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摘要： Background and Aims Studies of the identity and pathophysiology of fibrogenic HSCs have been hampered by a lack of genetic tools that permit specific and inducible fate-mapping of these cells in vivo. Here, by single-cell RNA sequencing of nonparenchymal cells from mouse liver, we identified transcription factor 21 (Tcf21) as a unique marker that restricted its expression to quiescent HSCs. Approach and Results Tracing Tcf21(+) cells by Tcf21-CreER (Cre-Estrogen Receptor fusion protein under the control of Tcf21 gene promoter) targeted ~10% of all HSCs, most of which were located at periportal and pericentral zones. These HSCs were quiescent under steady state but became activated on injuries, generating 62%-67% of all myofibroblasts in fibrotic livers and ~85% of all cancer-associated fibroblasts (CAFs) in liver tumors. Conditional deletion of Transforming Growth Factor Beta Receptor 2 (Tgfbr2) by Tcf21-CreER blocked HSC activation, compromised liver fibrosis, and inhibited liver tumor progression. Conclusions In conclusion, Tcf21-CreER-targeted perivenous stellate cells are the main source of myofibroblasts and CAFs in chronically injured livers. TGF-beta signaling links HSC activation to liver fibrosis and tumorigenesis.

关键词： Antibiotics   Carp   Cell line   Cytotoxicity   Ecotoxicity   Mussel  

摘要： The ubiquitous use of antibiotics leads exposure of these chemicals on non-target aquatic species, while the toxicity assays for these chemicals are time/labor consuming and expensive. Alternative approaches using primary cell cultures which retain the tissue functionality at its highest form have received global attention compared to cell lines. In the current study, the cytotoxic effects of two commonly used antibiotics from amphenicol (florfenicol) and macrolide (erythromycin) groups were evaluated on primary cell cultures of Unio crassus (mantle, digestive gland, gill, and gonad) and Cyprinus carpio (gill and liver) using MTT and Neutral Red assays. The highest cytotoxic effects were found on the mussel digestive gland and carp liver cells for florfenicol and erythromycin, while the lowest cytotoxic effects were found in mussel mantle cells for both drugs in the MTT test. In the NR test, the highest cytotoxic effects of erythromycin and florfenicol were found in the mussel gill, mantle, gonad, and carp gill cells;the lowest cytotoxic effect of erythromycin was found in the mussel digestive gland, while the lowest effect of florfenicol was found in the carp liver cells. The cytotoxicity of florfenicol was quite low for the carp liver, while the cytotoxicity of erythromycin was quite low in the mussel digestive tract. Thus, it was concluded that cells made from mussel tissues could be used in ecotoxicity tests, and sensitivity may vary according to the tissue.

关键词： Bestrophin-1   Best1 channel   DRG neurons   GABA receptors   Primary afferents   Satellite cells  

摘要： Primary afferent fibers express extrasynaptic GABA(A) and GABA(B) receptors in the axons and soma. However, whether these receptors are tonically activated by ambient GABA and the source of the neuro-transmitter is presently unknown. Here, we show that GABA release from dorsal root ganglia (DRG) does not depend on extracellular calcium, but depends upon calcium released from intracellular stores, and is mediated by Best1 channels. Using a preparation consisting of the spinal nerve in continuity with the DRG and the dorsal root, we found that endogenous GABA tonically activates GABA receptors, depressing the excitability of the primary afferents. In addition, using HPLC we found that GABA is released in the DRG, and by immunofluorescence microscopy we show the presence of GABA, the Best1 channel, and some enzymes of the putrescine pathway of GABA biosynthesis, in glutamine synthase- and GFAP-positive satellite glial cells. Last, we found that the blockade of the Best1 channel activity reduced the excitability of primary afferents and prevented the activation of the GABA receptors. These results suggest that satellite glial cells may be the source of endogenous GABA released in the DRG via Best1 channels, which tonically activates extrasynaptic GABA receptors. (C) 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

关键词： Primary angle closure suspects   Ganglion cell complex   Related factors   Biometry  

摘要： Introduction: This study aimed to investigate the ganglion cell complex (GCC) parameters in primary angle closure suspects (PACS) and identify the related factors. Methods: A total of 731 subjects, including 289 subjects with PACS and 442 subjects without PACS, underwent RTVue XR OCT. GCC parameters were compared between the two groups. The linear mixed-effects model was performed to evaluate the relationships between the GCC parameters and related factors. Results: Significant differences were found in gender, age, spherical refractive error, height, waist, anterior chamber depth, lens thickness, axial length, superior GCC thickness, ganglion cell complex focal loss volume, ganglion cell complex global loss volume, and ganglion cell complex root mean square between PACS and normal controls. The linear mixed-effects model showed that age (p = 0.008) and blood glucose (p = 0.001) were negatively correlated with average GCC thickness in PACS subjects, and PACS (p = 0.036) and age (p < 0.001) were the key influencing factors for average GCC thickness. Conclusion: GCC parameters in PACS subjects are different from those in normal controls. Careful explanation should be considered when evaluating changes of GCC parameters in patients with PACD. (C) 2021 The Author(s) Published by S. Karger AG, Basel

