Exosomal LRG1 promotes non-small cell lung cancer proliferation and metastasis by binding FN1 protein.

Leucine-rich α2-glycoprotein-1 (LRG1) is overexpressed in various cancers, including non-small cell lung cancer (NSCLC), but its role in NSCLC cell metastasis is not well understood. In this study, NSCLC cell exosomes were analyzed using different techniques, and the impact of exosomal LRG1 on NSCLC cell behavior was investigated through various assays both in vitro and in vivo. The study revealed that LRG1, found abundantly in NSCLC cells and exosomes, enhanced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Exosomal LRG1 was shown to promote NSCLC cell metastasis in animal models. Additionally, the interaction between LRG1 and fibronectin 1 (FN1) in the cytoplasm was identified. It was observed that FN1 could counteract the effects of LRG1 knockdown on cell regulation induced by exosomes derived from NSCLC cells. Overall, the findings suggest that targeting exosomal LRG1 or FN1 may hold therapeutic potential for treating NSCLC.

Research on the Recognition and Tracking of Group-Housed Pigs' Posture Based on Edge Computing.

The existing algorithms for identifying and tracking pigs in barns generally have a large number of parameters, relatively complex networks and a high demand for computational resources, which are not suitable for deployment in embedded-edge nodes on farms. A lightweight multi-objective identification and tracking algorithm based on improved YOLOv5s and DeepSort was developed for group-housed pigs in this study. The identification algorithm was optimized by: (i) using a dilated convolution in the YOLOv5s backbone network to reduce the number of model parameters and computational power requirements; (ii) adding a coordinate attention mechanism to improve the model precision; and (iii) pruning the BN layers to reduce the computational requirements. The optimized identification model was combined with DeepSort to form the final Tracking by Detecting algorithm and ported to a Jetson AGX Xavier edge computing node. The algorithm reduced the model size by 65.3% compared to the original YOLOv5s. The algorithm achieved a recognition precision of 96.6%; a tracking time of 46 ms; and a tracking frame rate of 21.7 FPS, and the precision of the tracking statistics was greater than 90%. The model size and performance met the requirements for stable real-time operation in embedded-edge computing nodes for monitoring group-housed pigs.

Ticagrelor versus clopidogrel in reducing inflammatory cell infiltration of thrombus aspirated in patients with ST-elevation myocardial infarction.

BACKGROUND: Ticagrelor provides more rapid, potent, and consistent anti-platelet efficacy than clopidogrel. This randomized trial aimed to evaluate the anti-inflammation effects of ticagrelor versus clopidogrel on thrombus aspirated from the ST-elevation myocardial infarction (STEMI) patients. METHOD: A total of 98 patients with STEMI and intended percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (600-mg loading dose) or ticagrelor (180-mg loading dose), of whom 55 with large thrombus burden underwent thrombus aspiration during PCI. Thrombus specimens were successfully aspirated from 49 patients. Finally, 24 patients in the clopidogrel group and 23 in the ticagrelor group completed the study. Inflammatory cells within thrombi were assessed by hematoxylin-eosin and immunohistochemistry stainings. RESULTS: Compared with the clopidogrel group, the number of total inflammatory cells per mm2 thrombus area in the ticagrelor group was decreased by 28% (P = 0.009). The numbers of neutrophils and myeloperoxidase-positive cells per mm2 thrombus area in the ticagrelor group were respectively decreased by 35% (P = 0.016) and 28% (P = 0.047), as compared with those in the clopidogrel group. Moreover, ticagrelor treatment reduced the ratio of monocytes number higher than 250 per mm2 thrombus area compared with clopidogrel treatment (4% versus 29%, P = 0.048). CONCLUSION: In patients with undergoing PCI for STEMI, the loading dose ticagrelor regimen was associated with a reduction in inflammatory cell infiltration within thrombus compared with the loading dose clopidogrel regimen.

