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Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilize a unique transgenic mouse model that mimics chronic non-bacterial prostatitis in men and investigate the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiation in vivo. We find that inflammation significantly enhances AR levels and activity in bPSC. More importantly, we identify interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA is one of the top molecules upregulated by inflammation, and inhibiting IL-1RA reverses the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appears to activate AR by counteracting IL-1α's inhibitory effect. Furthermore, using a lineage tracing model, we observe that inflammation induces bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovers mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia. Inflammation enhances androgen receptor levels and activity in basal prostate stem cells via IL-1RA, promoting their proliferation and differentiation, potentially contributing to benign prostate hyperplasia in mice. [ABSTRACT FROM AUTHOR]

The IL-2 receptor α chain (IL-2Rα/CD25) is constitutively expressed on double-negative (DN2/DN3 thymocytes and regulatory T cells (Tregs) but induced by IL-2 on T and natural killer (NK) cells, with Il2ra expression regulated by a STAT5-dependent super-enhancer. We investigated CD25 regulation and function using a series of mice with deletions spanning STAT5-binding elements. Deleting the upstream super-enhancer region mainly affected constitutive CD25 expression on DN2/DN3 thymocytes and Tregs, with these mice developing autoimmune alopecia, whereas deleting an intronic region decreased IL-2–induced CD25 on peripheral T and NK cells. Thus, distinct super-enhancer elements preferentially control constitutive versus inducible expression in a cell type–specific manner. The mediator-1 coactivator colocalized with specific STAT5-binding sites. Moreover, both upstream and intronic regions had extensive chromatin interactions, and deletion of either region altered the super-enhancer structure in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating previously unknown ways to manipulate CD25 expression in a cell type–specific fashion. Editor's summary: Regulation of the gene encoding IL-2Rα (CD25) has been studied extensively to understand discrete patterns of expression on lymphocyte subsets, including the influence of Il2ra super-enhancer elements. Spolski et al. undertook an exhaustive investigation of CD25 regulation and function using a panel of mice bearing different deletions within Il2ra super-enhancer elements that modulate binding of STAT5. Deletion of the upstream super-enhancer region markedly affected constitutive CD25 expression on double-negative (DN)2/DN3 thymocytes and Tregs and resulted in the development of mice with autoimmune alopecia. By contrast, deletion of an intronic region reduced IL-2–driven CD25 expression on peripheral NK and T cells. The upstream and intronic regions also exhibited chromatin interactions, and deletions resulted in changes in super-enhancer structures in mature T cells. These findings highlight roles of different super-enhancer elements in controlling CD25 expression. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Background: Infectious diseases are a major threat to public health, causing serious medical consumption and casualties. Accurate prediction of infectious diseases incidence is of great significance for public health organizations to prevent the spread of diseases. However, only using historical incidence data for prediction can not get good results. This study analyzes the influence of meteorological factors on the incidence of hepatitis E, which are used to improve the accuracy of incidence prediction. Methods: We extracted the monthly meteorological data, incidence and cases number of hepatitis E from January 2005 to December 2017 in Shandong province, China. We employ GRA method to analyze the correlation between the incidence and meteorological factors. With these meteorological factors, we achieve a variety of methods for incidence of hepatitis E by LSTM and attention-based LSTM. We selected data from July 2015 to December 2017 to validate the models, and the rest was taken as training set. Three metrics were applied to compare the performance of models, including root mean square error(RMSE), mean absolute percentage error(MAPE) and mean absolute error(MAE). Results: Duration of sunshine and rainfall-related factors(total rainfall, maximum daily rainfall) are more relevant to the incidence of hepatitis E than other factors. Without meteorological factors, we obtained 20.74%, 19.50% for incidence in term of MAPE, by LSTM and A-LSTM, respectively. With meteorological factors, we obtained 14.74%, 12.91%, 13.21%, 16.83% for incidence, in term of MAPE, by LSTM-All, MA-LSTM-All, TA-LSTM-All, BiA-LSTM-All, respectively. The prediction accuracy increased by 7.83%. Without meteorological factors, we achieved 20.41%, 19.39% for cases in term of MAPE, by LSTM and A-LSTM, respectively. With meteorological factors, we achieved 14.20%, 12.49%, 12.72%, 15.73% for cases, in term of MAPE, by LSTM-All, MA-LSTM-All, TA-LSTM-All, BiA-LSTM-All, respectively. The prediction accuracy increased by 7.92%. More detailed results are shown in results section of this paper. Conclusions: The experiments show that attention-based LSTM is superior to other comparative models. Multivariate attention and temporal attention can greatly improve the prediction performance of the models. Among them, when all meteorological factors are used, multivariate attention performance is better. This study can provide reference for the prediction of other infectious diseases. [ABSTRACT FROM AUTHOR]

