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In our previous work, a microbial consortium GF-20 (Qinggeer et al., 2016) was enriched from compost habitats and adapted to efficiently and stably degrade corn stover under low temperatures. While the main microorganism and degradation-related functions and degradation-related coding enzyme genes of GF-20 were not clear. Therefore, the current study used the metagenomic to decipher the systematic and functional contexts within such microbial consortium under low temperatures. The results showed that the dominant functional microbials in GF-20 consortium were bacteria. The dominant phylums in GF-20 consortium were Proteobacteria (62.84%) and Bacteroidetes (10.24%). The dominant genus was Pseudomonas (50.84%), followed by Dysgonomonas (5.86%), Achromobacter (4.94%), Stenotrophomonas (3.67%) and Flavobacterium (2.04%). The metabolism was mainly composed of carbohydrate metabolism and amino acid metabolism, and included signal transduction, cell transport and other metabolic modes. The functional genes encoded were mainly distributed in glycosidolytic enzyme genes, and the functional enzymes were β-glucosidase, acetyl-CoA, pyruvate dehydrogenase and galactosidase. The GF-20 microbial consortium degraded the cellulose in corn stover primarily by β-glucosidase and endoglucanase, which were produced by 12 genera of microorganisms. The hemicellulose synergistic effect was produced by 15 genera of microorganisms including xylanase, xyloglucanase, mannolanase and branching enzyme.

Innate immunity represents one of the main host responses to viral infection.1–3 STING (Stimulator of interferon genes), a crucial immune adapter functioning in host cells, mediates cGAS (Cyclic GMP-AMP Synthase) sensing of exogenous and endogenous DNA fragments and generates innate immune responses.4 Whether STING activation was involved in infection and replication of enterovirus remains largely unknown. In the present study, we discovered that human enterovirus A71 (EV-A71) infection triggered STING activation in a cGAS dependent manner. EV-A71 infection caused mitochondrial damage and the discharge of mitochondrial DNA into the cytosol of infected cells. However, during EV-A71 infection, cGAS-STING activation was attenuated. EV-A71 proteins were screened and the viral protease 2Apro had the greatest capacity to inhibit cGAS-STING activation. We identified TRAF3 as an important factor during STING activation and as a target of 2Apro. Supplement of TRAF3 rescued cGAS-STING activation suppression by 2Apro. TRAF3 supported STING activation mediated TBK1 phosphorylation. Moreover, we found that 2Apro protease activity was essential for inhibiting STING activation. Furthermore, EV-D68 and CV-A16 infection also triggered STING activation. The viral protease 2Apro from EV-D68 and CV-A16 also had the ability to inhibit STING activation. As STING activation prior to EV-A71 infection generated cellular resistance to EV-A71 replication, blocking EV-A71-mediated STING suppression represents a new anti-viral target.

China is known as one of the most diverse centres of wild Iris resources in the world, there are 60 species, 13 varieties, and five forms distributed in southwest, northwest, and northeast China. The goal of this study was to describe the distribution, collection, and evaluation of Iris species collected in southwest China. Wild populations were identified and classified into 23 species, two varieties, and one form based on their morphological characteristics. We discovered some species with new distribution and characteristics. Furthermore, we also used the analytical hierarchy process (AHP) method with 16 indicator points to evaluate the collected Iris resources based on their ornamental value, utilization potential, and ecological adaptability. The results showed that I. pseudacorus, I. delavayi, I. germanica, I. wilsonii, I. sibirica, and I. tectorum had excellent ornamental characters and best suited for sustained exploitation. This research also provided a good theoretical guidance and an important reference value for the application of Iris plants in landscaping and provided suggestions for the conservation and utilization of wild Iris resources.

To systematically explore and analyze the microbial composition and function of microbial consortium M44 with straw degradation in the process of subculture at low temperature. In this study, straw degradation characteristics of samples in different culture stages were determined. MiSeq high-throughput sequencing technology was used to analyze the evolution of community structure and its relationship with degradation characteristics of microbial consortium in different culture periods, and the PICRUSt function prediction analysis was performed. The results showed that straw degradation rate, endoglucanase activity, and filter paper enzyme activity of M44 generally decreased with increasing culture algebra. The activities of xylanase, laccase, and lignin peroxidase, as well as VFA content, showing a single-peak curve change with first an increase and then decrease. In the process of subculture, Proteobacteria, Bacteroidetes, and Firmicutes were dominant in different culture stages. Pseudomonas, Flavobacterium, Devosia, Brevundimonas, Trichococcus, Acinetobacter, Dysgonomonas, and Rhizobium were functional bacteria in different culture stages. It was found by PICRUSt function prediction that the functions were concentrated in amino acid transport and metabolism, carbohydrate transship and metabolism related genes, which may contain a large number of fibers and lignin degrading enzyme genes. In this study, the microbial community succession and the gene function in different culture periods were clarified and provide a theoretical basis for screening and rational utilization of microbial consortia.

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced Interferon beta production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenicity but not E7-Rb binding. HPV18 E7, severe acute respiratory syndrome coronavirus-2 open reading frame 3a, human immunodeficiency virus-2 viral protein X, and Kaposi's sarcoma-associated herpesvirus KSHV viral interferon regulatory factor 1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.

Recognizing aberrant cytoplasmic double-stranded DNA and stimulating innate immunity is essential for the host's defense against viruses and tumors. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that synthesizes the second messenger 2'3'-cGAMP and subsequently activates stimulator of interferon genes (STING)-mediated activation of TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) and the production of type I interferon (IFN-I). Both the cGAS-STING-mediated IFN-I antiviral defense and the countermeasures developed by diverse viruses have been extensively studied. However, recent studies have revealed a convergent evolutionary feature of severe acute respiratory syndrome coronavirus 2 and human immunodeficiency virus (HIV) viral proteins in terms of the selective regulation of cGAS-STING-mediated nuclear factor-κB (NF-κB) signaling without any effect on cGAS-STING-mediated TBK1/IRF3 activation and IFN production. The potential beneficial effect of this cGAS-STING-mediated, NF-κB-dependent antiviral effect, and the possible detrimental effect of IFN-I in the pathogenesis of coronavirus disease 2019 and HIV infection deserve more attention and future investigation.