Establishing an 8-gene immune prognostic model based on TP53 status for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) results in a majority of cancer burden worldwide. TP53 is the most commonly mutated in LUAD. This study aimed to reveal the relation between TP53 and tumor microenvironment (TME) for improving LUAD treatment. METHODS: Differentially expressed genes (DEGs) related to immunity were analyzed between TP53-WT and TP53-MUT groups. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to screen prognostic DEGs. Two independent datasets were included to evaluate the robustness of the prognostic model. RESULTS: An 8-gene prognostic model containing ANLN, CCNB1, DLGAP5, FAM83A, GJB2, NAPSA, SFTPB, and SLC2A1 was established based on DEGs. LUAD samples were classified into high- and low-risk groups with differential overall survival in the two datasets. M0 macrophages, M1 macrophages, and activated memory CD4 T cells were more enriched in high-risk group. Immune checkpoints of PDCD1, LAG3, and CD274 were also high-expressed in high-risk group. CONCLUSION: The study improved the understanding of the role of TP53 in the TME modulation. The 8-gene model had robust performance to predict LUAD prognosis in clinical practice. In addition, the eight prognostic genes may also serve as potential targets for designing therapeutic drugs for LUAD patients.

Mechanisms exploration of terrestrosin D on pulmonary fibrosis based on plasma metabolomics and network pharmacology.

Terrestrosin D (TED) is the active ingredient of Tribulus terrestris L., which is used in traditional Chinese medicine (TCM) formulations and has a wide range of pharmacological activities. A previous study showed that TED alleviated bleomycin (BLM)-induced pulmonary fibrosis (PF) in mice. However, the mechanisms underlying the therapeutic effect of TED are still unclear and need further investigation. In this study, we evaluated the effect of TED in a mice of BLM-induced PF in terms of histopathological and biochemical indices. UHPLC-MS-based plasma metabolomics combined with network pharmacology was used to explore the pathological basis of PF and the mechanism of action of TED. Histological and biochemical analyses showed that TED mitigated inflammatory injury in the lungs, especially at the dosage of 20 mg/kg. Furthermore, BLM changed the plasma metabolite profile in the mice, which was reversed by TED via regulation of amino acid and lipid metabolism. Subsequently, a biomarkers-targets-disease network was constructed, and tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 were identified as the putative therapeutic targets of TED. Both factors were quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA). Taken together, the combination of UHPLC-MS-based metabolomics and network pharmacology can unveil the mechanisms of diseases and drug action.

Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS.

A novel method of ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of four potential genotoxic impurities (PGIs) in the active pharmaceutical ingredients of TSD-1, a novel P2Y12 receptor antagonist. Four PGIs were named, 4-nitrobenzenesulfonic acid, methyl 4-nitrobenzenesulfonate, ethyl 4-nitrobenzenesulfonate, and isopropyl 4-nitrobenzenesulfonate. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying four PGIs at 15.0 ppm in samples of 0.5 mg/mL concentration. This validated approach presented very low limits (0.1512−0.3897 ng/mL), excellent linearity (coefficients > 0.9900), and a satisfactory recovery range (94.9−115.5%). The method was sufficient in terms of sensitivity, linearity, precision, accuracy, selectivity, and robustness and, thus, has high practicality in the pharmaceutical quality control of TSD-1.

Small ubiquitin-related modifier (SUMO)ylation of SIRT1 mediates (-)-epicatechin inhibited- differentiation of cardiac fibroblasts into myofibroblasts.

CONTEXT: (-)-Epicatechin (EPI) is a crucial substance involved in the protective effects of flavanol-rich foods. Previous studies have indicated EPI has a cardioprotective effect, but the molecular mechanisms in inhibition of cardiac fibrosis are unclear. OBJECTIVE: We evaluated the effect of EPI in preventing cardiac fibrosis and the underlying molecular mechanism related to the SIRT1-SUMO1/AKT/GSK3ß pathway. MATERIALS AND METHODS: Cardiac fibrosis mice model was established with transaortic constriction (TAC). Male C57BL/6 mice were randomly separated into 4 groups. Mice received 1 mg/kg/day of EPI or vehicle orally for 4 weeks. The acutely isolated cardiac fibroblasts were induced to myofibroblasts with 1 µM angiotensin II (Ang II). The cardiac function was measured with the ultrasonic instrument. Histological analysis of mice's hearts was determined with H&E or Masson method. The protein level of fibrosis markers, SUMOylation of SIRT1, and AKT/GSK3ß pathway were quantified by immunofluorescence and western blot. RESULTS: EPI treatment (1 mg/kg/day) could reverse the TAC-induced decline in LVEF (TAC, 61.28% ± 1.33% vs. TAC + EPI, 74.00% ± 1.64%), LVFS (TAC, 28.16% ± 0.89% vs. TAC + EPI, 37.18% ± 1.29%). Meantime, we found that 10 µM EPI blocks Ang II-induced transformation of cardiac fibroblasts into myofibroblasts. The underlying mechanism of EPI-inhibited myofibroblasts transformation involves activation of SUMOylation of SIRT1 through SP1. Furthermore, SUMOylation of SIRT1 inhibited Ang II-induced fibrogenic effect via the AKT/GSK3ß pathway. CONCLUSION: EPI plays a protective effect on cardiac fibrosis by regulating the SUMO1-dependent modulation of SIRT1, which provides a theoretical basis for use in clinical therapies.

LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes.

OBJECTIVES: Increasing evidence suggest that long non-coding RNAs (lncRNAs) play critical roles in cancers. However, the expression pattern and underlying mechanisms of lncRNAs in non-small cell lung cancer (NSCLC) remain incompletely understood. This study aimed to elucidate the functions and molecular mechanisms of a certain lncRNA in NSCLC. METHODS: LncRNA microarray was performed to identify differential expressed lncRNAs between pre- and postoperation plasma in NSCLC patients. The expression level of candidate lncRNA in NSCLC tissues, plasma and cells was determined by quantitative real-time PCR (qRT-PCR) and in situ hybridization. The functional roles of lncRNA were assessed in vitro and in vivo. Furthermore, RNA pull-down, RNA immunoprecipitation, microarray, qRT-PCR and rescue assays were conducted to explore the mechanism action of lncRNA in NSCLC cells. RESULTS: We identified a novel lncRNA (BRCAT54), which was significantly upregulated in preoperative plasma, NSCLC tissues and NSCLC cells, and its higher expression was associated with better prognosis in patients with NSCLC. Overexpression of BRCAT54 inhibited proliferation, migration and activated apoptosis in NSCLC cells. Conversely, knockdown of BRCAT54 reversed the suppressive effects of BRCAT54. Moreover, overexpression of BRCAT54 repressed NSCLC cell growth in vivo. Mechanistically, BRCAT54 directly bound to RPS9. Knockdown of RPS9 substantially reversed the promoting effects of si-BRCAT54 on cell proliferation and enhanced the inhibitive effect of si-BRCAT54 on BRCAT54 expression. In addition, silencing of RPS9 activated JAK-STAT pathway and suppressed calcium signaling pathway gene expressions. CONCLUSION: This study identified BRCAT54 as a tumor suppressor in NSCLC. Targeting the BRCAT54 and RPS9 feedback loop might be a novel therapeutic strategy for NSCLC.

LncRNA WT1-AS downregulates lncRNA UCA1 to suppress non-small cell lung cancer and predicts poor survival.

BACKGROUND: LncRNA WT1-AS inhibits gastric cancer, while its role in other cancers is unknown. We investigated the role of WT1-AS in non-small cell lung cancer (NSCLC). METHODS: Sixty-six NSCLC patients (40 males and 26 females; 36 to 68 years old; mean age 52.7 ± 6.4 years old) were selected from the 178 NSCLC patients operated on for lung cancer between 2010 and 2013. RT-qPCR was used to analyze the expression of lncRNA. Overexpression experiments were performed to assess interactions between lncRNAs. CCK-8 assay was carried to evaluate the roles of WT1-AS and UCA1 in regulating cell proliferation. Cell invasion and migration assays were performed to assess the roles of WT1-AS and UCA1 in regulating cell invasion and migration. Western-blot was performed to illustrate the effect of WT1-AS and UCA1 in EMT. RESULTS: WT1-AS was downregulated in NSCLC and was correlated with poor survival. The expression of WT1-AS in NSCLC was not correlated with clinical stages. LncRNA UCA1 was upregulated in cancer tissues and inversely correlated with WT1-AS. Overexpression of UCA1 did not affect WT1-AS, while overexpression of WT1-AS led to inhibited expression of UCA1. Overexpression of UCA1 resulted in increased proliferation, EMT, migration and invasion of NSCLC cells, while overexpression of WT1-AS showed opposite effects. In addition, overexpression of UCA1 inhibited the role of overexpression of WT1-AS. CONCLUSIONS: Therefore, overexpression of WT1-AS may inhibit the cell proliferation and EMT to decrease cell migration and invasion of NSCLC cells by downregulating UCA1.

