general public and 526 nurses (i.e., 234 front-line nurses and 292 non-front-line nurses) to evaluate vicarious traumatization scores via a mobile appbased questionnaire. Front-line nurses are engaged in the process of providing care for patients with COVID-19. The results showed that the vicarious traumatization scores for front-line nurses including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (P < 0.001). Interestingly, the vicarious traumatization scores of the general public were significantly higher than those of the front-line nurses (P < 0.001); however, no statistical difference was observed compared to the scores of nonfront-line nurses (P > 0.05). Therefore, increased attention should be paid to the psychological problems of the medical staff, especially non-front-line nurses, and general public under the situation of the spread and control of COVID-19. Early strategies that aim to prevent and treat vicarious traumatization in medical staff and general public are extremely necessary.

Locusts are one of the world’s most destructive agricultural pests and represent a useful model system in entomology. Here we present a draft 6.5 Gb genome sequence of Locusta migratoria, which is the largest animal genome sequenced so far. Our findings indicate that the large genome size of L. migratoria is likely to be because of transposable element proliferation combined with slow rates of loss for these elements. Methylome and transcriptome analyses reveal complex regulatory mechanisms involved in microtubule dynamic-mediated synapse plasticity during phase change. We find significant expansion of gene families associated with energy consumption and detoxification, consistent with long-distance flight capacity and phytophagy. We report hundreds of potential insecticide target genes, including cys-loop ligand-gated ion channels, G-protein-coupled receptors and lethal genes. The L. migratoria genome sequence offers new insights into the biology and sustainable management of this pest species, and will promote its wide use as a model system.

Since December 2019, more than 79,000 people have been diagnosed with infection of the Corona Virus Disease 2019 . A large number of medical staff were dispersed for Wuhan city and Hubei province to aid COVID-19 control. Psychological stress, especially vicarious traumatization (VT) caused by the COVID-19 pandemic, should not be ignored. To address this concern, the study employed a total of 214 general public (GP) and 526 nurses to evaluate VT scores via a mobile app-based questionnaire. Results showed that the VT scores slightly increased across periods of aiding COVID-19 control, although no statistical difference was noted (P = 0.083).However, the study found lower scores for VT in nurses [median = 69; interquartile range (IQR) = 56-85] than those of the GP (median = 75.5; IQR = 62-88.3) (P = 0.017). In addition, the VT scores for front-line nurses (FLNs; median = 64; IQR = 52-75), including scores for physiological and psychological responses, were significantly lower than those of non-front-line nurses (nFLNs; median = 75.5; IQR = 63-92) (P < 0.001). Interestingly, the VT scores of the GP were significantly higher than those of the FLNs (P < 0.001). However, no statistical difference was observed compared with those of nFLNs (P > 0.05). Importantly, nFLNs are more likely to suffer from VT, which might be related to two factors, namely, gender [odds ratio (OR) = 3.1717; 95% confidence interval (CI) = 4.247-18.808; P = 0.002] and fertility [OR = 2.072; 95%CI = 0.626-24.533; P = 0.039]. Therefore, increased attention should be paid to the psychological problems of the medical staff, especially nFLNs, and GP under the situation of the spread and control of COVID-19. Early strategies that aim . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed)The copyright holder for this preprint . https://doi.org/10. 1101/2020 to prevent and treat VT in medical staff and GP are extremely necessary.

