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To recognise clinical features of COVID-19 pneumonia and its differences from influenza pneumonia.246 patients were enrolled into COVID-19 cohort and 120 patients into influenza cohort. All data were collected and analysed retrospectively. The variables under focus included demographic, epidemiological, clinical, laboratory and imaging characteristics of COVID-19 pneumonia and comparison were made with influenza pneumonia.The COVID-19 cohort included 53.25% female and 46.75% male. Their main symptom was fever; while 28.05% of patients had only initially fever; 21.54% of them remained feverless. After excluding prior kidney diseases, some patients showed abnormal urinalysis (32.11%), elevated blood creatinine (15.04%) and blood urea nitrogen (19.11%). Typical CT features included ground glass opacity, consolidation and band opacity, which could present as characteristic 'bat wing sign'. Our data showed that male, aged 65 or above, smoking, with comorbidities including diabetes, cardiovascular and kidney diseases, would experience more severe COVID-19 pneumonia. In comparison, COVID-19 cohort showed significantly higher incidence of clustering; the influenza cohort showed higher rate of fever. Both cohorts showed reduced lymphocyte numbers; however, 6 influenza patients showed lymphocytes increased, which was statistical significant compared with COVID-19 cohort. Also, influenza cohort displayed higher white blood cell counts and PCT values.There is no significant gender difference in the incidence of COVID-19 pneumonia. It predominantly affects the lung as well as the kidney. Age, smoking and comorbidities could contribute to disease severity. Although COVID-19 is more infectious, the rate of secondary bacterial infection is lower than influenza.

Vanadium phosphate (VPO4) is attracting extensive attention because of its advantages of low cost, stable structure and high theoretical capacity. However, similar to other phosphates, VPO4 suffers from low electrical conductivity and large volume expansion, adversely influencing its electrochemical performance and thus limiting its application as an anode in lithium and sodium ion batteries. Herein, we propose a novel, facile strategy based on the organic–inorganic network of a nanostructured hybrid hydrogel for immobilizing VPO4 in a hierarchically porous carbon framework (3DHP-VPO4@C). VPO4 chemically interacts with the carbon framework via a P–C bond, functioning as a buffer layer to maintain structural stability during charge/discharge cycles. The carbon framework offers an efficient pathway for electron and Li+/Na+ transport to ensure high electronic conductivity of the electrode. The 3DHP-VPO4@C anode exhibits excellent lithium and sodium storage performances, and notably high capacities of 957 mA h g−1 at 0.1 A g−1 and 345.3 mA h g−1 at 5 A g−1 for lithium ion batteries. Full cells consisting of a LiFePO4 cathode and the 3DHP-VPO4@C anode also prove to have superior cycling stability and rate performance for LIBs.

Vanadium phosphate (VPO

The occurrence and development of hepatocellular carcinoma (HCC) is a complicate process involved in genetic mutation and epigenetic regulation. Successful HCC therapy needs multi-targets be involved. The aim of this study was to provide a triple effective RNA (teRNA) which composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3, and explored its anti-HCC roles and mechanism. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence staining, MTT, Annexin V-FITC flow cytometry, Transwell and in-vitro Angiogenesis assay were used to measure the cell biological functions and protein expression analysis. Furthermore in in-vivo mouse model, teRNA inhibited tumor growth were detected by immunohistochemistry and TUNEL assay. Results showed that the proliferation, migration and angiogenesis of HCC cells were inhibited by teRNA effectively, the cell apoptosis also was induced, and further tumor growth was suppressed in-vivo. The gene silencing mechanism of teRNA was in an Ago2-dependent manner with no interferon response. The study suggests that NET-1, VEGF and TLR3 might be better targets for HCC treatment and combined these targets in form of a multi-target small RNA, teRNA could be a stagey for the development of anti-HCC drugs.

Multiple targets RNAi strategy is a preferred way to treat multigenic diseases, especially cancers. In the study, multi-target siRNAs were designed to inhibit NET-1, EMS1 and VEGF genes in hepatocellular carcinoma (HCC) cells. And multi-target siRNAs showed better silencing effects on NET-1, EMS1 and VEGF, compared with single target siRNA. Moreover, multi-target siRNA showed greater suppression effects on proliferation, migration, invasion, angiogenesis and induced apoptosis in HCC cells. The results suggested that multi-target siRNA might be a preferred strategy for cancer therapy and NET-1, EMS1 and VEGF could be effective targets for HCC treatments.