Voltage and e-liquid composition affect nicotine deposition within the oral cavity and carbonyl formation.

INTRODUCTION: The diversity of e-liquids along with higher powered e-cigarette nicotine delivery devices are increasing. This study evaluated the effect of voltage and e-liquid composition on particle size, nicotine deposition in a human oral-trachea cast model and generation of carbonyls. METHODS: Nineteen e-liquids were evaluated for 30 common chemicals by gas chromatography-mass spectrometry (GC-MS). E-cigarette aerosols containing nicotine (1.2%) were generated at 4 and 5 volts for assessment of particle size distribution using Aerodynamic Particle Sizer (APS), Fast Mobility Particle Size (FMPS) and an In-Tox cascade impactor and nicotine deposition by GC-MS. Carbonyl formation in aerosols was assessed by liquid chromatography tandem triple-quad mass spectrometry. RESULTS: Total chemical burden ranged from 0.35 to 14.6 mg/mL with ethyl maltol present in all e-liquids. Increasing voltage was associated with an increase in median size of aerosol particles and the deposition of nicotine in the oral cast. Two e-liquids caused a 2.5-fold to 5-fold increase in nicotine deposition independent of particle size and voltage. Increasing voltage caused an increase in formaldehyde, acetaldehyde and acrolein in the presence and absence of nicotine. Most striking, aerosols from several e-liquids significantly increased levels of acetaldehyde and acrolein compared with unflavoured. CONCLUSIONS: Increasing voltage and composition of e-liquid can increase the exposure of the oral pharynx and bronchial airways to carbonyls that can react with DNA to generate adducts, induce oxidative stress, inflammation and cell death. The elevated nicotine and carbonyls readily enter the circulation where they can also cause cardiovascular stress. The growing popularity of higher voltage e-cigarette delivery devices will likely further elevate health risks from chronic exposure to these complex aerosols.

Molecular phylogenetic identification and morphological characteristics of Raillietina echinobothrida (Cestoda: Cyclophyllidea: Davaineidae) in commercial chickens in North China.

Raillietina echinobothrida (R. echinobothrida) is one of the most pathogenic and prevalent tapeworms threat to the commercial chickens in China. However, there is a lack of research on their molecular identification and morphological characteristics. This study explored the molecular identification markers for R. echinobothrida in North China based on 18s ribosomal RNA (18s rRNA) gene and the ribosomal DNA second internal transcribed spacer (ITS-2) gene. The BLAST results of 18s rRNA (1643 bp) and ITS-2 (564 bp) gene sequences showed that the isolated intestinal tapeworms were R. echinobothrida. Phylogenetic trees obtained by maximum likelihood (ML) or neighbor-joining (NJ) method revealed that the R. echinobothrida in North China had the closest evolutionary relationship with the species found on the Qinghai-Tibet plateau, China. Morphological observations by hematoxylin staining and scanning electron microscope showed four round suckers and a retractable rostellum on the spherical scolex of R. echinobothrida. Two rows of alternately arranged hooks distributed around the rostellum. There were 30-40 testes in each mature segment. A well-developed cirrus pouch lied outside the excretory duct of mature segment. The gravid segment contained 200-400 eggs and there was a well-developed oncosphere in each egg. In addition, abundant ultrastructural features in mature proglottid of R. echinobothrida in North China were identified by transmission electron microscopy. In conclusion, the present study established ways of molecular phylogenetic identification for R. echinobothrida based on 18s rRNA and ITS-2 gene, and identified the morphological and ultrastructural characteristics of R. echinobothrida in North China.

MOF Nanosheet Reconstructed Two-Dimensional Bionic Nanochannel for Protonic Field-Effect Transistors.

The construction of hydrophobic nanochannel with hydrophilic sites for bionic devices to proximally mimick real bio-system is still challenging. Taking the advantages of MOF chemistry, a highly oriented CuTCPP thin film has been successfully reconstructed with ultra-thin nanosheets to produce abundant two-dimensional interstitial hydrophobic nanochannels with hydrophilic sites. Different from the classical active-layer material with proton transport in bulk, CuTCPP thin film represents a new type of active-layer with proton transport in nanochannel for bionic proton field-effect transistor (H+ -FETs). The resultant device can reversibly modulate the proton transport by varying the voltage on its gate electrode. Meanwhile, it shows the highest proton mobility of ≈9.5×10-3  cm2 V-1 s-1 and highest on-off ratio of 4.1 among all of the reported H+ -FETs. Our result demonstrates a powerful material design strategy for proximally mimicking the structure and properties of bio-systems and constructing bionic electrical devices.