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity is essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-Type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral evasion of STING-triggered autophagy-mediated antiviral function are scarce. In the present study, we have discovered that SARS-CoV-2 ORF3a is a unique viral protein that can interact with STING and disrupt the STING-LC3 interaction, thus blocking cGAS-STING-induced autophagy but not IRF3-Type I IFN induction. This novel function of ORF3a, distinct from targeting autophagosome-lysosome fusion, is a selective inhibition of STING-triggered autophagy to facilitate viral replication. We have also found that activation of bat STING can induce autophagy and antiviral activity despite its defect in IFN induction. Furthermore, ORF3a from bat coronaviruses can block bat STING-triggered autophagy and antiviral function. Interestingly, the ability to inhibit STING-induced autophagy appears to be an acquired function of SARS-CoV-2 ORF3a, since SARS-CoV ORF3a lacks this function. Taken together, these discoveries identify ORF3a as a potential target for intervention against COVID-19.

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.

This study selected Dendrobium officinale protocorms as the experimental material and used different light-quality treatments and calcium signalling inhibitors to explore the mechanism of the biological response of calcium to light quality. The results indicate that a 1:3 red:blue (R:B) light ratio promotes the accumulation of biomass and polysaccharides in the protocorm. Nevertheless, this effect can be entirely counteracted by calmodulin (CaM) inhibitors and calcium ion-chelating agents. The possible mechanisms of this effect are as follows: (1) The Ca2+-CaM signal-regulated photosynthetic apparatus is improved by the R:B 1:3 light, increasing the CaM content and Ca2+-ATPase activity. Thus, R:B 1:3 light increases the development of the photosynthetic apparatus in the D. officinale protocorm, enhances its photosynthetic productivity, and promotes the activities of sucrose phosphatase; accordingly, biomass and sucrose accumulation increase. (2) R:B 1:3 light enhances Ca2+-CaM signalling and regulates glycometabolic processes to promote the activities of sucrose synthase, thus increasing fructose and glucose levels and providing sufficient synthetic precursors to promote polysaccharide production.

Purpose: FKBP4 is a member of the immunophilin protein family, which plays a role in immunoregulation and basic cellular processes involving protein folding and trafficking associated with HSP90. However, the relationship between abnormal expression of FKBP4 and clinical outcome in luminal A subtype breast cancer (LABC) patients remains to be elucidated. Methods: Oncomine, bc-GenExMiner and HPA database were used for data mining and analyzing FKBP4 and its co-expressed genes. GEPIA database was used for screening co-expressed genes of FKBP4. Results: For the first time, we found that higher FKBP4 expression correlated with LABC patients and worse survival. Moreover, the upregulated co-expressed genes of FKBP4 were assessed to be significantly correlated with worse survival in LABC, and might be involved in the biological role of FKBP4. Conclusion: The expression status of FKBP4 is a significant prognostic indicator and a potential drug target for LABC.

Innate immunity is the first line of host defence against pathogens. Suppression of innate immune responses is essential for the survival of all viruses. However, the interplay between innate immunity and HIV/SIV is only poorly characterized. We have discovered Vpx as a novel inhibitor of innate immune activation that associates with STING signalosomes and interferes with the nuclear translocation of NF-κB and the induction of innate immune genes. This new function of Vpx could be separated from its role in mediating degradation of the antiviral factor SAMHD1, and is conserved among diverse HIV-2/SIV Vpx. Vpx selectively suppressed cGAS-STING-mediated nuclear factor-κB signalling. Furthermore, Vpx and Vpr had complementary activities against cGAS-STING activity. Since SIVMAC lacking both Vpx and Vpr was less pathogenic than SIV deficient for Vpr or Vpx alone, suppression of innate immunity by HIV/SIV is probably a key pathogenic determinant, making it a promising target for intervention.

Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) is an effective and widely used method in gene expression studies. Selection of appropriate reference genes is key t...

The human adenovirus oncoprotein E4orf6 hijacks intracellular Cullin 5-based E3 ubiquitin ligases (CRL5s) to induce the degradation of host proteins, including p53, that impede efficient viral replication. The complex also relies on another viral protein, E1B55K, to recruit substrates for ubiquitination. However, the determinants of adenoviral E4orf6-CRL5 E3 ligase-mediated p53 degradation in the scaffolding protein Cullin5 remain rarely investigated. Here, we demonstrated that the viral protein E4orf6 triggered relocalization of the Cullin5 protein from the cytoplasm to the nucleus and induced activation of the CRL5 E3 ligase via facilitating neddylation. The expression of the deneddylase SENP8/Den1 was significantly downregulated by E4orf6. We then identified SENP8 as a natural restriction factor for E4orf6-induced p53 degradation. Furthermore, our results indicated that the NEDD8-conjugating E2 enzyme UBE2M was essential for E4orf6-mediated p53 degradation and that its dominant negative mutant UBE2M C111S dramatically blocked E4orf6 functions. The Nedd8-activating enzyme inhibitor MLN4924 decreased E4orf6-induced neddylation of the cullin5 protein and subsequently suppressed p53 degradation. Collectively, our findings illuminate the strategy by which this viral oncoprotein specifically utilizes the neddylation pathway to activate host CRL E3 ligases to degrade host restriction factors. Disrupting this post-translational modification is an attractive pharmacological intervention against human adenoviruses.

