HBV core promoter mutations and AKT upregulate S-phase kinase-associated protein 2 to promote postoperative hepatocellular carcinoma progression

Mutations in the hepatitis B virus (HBV) core promoter (CP) have been shown to be associated with hepatocellular carcinoma (HCC). The CP region overlaps HBV X gene, which activates AKT to regulate hepatocyte survival. However, the cooperation between these two cascades in HCC progression remains poorly understood. Here, we assayed virological factors and AKT expression in liver tissues from 56 HCC patients with better prognoses (BHCC, ≥5-year survival) and 58 with poor prognoses (PHCC, <5-year survival) after partial liver resection. Results showed double mutation A1762T/G1764A (TA) combined with other mutation(s) (TACO) in HBV genome and phosphorylated AKT (pAKT) were more common in PHCC than BHCC. TACO and pAKT levels correlated with proliferation and microvascularization but inversely correlated with apoptosis in HCC samples. These were more pronounced when TACO and pAKT co-expressed. Levels of p21 and p27 were decreased in TACO or pAKT overexpressing HCC due to SKP2 upregulation. Levels of E2F1 and both mRNA and protein of SKP2 were increased in TACO expressing HCC. Levels of 4EBP1/2 decreased and SKP2 mRNA level remained constant in pAKT-overexpressing HCC. Therefore, TACO and AKT are two independent predictors of postoperative survival in HCC. Their co-target, SKP2 may be a diagnostic or therapeutic marker

Loss to Follow-Up from HIV Screening to ART Initiation in Rural China.

BackgroundPatients who are newly screened HIV positive by EIA are lost to follow-up due to complicated HIV testing procedures. Because this is the first step in care, it affects the entire continuum of care. This is a particular concern in rural China.Objective(s)To assess the routine HIV testing completeness and treatment initiation rates at 18 county-level general hospitals in rural Guangxi.MethodsWe reviewed original hospital HIV screening records. Investigators also engaged with hospital leaders and key personnel involved in HIV prevention activities to characterize in detail the routine care practices in place at each county.Results699 newly screened HIV-positive patients between January 1 and June 30, 2013 across the 18 hospitals were included in the study. The proportion of confirmatory testing across the 18 hospitals ranged from 14% to 87% (mean of 43%), and the proportion of newly diagnosed individuals successfully initiated antiretroviral treatment across the hospitals ranged from 3% to 67% (mean of 23%). The average interval within hospitals for individuals to receive the Western Blot (WB) and CD4 test results from HIV positive screening (i.e. achieving testing completion) ranged from 14-116 days (mean of 41.7 days) across the hospitals. The shortest interval from receiving a positive EIA screening test result to receiving WB and CD4 testing and counseling was 0 day and the longest was 260 days.ConclusionThe proportion of patients newly screened HIV positive that completed the necessary testing procedures for HIV confirmation and received ART was very low. Interventions are urgently needed to remove barriers so that HIV patients can have timely access to HIV/AIDS treatment and care in rural China

EGF Stimulates Rab35 Activation and Gastric Cancer Cell Migration by Regulating DENND1A-Grb2 Complex Formation

Aims: The aim of this study was to reveal the specific molecular mechanisms by which DENND1A accepts EGF signaling and activates Rab35 in gastric cancer.Methods: The expression of proteins related to DENND1A was examined by western blot analysis. Activation of Rab35 was assessed by GST-pulldown. The interaction of DENND1A and Grb2 was assessed by GST-pulldown and co-immunoprecipitation assays. The relationship between DENND1A and cell migration and invasion was detected using wound healing and transwell by gene overexpression and RNA interference.Results: EGF stimulation significantly promoted cell migration, whereas transfection with siRab35 partially inhibited EGF-promoted cell migration. DENND1A is also involved in these processes and active Rab35. Moreover, DENND1A binds to the N-terminal and C-terminal SH3 domains of Grb2 through PRD. Of special interest is the observation that EGFR can recruit Grb2-DENND1A complex under EGF stimulation. Further results reveal that the higher the expression of DENND1A, the shorter progression-free survival of gastric cancer patients.Conclusion: In summary, we confirmed that EGF-Grb2-DENND1A-Rab35 signaling pathway with the interaction of DENND1A and Grb2 as a regulatory center could regulate gastric cancer cell migration and invasion. Ultimately, the expression level of DENND1A predicts the survival status of gastric cancer patients and may become one of the important targets for the treatment of gastric cancer

CFD investigation of gas-solids flow in a new fluidized catalyst cooler

In our previous work, a new concept of annular catalyst cooler (ACC) was proposed and validated experimentally, which showed that an internal circulation of solids could be formed by using two gas distributors and both hydrodynamics and heat transfer could be largely improved. The current work simulated detailed hydrodynamics of gas-solids flow to advance our understanding of the ACC by using the two-fluid model. The influences of effective particle diameter dp⁎ and specularity coefficient φ were examined and compared with experimental data. Optimum values of dp⁎ = 170 μm and φ = 0.3 were determined and used in the simulations. Detailed hydrodynamics of gas-solids flow were then obtained, and the influential parameters were examined. The results showed that the proper selection of the ratio of gas velocities and the position of the heat transfer tube were needed to form a stable internal solids circulation in the ACC. The ACC had a combined hydrodynamic feature of up-flow and down-flow catalyst coolers with bigger solids volume fraction and smaller particle resident time, which are beneficial for improving the heat transfer between solids and wall

Microbial Community and Functional Gene Changes in Arctic Tundra Soils in a Microcosm Warming Experiment

Microbial decomposition of soil organic carbon (SOC) in thawing Arctic permafrost is important in determining greenhouse gas feedbacks of tundra ecosystems to climate. However, the changes in microbial community structure during SOC decomposition are poorly known. Here we examine these changes using frozen soils from Barrow, Alaska, USA, in anoxic microcosm incubation at −2 and 8°C for 122 days. The functional gene array GeoChip was used to determine microbial community structure and the functional genes associated with SOC degradation, methanogenesis, and Fe(III) reduction. Results show that soil incubation after 122 days at 8°C significantly decreased functional gene abundance (P &lt; 0.05) associated with SOC degradation, fermentation, methanogenesis, and iron cycling, particularly in organic-rich soil. These observations correspond well with decreases in labile SOC content (e.g., reducing sugar and ethanol), methane and CO2 production, and Fe(III) reduction. In contrast, the community functional structure was largely unchanged in the −2°C incubation. Soil type (i.e., organic vs. mineral) and the availability of labile SOC were among the most significant factors impacting microbial community structure. These results demonstrate the important roles of microbial community in SOC degradation and support previous findings that SOC in organic-rich Arctic tundra is highly vulnerable to microbial degradation under warming