Objectives: To develop a modified CRISPR/Cas9 system with the β-glucuronidase (GusA) reporter and a dual sgRNA cassette for Nonomuraea gerenzanensis (N. gerenzanensis). Results: With the aid of a visual GusA reporter, the complicated and tedious process of cloning and gene identification could be abandoned entirely in the genetic editing of N. gerenzanensis. Moreover, introducing a dual sgRNA cassette into the CRISPR/Cas9 system significantly improved gene deletion efficiency compared to the single sgRNA element. Furthermore, the length of the homologous flanking sequences set to the lowest value of 500 bp in this system could still reach the relatively higher conjugation transfer frequency. Conclusions: The enhanced CRISPR/Cas9 system could efficiently perform genetic manipulation on the rare actinomycete N. gerenzanensis. [ABSTRACT FROM AUTHOR]

We probed the lifecycle of Epstein‐Barr virus (EBV) on a cell‐by‐cell basis using single cell RNA sequencing (scRNA‐seq) data from nine publicly available lymphoblastoid cell lines (LCLs). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350–LMP1hi cells, expressed high levels of HIF1A and was transcriptionally regulated by HIF1‐α. Treatment of LCLs with Pevonedistat, a drug that enhances HIF1‐α signaling, markedly induced this cluster. The second cluster, containing GP350+LMP1hi cells, expressed EBV lytic genes. Host genes that are controlled by super‐enhancers (SEs), such as transcription factors MYC and IRF4, had the lowest expression in this cluster. Functionally, the expression of genes regulated by MYC and IRF4 in GP350+LMP1hi cells were lower compared to other cells. Indeed, induction of EBV lytic reactivation in EBV+ AKATA reduced the expression of these SE‐regulated genes. Furthermore, CRISPR‐mediated perturbation of the MYC or IRF4 SEs in LCLs induced the lytic EBV gene expression, suggesting that host SEs and/or SE target genes are required for maintenance of EBV latency. Collectively, our study revealed EBV‐associated heterogeneity among LCLs that may have functional consequence on host and viral biology. [ABSTRACT FROM AUTHOR]

Objective: To improve the production of A40926, a combined strategy of constructing the engineered strain and optimizing the medium was implemented. Results: The engineered strain lcu1 with the genetic features of dbv23 deletion and dbv3-dbv20 coexpression increased by 30.6% in the production of A40926, compared to the original strain. In addition, a combined medium called M9 was designed to be further optimized by the central composite design method. The optimized M9 medium was verified to significantly improve the A40926 yield from 257 to 332 mg l−1. Conclusions: The engineered strain lcu1 could significantly promote A40926 production in the optimized M9 medium, which indicated that the polygenic genetic manipulation and the media optimization played an equally important role in increasing the A40926 yield. [ABSTRACT FROM AUTHOR]

Exosomes are small membrane-enclosed vesicles secreted by various types of cells. Exosomes not only participate in different physiological processes in cells, but also involve in the cellular responses to viral infection. Grass carp reovirus (GCRV) is a non-enveloped virus with segmented, double-stranded RNA genome. Nowadays, the exact role of exosomes in regulating the life cycle of GCRV infection is still unclear. In this study, the exosomes secreted from Ctenopharyngodon idellus kidney (CIK) cells infected or uninfected with GCRV were isolated, and the differential protein expression profiles were analyzed by proteomic technologies. A total of 1297 proteins were identified in the isolated exosomes. The differentially abundant proteins were further analyzed with functional categories, and numerous important pathways were regulated by exosomes in GCRV-infected CIK cells. These exosomal proteins were estimated to interact with the genes (proteins) of the top 10 most enriched signaling pathways. Furthermore, GW4869 exosome inhibitor suppressed the expression level of VP7 in GCRV-infected cells, suggesting that exosomes play a crucial role in the life cycle of GCRV infection. These findings could shed new lights on understanding the functional roles of exosomes in the cellular responses to GCRV infection. [ABSTRACT FROM AUTHOR]