Human immunodeficiency virus (HIV) actively modulates the protein stability of host cells to optimize viral replication. To systematically examine this modulation in HIV infection, we used isobaric tag-based mass spectrometry to quantify changes in the abundance of over 14,000 proteins during HIV-1 infection of human primary CD4+ T cells. We identified P-selectin glycoprotein ligand 1 (PSGL-1) as an HIV-1 restriction factor downregulated by HIV-1 Vpu, which binds to PSGL-1 and induces its ubiquitination and degradation through the ubiquitin ligase SCFβ-TrCP2. PSGL-1 is induced by interferon-γ in activated CD4+ T cells to inhibit HIV-1 reverse transcription and potently block viral infectivity by incorporating in progeny virions. This infectivity block is antagonized by Vpu via PSGL-1 degradation. We further show that PSGL-1 knockdown can significantly abolish the anti-HIV activity of interferon-γ in primary CD4+ T cells. Our study identifies an HIV restriction factor and a key mediator of interferon-γ's anti-HIV activity.

Nitrous acid (HONO) can produce hydroxyl radicals (OH) by photolysis and plays an important role in atmospheric photochemistry. Over the years, high concentrations of HONO have been observed in the Pearl River Delta region (PRD) of China, which may be one reason for the elevated atmospheric oxidation capacity. A comprehensive atmospheric observation campaign was conducted at an urban site in Guangzhou from 27 September to 9 November 2018. During the period, HONO was measured from 0.02 to 4.43 ppbv with an average of 0.74 ± 0.70 ppbv. The emission ratios (HONO/NOx) of 0.9 ± 0.4 % were derived from 11 fresh plumes. The primary emission rates of HONO at night were calculated to be between 0.04 ± 0.02 ppbv h−1 and 0.30 ± 0.15 ppbv h−1 based on a high-resolution emission inventory. The HONO formation rate by the homogeneous reaction of OH + NO at night was 0.26 ± 0.08 ppbv h−1, which can be seen as secondary results from primary emission. They were both much higher than the increase rate of HONO (0.02 ppbv h−1) during night. Soil emission rate of HONO at night was calculated to be 0.019 ± 0.001 ppbv h−1. Assuming dry deposition as the dominant removal process of HONO at night, and a deposition velocity of at least ~2.5 cm s−1 is required to balance the direct emissions and OH + NO reaction. Correlation analysis shows that NH3 and relative humidity (RH) may participate in the heterogeneous transformation from NO2 to HONO at night. In the daytime, the average primary emission Pemis was 0.12 ± 0.01 ppbv h−1, and the homogeneous reaction POH + NO was 0.79 ± 0.61 ppbv h−1, larger than the unknown sources PUnknown (0.65 ± 0.46 ppbv h−1). These results suggest primary emissions as a key factor affecting HONO at our site, both during daytime and nighttime. Similar to previous studies, the daytime unknown source of HONO, PUnknown, appeared to be related to the photo-enhanced conversion of NO2. The daytime average OH production rates by photolysis of HONO was 3.7 × 106 cm−3 s−1, lower than that from O1D + H2O at 4.9 × 106 cm−3 s−1. Simulations of OH and O3 with the Master Chemical Mechanism (MCM) box model suggested strong enhancement effect of HONO on OH and O3 by 59 % and 68.8 %, respectively, showing a remarkable contribution of HONO to the atmospheric oxidation in the fall season of Guangzhou.

Nitrous acid (HONO) can produce hydroxyl radicals (OH) by photolysis and plays an important role in atmospheric photochemistry. Over the years, high concentrations of HONO have been found in the Pearl River Delta region (PRD), which may be one of the reasons for the high atmospheric oxidation capacity. A comprehensive atmospheric observation was conducted at an urban site in Guangzhou from 27 September to 9 November 2018. During the period, HONO ranged from 0.02 to 4.43 ppbv with an average of 0.74±0.70 ppbv. The combustion emission ratio (HONO/NOx) of 0.9±0.4% was derived from 11 fresh plumes. The primary emission rate of HONO during night was calculated with the emission source inventory data to be between 0.04±0.02 and 0.30±0.15 ppbv/h. And the HONO produced by the homogeneous reaction of OH+NO at night was 0.26±0.08 ppbv/h, which can be seemed as secondary results from primary emission. They were both much higher than the increase rate of HONO (0.02 ppbv/h) during night. Soil emission rate of HONO at night was calculated to be 0.019±0.0003 ppbv/h. Deposition was the dominant removal process of HONO during night, and a deposition rate of at least 2.5 cm/s is required to balance the direct emissions and OH+NO reaction. Correlation analysis shows that NH3 and relative humidity (RH) may participate in the heterogeneous transformation from NO2 to HONO during night. In the daytime, the average primary emission Pemis was 0.12±0.01 ppbv/h, and the homogeneous reaction POH+NO was 0.79±0.61 ppbv/h, which was even larger than the unknown sources PUnknown (0.65±0.46 ppbv/h). The results showed that the direct and indirect contributions of primary emission to HONO are great at the site, both during daytime and nighttime. Similar to previous studies, PUnknown was suggested to be related to the photo-enhanced reaction of NO2. The mean OH production rates by photolysis of HONO and O3 were 3.7×106 cm-3·s-1 and 4.9×106 cm-3·s-1, respectively. We further studied the impact of HONO on the atmospheric oxidation by a Master Chemical Mechanism (MCM) box model. When constraining observed HONO in the model, OH and O3 increased 59% and 68.8% respectively, showing a remarkable contribution of HONO to the atmospheric oxidation of Guangzhou.