Screening and surveillance of multiple solid tumours using plasma placental-like chondroitin sulfate A (pl-CSA).

Rationale: Placental-like chondroitin sulfate A (pl-CSA) is known to be exclusively synthesized in multiple cancer tissues and associated with disease severity. Here, we aimed to assess whether pl-CSA is released into bio-fluids and can serve as a cancer biomarker. Methods: A novel ELISA was developed to analyse pl-CSA content in bio-fluids using pl-CSA binding protein and an anti-pl-CSA antibody. Immunohistochemical staining of tissue chips was used as the gold standard control. Results: The developed ELISA method was specific and sensitive (1.22 µg/ml). The pl-CSA content was significantly higher in lysates and supernatants of cancer cell lines than in those of normal cell lines, in plasma from mouse cancer models than in that from control mice, and in plasma from patients with oesophageal, cervical, ovarian, or lung cancer than in that from healthy controls. Similar to the tissue chip analysis, which showed a significant difference in pl-CSA positivity between cancer tissues and normal adjacent tissues, the plasma pl-CSA analysis had 100% sensitivity and specificity for differentiating oesophageal and lung cancer patients from healthy controls. Importantly, in oesophageal and lung cancer patients, the pl-CSA content was significantly higher in late-stage disease than in early-stage disease, and it dramatically decreased after surgical resection of the tumour. Conclusion: These data indicate a direct link between plasma pl-CSA content and tumour presence, indicating that plasma pl-CSA may be a non-invasive biomarker with clinical applicability for the screening and surveillance of patients with multiple types of solid tumours.

Antagonistic effect of N-acetyl-L-cysteine against cadmium-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages.

Cadmium is a highly toxic metal threatening human and animal health. N-acetyl-L-cysteine (NAC) was reported to play a positive role in disease treatment and immune regulation. The present study aimed to explore the effect of NAC administration on Cd-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages. Peritoneal macrophages isolated from Isa Brown male chickens were exposed to CdCl2 (20 or 50 µM) and/or NAC (500 µM) for different time periods. Results showed that Cd caused dose-dependent damage on chicken peritoneal macrophages characterized by morphologic and ultrastructural alterations, increased cell apoptosis, reactive oxygen species accumulation and mitochondrial injury. Cd exposure inhibited phagocytic activity of chicken peritoneal macrophages, and promoted transcriptional status of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in both unactivated macrophages and cells in response to lipopolysaccharide (LPS) stimuli. Pretreatment with 500 µM NAC did not affect growth of normal chicken peritoneal macrophages, while remarkably inhibiting Cd-caused cell death, oxidative stress, and mitochondrial membrane depolarization. NAC pretreatment significantly prevented intracellular Cd2+ accumulation in the Cd-exposed macrophages. Inhibitory effects of NAC on Cd-induced ROS accumulation and mitochondrial injury on chicken macrophages were confirmed in HD-11 macrophage cell line. In addition, NAC pretreatment promoted the phagocytic activity of Cd-exposed chicken peritoneal macrophages, and significantly inhibited expression of pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) in both Cd-exposed macrophages and Cd-treated cells in response to LPS stimuli. In conclusion, the present study firstly demonstrated the antagonistic effect of NAC against Cd-caused damage and abnormal immune response on chicken peritoneal macrophages. Protective effect of NAC on chicken macrophages was highly related to its suppression on Cd-induced ROS overproduction, pro-inflammatory reaction and intracellular Cd2+ accumulation.

Discovery of a novel series of hDHODH inhibitors with anti-pulmonary fibrotic activities.

Human dihydroorotate dehydrogenase (hDHODH) is a flavin-dependent enzyme essential to pyrimidine de novo biosynthesis, which serves as an attractive therapeutic target for the treatment of autoimmune disorders. A novel series of hDHODH inhibitors was developed based on a lead which was obtained by a medicinal chemistry exploration. Most compounds showed moderate to significant potency against hDHODH, compounds 5d, 5e, and 6a effectively inhibited the activities of hDHODH with IC50 values from 0.9 to 2.8 µM. Further studies showed that compound 5e also effectively suppressed proliferation of the activated PBMCs (IC50 = 20.35 µM). Surprisingly, compound 5e also showed anti-pulmonary fibrotic activity similar to that of pirfenidone in vitro assay. Therefore, compound 5e might have potential to be developed as a novel hDHODH inhibitors for autoimmune diseases therapy.

