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关键词： pig   liver resection   small-for-size syndrome   post-hepatectomy liver failure  

摘要： Simple Summary Liver resection is the best treatment for liver tumors;its clinical applicability, however, is limited by the mass and quality of the remnant liver. In this study, hepatic resections were performed in a pig model to define changes associated with sufficient and insufficient liver remnants. As well, somatostatin, a naturally occurring peptide hormone that exerts numerous largely inhibitory effects, was given in order to improve outcomes. We observed that extended major hepatectomy is associated with immediate changes in portal pressure leading to injury, stellate cell activation, collagen deposition, and cell death, all of which were improved with somatostatin therapy. This is one of few studies (potentially the first) describing collagen deposition as early as 24 h after extended major hepatectomy and implicating liver resection as potential cause for chronic liver injury. Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3-13) mmHg vs. 4 (2-6) mmHg and 4 (2-6) mmHg, respectively, p < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H

关键词： pumpkin leaf extracts   osteoblasts   osteoclasts  

摘要： Traditional medicines rely mainly on use of plant extracts to mitigate or treat a wide range of disorders, including those that affect skeletal homeostasis. In this study, we investigated for the first time the potential pro-osteogenic effects of hexane, acetone and methanol extracts of the leaves of Cucurbita moschata, a very popular pumpkin cultivar in Western countries. We found that in Cucurbita moschata leaves, there are acetone-extractable substances-in particular, fatty acids such as 13-OH-9Z,11E,15E-octadecatrienoic acid (PU-13OH-FA), which is capable of both stimulating the function of human primary osteoblasts, which are responsible for bone formation, and inhibiting the differentiation of human osteoclasts, which are responsible for bone resorption. This dual effect was monitored by analyzing Runx2 expression, deposition of mineralized matrix, ALP activity, TRAP and actin ring staining respectively. This study suggests that bioactive chemicals from Cucurbita moschata leaves are potentially suitable as therapeutics for managing metabolic bone disorders such as osteoporosis and rheumatoid arthritis, and promoting tissue healing and functional recovery after bone fractures. The data we obtained increase knowledge on the biological activities of Cucurbita moschata, and in particular underline the potential benefits of consuming leaves which are a part of the plant currently little considered in the Western world.

关键词： Virology   Medical Microbiology   Infectious Diseases  

摘要： Infectious bronchitis virus (IBV), an avian coronavirus, is highly contagious. Chickens with IBV infection develop acute pathogenesis in multiple organs, including the respiratory and urogenital tracts. Frequent recombination in the spike (S) glycoprotein gene has made vaccine strategies ineffective. To understand IBV pathogenesis, we analyzed the genetic distance between Korean IBV isolates and other coronaviruses, including SARS-CoV-2. To obtain comprehensive information about early immune responses such as innate cytokine production and associated immune regulation during IBV infection, we infected primary chicken embryonic kidney cells and performed transcriptome analysis. We observed that the functional pathways of innate immunity are regulated and confirmed expression of genes that coordinate early immune responses. Understanding the immune profile of the host cell may assist in vaccine development.

关键词： Bridges   Training   Morphology   Feature extraction   Convolution   Testing   Residual neural networks   Automatic defect classification   multi-lines bridge   scanning electron microscopy   convolutional neural network   residual neural network   hierarchical structure  

摘要： Defect classifications are the very important steps as the in-line defect inspection of the semiconductor manufacturing procedure. The conventional defect classifications are usually through visual judgement by engineer or technical assistant. However, it's time-consuming and laborious. In our recent study, the artificial intelligence automatic defect classification (AI-ADC) performed promisingly good accuracy and purity (A/P) of the auto defect classification by deep learning method. Nevertheless, some kinds of tiny defects are not only suffered lower A/P issues, but also suffered bad A/P stability of real defect classification. In this work, we propose the novel method, called "Hierarchical structure AI-ADC", which introduced a second binning classifier and it's based on hierarchical clustering to achieve more precise defect classification. As a result, the proposed method shown obvious improvements to the binning purity of multi-lines bridge defect from 56% to 88% as well as the stability variation has been reduced from 55% to 22%, besides it also can be applied to classify the similar defect types efficiently. Indeed this approach achieves excellent defect classification and highly stable performance.

关键词： IL-35   Immunosuppression   IL-15R alpha   Neutrophil   Grass carp  

摘要： IL-35 plays a key role in regulatory T (Treg) and regulatory B (Breg) cell functions in mammals. CD25 has been demonstrated as one of the markers of Treg cells, and CD19(+)CD25(hi)CD71(hi) cells have been verified as a type of Breg cells in humans. These results indicate that there is a close relationship between IL-35 and CD25(+) cells. In mammals, CD25 (alias IL-2R alpha) has been identified as having high affinity and specificity for IL-2 binding, and is closely linked and structurally related to IL-15R alpha, which having high affinity for IL-15 binding. In teleost, IL15R alpha can bind to both IL-2 and IL-15, with higher affinity to IL-15 than IL-2, and has been termed a CD25-like molecule in some research studies. To date, no studies of IL-35 and IL-15R alpha have been documented in fish. In this work, five isoforms of IL-15R alpha were cloned from grass carp, and a monoclonal antibody to the protein was developed. The results of flow cytometry and quantitative real-time PCR analyses demonstrated that grass carp IL-35 subunit genes EBI3a and IL-12p35 were mainly expressed in IL-15R alpha(+) cells, while the expression levels of IL-10 and TGF-beta in IL-15R alpha(+) and IL-15R alpha- cells were insignificant. Recombinant grass carp IL-35 (rgcIL-35) could increase the proportion of IL-15R alpha(+) cells in leukocytes, and a certain proportion of IL-15R alpha(+) cells also appeared in myeloid cell subset II after stimulation with rgcIL-35. Meanwhile, the migration, phagocytic ability, and bactericidal ability of grass carp neutrophils were significantly decreased after stimulation with certain concentrations of rgcIL-35. Moreover, neutrophil apoptosis could be significantly inhibited by rgcIL-35.