Plumbago auriculata Lam. is an ornamental plant native to South Africa and widely cultivated in China, but the cultivated plants are dominated by a single variety. The development of new varieties is of great commercial interest, and genetic diversity is the foundation of breeding programs. In this study, 85 progenies were obtained by crosses between Plumbago auriculata and Plumbago auriculata f. alba. The genetic diversity of these hybrids was evaluated using horticultural traits and ISSR and SRAP markers. Of the 25 horticultural traits evaluated, the largest variation was found in the beginning of the blooming period, and sepal length was the least variable trait. Correlation analysis showed that the wider the plant, the greater the number of inflorescences and the earlier the flowering. Seven factors explained 65.171% of the total variance; the first factor was leaf morphology, and the second factor was flower morphology. The genetic diversity of the 85 progenies was analyzed using seven pairs of SRAP primers and eight ISSR primers. The average number of effective alleles for 85 hybrids was 1.638, and the average Shannon index value was 0.507. The Nei genetic similarity coefficient indicated that the similarity between WLBS and WSBL was the highest, while that between BLWS and BSWL was the lowest. Analysis of molecular variance (AMOVA) indicated that the main variation was within populations. Cluster analysis based on horticultural traits and molecular markers divided all progenies into seven and five groups, respectively, and there were obvious differences between the two clusters. In this study, we created intermediate materials for future breeding, taking the first step in the cross-breeding of P. auriculata.

Human endogenous retroviruses (HERVs) are the remnants of ancient retroviruses that infected human germline cells and became integrated into the human genome millions of years ago. Although most of these sequences are incomplete and silent, several potential pathological roles of HERVs have been observed in numerous diseases, such as multiple sclerosis and rheumatoid arthritis, and especially cancer, including breast cancer and pancreatic carcinoma. The present review investigates the expression signatures and complex regulatory mechanisms of HERVs in cancer. The long terminal repeats-driven transcriptional initiation of HERVs are regulated by transcription factors (such as Sp3) and epigenetic modifications (such as DNA methylation), and are influenced by environmental factors (such as ultraviolet radiation). In addition, this review focuses on the dual opposing effects of HERVs in cancer. HERVs can suppress cancer via immune activation; however, they can also promote cancer. HERV env gene serves a prime role in promoting carcinogenesis in certain malignant tumors, including breast cancer, pancreatic cancer, germ cell tumors, leukemia and Kaposi's sarcoma. Also, HERV ENV proteins can promote cancer via immune suppression. Targeting ENV proteins is a potential future antitumor treatment modality.

Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated. Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD. Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.

Gastric cancer (GC) is the third most common cause of cancer-related death in the word. Immunotherapy is a promising treatment of cancer. However, it is unclear which GC subpopulation would benefit most from immunotherapy and it is necessary to develop effective biomarkers for predicting immunotherapy response. Nicotinamide N-methyltransferase (NNMT) is a metabolic regulator of cancer-associated fibroblast (CAF) differentiation and cancer progression. In this study, we explored the correlations of NNMT to tumor-infiltrating immune cells (TIICs) and immune marker sets in The Cancer Genome Atlas Stomach Adenocarcinoma STAD (TCGA-STAD). Subsequently, we screened the NNMT correlated genes and performed the enrichment analysis of these genes. We eventually predicted the 19 most potential small-molecule drugs using the connectivity map (CMap) and Comparative Toxicogenomics Database (CTD). Also, nadolol, tranexamic acid, felbinac and dapsone were considered the four most promising drugs for GC. In summary, NNMT can be used as a prognostic biomarker that reflect immune infiltration level and a novel therapeutic target in GC.

Tenofovir and entecavir are currently designated as the preferred oral antiviral drugs for chronic hepatitis B. However, only less than 40% of patients can achieve HBeAg seroconversion. We aim at investigating the role of intestinal microbiome in HBeAg seroconversion induced by oral antiviral therapy and describe multi-omics characteristics of HBeAg seroconversion associated intestinal flora. In this study, we prospectively collected fecal samples at baseline from the patients with HBeAg positive chronic hepatitis B who would have oral antiviral therapy. 16S rDNA sequencing and metabolomics were performed. We identified HBeAg seroconversion-related microbial signature and constructed prediction model for HBeAg seroconversion. Thirty-seven of these subjects achieved HBeAg seroconversion within 156 weeks after the initiation of oral antiviral therapy, while 41 subjects remained HBeAg positive even after over 156 weeks of therapy. A computational statistical and machine learning approach allowed us to identify a microbial signature for HBeAg seroconversion. Using random forest method, we further constructed a classifier based on the microbial signature, with area under curve being 0.749 for the test set. Patients who achieved HBeAg seroconversion tended to have lower abundance of certain fecal metabolites such as essential amino acids, and several dipeptides. By analyzing the fecal microbiota from the patients with and without HBeAg seroconversion, we showed intestinal microbiome play a critical role in HBeAg seroconversion induced by oral antiviral therapy. We also identified intestinal microbial signature that is associated with HBeAg seroconversion after oral antiviral therapy.

Mastoscopic axillary lymph node dissection (MALND) is a currently used and safe surgical treatment option for breast cancer. However, the extensive application of MALND is still debatable because of the use of conventional axillary lymph node dissection (CALND). Therefore, in the current study, we aimed to compare the efficacy and safety of MALND and CALND for obtaining evidence-based conclusions about the short-term and long-term outcomes of MALND for patients with breast cancer. PubMed, Web of Science, Cochrane Library, and CNKI were comprehensively searched for articles published between January 1998 and January 2019. Then Newcastle-Ottawa scale was used for quality assessment. The Review Manager software version 5.0 was utilized for generating forest maps and funnel plots. Twelve studies including 2157 patients were selected for the meta-analysis. There were no significant differences in the number of lymph node dissections, tumor recurrence rate, axillary drainage, postoperative hospitalization time, and tumor size between the MALND and CALND groups ( P > .05). In the MALND group, the surgery time was longer, while the incidence of intraoperative bleeding was lesser and the duration of drainage was shorter than those in the CALND group ( P < .01). The complications in the MALND group were also fewer than those in the CALND group ( P < .05). The results of the current study showed that MALND is reliable and feasible for breast cancer owing to the lesser incidence of intraoperative bleeding, shorter drainage duration, and lower incidence of complications compared to CALND.

