3'UTR of SARS-CoV-2 spike gene hijack host miR-296 or miR-520h to disturb cell proliferation and cytokine signaling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3'UTR of SARS-CoV-2 S (S-3'UTR) gene and bioinformatic predicted targeting miRNAs. The growth of 293T cells and HUVECs with overexpressed S-3'UTR was determined, while miRNAs and IL6, TNF-α levels were checked in this condition. Then, miR-296 and miR-602 mimic were introduced into 293T cells and HUVECs with overexpressed S-3'UTR, respectively, to reveal the underlying regulation mechanism. In results, we screened 19 miRNAs targeting the S-3'UTR, including miR-296 and miR-602. In 293T cell, S-3'UTR could inhibit 293T cell growth through down-regulation of miR-296. By reducing miR-602, S-3'UTR could induce HUVECs cell proliferation, alter the cell cycle, reduce apoptosis, and enhanced IL6 and TNF-αlevel. In conclusion, SARS-CoV-2 RNA could play as sponge of host miRNA to disturb cell growth and cytokine signaling. It suggests an important clue for designing COVID-19 drug and vaccine.

Meta-Analysis of Whole Blood Transcriptome Datasets Characterizes the Immune Response of Respiratory Syncytial Virus Infection in Children.

Respiratory syncytial virus (RSV) is the most common and critical viral pathogen causing acute lower respiratory tract infection in infants and young children and has a huge disease burden worldwide. At present, there are many studies on RSV transcriptomics exploring the mechanism of disease, but different studies show different gene expression patterns and results due to different sample collection platforms and data analysis strategies. A meta-analysis was performed on eight whole blood transcriptome datasets containing 436 children with acute RSV infection and 241 healthy children. A total of 319 differentially expressed genes (DEGs) (P value <0.0001) were identified in a meta-analysis using a random effect model. Functional enrichment analysis showed that several pathways related to immunity were significantly altered, including the "chemokine signaling pathway", "natural killer cell mediated cytotoxicity" and "cytokine-cytokine receptor interaction". Immune cell type analysis showed that the proportion of neutrophils in most RSV-infected children was higher than that in healthy children. These immune characteristics may help to provide new insights into RSV infection in children.

Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates with focus on antimicrobial resistance.

BACKGROUND: The enhancing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP)-mediated infections in Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017 is the motivation behind this investigation to study gene phenotypes and resistance-associated genes of emergence regarding the CRKP strains. In current study, seven inpatients are enrolled in the hospital with complete treatments. The carbapenem-resistant K. pneumoniae whole genome is sequenced using MiSeq short-read and Oxford Nanopore long-read sequencing technology. Prophages are identified to assess genetic diversity within CRKP genomes. RESULTS: The investigation encompassed eight CRKP strains that collected from the patients enrolled as well as the environment, which illustrate that blaKPC-2 is responsible for phenotypic resistance in six CRKP strains that K. pneumoniae sequence type (ST11) is informed. The plasmid with IncR, ColRNAI and pMLST type with IncF[F33:A-:B-] co-exist in all ST11 with KPC-2-producing CRKP strains. Along with carbapenemases, all K. pneumoniae strains harbor two or three extended spectrum ß-lactamase (ESBL)-producing genes. fosA gene is detected amongst all the CRKP strains. The single nucleotide polymorphisms (SNP) markers are indicated and validated among all CRKP strains, providing valuable clues for distinguishing carbapenem-resistant strains from conventional K. pneumoniae. CONCLUSIONS: ST11 is the main CRKP type, and blaKPC-2 is the dominant carbapenemase gene harbored by clinical CRKP isolates from current investigations. The SNP markers detected would be helpful for characterizing CRKP strain from general K. pneumoniae. The data provides insights into effective strategy developments for controlling CRKP and nosocomial infection reductions.

Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.

BACKGROUND: To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. METHODS: The week 12-34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 µg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. RESULTS: A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P < 0.001), respectively. CONCLUSIONS: Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.

Long-read nanopore sequencing-based draft genome of a carbapenem-resistant Pseudomonas aeruginosa isolate.

OBJECTIVES: Pseudomonas aeruginosa is a common Gram-negative bacterium causing various serious infections, such as lower respiratory tract infection and urinary tract infection in catheterised patients. Here we report the draft genome sequence of a carbapenem-resistant P. aeruginosa (CRPA) isolate. METHODS: The genome of the CRPA isolate was sequenced using a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. RESULTS: The resulting assembly was highly contiguous, containing a total of 6624003bp with a GC content of 66.21%. Annotation identified 6389 protein-coding genes. Mutations in the oprD and mexR genes conferred resistance to carbapenems in the CRPA isolate. CONCLUSION: The draft genome sequence of this CRPA isolate could provide a solid basis for further research on the resistance mechanisms and the development of drug therapy for drug resistance genes.

Structural Insights for Anti-Influenza Vaccine Design.

