Introduction Since the outbreak of coronavirus disease 2019 (COVID-19), more than 3000 (including clinical diagnosis) healthcare workers (HCWs) have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China. This study is aimed to investigate the risk perception and immediate psychological state of HCWs in the early stage of the COVID-19 epidemic. Methods This study utilized a cross-sectional survey designed on a convenient sample of 4357 HCWs in China. Its data were collected using anonymous structured questionnaires distributed through social software. 6 questions were set to evaluate the participants' risk perception of COVID-19, and a General Health Questionnaire was used to identify the participants' immediate psychological status. Descriptive statistics were used for data analysis. Risk perception and psychological status were compared by demographic characteristics and COVID-19 exposure experiences. Result A total of 4,600 questionnaires were distributed, and 4,357 qualified ones (94.7%) were collected. The main concerns of HCWs are: infection of colleagues (72.5%), infection of family members (63.9%), protective measures (52.3%) and medical violence (48.5%). And 39.1% of the HCWs had psychological distress, especially working in Wuhan, participating in frontline treatments, having been isolated and having family members or colleagues infected. Conclusions The finding indicating that, faced with the COVID-19 epidemic, HCWs, especially in Wuhan, were worried about the risks of infection and protective measures, resulting in psychological distress, so further actions should be taken.

We have compiled historical greenhouse gas emissions and their uncertainties on country and sector level and assessed their contribution to cumulative emissions and to global average temperature increase in the past and for a the future emission scenario. We find that uncertainty in historical contribution estimates differs between countries due to different shares of greenhouse gases and time development of emissions. Although historical emissions in the distant past are very uncertain, their influence on countries' or sectors' contributions to temperature increase is relatively small in most cases, because these results are dominated by recent (high) emissions. For relative contributions to cumulative emissions and temperature Climatic Change (2011) 106:359-391 rise, the uncertainty introduced by unknown historical emissions is larger than the uncertainty introduced by the use of different climate models. The choice of different parameters in the calculation of relative contributions is most relevant for countries that are different from the world average in greenhouse gas mix and timing of emissions. The choice of the indicator (cumulative GWP weighted emissions or temperature increase) is very important for a few countries (altering contributions up to a factor of 2) and could be considered small for most countries (in the order of 10%). The choice of the year, from which to start accounting for emissions (e.g. 1750 or 1990), is important for many countries, up to a factor of 2.2 and on average of around 1.3. Including or excluding land-use change and forestry or non-CO 2 gases changes relative contributions dramatically for a third of the countries (by a factor of 5 to a factor of 90). Industrialised countries started to increase CO 2 emissions from energy use much earlier. Developing countries' emissions from land-use change and forestry as well as of CH 4 and N 2 O were substantial before their emissions from energy use.

No abstract

Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made a novel discovery that co-administration of HDACIs (Trichostatin A (TSA) and others) and exogenous cell-permeable short-chain ceramide (C6) results in striking increase in cancer cell death and apoptosis in multiple cancer cells. These events are associated with perturbations in diverse cell signaling pathways, including inactivation of Akt/mTOR and increase in α-tubulin acetylation (both in vivo and in vitro). TSA interacts in a highly synergistic manner with C6-ceramide to disrupt HDAC6/protein phosphatase 1 (PP1)/tubulin complex, to induce α-tubulin hyperacetylation, and to release and activate PP1, which then leads to AKT dephosphorylation and eventually causes cancer cell death. Interestingly, TSA itself results in short-term ceramide accumulation, which as a result of metabolic (glycosylation) removal, does not result in evident increase of cancer cell death. However, adding C6-ceramide led to a very pronounced increase in ceramide level and marked increase in cell death. Importantly, the effective synergistic anti-tumor activity of TSA plus C6-ceramide is also seen in in vivo mice xenograft pancreatic and ovarian cancer models, indicating that this regimen (HDACI plus C6-ceramide) may represent a more effective form of therapy against pancreatic and ovarian carcinoma.

Purpose: Non-small cell lung cancer (NSCLC) metastasizes fairly often to the brain, but identifying which patients will develop brain metastases is problematic. The phosphoinositide 3-kinase (PI3K)-AKTmTOR signaling pathway is important in the control of cell growth, tumorigenesis, and cell invasion. We hypothesized that genotype variants in this pathway could predict brain metastasis in patients with NSCLC.Methods: We genotyped 16 single-nucleotide polymorphisms (SNP) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) by using DNA from blood samples of 317 patients with NSCLC, and evaluated potential associations with the subsequent development of brain metastasis, the cumulative incidence of which was estimated with Kaplan-Meier analysis. Multivariate Cox regression analysis was used to analyze correlations between genotype variants and the occurrence of brain metastasis.Results: In analysis of individual SNPs, the GT/GG genotype of AKT1: rs2498804, CT/TT genotype of AKT1: rs2494732, and AG/AA genotype of PIK3CA: rs2699887 were associated with higher risk of brain metastasis at 24-month follow-up [respective HRs, 1.860, 95% confidence interval (CI) 1.199-2.885, P ¼ 0.006; HR 1.902, 95% CI 1.259-2.875, P ¼ 0.002; and HR 1.933, 95% CI 1.168-3.200, P ¼ 0.010]. We further found that these SNPs had a cumulative effect on brain metastasis risk, with that risk being highest for patients carrying both of these unfavorable genotypes (P ¼ 0.003).Conclusions: Confirmation of our findings, the first to indicate that genetic variations in PI3K-AKTmTOR can predict brain metastasis, in prospective studies would facilitate stratification of patients for brain metastasis prevention trials.