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Abstract The characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low‐density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning‐directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL‐rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six‐point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL‐rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training.

Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson’s correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = −0.69, p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-γ+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.

Daptomycin (DAP), a last-resort antibiotic for treating Gram-positive bacterial infection, has been widely used in the treatment of vancomycin-resistant enterococci (VRE). Resistance to both daptomycin and vancomycin leads to difficulties in controlling infections of enterococci. A clinical multidrug-resistant Enterococcus faecium EF332 strain that shows resistance to both daptomycin and vancomycin was identified, for which resistance mechanisms were investigated in this work. Whole-genome sequencing and comparative genomic analysis were performed by third-generation PacBio sequencing, showing that E. faecium EF332 contains four plasmids, including a new multidrug-resistant pEF332-2 plasmid. Two vancomycin resistance-conferring gene clusters vanA and vanM were found on this plasmid, making it the second reported vancomycin-resistant plasmid containing both clusters. New mutations in chromosomal genes cls and gdpD that, respectively, encode cardiolipin synthase and glycerophosphoryl diester phosphodiesterase were identified. Their potential roles in leading to daptomycin resistance were further investigated. Through molecular cloning and phenotypic screening, two-dimensional thin-layer chromatography, fluorescence surface charge test, and analysis of cardiolipin distribution patterns, we found that mutations in cls decrease surface negative charges of the cell membrane (CM) and led to redistribution of lipids of CM. Both events contribute to the DAP resistance of E. faecium EF332. Mutation in gdpD leads to changes in CM phospholipid compositions, but cannot confer DAP resistance. Neither mutation could result in changes in cellular septa. Therefore, we conclude that the daptomycin resistance of E. faecium EF332 is conferred by new cls mutations. This work reports the genetic basis for vancomycin and daptomycin resistance of a multidrug-resistant E. faecium strain, with the finding of new mutations of cls that leads to daptomycin resistance.

Abstract Background Recurrent aphthous stomatitis (RAS) is the most common form of oral ulcerative disease, whose cause is still unknown. Researchers have found the association of many factors with the occurrence of RAS, and proposed oral bacterial infection could be a cause for this disease. Methods To investigate whether the occurrence of RAS is associated with oral bacterial infection, we performed high throughput sequencing analysis of bacterial samples collected from the normal oral mucosa and aphthous ulcers of 24 patients. Results Firmicutes, Proteobacteria and Bacteriodetes were the most abundant phyla in the microbiomes analysed. The alpha diversities of the oral mucosa and aphthous ulcer microbiomes were similar, suggesting a similar richness and diversity. The NMDS analysis showed the oral mucosa and aphthous ulcer microbiomes are significantly different. This suggestion is further supported by Anosim, MRPP, and Adonis analyses. More detailed comparison of the two groups of microbiomes suggested that the occurrence of RAS is significantly associated with the increase of Escherichia coli and Alloprevotella, as well as the decrease of Streptococcus. Conclusions Considering E. coli is a very common intestinal bacterium, we propose that E. coli colonization could be a cause for RAS, and controlling E. coli colonization could help curing RAS.

Polyphenols have long been used as functional compounds and are beneficial for host immunity and gut health. This three-phased study investigated the function of Ouli fermented juice (OF) in improving the immunity of cyclophosphamide (CTX)-immunosuppressed mice and regulating their intestinal microbiota and mucosal barrier. Lactobacillus plantarum fermentation increased the phenolic content in the OF. OF effectively improved host immunity and the intestinal mucosal barrier, including increasing serum immunoglobulin (Ig)A, IgG, and IgM levels and secreted IgA (sIgA) levels in the colon, and reduced CTX-induced pathological damage to the spleen and jejunum. Importantly, OF effectively increased the abundance of Lachnospiracea, Roseburia, Akkermansia, and butyric acid-producing microbes, subsequently increasing the levels of short chain fatty acids in the colon. OF with polyphenols exhibited better efficacy at altering the intestinal flora, which might affect the host immunity by changing the host-mucosal barrier-microbiota interaction.

New sensor technologies play an important role in quality evaluation of Chinese materia medica (CMM) and include near-infrared spectroscopy, chemical imaging, electronic nose and electronic tongue. This review on quality evaluation of CMM and the application of the new sensors in this assessment is based on studies from 2010 to 2015, with prospects and opportunities for future research.

The article focuses on developing a self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy. Topics discussed include the elimination of battery dependence, the minimally invasive intravascular implantation procedure, and the effective restoration of cardiac function, offering a promising solution for leadless and battery-free cardiac pacing.

