Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation.

Background & aimsBiotin is a water-soluble vitamin that is indispensable for human health. Biotin deficiency can cause failure-to-thrive, immunodeficiency, alopecia, dermatitis, and conjunctivitis. We previously reported that biotin deficiency also can lead to severe colitis in mice, which is completely reversed with supplementation. Our aim in this study was to determine if high-dose biotin supplementation can provide a therapeutic benefit in a preclinical model for inflammatory bowel disease (IBD) and to identify the molecular mechanism by which this occurs.MethodsMice were challenged with dextran sodium sulfate to induce colitis and were treated with 1 mmol/L biotin to induce or maintain remission. Clinical response was monitored by the Disease Activity Index and fecal calprotectin levels. The colon tissue was investigated for histology, length, as well as expression of inflammatory cytokines (interleukin 6, tumor necrosis factor-α, interleukin 1β), intestinal permeability, tight junctions (zonula occludens-1 and claudin-2), and the transcription factor nuclear factor-κB (NF-κB).ResultsBiotin therapy led to delayed onset and severity of colitis as well as accelerated healing. There was improvement in the Disease Activity Index, fecal calprotectin levels, colon length, and histology. In addition, biotin-treated mice had reduced expression of inflammatory cytokines, reduced intestinal permeability, and reduced activation of NF-κB.ConclusionsOral supplementation with biotin provides benefit for maintenance and induction of remission in the dextran sodium sulfate preclinical model for IBD. Biotin does this by reducing the activation of NF-κB, which prevents the production of inflammatory cytokines and helps maintain the integrity of the intestinal barrier. Clinically, the NF-κB pathway is important in the development of IBD and this finding suggests that biotin may have therapeutic potential for patients with IBD

Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism.

Colonocytes possess a specific carrier-mediated uptake process for the microbiota-generated thiamin (vitamin B1) pyrophosphate (TPP) that involves the TPP transporter (TPPT; product of the SLC44A4 gene). Little is known about the effect of exogenous factors (including enteric pathogens) on the colonic TPP uptake process. Our aim in this study was to investigate the effect of Enterohemorrhagic Escherichia coli (EHEC) infection on colonic uptake of TPP. We used human-derived colonic epithelial NCM460 cells and mice in our investigation. The results showed that infecting NCM460 cells with live EHEC (but not with heat-killed EHEC, EHEC culture supernatant, or with non-pathogenic E. Coli) to lead to a significant inhibition in carrier-mediated TPP uptake, as well as in level of expression of the TPPT protein and mRNA. Similarly, infecting mice with EHEC led to a significant inhibition in colonic TPP uptake and in level of expression of TPPT protein and mRNA. The inhibitory effect of EHEC on TPP uptake by NCM460 was found to be associated with reduction in the rate of transcription of the SLC44A4 gene as indicated by the significant reduction in the activity of the SLC44A4 promoter transfected into EHEC infected cells. The latter was also associated with a marked reduction in the level of expression of the transcription factors CREB-1 and ELF3, which are known to drive the activity of the SLC44A4 promoter. Finally, blocking the ERK1/2 and NF-kB signaling pathways in NCM460 cells significantly reversed the level of EHEC inhibition in TPP uptake and TPPT expression. Collectively, these findings show, for the first time, that EHEC infection significantly inhibit colonic uptake of TPP, and that this effect appears to be exerted at the level of SLC44A4 transcription and involves the ERK1/2 and NF-kB signaling pathways

Partially passivated quantum dots, process for making, and sensors therefrom.

A partially passivating core shell particle includes a luminescent nanocrystal core, and a partially passivating semiconducting core shell on a surface of the nanocrystal. The shell allows selected analytes to alter a luminescent response of the core shell particle. a quantum dot-based sensing system includes at least one partially passivating core shell particle, a light source for irradiating the partially passivating core shell particle, and a light detector for receiving emissions from the particle, wherein emissions from the core shell particle chance in response to the presence of at least one analyte

Tuberculous Osteomyelitis of the Patella 髕骨結核性骨髓炎：病例報告

AbstractPatellar tuberculosis is a rare occurrence despite the knee being the third most common osteoarticular site to be involved. This is the reason for its late diagnosis and the potential to spread posteriorly to the knee. We present an atypical case of patellar tuberculosis in an 8-year-old boy presenting with discharging sinus and diagnosed by biopsy

Enterotoxigenic Escherichia coli CS6 gene products and their roles in CS6 structural protein assembly and cellular adherence