Influenza A virus are a persistent and significant threat to human health, and current vaccines do not provide sufficient protection due to antigenic drift, which allows influenza viruses to easily escape immune surveillance and antiviral drug activity. Influenza hemagglutinin (HA) is a glycoprotein needed for the entry of enveloped influenza viruses into host cells and is a potential target for anti-influenza humoral immune responses. In recent years, a number of broadly neutralizing antibodies (bnAbs) have been isolated, and their relative structural information obtained from the crystallization of influenza antigens in complex with bnAbs has provided some new insights into future influenza vaccine research. Here, we review the current knowledge of the HA-targeted bnAbs and the structure-based mechanisms contributing to neutralization. We also discuss the potential for this structure-based approach to overcome the challenge of obtaining a highly desired "universal" influenza vaccine, especially on small proteins and peptides.

The Association between Meteorological Factors and the Prevalence of Acute-on-chronic Liver Failure: A Population-based Study, 2007-2016.

Background and Aims: The aim of this study was to investigate the effect(s) of meteorological factors on the prevalence of acute-on-chronic liver failure (ACLF) based on 10-years' worth of population data. Methods: We retrospectively collected ACLF case data from January 2007 to December 2016 from three major hospitals in Fuzhou City, China. Climatic data, including rainfall, mean temperature, differences in temperature (delta temperature) and mean humidity for each month were downloaded from the China Climatic Data Service Center. Following data collection, Poisson regression analysis was used to estimate the effect(s) of climatic factors on the risk of the prevalence of ACLF. Results: The population consisted of a total of 3510 cases, with a mean age of 44.7 ± 14.8 years-old and with 79.8% being male. Upon analyzing the population data, we found a growing trend and seasonal pattern of monthly counts of ACLF-related hospitalization throughout the past decade. Specifically, the primary peak of ACLF prevalence was in January and the secondary peak was in July. Poisson regression showed mean temperature (risk ratio = 0.991, 95%CI = 0.986-0.996) and mean humidity (risk ratio = 1.011, 95%CI = 1.006-1.017) to be independently correlated with the monthly cases of ACLF. The results suggest that every unit increase of mean temperature (1°C) and mean humidity (1%) are associated with 0.991- and 1.011-fold changes of ACLF cases, respectively. Rainfall and delta temperature did not appear to affect the prevalence of this disease. Conclusions: The hospitalization for ACLF peaks in January and July. Low temperature and high humidity appear to function as factors contributing to this seasonal pattern.

Quantitative Comparative Proteomics Reveal Biomarkers for Dengue Disease Severity.

Dengue fever (DF) could develop into dengue haemorrhagic fever (DHF) with increased mortality rate. Since the clinical characteristics and pathogen are same in DF and DHF. It's important to identify different molecular biomarkers to predict DHF patients from DF. We conducted a clinical plasma proteomics study using quantification (TMT)-based quantitative proteomics methodology to found the differential expressed protein in DF patients before they developed into DHF. In total 441 proteins were identified up or down regulated. There proteins are enriched in diverse biological processes such as proteasome pathway, Alanine, aspartate, and glutamate metabolism and arginine biosynthesis. Several proteins such as PLAT, LAMB2, and F9 were upregulated in only DF patients which developed into DHF cases, not in DF, compared with healthy-control. In another way, FGL1, MFAP4, GLUL, and VCAM1 were upregulated in both DHF and DF cases compare with healthy-control. RT-PCR and ELISA were used to validate these upregulated gene expression and protein level in 54 individuals. Results displayed the same pattern as proteomics analysis. All including PLAT, LAMB2, F9, VCAM1, FGL1, MFAP4, and GLUL could be considered as potential markers of predicting DHF since the levels of these proteins vary between DF and DHF. These new founding identified potential molecular biomarkers for future development in precision prediction of DHF in DF patients.

Late or Lack of Vaccination Linked to Importation of Yellow Fever from Angola to China.

During March and April 2016, 11 yellow fever cases were identified in China. We report epidemic and viral information for 10 of these patients, 6 of whom had been vaccinated before travel. Phylogenetic analyses suggest these viruses nested within the diversity of strains endemic to Angola, where an outbreak began in 2015.

Biochemical Characterization and Phylogenetic Analysis of the Virulence Factor Lysine Decarboxylase From Vibrio vulnificus.

Cadaverine is produced in organisms from the amino acid lysine in a decarboxylation reaction catalyzed by lysine decarboxylase (EC 4.1.1.18). The inducible lysine decarboxylase CadA plays a vital role in acid stress response for enteric bacteria. Vibrio vulnificus is an extremely virulent human pathogen causing gastroenteritis when the acid conditions that prevent survival of V. vulnificus in the stomach or small intestine are overcome. A gene encoding CadA was identified from V. vulnificus. Subsequent analyses showed that CadA from V. vulnificus (VvCadA) is a decamer with a 82-kDa subunit. Homogenous VvCadA was purified from Escherichia coli and used for lysine decarboxylation with an optimal pH of 6.0 and optimal temperature of 37°C. The apparent V max and K m for lysine were 9.45 ± 0.24 µM/min and 0.45 ± 0.05 mM, respectively. Mutation analysis suggested that the amino-acid-binding pyridoxal phosphate, the cofactor of the enzyme, plays a vital role in the reaction. Mutation of the negatively charged residues interacting with lysine also affected the activity of the enzyme to some extent. Quantitative RT-PCR showed that expression of VvcadA was up-regulated under low pH, low salinity, and oxidative stresses. Furthermore, the concentration of cadaverine released to the cell exterior also increased under these stresses. Protein sequence similarity network (SSN) analysis indicated that lysine decarboxylases with ornithine decarboxylases and arginine decarboxylases shared a common ancestor, and that lysine decarboxylases are more conserved during evolution. Our data provide evidence for the biochemical characteristics and important roles of VvCadA under stress conditions.