关键词： brain microvascular endothelial cells   neural stem cells   neurovascular unit   reconstituting   three-dimensional  

摘要： Neurovascular dysfunction is a primary or secondary cause in the pathogenesis of several cerebrovascular and neurodegenerative disorders, including stroke. Therefore, the overall protection of the neurovascular unit (NVU) is a promising therapeutic strategy for various neurovascular diseases. However, the complexity of the NVU limits the study of the pathological mechanisms of neurovascular dysfunction. Reconstituting the in vitro NVU is important for the pathological study and drug screening of neurovascular diseases. In this study, we generated a spontaneously assembled three-dimensional NVU (3D NVU) by employing the primary neural stem cells and brain microvascular endothelial cells in a Matrigel extracellular matrix platform. This novel model exhibits the fundamental structures and features of the NVU, including neurons, astrocytes, oligodendrocytes, vascular-like structures, and blood-brain barrier-like characteristics. Additionally, under oxygen-glucose deprivation, the 3D NVU exhibits the neurovascular- or oxidative stress-related pathological characteristics of cerebral ischemia and the injuries can be mitigated, respectively, by supplementing with the vascular endothelial growth factor or edaravone, which demonstrated that the availability of 3D NVU in ischemic stroke modeling. Finally, the 3D NVU promoted the angiogenesis and neurogenesis in the brain of cerebral ischemia rats. We expect that the proposed in vitro 3D NVU model will be widely used to investigate the relationships between angiogenesis and neurogenesis and to study the pathology and pharmacology of neurovascular diseases.

关键词： 装配式构件  

ISBN: (纸本)9787560396941

摘要： 本书以7章：绪论、大跨装配式钢桁架梁组合楼盖体系的组成与构造、大跨装配式组合楼盖体系关键连接节点受力性能试验、大跨装配式组合楼盖体系平面内刚度性能试验、大跨装配式组合楼盖体系平面内变形与刚度性能试验、大跨装配式组合楼盖体系的有限元分析与平面内刚度性能分析、大跨装配式组合楼盖体系抗连续倒塌性能。

摘要： Purpose: There is controversy about the need to target the mucosa of the larynx and hypopharynx during radiation therapy (RT) for squamous cell carcinoma of an unknown primary site (SCCA-UP). By 1997, the policy in our department was to target only the oropharynx and nasopharynx in patients with SCCA-UP metastatic to the level II cervical nodes. The purpose of this study was to report the rate of cancer recurrence in the larynx or hypopharynx using an approach that excluded these areas from the RT target volumes. Methods and Materials: The inclusion criteria for this study were RT in our department for SCCA-UP between January 1, 1997, and December 31, 2019;no history of surgery that could disrupt the cervical lymphatics;predominant adenopathy in level IIA;and neck stage N1-2c. We excluded N3 because the incidental dose to the larynx and hypopharynx is usually high in patients with a >6-cm nodal conglomerate. Results: The study population was comprised of 50 patients with a median follow-up after RT of 7.1 years. No patient developed recurrent cancer in a mucosal site (0/50), 2% (1/50) developed a neck recurrence in a high-dose area with synchronous distant metastases, and 2% (1/50) developed distant metastases with no evidence of local or regional recurrence. Conclusions: When delivering RT for SCCA-UP metastatic predominantly to level IIA, it is not necessary to target the mucosa of the larynx or hypopharynx. The extent to which the incidental RT dose to these areas contributes to cancer control is not evaluated in this study. (c) 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

关键词： primary cilia   2-IPMA   particulate matter (PM2   5)   inflammation   RPE cells  

摘要： Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-alpha, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.

关键词： Associative algebras   filiform   naturally graded   nilpotent   null-filiform   quasi-filiform  

摘要： In this paper we give the classification of 5-dimensional complex nilpotent associative algebras. We use chi(A) = odimA, dimA(2), dimA(3),..., dimA(n)) - the isomorphism invariant. We prove that there are only two possible isomorphism invariants chi(A) = (5, 2, 1, 0, 0) or chi(A) = (5, 3, 1, 0, 0) for any 5-dimensional complex nilpotent associative algebra A with the condition A(4) = 0 <^> A(3) not equal 0 and we give the classification (up to isomorphism) of such type algebras. 5-dimensional complex nilpotent associative algebras with the conditions A(6) = 0 A(5) not equal 0, A(5) = 0 <^> A(4) not equal 0 and A(3) = 0 <^> A(2) not equal 0 have already been classified. Thus, we complete the classification of 5-dimensional complex nilpotent associative algebras.