Enterotoxigenic Escherichia coli (ETEC) produces a variety of colonization factors necessary for attachment to the host cell, among which CS6 is one of the most prevalent in ETEC isolates from developing countries. The CS6 operon is composed of 4 genes, cssA, cssB, cssC, and cssD. The molecular mechanism of CS6 assembly and cell surface presentation, and the contribution of each protein to the attachment of the bacterium to intestinal cells remain unclear. In the present study, a series of css gene-deletion mutants of the CS6 operon were constructed in the ETEC genetic background, and their effect on adhesion to host cells and CS6 assembly was studied. Each subunit deletion resulted in a reduction in the adhesion to intestinal cells to the same level of laboratory E. coli strains, and this effect was restored by complementary plasmids, suggesting that the 4 proteins are necessary for CS6 expression. Bacterial cell fractionation and western blotting of the mutant strains suggested that the formation of a CssA–CssB–CssC complex is necessary for recognition by CssD and transport of CssA–CssB to the outer membrane as a colonization factor

Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters

Hypoxia exerts profound effects on cell physiology, but its effect on colonic uptake of the microbiota-generated forms of vitamin B1 (i.e., thiamin pyrophosphate [TPP] and free thiamine) has not been described. Here, we used human colonic epithelial NCM460 cells and human differentiated colonoid monolayers as in vitro and ex vivo models, respectively, and were subjected to either chamber (1%

Real-Time PCR-Based Mismatch Amplification Mutation Assay for Specific Detection of CS6-Expressing Allelic Variants of Enterotoxigenic Escherichia coli and Its Application in Assessing Diarrheal Cases and Asymptomatic Controls

Enterotoxigenic Escherichia coli (ETEC) expressing the colonization factor CS6 is widespread in many developing countries, including India. The different allelic variants of CS6, caused by point mutations in its structural genes, cssA and cssB, are designated AIBI, AIIBII, AIIIBI, AIBII, and AIIIBII. A simple, reliable, and specific mismatch amplification mutation assay based on real-time quantitative PCR (MAMA-qPCR) was developed for the first time for the detection of CS6-expressing ETEC, along with the identification of allelic variations. The assay was based on mismatched nucleotide incorporation at the penultimate base at the 3' ends of the reverse primers specific for cssA and cssB and was validated using 38 CS6-expressing ETEC isolates. This strategy was effective in detecting all the alleles containing single-nucleotide polymorphisms. Using MAMA-qPCR, we also tested CS6 allelic variants in 145 ETEC isolates from children with acute diarrhea and asymptomatic infections, with the latter serving as controls. We observed that the AIBI and AIIIBI allelic variants were mostly associated with cases rather than controls, whereas the AIIBII variants were detected mostly in controls. In addition, the AIBI and AIIIBI alleles were frequently associated with ETEC harboring the heat-stable toxin gene (est) alone or with the heat-labile toxin gene (elt), whereas the AIIBII allele was predominant in ETEC isolates harboring the elt gene. This study may help in understanding the association of allelic variants in CS6-expressing ETEC with the clinical features of diarrhea, as well as in ETEC vaccine studies

GaN Nanowire Schottky Barrier Diodes

A new concept of vertical gallium nitride (GaN) Schottky barrier diode based on nanowire (NW) structures and the principle of dielectric REduced SURface Field (RESURF) is proposed in this paper. High-threading dislocation density in GaN epitaxy grown on foreign substrates has hindered the development and commercialization of vertical GaN power devices. The proposed NW structure, previously explored for LEDs offers an opportunity to reduce defect density and fabricate low cost vertical GaN power devices on silicon (Si) substrates. In this paper, we investigate the static characteristics of high-voltage GaN NW Schottky diodes using 3-D TCAD device simulation. The NW architecture theoretically achieves blocking voltages upward of 700 V with very low specific on-resistance. Two different methods of device fabrication are discussed. Preliminary experimental results are reported on device samples fabricated using one of the proposed methods. The fabricated Schottky diodes exhibit a breakdown voltage of around 100 V and no signs of current collapse. Although more work is needed to further explore the nano-GaN concept, the preliminary results indicate that superior tradeoff between the breakdown voltage and specific on-resistance can be achieved, all on a vertical architecture and a foreign substrate. The proposed NW approach has the potential to deliver low cost reliable GaN power devices, circumventing the limitations of today's high electron mobility transistors (HEMTs) technology and vertical GaN on GaN devices

Spectrally resolved ion imaging from laser produced plasmas using CR-39 detectors

Intense laser-produced plasmas generate bright, ultrashort bursts of accelerated ions. Reducing the required laser intensity and increasing the repetition rate of the laser to generate high energy ions is important, and mesoscopic particle targets are an attractive option to address this issue. Newer experimental strategies to measure ion energies and their angular distribution are needed in studies of such systems. In this paper, we outline a method to simultaneously measure these quantities using a single CR39 film. Although CR-39 detectors are known for ion imaging or spectroscopy, combining these specially for lower ion energies and applications to low-intensity laser experiments is not common. The paradigm chosen in our study is to consider the spatial distribution of nuclear tracks on a CR-39 sheet, while simultaneously separating them by their track diameter. Our method achieves an energy resolution of about 100 keV and a spatial resolution of tens of micrometers. In addition, ion species other than protons, i.e., carbon and oxygen, can also be imaged in an energy-resolved manner. © 2021 Author(s)