not been elucidated. In this study, using a cohort of 36 CHB patients, we demonstrated a crucial role for HMGB1 to modulate balance between regulatory T (Treg) and T helper 17 (Th17) cells via the toll-like receptor (TLR)-4-interleukin (IL)-6 pathway. Serum HMGB1 levels were dramatically higher in CHB patients and increased along with liver injury, inflammation and fibrosis. Notably, HMGB1 increased along with decreased Treg/Th17 cells ratios in the periphery or intrahepatic microenvironment, which provides a clue for HMGB1 to favour Th17 responses whereas inhibit Treg responses. For in vitro studies, serum pools were constructed with serum from CHB patients at an advanced stage, whereas peripheral blood mononuclear cells (PBMC) pools were constructed with cells from those at an early stage. CHB-serum significantly enhanced retinoic acid-related orphan receptor-γt (RORγt), whereas they inhibited forkhead box P3 (Foxp3) expression in CHB-PBMC, which could be reversed by blocking of HMGB1, TLR4, or IL-6. Besides, recombinant HMGB1 (rHMGB1) dose-dependently up-regulated RORγt whereas down-regulated Foxp3 expression in CHB-PBMC, and meanwhile, rHMGB1 enhanced TLR4 and IL-6 expression in CHB-PBMC. Moreover, the axis of HMGB1-TLR4-IL-6-Treg/Th17 required noncontact interactions between CD4 and non-CD4 cells. In addition, rHMGB1 down-regulated anti-inflammatory proteins on CD4(+) CD25(+) cells whereas up-regulated pro-inflammatory cytokines in CD4(+) CD25(-) cells. In summary, enriched HMGB1 in CHB patients shifts Treg/Th17 balance to Th17 dominance via the TLR4-IL-6 pathway, which exacerbates liver injury and inflammation.

Background Maternal thyroid hormone deficiency is the most common disorder of thyroid function during pregnancy and can influence the outcome for mother and foetus. The purpose of this study was to investigate the prevalence of thyroid hormone deficiency during the first half of pregnancy in iodine sufficient areas of China.

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A synthesis of published and newly acquired stable and radiocarbon isotope data from soil, river, and marine particulate organic carbon (OC) from the South China Sea drainage and sedimentary basin reveals that OC derived from bedrock‐erosion (petrogenic OC) and marine productivity comprises the major contributors to bulk OC in particulate matter reaching abyssal depths, while soil‐derived OC appears negligible. Aluminum‐radiocarbon relationships of sediments suggest that soil OC initially associated with detrital terrestrial minerals is lost and replaced by marine OC during transport beyond the continental shelf. We estimate that petrogenic OC sinking to a ~30,000 km2 region of the deep northeastern South China Sea accounts for 0.6% of global petrogenic OC burial. The basin‐wide OC isotope patterns coupled with sediment trap observations highlight both the spatial variabilities of OC components as they propagate from source to sedimentary sink and the significance of petrogenic OC to deep ocean sediments.

Aims Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose–response effects. This meta-analysis aimed to find the dose–response relationship between alcohol, coffee or tea consumption and cognitive deficits. Methods Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose–response relationship graphs. Results The search identified 29 prospective studies from America, Japan, China and some European countries. The dose–response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92–0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits. Conclusions Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.