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Background Hepatitis E virus (HEV) generally causes self-limiting viral hepatitis. However, in pregnant women, HEV infection can be severe and has been associated with up to 30% mortality in the third trimester. Additionally, HEV infection in pregnancy is also associated with high rates of preterm labor and vertical transmission. Main body HEV is now recognized as a global health problem in both developing and industrialized countries. HEV can be transmitted via the fecal-oral route, zoonotic route, and blood transfusion route. An altered immune status, hormonal levels, and viral factors may be related to the severity of the disease. Currently, no established treatment is available for HEV in pregnant women. A Chinese vaccine has been demonstrated to be protective against HEV in the general population and seems to be safe in pregnancy; however, its safety and efficacy in a large population of pregnant women remain to be determined. Conclusion This review summarizes the current knowledge about HEV infection during pregnancy and focuses on the epidemiology, clinical manifestations, mechanisms underlying severe liver injury, and management and prevention of HEV infection during pregnancy. Considering that HEV infection during pregnancy may result in poor outcomes, screening for and monitoring HEV infection early in pregnancy should be taken into account. In addition, a better understanding of the pathogenesis will help to develop potential treatment strategies targeting HEV infection in pregnancy.

Among enteroviruses, echovirus can cause severe illnesses in neonates or infants, with high morbidity and mortality. Autophagy, a central component of host defense mechanisms, can function against diverse infections. In the present study, we investigated the interplay between echovirus and autophagy. We demonstrated that echovirus infection increases LC3-II expression dose-dependently, accompanied by an increased intracellular LC3 puncta level. In addition, echovirus infection induces the formation of autophagosome. These results suggest that echovirus infection induces autophagy machinery. Furthermore, phosphorylated mTOR and ULK1 were both decreased upon echovirus infection. In contrast, both levels of the vacuolar protein sorting 34 (VPS34) and Beclin-1, the downstream molecules which play essential roles in promoting the formation of autophagic vesicles, increased upon virus infection. These results imply that the signaling pathways involved in autophagosome formation were activated by echovirus infection. Moreover, induction of autophagy promotes echovirus replication and viral protein VP1 expression, while inhibition of autophagy impairs VP1 expression. Our findings suggest that autophagy can be induced by echovirus infection via regulating mTOR/ULK1 signaling pathway and exhibits a proviral function, revealing the potential role of autophagy in echovirus infection.

Background. Hepatocellular carcinoma (HCC) is recognized as the fourth in incidence and the third in mortality worldwide. The onset of HCC is insidious and often asymptomatic at the early stage. HCC is more prone to metastasis, recurrence, and drug resistance than other solid tumors owing to its feature of high heterogeneity. Therefore, what particularly important is to search for effective molecular markers in the occurrence and progression of HCC. Aim. To probe into the therapeutic potential of circACTG1 (hsa_circ_0046144) in HCC cell migration and invasion, providing a new insight and molecular target to diagnose and cure HCC patients. Methods. The circACTG1 expression in collected HCC cells was determined by quantitative polymerase chain reaction (qPCR). Assessment for circACTG1 diagnosing capability was analyzed by receiver operating characteristic (ROC) curves. Transwell assay, wound healing assay, and cell counting kit-8 assay were used for monitoring the effect of circACTG1 in HCC cell invasion, migration, and proliferation, respectively; qPCR, luciferase reporter assay, databases, and Western blot analysis were used for identifying the modulation mechanisms among circACTG1, miRNA-940, and RIF1. What is more, our study verified AKT-mTOR signaling after miR-940 mimic treatment or circACTG1 knockdown. Results. circACTG1 was overexpressed in HCC cells and tissues. Knockdown of circACTG1 restrained 97H and Huh7 cell migration and invasion. Significantly, circACTG1 was discovered to serve as a miR-940 sponge. miR-940 activation rebated the circACTG1 level, and conversely, miR-940 inhibition boosted the circACTG1 level. However, this effect or relationship was not seen after circACTG1 mutation. Furtherly, miR-940-downregulated expression was also found in HCC patients, and importantly, miR-940 inhibition reversed circACTG1 expression in 97H cells with circACTG1 knockdown. Moreover, the expression of RIF1 was significantly reduced after inhibiting circACTG1 or overexpressing miR-940 but rescued when both circACTG1 and miR-940 were inhibited. Finally, circACTG1 and miR-940 played significant roles of regulating AKT-mTOR signaling. Conclusion. circACTG1 expression remarkably ascended in HCC, which is of certain diagnostic value. Moreover, circACTG1 potentially regulates HCC cell proliferation, invasion, and migration via miR-940/RIF1/AKT/mTOR pathway.