Background Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods FKBP related miRNAs were obtained from miRWalk database. Then, potential lncRNAs, transcription factors as well as mRNAs of screened differentially expressed miRNAs (DE-miRNAs) were analysed by using LncBase v.2, miRGen v3 and miRWalk database. Additionally, differential expression and prognostic analysis of lncRNAs were evaluated using TANRIC database. Next, GO annotation and KEGG pathway analysis were processed using DAVID database. Protein-Protein Interaction (PPI) network was established and hub genes were identified using STRING database. Finally, differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Results Eleven DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. 482 predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top twenty lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients’ overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the toppest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients’ OS. Conclusions In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, thus exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. In the future, much more experiments should be conducted to verify our findings.

Although the host restriction factor APOBEC3G (A3G) has broad spectrum antiviral activity, whether A3G inhibits enterovirus 71 (EV71) has been unclear until now. In this study, we demonstrated for the first time that A3G could inhibit EV71 virus replication. Silencing A3G in H9 cells enhanced EV71 replication, and EV71 replication was lower in H9 cells expressing A3G than in Jurkat cells without A3G expression, indicating that the EV71 inhibition was A3G-specific. Further investigation revealed that A3G inhibited the 5′UTR activity of EV71 by competitively binding to the 5′UTR through its nucleic acid binding activity. This binding impaired the interaction between the 5′UTR and the host protein poly(C)-binding protein 1 (PCBP1), which is required for the synthesis of EV71 viral proteins and RNA. On the other hand, we found that EV71 overcame A3G suppression through its non-structural protein 2C, which induced A3G degradation through the autophagy–lysosome pathway. Our research provides new insights into the interplay mechanisms of A3G and single-stranded positive RNA viruses.

Lilium sargentiae E.H. Wilson (Liliaceae) is an ornamental and economic flowering bulb in China. Unfortunately, due to low natural bulb multiplication rates or long juvenile phases, commercial release of a new genotype may take 10 or even 20 years. In this study, bulbs were expanded in test tubes by adding sucrose, to shorten the duration of the commercial production cycle. Results indicated that when sucrose, with a concentration of 60 g l−1, was supplied to the culture medium, the bulblets could be most effectively induced and expanded. The effect of sucrose on the formation and expansion of L. sargentiae was obvious and dominant. It was not connected to the osmotic potential of sucrose, nor entirely explained by the function of sucrose as an energy and carbon source. We used sugar analogues in the culturing of explanted materials to research the effect of sucrose-specific signaling on bulblet formation and expansion. Results showed that exogenous 3-O-methyl glucose could not induce and expand test-tube bulblets, which was similar to mannose, whereas isomaltulose could generate similar results to those obtained with sucrose. The results further indicated that the specific signalling of sucrose could be responsible for the effect on bulblets formation and swelling. We used the exclusion method to confirm above results and hypothesis, and observed that only a small part of sucrose was transformed by cell wall invertase and entered the cells through hexose transporters, playing a certain effect on bulbelt growth and development through hexose or hexose signaling systems. Overall, the effect of sucrose on bulblet induction and swelling could be explained by sucrose-specific signaling. Furthermore, this effect has a direct correlation with the sucrose-specific vector.

Phylogenetic relationships among the six Iris subgenera were reconstructed by chloroplast trnL-F sequences data using maximum likelihood. The entire matrix of aligned bases analyzed includes 1043 characters and the length of all sequences varied from 747 bp to 893 bp, and mutation sites accounted for 18.79% of the total length. The cluster analysis results accorded well with the subgeneric classification of Chinese Iris species. Results suggested rhizomes and sepals lacking ornament are ancestral characters, and subg. Xyridion and subg. Limniris are more primordial than another four subgenera. Subgenus Nepalensis and subg. Xyridion were resolved as monophyletic.

The molecular orientation of thermal ensemble induced by two-color slow turn-on and rapid turn-off laser pulses is theoretically studied. The reason for the decrease of degree of orientation with the increase of temperature is explained. Further, three molecules are taken as models for investigating the influence of temperature and molecular parameters on molecular orientation. Interestingly, as the temperature increases, the order of the degree of orientation among the three molecules is reversed. Finally, the effects of peak intensity, rise time, and fall time of laser field on this scheme are discussed.

In order to simulate aircraft evacuation process vividly in the 90s certification trials, the influence elements of occupant evacuation during aircraft emergency need to be analyzed. These elements were achieved as evacuee element, aircraft type element, and aircraft external environment element. The three elements were consisted of several factors respectively. In evacuee element contained individual physiological factor and psychological factor, the diversities of individual behavior were discussed in the three escape stages. These factors were applied to cellular automata theory. Then, the cabin environment model was established according to the characteristics of occupant movement during emergency evacuation, and the non-wing exit escape time model was built through a self-designed jumping slide experiment. This research took B737-800 as the experiment prototype and developed the simulation software (EES-air) based on the above models and the existing research results. Three distribution plans of occupant evacuation in cabin area were designed in the simulation software. The simulation results were analyzed from the evacuation efficiency, the number of escape at different time, and the available exit utilization rate. The research results could provide strategy and guidance to emergency evacuation and emergency training for airline.

