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.

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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.

Furfural and acetic acid from lignocellulosic hydrolysates are the prevalent inhibitors to Zymomonas mobilis during cellulosic ethanol production. Developing a strain tolerant to furfural or acetic acid inhibitors is difficul by using rational engineering strategies due to poor understanding of their underlying molecular mechanisms. In this study, strategy of adaptive laboratory evolution (ALE) was used for development of a furfural and acetic acid-tolerant strain. After three round evolution, four evolved mutants (ZMA7-2, ZMA7-3, ZMF3-2, and ZMF3-3) that showed higher growth capacity were successfully obtained via ALE method. Based on the results of profiling of cell growth, glucose utilization, ethanol yield, and activity of key enzymes, two desired strains, ZMA7-2 and ZMF3-3, were achieved, which showed higher tolerance under 7 g/l acetic acid and 3 g/l furfural stress condition. Especially, it is the first report of Z. mobilis strain that could tolerate higher furfural. The best strain, Z. mobilis ZMF3-3, has showed 94.84% theoretical ethanol yield under 3-g/l furfural stress condition, and the theoretical ethanol yield of ZM4 is only 9.89%. Our study also demonstrated that ALE method might also be used as a powerful metabolic engineering tool for metabolic engineering in Z. mobilis. Furthermore, the two best strains could be used as novel host for further metabolic engineering in cellulosic ethanol or future biorefinery. Importantly, the two strains may also be used as novel-tolerant model organisms for the genetic mechanism on the "omics" level, which will provide some useful information for inverse metabolic engineering.

BackgroundCellulosic biofuels are sustainable compared to fossil fuels. However, inhibitors, such as acetic acid generated during lignocellulose pretreatment and hydrolysis, would significantly inhibit microbial fermentation efficiency. Microbial mutants able to tolerate high concentration of acetic acid are needed urgently to alleviate this inhibition.ResultsZymomonas mobilis mutants AQ8-1 and AC8-9 with enhanced tolerance against acetic acid were generated via a multiplex atmospheric and room temperature plasma (mARTP) mutagenesis. The growth and ethanol productivity of AQ8-1 and AC8-9 were both improved in the presence of 5.0–8.0 g/L acetic acid. Ethanol yield reached 84% of theoretical value in the presence of 8.0 g/L acetic acid (~ pH 4.0). Furthermore, a mutant tolerant to pH 3.5, named PH1-29, was generated via the third round of ARTP mutagenesis. PH1-29 showed enhanced growth and ethanol production under both sterilized/unsterilized conditions at pH 4.0 or 3.5. Intracellular NAD levels revealed that mARTP mutants could modulate NADH/NAD+ ratio to respond to acetic acid and low pH stresses. Moreover, genomic re-sequencing revealed that eleven single nucleic variations (SNVs) were likely related to acetic acid and low pH tolerance. Most SNVs were targeted in regions between genes ZMO0952 and ZMO0956, ZMO0152 and ZMO0153, and ZMO0373 and ZMO0374.ConclusionsThe multiplex mutagenesis strategy mARTP was efficient for enhancing the tolerance in Z. mobilis. The ARTP mutants generated in this study could serve as potential cellulosic ethanol producers.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1348-9) contains supplementary material, which is available to authorized users.

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