Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids.

Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral infection. However, very little information is available about which specific microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed light on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral infection and accelerate replication within the intestinal microenvironment.

Progress of nanopreparation technology applied to volatile oil drug delivery systems.

Traditional Chinese medicine volatile oil has a long history and possesses extensive pharmacological activity. However, volatile oils have characteristics such as strong volatility, poor water solubility, low bioavailability, and poor targeting, which limit their application. The use of volatile oil nano drug delivery systems can effectively improve the drawbacks of volatile oils, enhance their bioavailability and chemical stability, and reduce their volatility and toxicity. This article first introduces the limitations of the components of traditional Chinese medicine volatile oils, discusses the main classifications and latest developments of volatile oil nano formulations, and briefly describes the preparation methods of traditional Chinese medicine volatile oil nano formulations. Secondly, the limitations of nano formulation technology are discussed, along with future challenges and prospects. A deeper understanding of the role of nanotechnology in traditional Chinese medicine volatile oils will contribute to the modernization of volatile oils and broaden their application value.

Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota.

Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC. Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing. Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1ß,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics. Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.

[Variations and simulation of stable isotopes in precipitation in the Heihe River basin].

To study the variations of deltaD and delta18O in precipitation, 301 samples were sampled during 2002-2004 in 6 sites in the Heihe River basin, Northwestern China. The deltaD and delta18O values ranged from 59 per thousand to -254 per thousand and 6.5 per thousand to -33.4 per thousand, respectively. This wide range indicated that stable isotopes in precipitation were controlled by different condensation mechanisms as a function of air temperature and varying sources of moisture. delta18O in precipitation had a close positive relationship with the air temperature, i. e., a clear temperature effect existed in this area. At a monthly scale, no precipitation effect existed. On the other hand, a weak precipitation effect still accrued at precipitation events scale. The spatial variation of delta18O showed that the weighted average delta18O values decreased with the increasing altitude of sampling sites at a gradient of -0. 47 per thousand/100m. A regional Meteoric Water Line, deltaD = 7.82 delta18O + 7.63, was nearly identical to the Meteoric Water Line in the Northern China. The results of backward trajectory of each precipitation day at Xishui showed that the moisture of the precipitation in cold season (October to March) mainly originated from the west while the moisture source was more complicated in warm season (April to September). The simulation of seasonal delta18O variation showed that the stable isotope composition of precipitation tended to a clear sine-wave seasonal variation.