关键词： FFPE   formalin fixed and paraffin embedded   HC   healthy control   HCQ   hydroxychloroquine   HPF   high-power field   KC   keratinocyte   LCM   laser-capture microdissection   mDC   myeloid dendritic cell   pDC   plasmacytoid dendritic cell  

摘要： Dermatomyositis pathogenesis remains incompletely understood;however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-beta, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-beta in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-beta by immunofluorescence and laser-capture microdissection revealed increased IFN-beta mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-beta in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-beta in healthy controls (P < 0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P < 0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-beta production.

关键词： early-stage nodal diffuse large B cell lymphoma   SEER database   survival   primary site   enrichment analysis  

摘要： Simple Summary Few studies have examined the impact of primary tumor location on clinical outcome in patients with early-stage nodal diffuse large B-cell lymphoma (DLBCL). The objective of this study was to identify the association between primary tumor location and early-stage nodal DLBCL patient prognosis using a large population-based cohort and make an effort to uncover its underlying molecular mechanism using a public database. Our result shows that the prognosis of early-stage nodal DLBCL patients with tumors growing under the diaphragm is poorer. After screening DEGs and carrying out enrichment analysis, we found early-stage nodal diffuse large B-cell lymphoma located in different sites having different genetic characteristics. These results emphasize the importance of the primary tumor site on clinical decision-making and prognosis of patients with early-stage nodal diffuse large B-cell lymphoma. The prognostic role of primary tumor location for clinical outcomes of patients with early-stage nodal diffuse large B-cell lymphoma (DLBCL) remains uncertain. We evaluated the relationship between primary tumor site and overall survival (OS) in 9738 early-stage nodal DLBCL patients from the Surveillance, Epidemiology, and End Results (SEER) database. The primary site of the tumors was characterized as supradiaphragm and subdiaphragm according to the definition of lymph node distribution in the Ann Arbor staging. The OS was significantly better for patients of the supradiaphragm group (n = 6038) compared to the ones from the subdiaphragm group (n = 3655) (hazard ratio (HR) 1.24;95%CI: 1.16-1.33;P < 0.001), and it was preserved after propensity score matching (PSM) (HR 1.15;95% CI: 1.07-1.24;P < 0.001). Gene enrichment analyses demonstrated that the subdiaphragm group has an upregulated extracellular matrix (ECM)-related signaling, which reportedly can promote growth, invasion, and metastasis of the cancer, and downregulated interferon response, which is considered t

关键词： primary Sjogren's syndrome   tertiary lymphoid structures   stroma   chemokines   B cells   germinal centre  

摘要： Primary SS (pSS) is a chronic autoimmune condition characterized by infiltration of the exocrine glands and systemic B cell hyperactivation. This glandular infiltration is associated with loss of glandular function, with pSS patients primarily presenting with severe dryness of the eyes and mouth. Within the affected glands, the infiltrating lymphocytes are organized in tertiary lymphoid structures. Tertiary lymphoid structures subvert normal tissue architecture and impact on organ function, by promoting the activation and maintenance of autoreactive lymphocytes. This review summarizes the current knowledge about the role of stromal cells (including endothelium, epithelium, nerves and fibroblasts) in the pathogenesis of pSS, in particular the interactions taking place between stromal cells and infiltrating lymphocytes. We will provide evidences pointing towards the driving role of stromal cells in the orchestration of the local inflammatory milieu, thus highlighting the need for therapies aimed at targeting this compartment alongside classical immunosuppression in pSS.

关键词： compound screening   microfluidics   structural biology   protein crystallography   X-ray diffraction  

摘要： A novel capillary-based microfluidic strategy to accelerate the process of small-molecule-compound screening by room-temperature X-ray crystallography using protein crystals is reported. The ultra-thin microfluidic devices are composed of a UV-curable polymer, patterned by cleanroom photolithography, and have nine capillary channels per chip. The chip was designed for ease of sample manipulation, sample stability and minimal X-ray background. 3D-printed frames and cassettes conforming to SBS standards are used to house the capillary chips, providing additional mechanical stability and compatibility with automated liquid- and sample-handling robotics. These devices enable an innovative in situ crystal-soaking screening workflow, akin to high-throughput compound screening, such that quantitative electron density maps sufficient to determine weak binding events are efficiently obtained. This work paves the way for adopting a room-temperature microfluidics-based sample delivery method at synchrotron sources to facilitate high-throughput protein-crystallography-based screening of compounds at high concentration with the aim of discovering novel binding events in an automated manner.

关键词： GATA3   Cutaneous lymphoma   Mycosis fungoides   Anaplastic large cell lymphoma   Primary cutaneous CD30-positive T cell lymphoproliferative disorders   T helper cell  

摘要： Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.