COVID-19 hyperactivates complement: The complement system is a series of innate immune system proteins that help antibodies and phagocytes identify and eliminate pathogens. Activation of the complement system correlates with COVID-19 severity, but the cells that produce complement and potential treatments to inhibit complement activation during SARS-CoV-2 infection are not known. Here, Yan et al. used transcriptomics from patient bronchoalveolar lavage and infection models to demonstrate that SARS-CoV-2 infection induced complement-related genes and the activated complement component C3a in respiratory epithelial cells. C3a production was tied to IFN-induced JAK1/2-STAT1 signaling. Inhibition of JAK1/2 with ruxolitinib, with or without an antiviral, or a cell-permeable complement inhibitor repressed C3a production in SARS-CoV-2–infected epithelial cells. Thus, the use of JAK1/2 inhibitors may inhibit pathologies in patients with severe COVID-19. Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys, and gut. Angiotensin-converting enzyme 2 (ACE2), the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid, and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines but did not affect NF-κB–regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB signaling could potentially have clinical application for severe COVID-19. [ABSTRACT FROM AUTHOR]

Background: Accurate and reliable predictions of infectious disease can be valuable to public health organizations that plan interventions to decrease or prevent disease transmission. A great variety of models have been developed for this task. However, for different data series, the performance of these models varies. Hepatitis E, as an acute liver disease, has been a major public health problem. Which model is more appropriate for predicting the incidence of hepatitis E? In this paper, three different methods are used and the performance of the three methods is compared. Methods: Autoregressive integrated moving average(ARIMA), support vector machine(SVM) and long short-term memory(LSTM) recurrent neural network were adopted and compared. ARIMA was implemented by python with the help of statsmodels. SVM was accomplished by matlab with libSVM library. LSTM was designed by ourselves with Keras, a deep learning library. To tackle the problem of overfitting caused by limited training samples, we adopted dropout and regularization strategies in our LSTM model. Experimental data were obtained from the monthly incidence and cases number of hepatitis E from January 2005 to December 2017 in Shandong province, China. We selected data from July 2015 to December 2017 to validate the models, and the rest was taken as training set. Three metrics were applied to compare the performance of models, including root mean square error(RMSE), mean absolute percentage error(MAPE) and mean absolute error(MAE). Results: By analyzing data, we took ARIMA(1, 1, 1), ARIMA(3, 1, 2) as monthly incidence prediction model and cases number prediction model, respectively. Cross-validation and grid search were used to optimize parameters of SVM. Penalty coefficient C and kernel function parameter g were set 8, 0.125 for incidence prediction, and 22, 0.01 for cases number prediction. LSTM has 4 nodes. Dropout and L2 regularization parameters were set 0.15, 0.001, respectively. By the metrics of RMSE, we obtained 0.022, 0.0204, 0.01 for incidence prediction, using ARIMA, SVM and LSTM. And we obtained 22.25, 20.0368, 11.75 for cases number prediction, using three models. For MAPE metrics, the results were 23.5%, 21.7%, 15.08%, and 23.6%, 21.44%, 13.6%, for incidence prediction and cases number prediction, respectively. For MAE metrics, the results were 0.018, 0.0167, 0.011 and 18.003, 16.5815, 9.984, for incidence prediction and cases number prediction, respectively. Conclusions: Comparing ARIMA, SVM and LSTM, we found that nonlinear models(SVM, LSTM) outperform linear models(ARIMA). LSTM obtained the best performance in all three metrics of RSME, MAPE, MAE. Hence, LSTM is the most suitable for predicting hepatitis E monthly incidence and cases number. [ABSTRACT FROM AUTHOR]