Background It is reported that the iron-responsive element-binding protein 2 (IREB2) gene rs2568494 polymorphism might be associated with COPD risk. The purpose of this meta-analysis was to collect all eligible studies to review the association between IREB2 gene rs2568494 polymorphism and susceptibility to COPD. Material/Methods We carried out a comprehensive document search of electronic databases of PubMed, MEDLIN, Web of Science, and included 4 eligible studies that examined the association between IREB2 rs2568494 polymorphism and COPD susceptibility. We performed a meta-analysis of these studies based on IREB2 rs2568494 genotypes. Results After meta-analysis with fixed or random effects, no significant associations were found under the heterozygote model (GG/GA; OR=0.908, 95%CI: 0.790–1.043; P=0.172), homozygote model (GG/AA; OR=0.880, 95%CI: 0.497–1.557; P=0.661), dominant model (GG/AA+GA; OR=0.941, 95%CI: 0.748–1.182; P=0.599), or allelic model (G/A; OR=0.953, 95%CI: 0.770–1.179; P=0.655). However, we found a significant correlation under the recessive model (AA/GA+GG; OR=1.384, 95%CI: 1.092–1.755; P=0.007). Conclusions The current results revealed that there was significant association between IREB2 gene rs2568494 polymorphism with susceptibility to COPD; the presence of allelic A might a genetic factor conferring susceptibility to COPD.

HER2/neu oncogene is frequently overexpressed in various types of cancer, and the (PI3K)-Akt signaling pathway is often activated in HER2-overexpressing cancer cells. CSN6, subunit 6 of the COP9 signalosome complex, is pivotal in regulating MDM2 to destabilize p53, but its upstream regulators remain unclear. Here we show that the HER2-Akt axis is linked to CSN6 regulation, and that Akt is a positive regulator of CSN6. Ectopic expression of Akt can increase the expression of CSN6; accordingly, Akt inhibition leads to CSN6 destabilization. Mechanistic studies show that Akt causes CSN6 phosphorylation at Ser 60, which, in turn, reduces ubiquitin-mediated protein degradation of CSN6. Significantly, Akt’s positive impact on CSN6 elevation translates into p53 degradation, potentiating transformational activity and increasing DNA damage. Akt inhibition can attenuate these defects caused by CSN6. These data suggest that Akt is an important positive regulator of CSN6, and that activation of Akt in many types of cancer could lead to abnormal elevation of CSN6 and result in downregulated p53 and increased DNA damage, which promotes cancer cell growth.

Immune inhibitory receptors play an important role in organ transplantation, autoimmune diseases and cancers. Immunoglobulin-like transcript (ILT)2 and ILT3 belong to the inhibitory receptors of the ILT family, which have been reported to regulate a broad range of cellular functions involved in the immune response. They contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which are related to immune regulation. Although ILT receptors have been studied in dendritic cells (DCs), T cells, NK cells and other cell types, the expression and clinical significance of ILT2 and ILT3 in gastric cancer have yet to be elucidated. Here, the expression of ILT2 and ILT3 in gastric cancer cell lines and pathologic tissues, as well as their effects on the cytotoxicity of NK92MI against the gastric cancer cell lines MKNI with ILT2lowILT3low and HGC-27 with ILT2highILT3high were detected. The results suggest that ILT2 and ILT3 are expressed with diverse degrees in gastric cancer cells and tissues, and the expression of ILT2 is related with differentiation and size of tumors. Furthermore, the cytotoxic activity of NK92MI against the MKNI cell line was stronger than that against HGC-27. This study indicates that ILT2 and ILT3 play a key role in gastric cancer immune escape, and ILT2 may be a new target in the clinical diagnosis and treatment of gastric cancer.

Summary Cullin-RING ubiquitin ligases (CRL) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)–Cullin signaling axis and that CSN6 is a positive regulator of Myc. CSN6 enhanced neddylation of Cullin-1 and facilitated auto-ubiquitination/degradation of Fbxw7, a component of CRL involved in Myc ubiquitination, thereby stabilizing Myc. Csn6 haplo-insufficiency decreased Cullin-1 neddylation but increased Fbxw7 stability to compromise Myc stability and activity in an Eµ-Myc mouse model, resulting in decelerated lymphomagenesis. We found that CSN6 overexpression, which leads to aberrant expression of Myc target genes, is frequent in human cancers. Together, these results define a mechanism for the regulation of Myc stability through the CSN-Cullin-Fbxw7 axis and provide insights into the correlation of CSN6 overexpression with Myc stabilization/activation during tumorigenesis.

