Tight junction CLDN2 gene is a direct target of the vitamin D receptor

The breakdown of the intestinal barrier is a common manifestation of many diseases. Recent evidence suggests that vitamin D and its receptor VDR may regulate intestinal barrier function. Claudin-2 is a tight junction protein that mediates paracellular water transport in intestinal epithelia, rendering them "leaky". Using whole body VDR(-/-) mice, intestinal epithelial VDR conditional knockout (VDR(ΔIEC)) mice, and cultured human intestinal epithelial cells, we demonstrate here that the CLDN2 gene is a direct target of the transcription factor VDR. The Caudal-Related Homeobox (Cdx) protein family is a group of the transcription factor proteins which bind to DNA to regulate the expression of genes. Our data showed that VDR-enhances Claudin-2 promoter activity in a Cdx1 binding site-dependent manner. We further identify a functional vitamin D response element (VDRE) 5΄-AGATAACAAAGGTCA-3΄ in the Cdx1 site of the Claudin-2 promoter. It is a VDRE required for the regulation of Claudin-2 by vitamin D. Absence of VDR decreased Claudin-2 expression by abolishing VDR/promoter binding. In vivo, VDR deletion in intestinal epithelial cells led to significant decreased Claudin-2 in VDR(-/-) and VDR(ΔIEC) mice. The current study reveals an important and novel mechanism for VDR by regulation of epithelial barriers.status: publishe

Structured air lasing of N2+

Structured light has attracted great interest in scientific and technical fields. Here, we demonstrate the first generation of structured air lasing in N2+ driven by 800 nm femtosecond laser pulses. By focusing a vortex pump beam at 800 nm in N2 gas, we generate a vortex superfluorescent radiation of N2+ at 391 nm, which carries the same photon orbital angular momentum as the pump beam. With the injection of a Gaussian seed beam at 391 nm, the coherent radiation is amplified, but the vorticity is unchanged. A new physical mechanism is revealed in the vortex N2+ superfluorescent radiation: the vortex pump beam transfers the spatial spiral phase into the N2+ gain medium, and the Gaussian seed beam picks up the spatial spiral phase and is then amplified into a vortex beam. Moreover, when we employ a pump beam with a cylindrical vector mode, the Gaussian seed beam is correspondingly amplified into a cylindrical vector beam. Surprisingly, the spatial polarization state of the amplified radiation is identical to that of the vector pump beam regardless of whether the Gaussian seed beam is linearly, elliptically, or circularly polarized. Solving three-dimensional coupled wave equations, we show how a Gaussian beam becomes a cylindrical vector beam in a cylindrically symmetric gain medium. This study provides a novel approach to generating structured light via N2+ air lasing.Comment: 18 pages, 5 figures, 3 equation

Energy transmission processes in the effectuation chain of solar forcing to the terrestrial atmosphere—a review

The Sun has an obvious quasi-11-year cycle and numerous short-term eruptive activities. There are four processes of energy transmission in the effectuation chain of solar forcing to the climate system: solar energy input into the atmosphere, atmospheric absorption of the input energy, transformation of the absorbed energy into dynamic and thermodynamic responses in the atmosphere, and coupling among all the layers affected by solar forcings. However, the four processes have not been discussed in their entirety. This present paper reviews studies over the last decade on how solar radiation varies during the solar cycle and solar eruptions, and, correspondingly, how the terrestrial atmosphere absorbs the input solar energy

