Effects of Xiao Chengqi Formula on Slow Transit Constipation by Assessing Gut Microbiota and Metabolomics Analysis in vitro and in vivo

The Xiao Chengqi (XCQ) formula is a newly constituted traditional Chinese medicine prescription in the treatment of intestinal motility deficiency and is effective in patients with slow transit constipation (STC). XCQ formula was reconstructed based on a “Chengqi” decoction. Astragali Radix, Angelicae Sinensis Radix, and cooked ground Salviae Miltiorrhizae Radix et Rhizoma were added to the prescription to enhance. An STC rat model was constructed and treated with the formula to understand the detailed mechanism by which XCQ promotes intestinal peristalsis. The effects of the XCQ formula on intestinal microflora and metabolic levels and the possible molecular mechanism of its regulation were explored using 16S rDNA sequencing, metabolomics sequencing, and tissue RNA sequencing. The results showed a significant decrease in the abundance of Roseburia spp. in the feces of STC rats, a significant decrease in the content of butyl aminobenzene (BAB) in feces, and an increase in the number of interstitial cells of Cajal (ICC) in the colon of STC rats. Furthermore, in vitro and in vivo experiments revealed that BAB could activate IL-21R on the ICC surface, upregulate the phosphorylation of the downstream molecules STAT3 and ERK, and inhibit loperamide-induced ICC apoptosis. Therefore, the XCQ formula can improve the defecation status of patients with STC by protecting ICC activity, promoting the colonization of Roseburia spp. to promote peristalsis, and increasing the BAB content after metabolism

Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells

Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota.Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation

Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data.</p> <p>Methods</p> <p>pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively.</p> <p>Results</p> <p>pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; <it>P </it>< 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (<it>P </it>= 0.001), lymph node metastasis (<it>P </it>< 0.001), distant metastasis (<it>P </it>< 0.001) and high preoperative CEA level (<it>P </it>< 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (<it>P </it>< 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (<it>P </it>= 0.002) and 5-year overall survival rate (<it>P </it>< 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: <it>P </it>= 0.139; OS: <it>P </it>= 0.071).</p> <p>Conclusions</p> <p>pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.</p

Critical Leaf Water Content for Maize Photosynthesis under Drought Stress and Its Response to Rewatering

Crop photosynthesis is closely related to leaf water content (LWC), and clarifying the LWC conditions at critical points in crop photosynthesis has great theoretical and practical value for accurately monitoring drought and providing early drought warnings. This experiment was conducted to study the response of LWC to drought and rewatering and to determine the LWC at which maize photosynthesis reaches a maximum and minimum and thus changes from a state of stomatal limitation (SL) to non-stomatal limitation (NSL). The effects of rehydration were different after different levels of drought stress intensity at different growth stages, and the maize LWC recovered after rewatering following different drought stresses at the jointing stage; however, the maize LWC recovered more slowly after rewatering following 43 days and 36 days of drought stress at the tasselling and silking stages, respectively. The LWC when maize photosynthesis changed from SL to NSL was 75.4% ± 0.38%, implying that the maize became rehydrated under physiologically impaired conditions. The LWCs at which the maize Vcmax25 reached maximum values and zero differed between the drought and rewatering periods. After exposure to drought stress, the maize exhibited enhanced drought stress tolerance, an obviously reduced suitable water range, and significantly weakened photosynthetic capacity. These results provide profound insight into the turning points in maize photosynthesis and their responses to drought and rewatering. They may also help to improve crop water management, which will be useful in coping with the increased frequency of drought and extreme weather events expected under global climate change

Dynamic Characteristics of Canopy and Vegetation Water Content during an Entire Maize Growing Season in Relation to Spectral-Based Indices