AZ64 is a novel antitumor agent designed as a tropomyosin-related kinase (Trk) inhibitor; however, its effect on lung cancer and its mechanism of action remain unclear. This study aimed to elucidate the antitumor activity of AZ64 and its mechanism of action against non-small cell lung cancer (NSCLC). Our results demonstrate that AZ64 has a potent anti-proliferative effect on NSCLC cells and acts in a dose- and time-dependent manner. We also demonstrate that AZ64 suppresses the anchorage-independent growth and invasion of NSCLC cells. In vivo experiments demonstrated that AZ64 significantly reduced the tumor growth of NSCLC xenografts in nude mice and was well-tolerated. Mechanistic experiments revealed that AZ64 induced the G2/M arrest of NSCLC cells by the accumulation of phospho-cdc2 (Tyr15) at the G2/M transition, following the downregulation of Cdc25C expression. Collectively, our data demonstrate that AZ64 is a potential antitumor drug that may be used for the treatment of NSCLC, which functions by targeting the G2/M transition via the inhibition of the dephosphorylation of phospho-cdc2 (Tyr15).

7552 Background: FGFR-1 is a novel target for therapy in non-small cell lung carcinoma (NSCLC). FGFR1 gene has been shown to be amplified in ~20% of squamous cell carcinomas (SCC) of the lung. The frequency of FGFR1 copy number gain (CNG) and gene amplification (GA) in lung adenocarcinoma (AC) is unknown, and the clinicopathological and molecular characteristics of the NSCLC tumors with FGFR1gene increase have not been fully described. Methods: We examined FGFR1 gene copy number (GCN) by fluorescent in-situ hybridization (FISH) and FGFR1 protein expression by immunohistochemistry in 475 surgically resected NSCLCs (162 SCCs, and 313 ACs) stages I-III in tissue microarrays. Three FGFR1 FISH categories were identified: a) no CNG; b) CNG, defined as ≥4 gene copies in ≥40% of cells; c) GA, defined as ratio of copies of FGFR1:CEP8 ≥2 or presence of tight gene clusters in ≥10% of cells. FGFR1 protein expression in the cytoplasm and membrane of tumor cells was quantified using H score. Results: FGFR1 GA was detected only in SCCs (14 cases, 9%). CNG was detected in both SCC (39 cases, 24%) and AC (80 cases, 26%). In AC, significantly higher frequency of CNG was detected in patients with smoking history (P=0.008) and in tumors with low differentiated histology (P=0.0005). No correlation was detected between FGFR1 CNG and mutation of KRAS and EGFR in AC. In SCC, tumors with FGFR1 CNG/GA had higher cytoplasmic FGFR1 protein expression than those with no copy changes (49±39 vs. 26±21, P

Background Epigenetic silencing is a common mechanism to inactivate tumor suppressor genes during carcinogenesis. Enhancer of Zeste 2 (EZH2) is the histone methyltransferase subunit in polycomb repressive complex 2 which mediates transcriptional repression through histone methylation. EZH2 overexpression has been linked to aggressive phenotypes of certain cancers. However, the mechanism that EZH2 played in promoting malignancy in non-small cell lung cancer (NSCLC) remains unclear. In addition, the correlation of EZH2 overexpression and the prognosis of NSCLC patients in non-Asian cohort need to be determined. Methodology/Principal Findings Up-regulation of EZH2 was found in NSCLC cells compared with normal human bronchial epithelial cells by western blot assay. Upon EZH2 knockdown using small interfering RNA (siRNA), the proliferation, anchorage-independent growth and invasion of NSCLC cells were remarkably suppressed with profound induction of G1 arrest. Furthermore, the expression of cyclin D1 was notably reduced whereas p15INK4B, p21Waf1/Cip1 and p27Kip1 were increased in NSCLC cells after EZH2-siRNA delivery. To determine whether EZH2 expression contributes to disease progression in patients with NSCLC, Taqman quantitative real-time RT-PCR was used to measure the expression of EZH2 in paired tumor and normal samples. Univariate analysis revealed that patients with NSCLC whose tumors had a higher EZH2 expression had significantly inferior overall, disease-specific, and disease-free survivals compared to those whose tumors expressed lower EZH2 (P = 0.005, P = 0.001 and P = 0.003, respectively). In multivariate analysis, EZH2 expression was an independent predictor of disease-free survival (hazard ratio = 0.450, 95% CI: 0.270 to 0.750, P = 0.002). Conclusions/Significance Our results demonstrate that EZH2 overexpression is critical for NSCLC progression. EZH2 mRNA levels may serve as a prognostic predictor for patients with NSCLC.