The glycopeptide A40926 biosynthesized by Nonomuraea gerenzanensis is a precursor of the second generation glycopeptide antibiotic dalbavancin. The skeleton of this glycopeptide consists of seven amino acids and is biosynthesized by the NRPS gene module. L-valine, a branched amino acid, is also a significant precursor for A40926 production. This study details the use of pH-responsive alginate–chitosan microspheres loaded with L-valine prepared by internal emulsification gelation. The effects of process and formulation variables on microsphere size, loading capacity, and encapsulation efficiency were investigated. Then, effects on A40926 production by the pH-responsive microspheres were evaluated in a 10-L fermenter. Results demonstrated that use of the pH-responsive microspheres could improve A40926 yield from 465 to 602 mg L−1 in a 10-L scale fermenter. [ABSTRACT FROM AUTHOR]

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens in sericulture and causes huge economic loss annually. The roles of N6-methyladenosine (m6A) modification in silkworms following BmNPV infection are currently unclear. Here, methylated RNA immunoprecipitation with next-generation sequencing were applied to investigate the m6A profiles in silkworm midgut following BmNPV infection. A total of 9144 and 7384 m6A peaks were identified from the BmNPV-infected (TEST) and uninfected silkworm midguts (CON), respectively, which were distributed predominantly near stop codons. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of common m6A peaks in nuclear genes revealed that these m6A-related transcripts were associated with crucial signaling pathways. Comparative transcriptome analysis showed that 1221 differential expressed m6A peaks were identified between TEST and CON, indicating that m6A modification is regulated following BmNPV infection. GO and KEGG pathway analysis of the differentially expressed m6A peaks showed their association with signal transduction, translation, and degradation. To understand further the effect of the m6A machinery on virus infection, expression levels of m6A-related genes were altered in silencing and overexpression experiments. Expression of viral structural protein VP39 was increased in BmN cells by siRNA-mediated depletion of methyltransferase-like (METTL) enzyme genes (BmMETTL3, BmMETTL14) and cytoplasmic YTH-domain family 3 (BmYTHDF3), while the reverse results were found after overexpression of the m6A-related enzymes in BmN cells. Overall, m6A modification might be a novel epigenetic mechanism that regulation BmNPV infection and interference with this mechanism may provide a novel antiviral strategy for preventing BmNPV disease. [ABSTRACT FROM AUTHOR]

Diet is known to play a major role in determining the composition and function of the gut microbiota. Previous studies have often focused on the immediate effects of dietary intervention. How dietary history prior to a given dietary intervention influences the gut microbiota is, however, not well understood. To assess the influence of dietary history, in this study, mice with different dietary histories were subjected to the same dietary interventions, and the gut microbial communities of these mice were characterized by 16S rDNA sequencing. We found that dietary history played a long-lasting role in the composition of the gut microbiota when the dietary switch was moderate. In sharp contrast, such effects nearly vanished when the diet was switched to certain extreme dietary conditions. Interestingly, the abundance of Akkermansia, a bacterial genus associated with loss of body weight, was elevated dramatically in mice subjected to a diet composed exclusively of meat. Our results revealed a more complex picture of the influence of dietary history on gut microbiota than anticipated. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial.Methods: Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups.Results: The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05).Conclusions: This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment.Clinical Trials Registration: NCT 02898922. [ABSTRACT FROM AUTHOR]

Spontaneous cell-cell fusion has been recognized to be an important mechanism for tissue and organ development and repair. In cancer, cell fusion is critically involved in tumourigenesis, metastasis and drug resistance, as illustrated by in vitro experiments. However, there has been no direct detection of tumour cell fusion or hybridization in an in vivo tumour environment, and the features of hybridized cells under selective pressures, such as chemotherapy, are unknown. Here, we expressed two fluorescent marker proteins in the human breast cancer cell line SKBR3 to detect tumour cell hybridization in vivo and performed a xenograft chemotherapy experiment in mice to evaluate the chemotherapeutic response of the hybrids. The mice treated by epirubicin showed that chemotherapy promoted tumour cell hybridization in vivo, which elicited the production of more hybrids in the outer section of the tumour. These results provide the first in vivo evidence of tumour cell fusion and indicate that chemotherapy may contribute to a poor prognosis by enriching for fused cells, which are more malignant. It is therefore necessary to reassess chemotherapy strategies. [ABSTRACT FROM AUTHOR]