Cassia fistula L. which is known as “Golden Shower”, is used as an ornamental plant due to its flowers, and fruit parts of this plant have a high medicinal value. There are few reports providing a comprehensive overview of the chemical composition of its fruit or explaining the differences between samples from different sources because of the complexity of its chemical components. The purpose of the present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) for the composition identification and quality control of this herb. Twelve samples from Xinjiang and Sichuan provinces in China and India were analyzed by HPLC, and there were fifteen common peaks in the twelve batches. Molecular weight and formula information can be derived from thirty-one peaks by UHPLC/LTQ-Orbitrap MSn, molecular structure information of twenty components was obtained, of which ten compounds were identified by comparison with standard materials. Samples of twelve batches were divided according to their similarity into four groups, which were basically consistent with three different C.fistula fruit-producing areas. Five compounds were finally considered to be chemical markers to determine the quality of this herb. A fingerprints method combined with chemometrics was established to differentiate the origin of the fruit of C. fistula which has the advantages of effectivity and convenience, laying the foundation for the quality evaluation of this herb from different sources.

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, b-lactoglobulin (bLG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of bLG-specific immunoglobulins E (b-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-kB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-g+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce b-LGinduced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy. [ABSTRACT FROM AUTHOR]

Organic thin-film transistors (OTFTs) and other organic electronic devices have attracted more and more attention for next-generation wearable and flexible devices. Because of low conductivity of organic materials, working OTFTs need a channel structure with a very large aspect ratio (or ratio between channel width and length) to enable a sizable drive current. Therefore, to produce densely arranged OTFTs with microscale footprint areas, the OTFT channel length needs to be scaled down to sub-100 nm regimes. To enable cost-effective manufacturing of such nanoscale OTFT arrays, solvent-processing methods, such as spin-coating and roll-to-roll coating, are highly desirable, but such processes inevitably result in air voids in nanoscale OTFT channels, leading to poor and inconsistent gate modulation characteristics. In this work, the authors reveal the nanofluidic mechanisms responsible for the formation of air voids through characterizing the cross-sectional morphologies of as-fabricated nanoscale OTFT channels using electron microscopy and simulating the nanofluidic flows of organic materials into nanoscale transistor channel gaps using a computational fluidic dynamics tool. This work suggests that a post-fabrication thermal pressing process is needed for eliminating air voids and significantly improving gate modulation characteristics. Using this process, the authors demonstrate poly(3-hexylthiophene) OTFT arrays with channel length of 66 nm, which exhibits highly consistent on/off ratios up to ~106. This work advances the technical and scientific knowledge for processing solution-based organic electronic materials into nanoscale devices. The presented thermal pressing process can be generically implemented for processing a broad range of solution-based organic materials. [ABSTRACT FROM AUTHOR]

This paper presents a new voltage driving scheme with current feedback for polycrystalline silicon (poly-Si) thin-film transistors (TFTs) to drive active matrix organic light-emitting diode (AMOLED) displays. The pixel circuit is relatively simple, which is composed of 3 TFTs and 1 capacitor. Circuit simulation results show that the proposed driving scheme can effectively suppress the influence of nonidealities of typical poly-Si TFTs including kink effects, spatial nonuniformity of the electrical characteristics. This method also presents a settling time less than 3 μs with panel load of 100 pF/1.5 kΩ at all OLED current levels. [ABSTRACT FROM AUTHOR]

In this work, the conventional threshold voltage ( Vth) extraction method assuming ohmic contacts in organic thin-film transistors (OTFTs) was shown to be difficult to obtain the intrinsic Vth values for devices with non-negligible contact properties. A simple Vth extraction method based on a modified analytical current-voltage expression in the saturation regime was thus proposed to exclude the influence of the contact properties. By applying the method to experimental devices of two different contacts, apparent Vth values close to the intrinsic values were obtained, which proved the method to be useful for accurate device characterization and modeling of OTFTs. [ABSTRACT FROM PUBLISHER]

The noise margin (NM) of an inverter is an important feature for the operation stability of the digital circuits. Owing to their simple structure, easy processes, and relatively high gain, the unipolar zero-VGS-load logic design is widely used for implementation of digital circuits in various thin-film transistor (TFT) technologies. In this paper, a simple NM model clarifying the relationship between the NM and electrical/device parameters is developed for the zero-VGS-load inverter. The model is verified by circuit simulations, and is capable of providing a useful guideline for optimal design of unipolar TFT logic circuits. Finally, the application of the derived model in a static random access memory cell design is discussed. [ABSTRACT FROM AUTHOR]