Protein phosphorylation/dephosphorylation is a major signalling event induced by abiotic stresses in plants. Sucrose nonfermenting 1-related protein kinase 2 (SnRK2) plays important roles in response to osmotic stress. In the present study, four SnRK2s, TpSnRK2.1/3/7/8, were cloned and characterized from Triticum polonicum L. (dwarf Polish wheat, DPW, AABB). All of these were individually located on 2AL, 1AL, 2AL, and 5BL. Two spliced isoforms of TpSnRK2.8 (TpSnRK2.8a and TpSnRK2.8b) were observed. TpSnRK2.1 and TpSnRK2.3 were classified into the group II; TpSnRK2.7 was classified into the group I; and TpSnRK2.8a/b were classified into the group III. Expression patterns revealed that TpSnRK2.1 responded to cold, NaCl, polyethylene glycol (PEG), and abscisic acid (ABA) in both roots and leaves; TpSnRK2.3 was strongly regulated by cold, NaCl, and ABA in both roots and leaves, and by PEG in roots; TpSnRK2.7 was induced by NaCl and PEG in roots, but was not activated by ABA; and TpSnRK2.8s were significantly activated by cold, NaCl, PEG, and ABA in both roots and leaves. From the above results, we inferred that TpSnRK2.1/3/8 may participate in the responses to environmental stresses in ABA-dependent signal transduction pathway but TpSnRK2.7 is possibly involved in responses to environmental stresses in a non-ABA-dependent manner. They play important roles in specific tissues under different stresses.

Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 are linked with autoimmune diseases such as systemic lupus erythematosus, Aicardi–Goutières syndrome (AGS) and familial chilblain lupus. However, TREX1 mutants competent for DNA exonuclease activity are also linked to AGS. Here, we report a nuclease-independent involvement of TREX1 in preventing the L1 retrotransposon-induced DNA damage response. TREX1 interacted with ORF1p and altered its intracellular localization. Furthermore, TREX1 triggered ORF1p depletion and reduced the L1-mediated nicking of genomic DNA. TREX1 mutants related to AGS were deficient in inducing ORF1p depletion and could not prevent L1-mediated DNA damage. Therefore, our findings not only reveal a new mechanism for TREX1-mediated L1 suppression and uncover a new function for TREX1 in protein destabilization, but they also suggest a novel mechanism for TREX1-mediated suppression of innate immune activation through maintaining genome integrity.

Tetraploid wheat (AABB or AAGG, 2n = 4x = 28) holds an important place in Triticum. It includes two allopolyploid species, Triticum turgidum and Triticum timopheevii. Many problems concerning the phylogenetic relationships among tetraploid wheat species remain unresolved. In this study, sequences data for the nuclear DMC1 gene from 61 accessions of Triticum and Aegilops species, representing diploid and tetraploid species, were used to examine the phylogenetic relationships among tetraploid wheat. Phylogenetic trees were constructed using maximum-likelihood and neighbor-joining approaches, and gene flow and genetic differentiation values were computed. The results indicated that the A genome of tetraploid wheat originated from T. urartu rather than T. monococcum, and Aegilops speltoides was the donor of the B and G genomes. Hulled tetraploid wheat accessions formed a subclade, and naked tetraploid wheat got other subclade, indicating that at least two intermediary subspecies were involved in the evolution of T. turgidum. Triticum turgidum and T. timopheevii might have simultaneously originated from a hybridization events. These results indicated that the DMC1 gene sequences are useful for resolution of the molecular phylogenetic relationships of tetraploid wheat.

Cadmium (Cd) and zinc (Zn) coexist in the environment but interact differently in plants. Cosmos bipinnatus has been potentially considered as a Cd-accumulator. Thus, this study investigated the detoxification mechanism in C. bipinnatus seedlings under Cd, Zn and Cd + Zn stresses. In the present study, the presence of Zn inhibited Cd uptake and translocation, whereas Cd merely hindered Zn uptake. The concentration of Cd in soluble fraction significantly decreased and Cd was bounded to the cell wall in root under Cd + Zn stress. Meanwhile, Zn and Cd mutually decreased their concentrations in the ethanol extractable form (FE) and water extractable form (FW) in roots and shoots. Furthermore, Cd + Zn stress enhanced the activities of superoxide dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.6) compared to Cd stress alone. These results suggested that Zn effectively decreased Cd uptake and translocation, changed their subcellular distributions, regulated their chemical forms composition and increased antioxidative enzyme activities, thereby enhancing the tolerance to Cd in C. bipinnatus. This study physiologically revealed the interactive effect of Cd and Zn on the detoxification mechanism of Cd in C. bipinnatus and provided new information on phytoremediation of the heavy metal contaminated soils.

Background Tumor-infiltrating lymphocytes (TILs) play a critical role in tumor immune surveillance and immune suppression. Understanding tumor infiltrating T cell subset density, location and PD-1/PD-L1 expression might provide insight for the prediction of tumor therapeutic response and clinical outcome. The purpose of this study was to evaluate the expression and localization of CD8, FoxP3, PD-1, and PD-L1 in primary tumor tissues and their effects on prognosis of stage IV M0 locally advanced nasopharyngeal carcinoma (NPC) patients. Methods Sixty NPC patients with stage IV M0 locally advanced disease were treated with definitive chemoradiation. Tumor biopsies from primary lesion were analyzed for the expression and localization of CD8, FoxP3, PD-1, and PD-L1 by immunohistochemistry. Their associations with local disease control and survival of NPC were analyzed. Results The average follow-up time was 43 months (range from 14 to 61 months). High expression of CD8+, FoxP3+, PD-1+ and PD-L1+ was observed in 60, 86.7, 56.7, and 91.7% of patients, respectively. There was no correlation between clinicopathological features and the expression of these immune markers. High PD-1 expression was found to be associated with lower local disease control (5-year LRFS 23.2% vs 96.8%, p