No response to hepatitis B vaccination is a complex phenomenon, which is induced by the combinations of environmental and genetic factors. The aim of the study was to investigate the association between the polymorphisms of the butyrophilin-like 2 (BTNL2) gene and the immune response to hepatitis B vaccination in a Chinese Han population. A total of 7 single nucleotide polymorphisms in the BTNL2 gene were analyzed in 566 non-responders and 1,040 high-responders to hepatitis B vaccination. The alleles T, T, C, A, G of rs3763316, rs3763311, rs9268494, rs3806156, and rs2076530 were associated with no response to hepatitis B vaccination ( P = 0.015, odds ratio (OR) = 1.20; P = 0.029, OR = 1.18; P = 2.00E−07, OR = 1.58; P = 0.002, OR = 1.27; P = 2.90E−06, OR = 1.41, respectively). Whereas, the alleles T, C of rs9268501 and rs3763313 played significantly protective roles in the immune response to hepatitis B vaccination ( P = 0.007, OR = 0.81; P = 0.004, OR = 0.74). Besides, the risks of no response to hepatitis B vaccination were increased significantly among individuals harbored the haplotypes of G-T-A-T-C-A-G ( P = 0.038, OR = 1.48), G-T-A-T-C ( P < 0.0001, OR = 2.34), A-A ( P < 0.0001, OR = 4.08), and C-G ( P < 0.0001, OR = 4.75). However, the haplotype of G-C-A-T-C ( P = 1.00E−04, OR = 0.54) exhibited a protective role in the immune response to hepatitis B vaccination in the study. These findings suggest that polymorphisms in the BTNL2 gene might play a vital role in determining the outcome of the immune response to hepatitis B vaccination. J. Med. Virol. 86:1105-1112, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Simple Summary: The cause of Chinese mitten crab Eriocheir sinensis hepatopancreas necrosis disease (HPND) remains a mystery. In this study, metatranscriptomics sequencing was conducted to characterize the changes in the structure and gene expression of hepatopancreatic flora of crabs with and without typical symptoms of HPND; an imbalance of hepatopancreatic flora can be found in the crab with HPND, and the detected microbial taxa decreased, whereas the prevalence of Spiroplasma eriocheiris significantly increased in the hepatopancreatic flora of crabs with typical symptoms of HPND, and the relative abundances of the virus and microsporidia in crabs with HPND were very low and did not increase with disease progression. The differentially-expressed genes (DEGs) in hepatopancreatic flora between crabs with and without HPND were enriched ribosome, retinol metabolism, and biosynthesis of unsaturated fatty acid KEGG pathways. These results suggested that an imbalance of hepatopancreatic flora was associated with crab HPND, and the enriched pathways of DEGs were associated with the pathological mechanism of HPND. Hepatopancreas necrosis disease (HPND) of the Chinese mitten crab Eriocheir sinensis causes huge economic loss in China. However, the pathogenic factors and pathogenesis are still a matter of dissension. To search for potential pathogens, the hepatopancreatic flora of diseased crabs with mild symptoms, diseased crabs with severe symptoms, and crabs without visible symptoms were investigated using metatranscriptomics sequencing. The prevalence of Absidia glauca and Candidatus Synechococcus spongiarum decreased, whereas the prevalence of Spiroplasma eriocheiris increased in the hepatopancreatic flora of crabs with HPND. Homologous sequences of 34 viral species and 4 Microsporidian species were found in the crab hepatopancreas without any significant differences between crabs with and without HPND. Moreover, DEGs in the hepatopancreatic flora between crabs with severe symptoms and without visible symptoms were enriched in the ribosome, retinol metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism—cytochrome P450, biosynthesis of unsaturated fatty acids, and other glycan degradation. Moreover, the relative abundance of functions of DEDs in the hepatopancreatic flora changed with the pathogenesis process. These results suggested that imbalance of hepatopancreatic flora was associated with crab HPND. The identified DEGs were perhaps involved in the pathological mechanism of HPND; nonetheless, HPND did not occur due to virus or microsporidia infection. [ABSTRACT FROM AUTHOR]

