One of the most efficient methods to control the high infection rate of the coronavirus disease 2019 (COVID-19) is to have a high coverage of COVID-19 vaccination worldwide. Therefore, it is important to understand individuals’ intention to get COVID-19 vaccinated. The present study applied the Theory of Planned Behavior (TPB) to explain the intention to get COVID-19 vaccinated among a representative sample in Qazvin, Iran. The TPB uses psychological constructs of attitude, subjective norm, and perceived behavioral control to explain an individual’s intention to perform a behavior. Fear and perceived infectability were additionally incorporated into the TPB to explain the intention to get COVID-19 vaccinated. Utilizing multistage stratified cluster sampling, 10,843 participants (4092 males; 37.7%) with a mean age of 35.54 years (SD = 12.00) completed a survey. The survey assessed TPB constructs (including attitude, subjective norm, perceived behavioral control, and intention related to COVID-19 vaccination) together with fear of COVID-19 and perceived COVID-19 infectability. Structural equation modeling (SEM) was performed to examine whether fear of COVID-19, perceived infectability, and the TPB constructs explained individuals’ intention to get COVID-19 vaccinated. The SEM demonstrated satisfactory fit (comparative fit index = 0.970; Tucker-Lewis index = 0.962; root mean square error of approximation = 0.040; standardized root mean square residual = 0.050). Moreover, perceived behavioral control, subjective norm, attitude, and perceived COVID-19 infectability significantly explained individuals’ intention to get COVID-19 vaccinated. Perceived COVID-19 infectability and TPB constructs were all significant mediators in the relationship between fear of COVID-19 and intention to get COVID-19 vaccinated. Incorporating fear of COVID-19 and perceived COVID-19 infectability effectively into the TPB explained Iranians’ intention to get COVID-19 vaccinated. Therefore, Iranians who have a strong belief in Muslim religion may improve their intention to get COVID-19 vaccinated via these constructs.

Colorectal cancer lethality usually results from post-treatment relapse in the majority of stage II-IV patients, due to the enhanced resistance of Cancer Stem Cells (CSCs). Here, we show that the nuclear receptor Pregnane X Receptor (PXR, NR1I2), behaves as a key driver of CSC-mediated tumor recurrence. First, PXR is specifically expressed in CSCs, where it drives the expression of genes involved in self-renewal and chemoresistance. Clinically, high levels of PXR correlate with poor recurrence-free survival in a cohort of >200 stage II/III colorectal cancer patients treated with chemotherapy, for whom finding biomarkers of treatment outcome is an urgent clinical need. shRNA silencing of PXR increased the chemo-sensitivity of human colon CSCs, reduced their self-renewal and tumor-initiating potential, and drastically delayed tumor recurrence in mice following chemotherapy. This study uncovers PXR as a key factor for CSC self-renewal and chemoresistance and targeting PXR thus represents a promising strategy to minimize colorectal cancer relapse by selectively sensitizing CSCs to chemotherapy.

Background: There are reports that stress-related disorders are increasing during coronavirus disease 2019 (COVID-19) pandemic. Patients with Multiple Sclerosis (MS) are at higher risk of developing psychiatric disorders, which result in worsening of their disability. There are concerns about the mental health of MS patients during this pandemic. Objective: We aimed to evaluate the prevalence of anxiety, depression, and levels of fear about Corona in MS patients during the COVID-19 pandemic. Materials and methods: This was a cross-sectional study on MS patients who were admitted to the MS clinics affiliated with Isfahan University of medical sciences from May to June 2020. Anxiety and depression were evaluated according to the Hospital Anxiety and Depression Scale (HADS). The Corona Fear Questionnaire developed by Ahorsu et al. was applied to evaluate the state of fear about COVID-19. Chi-square tests were used to compare depression and anxiety between different groups, Kruskal-Wallis was used for fear scores, Spearman correlation coefficient was also reported for correlations. Results: 410 MS patients with a mean age of 38.6 years (±10.35) were enrolled in the study. Among those patients who answered the HADS questionnaire completely (n=399, n=388, for anxiety and depression subscales respectively) the prevalence of anxiety and depression were 31.2% (n=128) and 39.3% (n=161), respectively. There was no significant relationship between anxiety and depression with any of the following variables: sex, marital status, history of drug abuse, smoking, duration of taking psychiatric medication, being tested for COVID-19, being quarantined. Regarding fear about COVID-19, patients with depression or anxiety showed higher scores on the fear questionnaire (p-value=0.03, p-value=0.008 respectively). Conclusions: The prevalence of anxiety and depression in MS patients was higher than previously reported. Fear about COVID-19 was correlated with anxiety and depression. Multicenter studies are required to develop specific recommendations for screening mental health problems in MS patients during COVID pandemic.

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The great potential of pharmacologically active secondary plant metabolites is often limited by low yield and availability of the producing plant. Chemical synthesis of these complex compounds is often too expensive. Plant cell fermentation offers an alternative strategy to overcome these limitations. However, production in batch cell cultures remains often inefficient. One reason might be the fact that different cell types have to interact for metabolite maturation, which is poorly mimicked in suspension cell lines. Using alkaloid metabolism of tobacco, we explore an alternative strategy, where the metabolic interactions of different cell types in a plant tissue are technically mimicked based on different plant-cell based metabolic modules. In this study, we simulate the interaction found between the nicotine secreting cells of the root and the nicotine-converting cells of the senescent leaf, generating the target compound nornicotine in the model cell line tobacco BY-2. When the nicotine demethylase NtomCYP82E4 was overexpressed in tobacco BY-2 cells, nornicotine synthesis was triggered, but only to a minor extent. However, we show here that we can improve the production of nornicotine in this cell line by feeding the precursor, nicotine. Engineering of another cell line overexpressing the key enzyme NtabMPO1 allows to stimulate accumulation and secretion of this precursor. We show that the nornicotine production of NtomCYP82E4 cells can be significantly stimulated by feeding conditioned medium from NtabMPO1 overexpressors without any negative effect on the physiology of the cells. Co-cultivation of NtomCYP82E4 with NtabMPO1 stimulated nornicotine accumulation even further, demonstrating that the physical presence of cells was superior to just feeding the conditioned medium collected from the same cells. These results provide a proof of concept that combination of different metabolic modules can improve the productivity for target compounds in plant cell fermentation.

Plants can use volatiles for remote suppression of competitors. Mints produce essential oils, which are known to affect the growth of other plants. We used a comparative approach to identify allelopathic compounds from different Mints (genus Mentha, but also including Cat Mint, Nepeta cataria, and Corean Mint, Agastache rugosa, belonging to sisters clades within the Mentheae) using the standard cress germination assay as readout. To understand the mechanism behind this allelopathic effect, we investigated the response of tobacco BY-2 cell lines, expressing GFP-tagged markers for microtubules and actin filaments to these essential oils. Based on the comparison between bioactivity and chemical components, we identified menthone as prime candidate for the allelopathic effect, and confirmed this bioactivity targeted to microtubules experimentally in both, plant cells (tobaccoBY-2), and seedlings (Arabidopsis thaliana). We could show that menthone disrupted microtubules and induced mortality linked with a rapid permeabilization (less than 15 min) of the plasma membrane. This mortality was elevated in a tubulin marker line, where microtubules are mildly stabilized. Our study paves the way for the development of novel bioherbicides that would be environmentally friendly.