A variety of spectral vegetation indices (SVIs) have been constructed to monitor crop water stress. However, their abilities to reflect dynamic canopy water content (CWC) and vegetation water content (VWC) during the growing season have not been concurrently examined, and the underlying mechanisms remain unclear, especially in relation to soil drying. In this study, a field experiment was conducted and designed with various irrigation regimes applied during two consecutive growing seasons of maize. The results showed that CWC, VWC, and the SVIs exhibited obvious trends of first increasing and then decreasing within a growing season. In addition, VWC was allometrically related to CWC across the two growing seasons. A linear relationship between the five SVIs and CWC occurred within a certain CWC range (0.01&ndash;0.41 kg m&minus;2), while the relationship between these SVIs and VWC was nonlinear. Furthermore, the five SVIs indicated critical values for VWC, and these values were 1.12 and 1.15 kg m&minus;2 for the water index (WI) and normalized difference water index (NDWI), respectively; however, the normalized difference infrared index (NDII), normalized difference vegetation index (NDVI), and optimal soil-adjusted vegetation index (OSAVI) had the same critical value of 0.55 kg m&minus;2. Therefore, in comparison to the NDII, NDVI, and OSAVI, the WI and NDWI better reflected the crop water content based on their sensitives to CWC and VWC. Moreover, CWC was the most important direct biotic driver of the dynamics of SVIs, while leaf area index (LAI) was the most important indirect biotic driver. VWC was a critical indirect regulator of WI, NDWI, NDII, and OSAVI dynamics, whereas vegetation dry mass (VDM) was the critical indirect regulator of NDVI dynamics. These findings may provide additional information for estimating agricultural drought and insights on the impact mechanism of soil water deficits on SVIs

FASFLNet: feature adaptive selection and fusion lightweight network for RGB-D indoor scene parsing

RGB-D indoor scene parsing is a challenging task in computer vision. Conventional scene-parsing approaches based on manual feature extraction have proved inadequate in this area because indoor scenes are both unordered and complex. This study proposes a feature adaptive selection, and fusion lightweight network (FASFLNet) for RGB-D indoor scene parsing that is both efficient and accurate. The proposed FASFLNet utilizes a lightweight classification network (MobileNetV2), constituting the backbone of the feature extraction. This lightweight backbone model guarantees that FASFLNet is not only highly efficient but also provides good performance in terms of feature extraction. The additional information provided by depth images (specifically, spatial information such as the shape and scale of objects) is used in FASFLNet as supplemental information for feature-level adaptive fusion between the RGB and depth streams. Furthermore, during decoding, the features of different layers are fused from top-bottom and integrated at different layers for final pixel-level classification, resulting in an effect similar to that of pyramid supervision. Experimental results obtained on the NYU V2 and SUN RGB-D datasets indicate that the proposed FASFLNet outperforms existing state-of-the-art models and is both highly efficient and accurate.Published versionThis work was funded by National Natural Science Foundation of China (61502429)

Interactions among -2, and variants are associated with aspirin responsiveness and adverse events in patients with ischemic stroke

Background: The effect of gene variants and their interactions on response to aspirin and clinical adverse outcomes after an acute ischemic stroke (IS) is not fully understood. The aim of this study was to investigate the association of aspirin-relevant gene variants and their interactions with clinical adverse outcomes in IS patients taking aspirin. Methods: A total of 14 variants from six genes encoding COX enzymes ( COX-1, COX-2 ), platelet membrane receptors ( TXAS1, P2Y1, P2Y12 ) and glycoprotein receptor (GPIIIa) were examined in 850 acute IS patients. Gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients were followed up for 1 year after admission. Primary outcome was a composite of recurrent ischemic stroke (RIS), myocardial infarction (MI) and death. Results: The primary outcome occurred in 112 (13.5%) patients (81 RIS, 16 MI and 15 deaths). There were no significant differences in the frequencies of the genotypes of the 14 variants between the patients with and without primary outcome using single-locus analytical approach. However, there was significant gene–gene interaction among rs20417, rs1371097 and rs2317676. The high-risk interactive genotypes of rs20417, rs1371097 and rs2317676 were independently associated with primary adverse outcome of RIS, MI, and death after acute IS. Conclusion: The three-loci interactions are associated with sensitivity of IS patients to aspirin and aspirin-induced adverse clinical events. The combinatorial analysis used in this study may be helpful to elucidate complex genetic risk of aspirin resistance (AR). Clinical trial registration: The study described here is registered at http://www.chictr.org/ (unique identifier: ChiCTR-OCH-14004724)