A novel fowl adenovirus 4 (FAdV-4) has caused significant economic losses to the poultry industry in China since 2015. We established an easy-to-use reverse genetics system for modification of the whole right and partial left ends of the novel FAdV-4 genome, which worked through cell-free reactions of restriction digestion and Gibson assembly. Three recombinant viruses were constructed to test the assumption that species-specific viral genes of ORF4 and ORF19A might be responsible for the enhanced virulence: viral genes of ORF1, ORF1b and ORF2 were replaced with GFP to generate FAdV4-GFP, ORF4 was replaced with mCherry in FAdV4-GFP to generate FAdV4-GX4C, and ORF19A was deleted in FAdV4-GFP to generate FAdV4-CX19A. Deletion of ORF4 made FAdV4-GX4C form smaller plaques while ORF19A deletion made FAdV4-CX19A form larger ones on chicken LMH cells. Coding sequence (CDS) replacement with reporter mCherry demonstrated that ORF4 had a weak promoter. Survival analysis showed that FAdV4-CX19A-infected chicken embryos survived one more day than FAdV4-GFP- or FAdV4-GX4C-infected ones. The results illustrated that ORF4 and ORF19A were non-essential genes for FAdV-4 replication although deletion of either gene influenced virus growth. This work would help function study of genes on the right end of FAdV-4 genome and facilitate development of attenuated vaccines. [ABSTRACT FROM AUTHOR]

The article discusses a study aimed at determining the circulation of Hepatitis E virus (HEV) strains among yellow cattle (Bos taurus) in Shandong Province, China. In the study, blood samples from yellow cattle of local breeds as well serum samples from domestic sheep, dogs and chickens were examined for total antibodies against HEV. The study indicated the occurrence of HEV infection in yellow cattle, suggesting their role as a reservoir of HEV.

The solvent-free selective hydrogenation of nitroaromatics to azoxy compounds is highly important, yet challenging. Herein, we report an efficient strategy to construct individually dispersed Co atoms decorated on niobium pentaoxide nanomeshes with unique geometric and electronic properties. The use of this supported Co single atom catalysts in the selective hydrogenation of nitrobenzene to azoxybenzene results in high catalytic activity and selectivity, with 99% selectivity and 99% conversion within 0.5 h. Remarkably, it delivers an exceptionally high turnover frequency of 40377 h–1, which is amongst similar state-of-the-art catalysts. In addition, it demonstrates remarkable recyclability, reaction scalability, and wide substrate scope. Density functional theory calculations reveal that the catalytic activity and selectivity are significantly promoted by the unique electronic properties and strong electronic metal-support interaction in Co1/Nb2O5. The absence of precious metals, toxic solvents, and reagents makes this catalyst more appealing for synthesizing azoxy compounds from nitroaromatics. Our findings suggest the great potential of this strategy to access single atom catalysts with boosted activity and selectivity, thus offering blueprints for the design of nanomaterials for organocatalysis. Single atom catalysts can endow exceptional activity and selectively. Here, the authors report a single atom Co catalyst and reveal the importance of geometric and electronic properties for synthesizing azoxy compounds under solvent-free conditions. [ABSTRACT FROM AUTHOR]

Background: Persons with chronic hepatitis B (CHB) infection were reported to suffer severe disease after hepatitis E virus (HEV) superinfection, but the studies regarding HEV seroprevalence in this population were limited. A recent study in Vietnam found higher HEV seroprevalence among CHB patients compared with healthy controls.Methods: A community-based case-control study was conducted in two counties of Shandong province, China, where hepatitis E incidence was at the highest (Rushan) and lowest (Zhangqiu) in the province based on data from routine public health surveillance. Four townships were selected randomly from each county and all residents in these townships were tested for hepatitis B surface antigen (HBsAg). Those tested positive for HBsAg (CHB group) and the 1:1 age and sex-matched HBsAg-negative residents (control group) were included. Anti-HEV IgM and IgG were tested and positive rates of IgG and IgM were compared between the CHB group and the control group.Results: In total, 2048 CHB participants and 2054 controls were included in the study. In the CHB group, HEV IgG seroprevalence was 9.16% (95% CI: 7.47-11.09) in Zhangqiue and 38.06% (95% CI: 35.07-41.19) in Rushan (P < 0.001); the corresponding rates of IgM were 0.1% (95% CI: 0.002-0.54) and 1.57% (95% CI: 0.90-2.53), respectively (P < 0.001). HEV IgG seroprevalence was similar between CHB group and the control group in both counties (P = 0.21, P = 0.47, respectively) and the same results were found for the positive rate of IgM (P = 0.103, P = 0.262, respectively). Multivariable analysis showed the status of HBsAg was not independently associated with the status of anti-HEV IgG in either Zhangqiu or Rushan [P = 0.187, OR = 1.23(95% CI: 0.90, 1.68); P = 0.609, OR = 1.05 (95% CI: 0.87, 1.26)].Conclusions: The seroprevalence of HEV varies greatly in different geographic areas, but the seroprevalence is similar between populations with and without CHB. CHB patients residing in high HEV endemic areas might be at higher risk for HBV-HEV superinfection. [ABSTRACT FROM AUTHOR]