Prognostic nomogram for acute-on-chronic hepatitis B liver failure.

BACKGROUND & AIMS: To establish an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF). MATERIALS AND METHODS: The nomogram was based on clinical data of 203 ACHBLF patients who admitted to the First Affiliated Hospital of Fujian Medical University from 2009 to 2014. The area under the receiver-operating characteristic curve (AUC) and calibration curve were carried out to verify the predictive accuracy ability of the nomogram. The result was validated in internal and external validation cohorts. Kaplan-Meier survival curve was used in survival analysis. RESULTS: We developed a new prognostic nomogram to predict 3-month mortality based on risk factors selected by multivariate analysis. This nomogram consisted three independent factors: age, liver to abdominal area ratio (LAAR) and model for end-stage liver disease (MELD) score. The AUC of this nomogram for survival prediction was 0.877 (95% CI 0.831-0.923), which was higher than that of MELD score, MELD-Na and Child-Turcotte-Pugh (CTP). Good agreement of calibration plot for the probability of survival at 3-month was shown between the prediction by nomogram and actual observation. These results were supported by internal and external validation studies. CONCLUSIONS: The ACHBLF nomogram could predict the short-term survival for ACHBLF patients.

Stimuli-triggered growth and removal of a bioreducible nanoshell on nanoparticles.

A new and easy method of stimuli-triggered growth and removal of a bioreducible nanoshell on nanoparticles is reported. The results show that pH or temperature could induce the aggregation of disulfide-contained branched polymers at the surface of nanoparticles; subsequently, the aggregated polymers could undergo intermolecular disulfide exchange to cross-link the aggregated polymers, forming a bioreducible polymer shell around nanoparticles. When these nanoparticles with a polymer shell are treated with glutathione (GSH) or d,l-dithiothreitol (DTT), the polymer shell could be easily removed from the nanoparticles. The potential application of this method is demonstrated by easily growing and removing a bioreducible shell from liposomes, and improvement of in vivo gene transfection activity of liposomes with a bioreducible PEG shell.

ABCC4 copy number variation is associated with susceptibility to esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the eighth most common cause of cancer-related death worldwide. However, previous genome-wide single nucleotide polymorphism association analyses have not explained the high heritability associated with ESCC. In this study, we performed genome-wide copy number variation (CNV) analysis on 128 discordant sibling pairs to identify novel genes that contribute to ESCC susceptibility. A total of 57 774 individual CNVs were identified, and an interactive network of common CNV-associated genes was constructed, which showed that several ABC transporter genes contain CNVs in ESCC patients. Independent validation of a CNV at 13q32.1 in 1048 northern Chinese Han subjects demonstrated that the amplification of ABCC4 significantly correlated with ESCC risk [odds ratio: 3.36 (1.65-7.93), P = 0.0013]. Immunohistochemistry staining suggested that high copy numbers correlated with increased protein levels. High expression of ABCC4 was an independent poor prognostic factor for ESCC [relative risk: 1.73 (1.10-2.73), P = 0.0181]. The CNV region showed strong enhancer activity. Furthermore, inhibition of ABCC4 protein in ESCC cells decreased cell proliferation and motility via the inhibition of COX-2, PGE2 receptors and c-Myc expression; AKT, extracellular signal-regulated kinase and cAMP response element-binding protein phosphorylation; and ß-catenin nuclear translocation in ESCC cells. In conclusion, the CNV at 13q32.1 is associated with ESCC susceptibility, and a gene within this locus, ABCC4, activates the oncogenic pathways in ESCC and thus facilitates cancer cell development and progression. A direct genetic contribution of ESCC risk through CNV common variants was determined in this study, and ABCC4 might therefore have predictive and therapeutic potential for ESCC.

Temperature and electron density dependence of spin relaxation in GaAs/AlGaAs quantum well.

Temperature and carrier density-dependent spin dynamics for GaAs/AlGaAs quantum wells (QWs) with different structural symmetries have been studied by using time-resolved Kerr rotation technique. The spin relaxation time is measured to be much longer for the symmetrically designed GaAs QW comparing with the asymmetrical one, indicating the strong influence of Rashba spin-orbit coupling on spin relaxation. D'yakonov-Perel' mechanism has been revealed to be the dominant contribution for spin relaxation in GaAs/AlGaAs QWs. The spin relaxation time exhibits non-monotonic-dependent behavior on both temperature and photo-excited carrier density, revealing the important role of non-monotonic temperature and density dependence of electron-electron Coulomb scattering. Our experimental observations demonstrate good agreement with recently developed spin relaxation theory based on microscopic kinetic spin Bloch equation approach.