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Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3′-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent. [Display omitted] • CDK inhibitor IM inhibited HAdV replication in vitro with low cytotoxicity. • IM suppressed HAdV E1A transcription by downregulating phosphorylated CTD. • IM alleviated HAdV infection in the tri-receptor transgenic mouse model. • IM curbed inflammatory responses induced by HAdV infection in mice. [ABSTRACT FROM AUTHOR]

Since the plasmid-mediated polymyxin resistance gene mcr - 1 was first reported in Escherichia coli and Klebsiella pneumoniae in China, only one mcr-1 -positive isolate of Shigella sonnei , containing inactivated mcr-1 , has been reported worldwide. In this study, 1650 historical S. sonnei strains isolated from 2003–2015 in China were screened for the mcr - 1 gene. Antimicrobial susceptibilities and resistance genes of mcr - 1 -positive isolates were determined, and the transferability of polymyxin resistance by plasmid conjugation was investigated. Pulsed-field gel electrophoresis (PFGE), plasmid profiles and Southern blotting were used to analyse genetic relationships and plasmid characteristics, and mcr - 1 -positive plasmids were sequenced. Six mcr - 1 -positive S. sonnei isolates from Shanghai (2010–2012) with polymyxin B resistance (MICs 4–8 μg/mL) were identified. Four of these exhibited multidrug resistance, including resistance to azithromycin and third-generation cephalosporins, and co-harboured bla CTX-M-14 , mph (A) and bla TEM on different plasmids. mcr - 1 -positive plasmids shared highly similar IncI2 backbones that resembled reference plasmids, although some differences were observed, including various and abundant insertion sequences/patterns (IS 1294 , IS 1 and IS Apl1 ) and a diverse recombination shufflon region. mcr - 1 in S. sonnei may date back to mid-2006. Here we report for the first time the presence of active mcr-1 in multidrug-resistant S. sonnei in China, which has existed since at least 2010. This study highlights the diverse mobile genetic elements on mcr - 1 -harboring plasmids, potentially resulting in high rates of mcr - 1 horizontal transfer among Enterobacteriaceae. These findings emphasise the importance of continuous national and international surveillance of mcr - 1 -positive Shigella and changes in antibiotic resistance patterns. [ABSTRACT FROM AUTHOR]

Accurate detection of severe acute respiratory syndrome coronavirus 2 is not only necessary for viral load monitoring to optimize treatment in hospitalized coronavirus disease 2019 patients, but also critical for deciding whether the patient could be discharged without any risk of viral shedding. Digital droplet PCR (ddPCR) is more sensitive than reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and is usually considered the superior choice. In the current study, we compared the clinical performance of RT-qPCR and ddPCR using oropharyngeal swab samples from patients hospitalized in the temporary Huoshenshan Hospital, Wuhan, Hubei, China. Results demonstrated that ddPCR was indeed more sensitive than RT-qPCR. Negative results might be caused by poor sampling technique or recovered patients, as the range of viral load in these patients varied significantly. In addition, both methods were highly correlated in terms of their ability to detect all three target genes as well as the ratio of copies of viral genes to that of the IC gene. Furthermore, our results evidenced that both methods detected the N gene more easily than the ORF gene. Taken together, these findings imply that the use of ddPCR, as an alternative to RT-qPCR, is necessary for the accurate diagnosis of hospitalized coronavirus disease 2019 patients. [ABSTRACT FROM AUTHOR]

• A modified Hooke's law estimates the maximum stresses of a driving wheel. • A minimal model estimates the wheel-terrain interaction force with high accuracy. • A minimalist model estimates the wheel-terrain interaction force qualitatively. • One more parameter extends the proposed models to adapt to various loads. Terramechanics plays an important role in planetary exploration rovers. Conventional terramechanics models contain approximately eight parameters and several variables. The coupled equations are complex and computationally expensive. The wheel–terrain interaction data under various slip ratios are required to identify the parameters. However, there is no guarantee that the desired slip states will be achieved, when a rover is exploring. Moreover, high accurate measurement of the slip ratios is difficult. In this study, a novel model for calculating the maximum stresses of a wheel is proposed, which satisfies a modified Hooke's law. Two minimized models for estimating the interaction forces are then derived. The first minimal model contains four parameters and two variables, and the estimation errors are mostly within 10%. By simplifying further, a second minimalist model, containing two parameters and one variable is obtained. Finally, by introducing an additional parameter, which can be identified with the data obtained under different vertical loads, the proposed models extended to adapt to various loads. The results from single-wheel experiments demonstrate the high efficiency and accuracy of the proposed models. [ABSTRACT FROM AUTHOR]

Shigella sonnei has become predominant species causing shigellosis in Shanghai. Two hundred ninety-three S . sonnei were isolated in sentinel hospitals of Shanghai in 2011. We found an emergence of 8 strains of S . sonnei with negative phenotype for o-nitrophenyl-β- d -galactopyranoside in late August, which showed distinct pulsed-field gel electrophoresis patterns from the other 285 S . sonnei and had genes deletion in lac and mhp operons. [ABSTRACT FROM AUTHOR]

Laryngeal carcinoma (LC) is one of the most common malignant head and neck cancers with high incidence and mortality rates. Erchen decoction plus Huiyanzhuyu decoction (EHD) is commonly used for treating LC patients and produces beneficial results. However, the mechanisms underlying the effects of EHD remain unclear. The present study aimed to analyse the anticancer effects of EHD on the LC cell cycle, apoptosis, migration and invasion in vitro and to explore the underlying biological mechanisms. TU212 and Hep-2 cells were used. The antitumour effects of EHD were detected by CCK8, microscopy, flow cytometry, EdU incorporation, Hoechst 33342 staining, wound-healing, and transwell assays to assess viability, morphology, apoptosis, cell cycle, migration and invasion, respectively. Furthermore, STAT3 and related proteins were evaluated in laryngeal squamous cell carcinoma (LSCC) cells by Western blot (WB) analysis. EHD treatment significantly decreased STAT3 and p-STAT3 protein expression levels in LSCC cells. EHD blocked the cell cycle at the G0/G1 phase and induced LSCC apoptosis. Moreover, the viability, migration, and invasion of LSCC cells were markedly inhibited by EHD. In addition, the expression of the cell cycle-related proteins cyclin D1 and cyclin B1 was downregulated in LSCC cells, but P27 expression was increased after EHD treatment. Regarding apoptosis-related proteins, EHD also reduced Bcl-2 expression but upregulated Bax and caspase-3 expression in LSCC cells. In the migration- and invasion-related protein analyses, EHD downregulated MMP-9 expression and upregulated E-cadherin expression. These results suggest that EHD has an anticancer effect in LSCC. EHD treatment induces apoptosis and inhibits the cell cycle, migration and invasion of LSCC cells, but further work is warranted to address the mechanisms. Image 1 [ABSTRACT FROM AUTHOR]