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Background Identification of new HIV infections (HIV incidence) is critical for monitoring AIDS epidemic and assessing the effectiveness of intervention measures. However, current methods for distinguishing new infections from newly diagnosed HIV-1 patients are still imperfect. We explored utilizing miRNAs as biomarker to identify HIV new infections. Methods According to the HIV-1 status and the estimated duration of infection (EDI), we enrolled participants and divided them into three groups: healthy control, new infection (within 1 year), and old infection (longer than 1 year). Participants were assigned into screening set or validation set. miRNA microarray was performed in screening set and the differentially expressed miRNAs were screened out. The differentially expressed miRNAs were further confirmed in validation set and HIV-1 IIIB-MT2 cells infection system. Results In screening set, 5 miRNAs including miR-1291, miR-3609, miR-3162-3p, miR-874-5p and miR-4258 were screened out for their differential expression in plasma among three groups. In validation set, down- trend of miR-3162-3p was validated from healthy control, new infection to old infection groups. In HIV-1 IIIB-MT2 system, the levels of miR-3162-3p also decreased along with infection duration in vitro. Sensitivity and specificity for miR-3162-3p to distinguish new infection from old infection were 100.0% and 71.43%, respectively, with the cut-off value of 0.916. Conclusion miR-3162-3p in plasma could be a potential microRNA biomarker to identify HIV new infections in HIV-1 infected patients.

Type-III interferon (IFN-λ), the most recently discovered family of IFNs, shares common features with type I IFNs, but also has many distinctive activities. It is not clear that whether IFN-λ has additional antiviral mechanisms. In this study, we investigated the effects of IFN-λ on autophagy, a cellular process closely related to hepatitis C virus (HCV) infection in human hepatoma Huh7 cells. Our results showed that IFN-λ1 treatment inhibit autophagic activity in Huh7 cells, as evidenced by the decreased expression of microtubule-associated protein 1 light chain 3B (LC3B)-II and conversion of LC3B-I to LC3B-II, decreased formation of GFP-LC3 puncta and accumulation of autophagosomes. IFN-λ1 could also inhibit HCV-induced or tunicamycin (a known inducer of autophagy with similar mechanism to HCV infection) -induced LC3B-II expression and autophagosome formation. Through PCR array, real time RT PCR, and western blot, two autophagy-related genes, ATG5 and GABARAP, were identified and verified to be down-regulated by IFN-λ1 treatment, either in HCV-uninfected Huh7 cells or in HCV JFH-1-infected cells. Overexpression of ATG5 and/or GABARAP could partly recover the IFN-λ1-inhibited HCV replication. Mechanism research demonstrated that IFN-λ1 could induce the expression of miR-181a and miR-214 (targeting ATG5 and GABARAP respectively), by which down-regulates ATG5 and GABARAP expression. Taken together, our results indicate that suppression of the autophagy response by IFN-λ1 contributes to IFN-λ1 anti-HCV activity. The results also provide a theoretical basis for improving the effectiveness of IFN treatment of HCV infection through inhibition of the HCV-induced autophagy response.

Background: The gut microbiome is known to change following HIV infection. However, previous studies have generated inconsistent results regarding the differences in the gut microbiome between HIV positive and negative individuals. Methods: A bioinformatics analysis was performed on nine 16S rRNA gene sequencing data generated from 1082 stool samples (646 from HIV positive individuals and 436 from HIV negative individuals). We compared the differences in the gut microbiome between HIV positive and negative individuals across various factors. Results: The diversity of the gut microbiome differed between HIV positive and negative individuals with respect to age, gender, and whether or not antiretroviral therapy (ART) was initiated. Our analysis showed that ART did not restore the diversity of the gut microbiome. HIV infection changed the dominant genera of the intestine such that the prevalence of Prevotella increased and that of Bacteroides decreased in HIV positive individuals, especially in men who have sex with men (MSMs). Sutterella, Butyricimonas, Lachnospira etc. had significant correlations with the number of CD4+T cells and HIV viral load. In addition, the differentially enriched genera were found to be associated with functional pathways that correlated with ART. Conclusions: This study explored the changes in the gut microbiome in HIV positive individuals and revealed the association between differentially enriched genera and functional pathways involved in ART, which might help to elucidate the effects of HIV infection on the human gut microbiome. Funding Statement: This study was supported by the National Natural Science Foundation of China (NSFC, 81660334), Guangxi Natural Science Foundation (2017GXNSFAA198190, 2018GXNSFAA050099), National Key Science and Technology Project of China (2018ZX10101002-001-006). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors stated: "Reusable data for our analysis complied with all relevant ethical regulations."

This paper first defines a new 3-dimensional space and function of decision making. The decision making space is consists of three sets of participants, attributes and feasible alternatives.Then the paper gives the concrete decision making model with fuzzy information.lt classifies the attributes into two parts, one is the set of directly measurable attributes, the other is the set of non-directly measurable attributes. As to the two types of fuzzy appraisal scores associated with the attributes discussed above the paper fully describes a method of ranking of alternatives.