ObjectivesPatients with type 2 diabetes mellitus (T2DM) exhibit strong insulin resistance or abnormal insulin production. Probiotics, which are beneficial live micro-organisms residing naturally in ...the intestinal tract, play indispensable roles in the regulation of host metabolism. However, the detailed mechanisms remain unclear. Here, we evaluate the mechanisms by which probiotic strains mediate glycemic regulation in the host. The findings should enable the development of a safe and natural treatment for patients with T2DM.Research designs and methodsSugar consumption by more than 20 strains of Lactobacillus species was first evaluated. The probiotic strains that exhibited high efficiency of sugar consumption were further coincubated with Caco-2 cells to evaluate the regulation of sugar absorption in gut epithelial cells. Finally, potential probiotic strains were selected and introduced into a T2DM animal model to study their therapeutic efficacy.ResultsAmong the tested strains, Lactobacillus salivarius AP-32 and L. reuteri GL-104 had higher monosaccharide consumption rates and regulated the expression of monosaccharide transporters. Glucose transporter type-5 and Na+-coupled glucose transporter mRNAs were downregulated in Caco-2 cells after AP-32 and GL-104 treatment, resulting in the modulation of intestinal hexose uptake. Animal studies revealed that diabetic mice treated with AP-32, GL-104, or both showed significantly decreased fasting blood glucose levels, improved glucose tolerance and blood lipid profiles, and attenuated diabetes-mediated liver and kidney injury.ConclusionOur data elucidate a novel role for probiotics in glycemic regulation in the host. L. salivarius AP-32 and L. reuteri GL-104 directly reduce monosaccharide transporter expression in gut cells and have potential as therapeutic probiotics for patients with T2DM.
Conventional rule‐based approaches use exact template matching to capture linguistic information and necessarily need to enumerate all variations. We propose a novel flexible template generation and ...matching scheme called the principle‐based approach (PBA) based on sequence alignment, and employ it for reference metadata extraction (RME) to demonstrate its effectiveness. The main contributions of this research are threefold. First, we propose an automatic template generation that can capture prominent patterns using the dominating set algorithm. Second, we devise an alignment‐based template‐matching technique that uses a logistic regression model, which makes it more general and flexible than pure rule‐based approaches. Last, we apply PBA to RME on extensive cross‐domain corpora and demonstrate its robustness and generality. Experiments reveal that the same set of templates produced by the PBA framework not only deliver consistent performance on various unseen domains, but also surpass hand‐crafted knowledge (templates). We use four independent journal style test sets and one conference style test set in the experiments. When compared to renowned machine learning methods, such as conditional random fields (CRF), as well as recent deep learning methods (i.e., bi‐directional long short‐term memory with a CRF layer, Bi‐LSTM‐CRF), PBA has the best performance for all datasets.
SARS-CoV-2 has spread rapidly, causing deaths worldwide. In this study, we evaluated the performance of the BD MAX Open System module for identifying viral pathogens, including SARS-CoV-2, in ...nasopharyngeal specimens from individuals with symptoms of upper respiratory tract infection. We developed and validated a rapid total nucleic acid extraction method based on real-time reverse transcription-polymerase chain reaction (RT-PCR) for the reliable, high-throughput simultaneous detection of common cold viral pathogens using the BD MAX Platform. The system was evaluated using 205 nasopharyngeal swab clinical samples. For assessment of the limit of detection (LoD), we used SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV) RNA standards. The BD MAX dual multiplex real-time RT-PCR panel demonstrated a sensitivity comparable to that of the World Health Organization-recommended SARS-CoV-2 assay with an LoD of 50 copies/PCR. The LoD of influenza A/B and RSV was 100-200 copies/PCR. The overall percent agreement between the BD MAX panel and laboratory-developed RT-PCR test on 55 SARS-CoV-2-positive clinical samples was 100%. Among the 55 positive cases of COVID-19 analysed, no coinfection was detected. The BD MAX rapid multiplex PCR provides a highly sensitive, robust, and accurate assay for the rapid detection of SARS-CoV-2, influenza A/B, and RSV.
Polyphyllin G, a pennogenyl saponin extracted from Paris polyphylla, has been shown to possess antitumor effects. In this study, we demonstrated that doxycycline, an antibiotic medicine, could ...significantly enhance the sensitivities of osteosarcoma cell lines to polyphyllin G. As the cells were pretreated with doxycycline at non‐toxic concentrations and then co‐exposed to polyphyllin G, this combination could induce a rapid cell death distinct from apoptosis. The non‐apoptotic cell death was characterized by a loss of integrity of plasma membrane without externalization of phosphatidyl serine. Furthermore, this combined treatment resulted in suppression of cell viability and colony‐forming ability, and increased the level of γ‐H2A.X, a critical marker for DNA damage, in osteosarcoma cell lines. When examining the underlying mechanism, it was revealed combination of polyphyllin G and doxycycline triggered an enhanced generation of reactive oxygen species (ROS), and up‐regulated mitochondrial oxidative stress within 0.5 h. Co‐administration of the ROS inhibitor NAC reversed the suppressed cell viability and colony‐forming ability, and abolished the increased level of γ‐H2A.X in the cells with the combined treatment, indicating that the enhanced ROS was involved in the anti‐proliferative effect of the combined treatment. Overall, the results demonstrated that doxycycline may function as chemosensitizers by inducing an acute and lethal ROS production to enhance cytotoxic of polyphyllin G in osteosarcoma cell lines, and the combined use of drugs may provide an alternative thinking for the development of new therapeutic agents.