Zombie Cells, Composite Cells of Fungal-Human Keratinocytes of Plantar Hyperkeratosis-Like Lesions.

Foot hyperkeratosis is common. They often coincide with fungal infections, are difficult to cure and relapse rates are high. In this case study, longstanding and intractable plantar hyperkeratotic lesions were investigated for potential causative agents by histological examinations, by using human cell culture medium to grow the infected skin tissue, by sequencing ribosomal DNA and whole genome. Aspergillus sydowii was identified as the pathogen in the hyperkeratotic lesions. A peculiars intracellular infection of the fungus appeared to merge with anucleated epithelial cells of the skin, in which not fungal cells but basophilic nucleus-like bodies and abundant fungal proteins were seen in the cells. The composite fungal-human zombie-like cells were found to grow in the culture and in hyperkeratotic lesions, and some were readily transformed to natural fungus. Such zombie cells might play roles in the pathogenesis and recurrences of plantar hyperkeratotic lesions, resistance to antifungal drugs and relapses of the fungal infections.

Design, synthesis, and biological evaluation of novel substituted benzamide derivatives bearing a 1,2,3-triazole moiety as potent human dihydroorotate dehydrogenase inhibitors.

A novel series of substituted benzamide derivatives bearing a 1,2,3-triazole moiety were designed and synthesized by click chemistry. Human dihydroorotate dehydrogenase inhibition assay was used to evaluate the synthesized compounds as potent hDHODH inhibitors. Most compounds showed moderate to significant potency, accompanied with a suitable clogD7.4 value and compounds 4d, 4o, and 5j effectively inhibited the activity of hDHODH with IC50 values of 2.1, 2.1 and 1.5 µM, respectively. Compound 4o also effectively suppressed proliferation of the activated PBMCs. The study of structure-activity relationships also revealed that a suitable substitution on para-position of terminal phenyl ring was crucial for high activity. Together, the most promising compound 4o might serve as a novel hDHODH inhibitors for further investigation.

Porous Field-Effect Transistors Based on a Semiconductive Metal-Organic Framework.

Recently, the emergence of conductive metal-organic frameworks (MOFs) has given great prospects for their applications as active materials in electronic devices. In this work, a high-quality, free-standing conductive MOF membrane was prepared by an air-liquid interfacial growth method. Accordingly, field-effect transistors (FETs) possessing a crystalline microporous MOF channel layer were successfully fabricated for the first time. The porous FETs exhibited p-type behavior, distinguishable on/off ratios, and excellent field-effect hole mobilities as high as 48.6 cm2 V-1 s-1, which is even comparable to the highest value reported for solution-processed organic or inorganic FETs.

Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors.

A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety were synthesized and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against five cancer cell lines (HT-29, H460, A549, MKN-45 and U87MG) in vitro. Most of the compounds exhibited moderate-to-significant cytotoxicity as compared with foretinib. The most promising compound 41 (with c-Met IC50 value of 0.90nM) showed remarkable cytotoxicity against HT-29, H460, A549, MKN-45 and U87MG cell lines with IC50 values of 0.06µM, 0.05µM, 0.18µM, 0.023µM and 0.66µM, respectively, and thus it was 1.22- to 3.50-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.

Layer-by-Layer Assembled Conductive Metal-Organic Framework Nanofilms for Room-Temperature Chemiresistive Sensing.

The utility of electronically conductive metal-organic frameworks (EC-MOFs) in high-performance devices has been limited to date by a lack of high-quality thin film. The controllable thin-film fabrication of an EC-MOF, Cu3 (HHTP)2 , (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene), by a spray layer-by-layer liquid-phase epitaxial method is reported. The Cu3 (HHTP)2 thin film can not only be precisely prepared with thickness increment of about 2 nm per growing cycle, but also shows a smooth surface, good crystallinity, and high orientation. The chemiresistor gas sensor based on this high-quality thin film is one of the best room-temperature sensors for NH3 among all reported sensors based on various materials.