Influenza is a highly contagious acute viral illness that affects the respiratory system, posing a significant global public health concern. Influenza B virus (IBV) causes annual seasonal epidemics. The exploration of molecular biology and reverse genetics of IBV is pivotal for understanding its replication, pathogenesis, and evolution. Reverse genetics empowers us to purposefully alter the viral genome, engineer precise genetic modifications, and unveil the secrets of virulence and resistance mechanisms. It helps us in quickly analyzing new virus strains by viral genome manipulation and the development of innovative influenza vaccines. Reverse genetics has been employed to create mutant or reassortant influenza viruses for evaluating their virulence, pathogenicity, host range, and transmissibility. Without this technique, these tasks would be difficult or impossible, making it crucial for preparing for epidemics and protecting public health. Here, we bring together the latest information on how we can manipulate the genes of the influenza B virus using reverse genetics methods, most importantly helper virus-independent techniques.

Background Prodigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eye-catching research point in recent years for its anticancer activity. However, the role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague. Methods The proliferation of CCA cells was detected by Cell Counting Kit-8(CCK-8), Colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was evaluated by flow cytometry assay and western blot assay. The effects of PG or SNAREs on cell autophagy were measured by autophagy flux assay and western blot assay. Xenograft mouse models were used to assess the role of PG in CCA cells in vivo. Results PG could inhibit the proliferation and viability of CCA cells in a concentration- and time-dependent manner via suppressing the late stage of autophagy. Mechanistically, PG inhibits the fusion of autophagosomes and lysosomes by blocking STX17 and SNAP29, components of soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs)complex. When STX17 and SNAP29 were overexpressed, the inhibitory effect of PG on CCA cells autophagy was relieved. In addition, PG showed obvious inhibitory effects on cancer cell viability but no toxic effects on organs in xenotransplantation models. Conclusion Taken together, our results demonstrated that PG inhibits CCA cell proliferation via suppressing SNAREs-dependent autophagy, implying that PG could be a potential chemotherapy drug for advanced CCA.

The problem of solutions to a class of quasilinear coupling parabolic system was studied. By constructing weak upper-solutions and weak lower-solutions, we obtain the global existence and blow-up of solutions under appropriate conditions.

Cellular microRNAs (miRNAs) are able to influence hepatitis B virus (HBV) replication directly by binding to HBV transcripts or indirectly by targeting cellular factors. Here, we investigate the effect of epigenetically regulated miR-449a on HBV replication and the underlying mechanisms. miR-449a expression was lower in human hepatocellular carcinoma (HCC) cells than in primary hepatocytes and could be induced by trichostatin A. Ectopic miR-449a expression in HCC cells strongly enhanced HBV replication, transcription, progeny virions secretion and antigen expression in a dose-dependent manner. miR-449a directly targeted cAMP-responsive element binding protein 5 (CREB5), which in turn induced the expression of farnesoid X receptor α (FXRα), a transcription factor that facilitates HBV replication. CREB5 knockdown and overexpression demonstrated that it is a negative regulator of HBV replication. Additionally, miR-449a overexpression inhibited proliferation, caused cell cycle arrest and promoted HCC cell differentiation. The results indicated that epigenetically regulated miR-449a targets CREB5 to increase FXRα expression, thereby promoting HBV replication and gene expression. Our findings provide a new understanding of the role of miRNAs in HBV replication.

An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.

Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming “herd-immunity” through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.