The lentiviral accessory protein Vpx enhances viral replication in macrophages, dendritic cells and resting CD4+ T cells by utilizing the host CRL4-DCAF1 E3 ligase to trigger the degradation of the intrinsic antiviral factor SAMHD1. Distinct from the species-specific recognition of either the N or C-terminus of SAMHD1 by Vpx proteins of different HIV-2 and SIV lineages, Vpx recruits SAMHD1 onto the same CRL4-DCAF1 complex. However, the determinants in DCAF1 that are required for Vpx-mediated SAMHD1 degradation have not been well characterized. Here, we demonstrate that the viral protein Vpx is resistant to suppression by a cellular inhibitor of the CRL4-DCAF1 E3 ligase, Merlin/NF2, through targeting a separate binding region in DCAF1. The Merlin binding-deficient DCAF1 truncation mutant (1-1417) is sufficient for Vpx-CRL4-DCAF1 E3 ligase assembly and SAMHD1 degradation. We found that the carboxyl-terminus ED-rich region (1312-1417) of DCAF1 is required for the nuclear localization of DCAF1 and for the Vpx-DCAF1 interaction. We identified the DCAF1 (1-1311) truncation mutant as a dominant negative mutant of wild-type DCAF1 that inhibits Vpx-mediated SAMHD1 degradation. These results suggest a unique strategy by which Vpx exploits DCAF1 to counteract this host restriction factor.

Exosomes are cell-derived vesicles of 30 to 150 nm that contain diverse proteins, nucleic acids, and lipids. These vesicles facilitate effective intercellular communication and trigger profound environmental changes. In recent years, many studies have identified diverse roles for exosomes in tumor metastasis, a major cause of cancer-related deaths; furthermore, circulating tumor-derived exosomes can drive the initiation and progression of metastasis and determine the specific target organs affected. Fortunately, our growing understanding of exosomes and relevant modification technology have provided new ideas for potential treatment of tumor metastases. Here we review recent advances concerning the role of exosomes in metastasis, focusing on their regulatory mechanisms and therapeutic targeting in advanced cancer.

Interaction between HIV-1 Vif and host factor CBFβ leads to the assembly of the Vif-Cul5-EloB/C ubiquitin ligase (E3 complex). By inducing the formation of E3 complex, Vif depletes host APOBEC3 restriction factors and promotes HIV-1 infection. In addition, Vif is known to arrest host cells at G2/M phase (G2 arrest), benefiting HIV-1 replication and contributing to the depletion of CD4+ T cells. However, whether CBFβ is also involved in Vif-induced cell cycle arrest remains unclear. In the present study, we report that CBFβ is an essential factor for Vif-induced G2 arrest. Reducing endogenous CBFβ expression significantly compromised Vif's potency in cell cycle regulation. In addition, tests with CBFβ and Vif mutants indicated that Vif-CBFβ interaction is crucial for Vif to induce G2 arrest. Furthermore, suppressors against Vif-hijacked E3 complex or proteasome-mediated proteolysis also abolished Vif's ability to cause G2 arrest. In general, our data indicated that Vif induces G2 arrest through depletion of a yet-unknown cellular factor, where the involvement of CBFβ is essential. On the other hand, our data also suggested that, antiviral drugs targeting the Vif-CBFβ interaction have the potential to abolish Vif's ability to cause APOBEC3 degradation as well as G2 arrest in host cells, thus reducing both HIV-1 replication and Vif-induced CD4+ T-cell depletion.

Although human respiratory syncytial virus (RSV) is one of the most common viruses inducing respiratory tract infections in young children and the elderly, the genotype distribution and characteristics of RSV in northeastern China have not been investigated. Here, we identified 25 RSV-A and 8 RSV-B strains from 80 samples of patients with respiratory infections between February 2015 and May 2015. All 25 RSV-A viruses were classified as the ON1 genotype, which rapidly spread and became the dominant genotype in the world since being identified in Ontario (Canada) in December 2010. All eight RSV-B viruses belonged to the BA genotype with a 60-nucleotide duplication, seven of which formed two new genotypes, BA-CCA and BA-CCB. The remaining RSV-B virus clustered with one of the Hangzhou strains belonging to genotype BA11. Construction of a phylogenetic tree and amino acid substitution analysis showed that Changchun ON1 viruses exclusively constituted Lineages 3, 5 and 6, and contained several unique and newly identified amino acid substitutions, including E224G, R244K, L289I, Y297H, and L298P. Selective pressure was also evaluated, and various N and O-glycosylation sites were predicted. This study provides the first genetic analysis of RSV in northeastern China and may facilitate a better understanding of the evolution of this virus locally and globally. J. Med. Virol. 89:222-233, 2017. © 2016 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

Herein, we report a versatile strategy to fabricate three-dimensional melamine sponge (MS)-Au/ceria nanowire (NW) networks to realize in situ continuous reduction of p-nitrophenol in a consecutive flow system. This system has proven to be high activity and stability. The ceria NW networks with large surface area can stabilize tiny Au nanoparticles dispersed on the ceria NWs, which are loaded on the framework of MS by dip-coating, and enhance the synergistic effect between ceria NWs networks and Au nanoparticles, leading to extremely high activity and good stability for catalytic application. The low-cost raw materials and catalyst with high activity and stability may make this three-dimensional MS-Au/ceria NWs composite material promising for continuous catalytic reaction application in industry or other fields.

Primate SAMHD1 proteins are potent inhibitors of viruses, including retroviruses such as HIV-1, HIV-2, and SIV. Vpx, a distinctive viral protein expressed by HIV-2 and some SIVs, induces SAMHD1 degradation by forming a Vpx-DCAF1-based ubiquitin ligase complex. Either the N- or the C-terminus of SAMHD1 is critical for Vpx-induced degradation, depending on the types of SAMHD1 and Vpx proteins. However, it was not fully understood whether other regions of SAMHD1 also contribute to its depletion by Vpx. In the present study, we report that SAMHD1 from chicken (SAMHD1GG) was not degraded by SIVmac Vpx, in contrast with results for human SAMHD1 (SAMHD1HS). Results regarding to SAMHD1HS and SAMHD1GG fusion proteins supported previous findings that the C-terminus of SAMHD1HS is essential for Vpx-induced degradation. Internal domain substitution, however, revealed that the HD domain also contributes to Vpx-mediated SAMHD1 degradation. Interestingly, the HD domain influenced Vpx-mediated SAMHD1 degradation without affecting Vpx-SAMHD1 interaction. Therefore, our findings revealed that factors in addition to Vpx-SAMHD1 binding influence the efficiency of Vpx-mediated SAMHD1 degradation.