Bacillus strains are widely distributed in terrestrial and marine environments, and some of them are used as biocontrol organisms for their biofilm-formation ability. In Bacillus subtilis, biofilm formation is fine-tuned by a complex network, a clear understanding of which still requires study. In bacteria, tmRNA, encoded by the ssrA gene, catalyzes trans-translation that can rescue ribosomes stalled on mRNA transcripts lacking a functional stop codon. tmRNA also affects physiological bioprocesses in some bacteria. In this study, we constructed a ssrA mutant in B. subtilis and found that the biofilm formation in the ssrA mutant was largely impaired. Moreover, we isolated a biofilm-formation suppressor of ssrA, in which the biofilm formation was restored to a level even stronger than that in the wild type. We further performed RNAseq assays with the wild type, ssrA mutant, and suppressor of ssrA for comparisons of their transcriptomes. By analyzing the transcriptomic data, we predicted the possible functions of some differentially expressed genes (DEGs) in the tmRNA regulation of biofilm formation in B. subtilis. Finally, we found that the overexpression of two DEGs, acoA and yhjR, could restore the biofilm formation in the ssrA mutant, indicating that AcoA and YhjR were immediate regulators involved in the tmRNA regulatory web controlling biofilm formation in B. subtilis. Our data can improve the knowledge about the molecular network involved in Bacillus biofilm formation and provide new targets for manipulation of Bacillus biofilms for future investigation. [ABSTRACT FROM AUTHOR]

To realize the effective positioning in urban canyons, an enhanced map-aided Global Positioning System (GPS)/three-dimensional (3D) reduced inertial sensor system (RISS) tightly combined positioning strategy is proposed. First, the 3D RISS is only based on the built-in controller area network (CAN). CAN bus sensor without additional sensors is first constructed to lower the cost. Then, a simple but effective enhanced map is created to assist positioning. Based on the map, a Kalman filtering (KF) tightly coupled method is proposed to fuse the 3D RISS with GPS information and to achieve the preliminary positioning. In KF-based preliminary positioning method, a simply observation noise variance optimization algorithm based on 2D enhanced map is proposed to improve KF method. In this algorithm, the value of the observation noise variance matrix is determined only according to the building plane information which is contained in the enhanced map. Further, a multiweight map matching algorithm is proposed for optimizing the initial positioning results. In this algorithm, factors such as distance, direction, road network topology, and lane change are considered and applied to map matching to further increase the positioning performance and form the final positioning results. Finally, the effectiveness of the strategy is proved by field test. The results show that this method has better accuracy and reliability than the conventional method. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) patients exhibit deficits in oculomotor behavior, yet the results are inconsistent across studies. In addition, how these results are associated with clinical symptoms is unclear, especially in China. Methods: We designed a case-control study in China including 37 PD patients and 39 controls. Clinical manifestations in PD patients were recorded. Oculomotor performance was measured by a video-based eye tracker system. Results: We found that six oculomotor parameters, including fixation stability, saccadic latency, smooth pursuit gain, saccade frequency, viewing range, and saccade frequency during free-viewing context, were significantly different in PD patients and control group. Combining application of these six parameters could improve diagnostic accuracy to over 90%. Moreover, pursuit gain was significantly associated with PD duration, UPDRS III, in PD patients. Saccade latency was significantly associated with PD duration, Berg balance score, RBD score, and Total LEDD in PD patients. Conclusions: PD patients commonly exhibit oculomotor deficits in multiple behavioral contexts, which are associated with both motor and non-motor symptoms. Oculomotor test may provide a valuable tool for the clinical assessment of PD. [ABSTRACT FROM AUTHOR]