Indole-thiazolidinone conjugate inhibits nasopharyngeal carcinoma cell migration and invasion by targeting NF κB pathway

Purpose: To investigate the effect of indole-thiazolidinone on metastasis in HK1 nasopharyngeal carcinoma cells. Methods: HK1 cell proliferation was determined colorimetrically using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Invasion and migration of HK1 cells were assessed using Matrigel™ chamber coated invasion and wound healing assays, respectively. Results: Indole-thiazolidinone suppressed proliferation of HK1 and NPC 039 NPC cell lines at 72 h. The degree of proliferation of HK1 cells on treatment with 0.25, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 μM indolethiazolidinone was 99, 87, 71, 64, 49, 38 and 31 %, respectively. In HK1 cell cultures, migration potential was reduced to 58.32, 47.54, 28.91 and 17.65 %, on exposure to 1.5, 2.0, 2.5 and 3.0 μM indole-thiazolidinone, respectively. Incubation with 1.5, 2.0, 2.5 and 3.0 μM indole-thiazolidinone resulted in cell invasion values of 63.41, 49.37, 35.12 and 19.67 %, respectively. There was a marked decrease in the expressions of matrix metalloproteinase 2 and matrix metalloproteinase 9 in HK1 cells on treatment with indole-thiazolidinone (p < 0.05). In addition, indole-thiazolidinone treatment resulted in decrease in p65 and p50 in nuclear fraction. Treatment of HK1 and NPC 039 cells with indolethiazolidinone and henenalin synergistically decreased cell proliferation. Indole-thiazolidinone treatment caused significant decrease in tumor growth in mice (p < 0.05). Conclusion: Indole-thiazolidinone inhibits proliferation and metastasis in nasopharyngeal carcinoma cells. Therefore, it has potential for development as a therapeutic management of nasopharyngeal carcinoma in humans

ZnO homojunction photodiodes based on Sb-doped p-type nanowire array and n-type film for ultraviolet detection

ZnO p-n homojunctions based on Sb-doped p-type nanowire array and n-type film were grown by combining chemical vapor deposition (for nanowires) with molecular-beam epitaxy (for film). Indium tin oxide and Ti/Au were used as contacts to the ZnO nanowires and film, respectively. Characteristics of field-effect transistors using ZnO nanowires as channels indicate p-type conductivity of the nanowires. Electron beam induced current profiling confirmed the existence of ZnO p-n homojunction. Rectifying I-V characteristic showed a turn-on voltage of around 3 V. Very good response to ultraviolet light illumination was observed from photocurrent measurements

KCAT: A Knowledge-Constraint Typing Annotation Tool

Fine-grained Entity Typing is a tough task which suffers from noise samples extracted from distant supervision. Thousands of manually annotated samples can achieve greater performance than millions of samples generated by the previous distant supervision method. Whereas, it's hard for human beings to differentiate and memorize thousands of types, thus making large-scale human labeling hardly possible. In this paper, we introduce a Knowledge-Constraint Typing Annotation Tool (KCAT), which is efficient for fine-grained entity typing annotation. KCAT reduces the size of candidate types to an acceptable range for human beings through entity linking and provides a Multi-step Typing scheme to revise the entity linking result. Moreover, KCAT provides an efficient Annotator Client to accelerate the annotation process and a comprehensive Manager Module to analyse crowdsourcing annotations. Experiment shows that KCAT can significantly improve annotation efficiency, the time consumption increases slowly as the size of type set expands.Comment: 6 pages, acl2019 demo pape

Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy

<p>Abstract</p> <p>Background</p> <p>Although 70% (or 2/3) partial hepatectomy (PH) is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH) has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s) under this milder but clinically more relevant condition.</p> <p>Results</p> <p>Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones) identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration.</p> <p>Conclusions</p> <p>Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.</p

Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient model of autism

The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown. Here, we utilized the Shank3B mutant mouse model of autism to investigate how Shank3 mutation may differentially affect striatonigral (direct pathway) and striatopallidal (indirect pathway) medium spiny neurons (MSNs) and its relevance to repetitive grooming behavior in Shank3B mutant mice. We found that Shank3 deletion preferentially affects synapses onto striatopallidal MSNs. Striatopallidal MSNs showed profound defects, including alterations in synaptic transmission, synaptic plasticity, and spine density. Importantly, the repetitive grooming behavior was rescued by selectively enhancing the striatopallidal MSN activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq), a type of designer receptors exclusively activated by designer drugs (DREADD). Our findings directly demonstrate the existence of distinct changes between 2 striatal pathways in a mouse model of autism and indicate that the indirect striatal pathway disruption might play a causative role in repetitive behavior of Shank3B mutant mice.National Institute of Mental Health (U.S.) (Grant 5R01MH097104

Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects

Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutatio n manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients.National Institute of Mental Health (U.S.) (Grant 5R01MH097104)National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institutes of Health (U.S.) (Grant R01-NS 07312401