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

Background: In recent years, the incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. Shan Ci Gu is commonly used as an anticancer drug in traditional Chinese medicine; however, its specific mechanism against NSCLC has not yet been elucidated. Here, the mechanism was clarified through network pharmacology and molecular docking.Methods: The Traditional Chinese Medicine Systems Pharmacology database was searched for the active ingredients of Shan Ci Gu, and the relevant targets in the Swiss Target Prediction database were obtained according to the structure of the active ingredients. GeneCards were searched for NSCLC-related disease targets. We obtained the cross-target using VENNY to obtain the core targets. The core targets were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins database, and Cytoscape software was used to operate a mesh chart. R software was used to analyze the Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The core targets and active compounds were molecularly docked through Auto-Dock Vina software to predict the detailed molecular mechanism of Shan Ci Gu for NSCLC treatment. We did a simple survival analysis with hub gene to assess the prognosis of NSCLC patients.Results: Three compounds were screened to obtain 143 target genes and 1,226 targets related to NSCLC, of which 56 genes were related to NSCLC treatment. Shan Ci Gu treatment for NSCLC involved many BPs and acted on main targets including epidermal growth factor receptor (EGFR), ESR1, and SRC through signaling pathways including the endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways. Shan Ci Gu might be beneficial for treating NSCLC by inhibiting cell proliferation and migration. Molecular docking revealed that the active compounds β-sitosterol, stigmasterol, and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol had good affinity with the core target genes (EGFR, SRC, and ESR1). Core targets included EGFR, SRC, ESR1, ERBB2, MTOR, MCL1, matrix metalloproteinase 2 (MMP2), MMP9, KDR, and JAK2. Key KEGG pathways included endocrine resistance, EGFR tyrosine kinase inhibitor resistance, ErbB signaling, PI3K-Akt signaling, and Rap1 signaling pathways. These core targets and pathways have an inhibitory effect on the proliferation of NSCLC cells.Conclusion: Shan Ci Gu can treat NSCLC through a multi-target, multi-pathway molecular mechanism and effectively improve NSCLC prognosis. This study could serve as a reference for further mechanistic research on wider application of Shan Ci Gu for NSCLC treatment

Discriminant Analysis of Jiang-Flavor Baijiu of Different Grades by Gas Chromatography-Mass Spectrometry and Electronic Tongue

Gas chromatography-mass spectrometry (GC-MS) and electronic tongue were used to quantitatively determine the volatile compounds and taste indices of 21 Jiang-flavor baijiu samples of different grades. These samples were differentiated by chemometrics, and key differential compounds among grades were identified. Finally, a discriminant model was established by machine learning. The results showed that there were differences in the contents of volatile compounds in Jiang-flavor baijiu of three grades, indicating the feasibility of further discriminant analysis. The total content of flavor compounds in second-grade baijiu (4 908 mg/L) was significantly lower than that in premium-grade (6 583 mg/L) and first-grade baijiu (8 254 mg/L), while the proportion of several esters responsible for floral and fruity aromas in total esters showed a decreasing trend as the grade decreased. Partial least squares-discriminant analysis (PLS-DA) identified 16 key differential compounds represented by ethyl palmitate and acetic acid. The results of electronic tongue showed that the taste indexes of premium-grade baijiu were more consistent, with lower bitterness and astringency aftertaste. The taste indexes of second-grade baijiu showed significant intersample differences. Principal component analysis (PCA) showed clear discrimination of Jiang-flavor baijiu of different grades according to their taste indexes. The above results provide a basis for the establishment of Jiang-flavor baijiu quality system. Four discriminant models were established based on 25 differential compounds and taste indexes identified. The accuracy of all models was higher than 90%, and the support vector machine (SVM) model performed best, with an accuracy of 100%

Prompt-to-afterglow transition of optical emission in a long gamma-ray burst consistent with a fireball

Long gamma-ray bursts (GRBs), which signify the end-life collapsing of very massive stars, are produced by extremely relativistic jets colliding into circumstellar medium. Huge energy is released both in the first few seconds, namely the internal dissipation phase that powers prompt emissions, and in the subsequent self-similar jet-deceleration phase that produces afterglows observed in broad-band electromagnetic spectrum. However, prompt optical emissions of GRBs have been rarely detected, seriously limiting our understanding of the transition between the two phases. Here we report detection of prompt optical emissions from a gamma-ray burst (i.e. GRB 201223A) using a dedicated telescope array with a high temporal resolution and a wide time coverage. The early phase coincident with prompt {\gamma}-ray emissions show a luminosity in great excess with respect to the extrapolation of {\gamma}-rays, while the later luminosity bump is consistent with onset of the afterglow. The clearly detected transition allows us to differentiate physical processes contributing to early optical emissions and to diagnose the composition of the jetComment: Authors' version of article published in Nature Astronomy, see their website for official versio