Dwarf bamboo Sasa argenteostriata (Regel) E.G. Camus is considered as potential plants for metal phytoremediation in previous filed observations. However, the mechanisms of lead (Pb) detoxification has not been described. The objective of this study was to explore the difference strategies or mechanisms of Pb detoxification in plant tissues. In this regard, four Pb treatments with hydroponics including 0 (control), 300, 600, and 900 mg L−1 were conducted to examine subcellular compartmentalization, Pb accumulation/species and antioxidant-assisted chelation. Our findings showed the retention of Pb by the whip-root system is one of its detoxification mechanisms to avoid damage the shoots. In addition, the cell wall retention is the dominant detoxification strategy of whips, new roots, old roots and new/old stems, while vacuolar compartmentalization is for new/old leaves. Interestingly, four low-mobility/-toxicity Pb species (i.e., FNaCl, FHAc, FHCl and FR) are distributed in roots, whips and stems, while two high-mobility/-toxicity Pb species (FE and FW) in leaves. The conversion of Pb to low-toxicity/-migration is a Pb-detoxification strategy in roots, whips and stems but not in leaves. Besides, the new/old roots and leaves can alleviate Pb damage through the synthesis of non-protein thiol, glutathione and phytochelatins. Among these, phytochelatins play a leading role in the detoxification in new/old roots, while glutathione is in new/old leaves. This study provides the first comprehensive evidence regarding the different strategies for Pb detoxification in dwarf bamboo tissues from physiological to cellular level, supporting that this plant could be rehabilitated for phytoremediation in Pb-contaminated media.

SAMHD1 possesses multiple functions, but whether cellular factors regulate SAMHD1 expression or its function remains not well characterized. Here, by investigating why cultured RD and HEK293T cells show different sensitivity to enterovirus 71 (EV71) infection, we demonstrate that SAMHD1 is a restriction factor for EV71. Importantly, we identify TRIM21, an E3 ubiquitin ligase, as a key regulator of SAMHD1, which specifically interacts and degrades SAMHD1 through the proteasomal pathway. However, TRIM21 has no effect on EV71 replication itself. Moreover, we prove that interferon production stimulated by EV71 infection induces increased TRIM21 and SAMHD1 expression, whereas increasing TRIM21 overrides SAMHD1 inhibition of EV71 in cells and in a neonatal mouse model. TRIM21‐mediated degradation of SAMHD1 also affects SAMHD1‐dependent restriction of HIV‐1 and the regulation of interferon production. We further identify the functional domains in TRIM21 required for SAMHD1 binding and the ubiquitination site K622 in SAMHD1 and show that phosphorylation of SAMHD1 at T592 also blocks EV71 restriction. Our findings illuminate how EV71 overcomes SAMHD1 inhibition via the upregulation of TRIM21., SAMHD1, a well‐studied HIV‐1 restriction factor, counteracts also the hand‐foot‐and‐mouth disease pathogen EV71. Upon infection, the E3 ligase TRIM21 is up‐regulated in an IFN‐dependent manner to induce SAMHD1 degradation and to relieve virus restriction.

Atmospheric volatile organic compounds (VOCs) were measured in an urban area of Guangzhou on July 2016 using an on-line gas chromatography mass spectrometry/fire ion detector. Seventy-three VOCs were detected with an average concentration of (118.83±79.40) μg·m

Nitrous acid (HONO) plays an important role in atmospheric photochemistry processes because its photolysis provides an efficient source of hydroxyl (OH) radicals in the troposphere. However, few studies exist on HONO in nocturnal chemistry processes. Using the observation data of HONO and related parameters for a super site at Guangzhou Jinan University in October 2015, the pollution processes and sources of HONO during nighttime were analyzed in this study. The results showed that the average concentration of HONO was 4.32 μg ·m

Human immunodeficiency virus (HIV) actively modulates the protein stability of host cells to optimize viral replication. To systematically examine this modulation in HIV infection, we used isobaric tag-based mass spectrometry to quantify changes in the abundance of over 14,000 proteins during HIV-1 infection of human primary CD4

Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains. IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

Background Differential microRNA (miRNA) expression profiles in plasma or serum were identified, providing foundation for studying their potentially diagnostic role in colorectal cancer (CRC). Methods We performed S-poly(T) Plus PCR assay to select and validate differentially expressed plasma miRNAs from a sample set including 101 CRC patients, 20 patients with colorectal noncancerous polyps (NCP), and 134 healthy controls. And bioinformatics methods was used to integrated predicted or validated targets of the differentially dysregulated miRNAs and analyzed their overrepresented pathways. Results After the two-phase selection and validation process, we identified a miRNA panel (miR-144-3p, miR-425-5p, and miR-1260b) with high diagnostic efficiency for CRC; the panel distinguished CRC patients from controls with 93.8% sensitivity and 91.3% specificity. Results indicated that the dysregulated miRNAs in CRC were functionally involved in several key cancer-related pathways, such as axonal guidance, PI3K, and calcium signaling pathways. Conclusions Our study demonstrated that a plasma 3-miRNA panel may serve as a novel noninvasive biomarker to diagnose CRC. This plasma 3-miRNA panel may be related to CRC development. However, further studies are needed to highlight its theoretical strengths.