Background How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood. Methods The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB. Internalization of macrophages-secreted exosomes in EOC cells was detected by Confocal microscope. Subsequently, Dual-luciferase reporter assay verified PTEN was the target of miR-223. Gain- and loss-of-function experiments, rescue experiments, and SKOV3 xenograft models were performed to uncover the underlying mechanisms of miR-223 and PTEN-PI3K/AKT pathway, as well as the exosomal miR-223 in inducing multidrug resistance in vitro and in vivo. Results Here, we showed hypoxic EOC cells triggered macrophages recruitment and induced macrophages into a tumor-associated macrophage (TAM)-like phenotype; exosomes derived from hypoxic macrophages enhanced the malignant phenotype of EOC cells, miR-223 was enriched in exosomes released from macrophages under hypoxia, which could be transferred to the co-cultivated EOC cells, accompanied by enhanced drug resistant of EOC cells. Besides, results from a functional assay revealed that exosomal miR-223 derived from macrophages promoted the drug resistance of EOC cells via the PTEN-PI3K/AKT pathway both in vivo and in vitro. Furthermore, patients with high HIF-1a expression had statistically higher CD163+ cell infiltration and intertumoral levels of miR-223. Finally, circulating exosomal miR-223 levels were closely related to the recurrence of EOC. Conclusions These data indicate a unique role of exosomal miR-223 in the cross-talk between macrophages and EOC cells in chemotherapy resistance, through a novel exosomal miR-223/PTEN-PI3K/AKT signaling pathway. Electronic supplementary material The online version of this article (10.1186/s13046-019-1095-1) contains supplementary material, which is available to authorized users.

Epidermal growth factor (EGF) is present in the maternal-fetal environment and has an important role in placental development. Matrix metalloproteinase-9 (MMP-9) expression/activation is a pre-requisite in extravillous trophoblast invasion. Whereas EGF up-regulates MMP-9 activity in a variety of cell types, there is no direct evidence for the stimulation of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion by EGF in extravillous trophoblasts. In addition, the signalling pathways involved in this regulation are not clear. In the present study, we have examined the possible involvement of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in the regulation of the MMP-9/TIMP-1 system by EGF in vitro. We used a well-established invasive extravillous trophoblast cell line (HTR8/Svneo) and measured gene and protein expression by semi-quantitative RT-PCR and western analysis respectively. MMP activity was determined by zymography. We showed for the first time that EGF activated both PI3K/Akt and MAPK/extracellular-signal regulated kinase (ERK) signalling in HTR8/SVneo, and increased both MMP-9 and TIMP-1 mRNAs and protein concentrations. Interfering with either signalling pathway via PI3K inhibitor LY294002 or MEK inhibitor U0126 in EGF-stimulated HTR8/SVneo cells blocked the induction of MMP-9 and TIMP-1. LY294002 inhibited Akt phosphorylation, but had no effect on ERK phosphorylation; U0126 suppressed ERK phosphorylation without interfering with the phosphorylation of Akt. In addition, expression of constitutively active Akt (Myr-Akt1, Myr-Akt2, Myr-Akt3) was not sufficient to induce proMMP-9 and TIMP-1 secretion. Our results suggest that the activation of both PI3K and MAPK pathways in extravillous trophoblasts is necessary for the up-regulation of MMP-9 and TIMP-1 expression by EGF.

Phenotypic plasticity is ubiquitous and primarily controlled by interactions between environmental and genetic factors. The migratory locust, a worldwide pest, exhibits pronounced phenotypic plasticity, which is a population density-dependent transition that occurs between the gregarious and solitary phases. Genes involved in dopamine synthesis have been shown to regulate the phase transition of locusts. However, the function of microRNAs in this process remains unknown. In this study, we report the participation of miR-133 in dopamine production and the behavioral transition by negatively regulating two critical genes, henna and pale, in the dopamine pathway. miR-133 participated in the post-transcriptional regulation of henna and pale by binding to their coding region and 3′ untranslated region, respectively. miR-133 displayed cellular co-localization with henna/pale in the protocerebrum, and its expression in the protocerebrum was negatively correlated with henna and pale expression. Moreover, miR-133 agomir delivery suppressed henna and pale expression, which consequently decreased dopamine production, thus resulting in the behavioral shift of the locusts from the gregarious phase to the solitary phase. Increasing the dopamine content could rescue the solitary phenotype, which was induced by miR-133 agomir delivery. Conversely, miR-133 inhibition increased the expression of henna and pale, resulting in the gregarious-like behavior of solitary locusts; this gregarious phenotype could be rescued by RNA interference of henna and pale. This study shows the novel function and modulation pattern of a miRNA in phenotypic plasticity and provides insight into the underlying molecular mechanisms of the phase transition of locusts.

Background: Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. Methods: qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. Results: Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. Conclusions: Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.

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