Three-dimensional (3D) configuration of in vitro cultivated cells has been recognised as a valuable tool in developing stem cell and cancer cell therapy. However, currently available imaging ...approaches for live cells have drawbacks, including unsatisfactory resolution, lack of cross-sectional and 3D images, and poor penetration of multi-layered cell products, especially when cells are cultivated on semitransparent carriers. Herein, we report a prototype of a full-field optical coherence tomography (FF-OCT) system with isotropic submicron spatial resolution in en face and cross-sectional views that provides a label-free, non-invasive platform with high-resolution 3D imaging. We validated the imaging power of this prototype by examining (1) cultivated neuron cells (N2A cell line); (2) multilayered, cultivated limbal epithelial sheets (mCLESs); (3) neuron cells (N2A cell line) and mCLESs cultivated on a semitransparent amniotic membrane (stAM); and (4) directly adherent colonies of neuron-like cells (DACNs) covered by limbal epithelial cell sheets. Our FF-OCT exhibited a penetrance of up to 150 μm in a multilayered cell sheet and displayed the morphological differences of neurons and epithelial cells in complex coculture systems. This FF-OCT is expected to facilitate the visualisation of cultivated cell products in vitro and has a high potential for cell therapy and translational medicine research.
Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. ...In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-κB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation.
•Exercise reversed Hyperhomocysteinemia(HHcy)-mitigated expression levels of SIRT1 and AMPK.•Exercise reduced Hyperhomocysteinemia(HHcy)-induced oxidative stress by NADPH oxidase inhibition in the aortic endothelium.•Exercise reduced the HHcy-induced activation of LOX-1 signaling.•Exercise reduces HHcy-induced apoptosis and inflammation in the aortic endothelium.
Tuberous sclerosis complex (TSC) is a rare hereditary disease, which results from the mutation of either TSC1 or TSC2, and its clinical features include benign tumors and dysfunctions in numerous ...organs, including the brain. Many individuals with TSC manifest neuropsychiatric symptoms, such as learning impairments, cognitive deficits and anxiety. Current pharmacological treatment for TSC is the use of mTOR inhibitors. However, they are not effective in treating neuropsychiatric symptoms. We previously used curcumin, a diet‐derived mTOR inhibitor, which possesses both anti‐inflammatory and antiproliferative properties, to improve learning and memory deficits in Tsc2+/− mice. Diffusion tensor imaging (DTI) provides microstructural information in brain tissue and has been used to study the neuropathological changes in TSC. In this study, we confirmed that the impaired recognition memory and increased anxiety‐like behavior in Tsc2+/− mice can be reversed by curcumin treatment. Second, we found altered fractional anisotropy and mean diffusivity in the anterior cingulate cortex and the hippocampus of the Tsc2+/− mice, which may indicate altered circuitry. Finally, the mTOR complex 1 hyperactivity was found in the cortex and hippocampus, coinciding with abnormal cortical myelination and increased glial fibrillary acidic protein expression in the hippocampal CA1 of Tsc2+/− mice, both of which can be rescued with curcumin treatment. Overall, DTI is sensitive to the subtle alterations that cannot be detected by conventional imaging, suggesting that noninvasive DTI may be suitable for longitudinally monitoring the in vivo neuropathology associated with the neuropsychiatric symptoms in TSC, thereby facilitating future clinical trials of pharmacological treatments.
Coronavirus disease 2019 has become a worldwide pandemic. By April 7, 2020, approximately 1,279,722 confirmed cases were reported worldwide including those in Asia, European Region, African Region ...and Region of the Americas. Rapid and accurate detection of Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) is critical for patient care and implementing public health measures to control the spread of infection. In this study, we developed and validated a rapid total nucleic acid extraction method based on real‐time RT-PCR for reliable, high‐throughput identification of SARS-CoV-2 using the BD MAX platform. For clinical validation, 300 throat swab and 100 sputum clinical samples were examined by both the BD MAX platform and in-house real-time RT-PCR methods, which showed 100% concordant results. This BD MAX protocol is fully automated and the turnaround time from sample to results is approximately 2.5 h for 24 samples compared to 4.8 h by in-house real-time RT-PCR. Our developed BD MAX RT-PCR assay can accurately identify SARS-CoV-2 infection and shorten the turnaround time to increase the effectiveness of control and prevention measures for this emerging infectious disease.
Three m-terphenyl oxadiazole derivatives, 3,3″-bis(5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl)-1,1′:3′,1″-terphenyl (4PyOXD), 3,3″-bis(5-(pyridin-3-yl)-1,3,4-oxadiazol-2-yl)-1,1′:3′,1″-terphenyl ...(3PyOXD), and 3,3″-bis(5-phenyl-1,3,4-oxadiazol-2-yl)-1,1′:3′,1″-terphenyl (PhOXD), were synthesized. They exhibit relatively high electron mobilities compared with those of known electron-transport materials such as TAZ, BAlq, and BCP+Alq3. These materials were then utilized as electron transporters and hole/exciton blockers for blue, green, and red phosphorescent organic light-emitting diodes. The devices exhibited reduced driving voltages, very high efficiency, and negligible roll-off. More importantly, among these three oxadiazole derivatives, PhOXD performed as an ideal electron-transporting material for the blue, green, and red devices with excellent external quantum efficiencies (EQEs, >26%) as well as current and power efficiencies. Using these materials as an electron-transporting/exciton-blocking layer, low roll-off was achieved for the devices, indicative of excellent confinement of the triplet excitons in the emitting layer even at high current densities. At the normal operation brightness of 1000 cd m–2, the EQEs remained >21.3% for these basic color devices. In addition, the relationships between physical properties and structures of the molecules such as the electron mobility, triplet energy gap, and efficiency can be clearly rationalized.
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