Recent genome-wide association studies suggest distinct roles for 12 human interferon-alpha (IFN-α) and 3 IFN-λ subtypes that may be elucidated by defining the expression patterns of these sets of genes. To overcome the impediment of high homology among each of the sets, we designed a quantitative real-time PCR assay that incorporates the use of molecular beacon and locked nucleic acid (LNA) probes, and in some instances, LNA oligonucleotide inhibitors. We then measured IFN subtype expression by human peripheral blood mononuclear cells and by purified monocytes, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), and monocyte-derived macrophages (MDM), and –dendritic cells (MDDC) in response to poly I:C, lipopolysaccharide (LPS), imiquimod and CpG oligonucleotides. We found that in response to poly I:C and LPS, monocytes, MDM and MDDC express a subtype pattern restricted primarily to IFN-β and IFN-λ1. In addition, while CpG elicited expression of all type I IFN subtypes by pDC, imiquimod did not. Furthermore, MDM and mDC highly express IFN-λ, and the subtypes of IFN-λ are expressed hierarchically in the order IFN-λ1 followed by IFN-λ2, and then IFN-λ3. These data support a model of coordinated cell- and ligand-specific expression of types I and III IFN. Defining IFN subtype expression profiles in a variety of contexts may elucidate specific roles for IFN subtypes as protective, therapeutic or pathogenic mediators.

In order to solve the problems of poor image quality, loss of detail information and excessive brightness enhancement during image enhancement in low light environment, we propose a low-light image enhancement algorithm based on improved multi-scale Retinex and Artificial Bee Colony (ABC) algorithm optimization in this paper. First of all, the algorithm makes two copies of the original image, afterwards, the irradiation component of the original image is obtained by used the structure extraction from texture via relative total variation for the first image, and combines it with the multi-scale Retinex algorithm to obtain the reflection component of the original image, which are simultaneously enhanced using histogram equalization, bilateral gamma function correction and bilateral filtering. In the next part, the second image is enhanced by histogram equalization and edge-preserving with Weighted Guided Image Filtering (WGIF). Finally, the weight-optimized image fusion is performed by ABC algorithm. The mean values of Information Entropy (IE), Average Gradient (AG) and Standard Deviation (SD) of the enhanced images are respectively 7.7878, 7.5560 and 67.0154, and the improvement compared to original image is respectively 2.4916, 5.8599 and 52.7553. The results of experiment show that the algorithm proposed in this paper improves the light loss problem in the image enhancement process, enhances the image sharpness, highlights the image details, restores the color of the image, and also reduces image noise with good edge preservation which enables a better visual perception of the image.

The design and development of novel methodologies and customized materials to fabricate patient-specific 3D printed organ models with integrated sensing capabilities could yield advances in smart surgical aids for preoperative planning and rehearsal. Here, we demonstrate 3D printed prostate models with physical properties of tissue and integrated soft electronic sensors using custom-formulated polymeric inks. The models show high quantitative fidelity in static and dynamic mechanical properties, optical characteristics, and anatomical geometries to patient tissues and organs. The models offer tissue-mimicking tactile sensation and behavior and thus can be used for the prediction of organ physical behavior under deformation. The prediction results show good agreement with values obtained from simulations. The models also allow the application of surgical and diagnostic tools to their surface and inner channels. Finally, via the conformal integration of 3D printed soft electronic sensors, pressure applied to the models with surgical tools can be quantitatively measured.

Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI. The microglia transformed into amoeba-like and discharged many microvesicle (MV)-like particles in the injured and adjacent regions. A P2X7R antagonist (A804598) and an immune inhibitor (FTY720) reduced significantly the number of MVlike particles in the injured/adjacent regions and in cerebrospinal fluid, reduced the number of neurons undergoing apoptotic cell death, and increased the survival of neurons in the cerebral cortex injured and adjacent regions. Blockade of the P2X7R and FTY720 reduced interleukin-1βexpression, P38 phosphorylation, and glial activation in the cerebral cortex and improved neurobehavioral outcomes after TBI. These data indicate that MV-like particles discharged by microglia after TBI may be involved in the development of local inflammation and secondary nerve cell injury.

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Expression of P2X(4) and P2X(6) receptor subunits in the gastrointestinal tract of the rat was studied with double-labeling fluorescence immunohistochemistry. The results showed that P2X(6) receptors were expressed widely in the submucosal and myenteric plexuses. In the myenteric plexus, P2X(6) receptors were expressed mainly in large size neurons which resembled Dogiel type II neurons. These P2X(6) receptor-immunoreactive (ir) neurons also expressed calbindin 28K, calretinin and neuronal nuclei (NeuN), proteins that are markers of intrinsic sensory neurons. In the submucosal plexus, all the calbindin 28K, calretinin and NeuN-ir cells were immunoreactive for P2X(6) receptors. P2X(6) receptors do not form homomultimers, but rather heteromultimers with either P2X(2) or P2X(4) receptors. P2X(4) receptors were not expressed in neurons, but were expressed in macrophages of the rat gastrointestinal tract. These data indicate that P2X(6) receptors are mainly expressed on intrinsic sensory neurons and that ATP, via P2X(6) receptors probably in heteromeric combination with P2X(2) receptors, may be involved in regulating the physiological functions of these neurons.

As a therapeutic target for antitumor necrosis factor (TNF)-α interventions, UbcH5c is one of the key ubiquitin-conjugating enzymes catalyzing ubiquitination during TNF-α-triggered nuclear factor kappa B (NF-κB) activation. In the present study, three series of analogues were designed and synthesized from α-santonin, and their UbcH5c inhibitory activities were screened by Western blotting and NF-κB luciferase assay. Further BIAcore, in-gel fluorescence imaging, and immunoprecipitation assays demonstrated that compound 6d exhibited robust and specific inhibition of UbcH5c, exceeding that of the positive compound 1 (IJ-5). Mechanistic investigations revealed that compound 6d preferentially bound to and inactivated UbcH5c by forming a covalent adduct with its active site Cys85. Furthermore, compound 6d exhibited potent anti-inflammatory activity against complete Freund's adjuvant-induced adjuvant arthritis in vivo. These findings suggest that the novel α-santonin-derived UbcH5c inhibitor 6d is a promising lead compound for the development of new antirheumatoid arthritis (RA) agent.

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