The multicopper oxidase laccase is widespread in fungi and has great industrial importance. One puzzle regarding laccase production in the basidiomycetous yeast Cryptococcus neoformans is that it is inhibited by high temperature (e.g., 37°C). In this paper, we report identification of a nitrogen metabolite repression-related gene, TAR1, which is responsible for laccase repression. Disruption of TAR1 results in a significant increase in the level of LAC1 mRNA at 37°C. The putative protein Tar1 shares a moderate level of similarity with the nitrogen metabolite repressors Nmr1 and NmrA from Neurospora crassa and Aspergillus nidulans, respectively. Likewise, Tar1 has a negative role in the utilization of nitrate. Furthermore, the structure of Tar1 is unique. Tar1 lacks the long C-terminal region of Nmr1 and NmrA. It contains the canonical Rossmann fold motif, GlyXXGlyXXGly, whereas Nmr1 and NmrA have variable residues at the Gly positions. Interestingly, the promoter region of TAR1 contains three TTC/GAA repeats which are likely the heat shock factor (Hsf) binding sites, implying that Hsf has a role in laccase inhibition. TAR1 mediation of temperature-associated repression of LAC1 suggests a novel mechanism of laccase regulation and a new function for Nmr proteins. Our work may be helpful for industry in terms of promotion of laccase activity.

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Roles of the high-affinity copper transporter Ctr4 in the virulence of Cryptococcus neoformans remain to be fully determined. Here we demonstrate that Ctr4 plays a necessary role in virulence and tolerance to a number of stress conditions. We first observed, with the method of flame atomic absorption spectrometry, that deletion of CTR4 resulted in a significant decrease in intracellular copper level, confirming the role of Ctr4 as a copper transporter in C. neoformans. Furthermore, CTR4 was critical for the yeast to survive at both elevated and low temperatures, as the growth rate of the ctr4Δ mutant at 4 and 37 °C was significantly decreased. The mutant ctr4Δ also exhibited hypersensitivity to osmotic stress imposed by 2 M NaCl or KCl, indicating the possible crosstalk of Ctr4 with the HOG signalling pathway. Moreover, cell wall and plasma membrane integrity appeared to be impaired in the ctr4Δ strain. The virulence of ctr4Δ in two mouse cryptococcosis models was remarkably reduced either via an intranasal or intravenous inoculation. Our work confirms the roles of Ctr4 in virulence and copper homeostasis as well as other additional novel functions.

Introduction: Although syphilis is a frequent co-infection in patients with human immunodeficiency virus (HIV) infection, the influence of syphilis on immune response and virologic failure in HIV-infected patients following initiation of antiretroviral therapy (ART) is not well-defined. Methods: A retrospective study was conducted at Tianjin Second People's Hospital to evaluate the prevalence of syphilis and immune status in 4171 ART-naïve patients. The study included patients who initiated ART between August 2009 and June 2019. Results: The prevalence of syphilis was 40.1% in all ART-naïve patients and 42.5% in ARTnaïve men who have sex with men. HIV/syphilis co-infection was associated with higher virologic failure (odds ratio (95% confidence interval): 1.30 (1.04, 1.63)). Patients with HIV/ syphilis co-infection had lower median CD4 + T cell counts and CD4/CD8 ratios at baseline. After initiation of ART, patients co-infected with HIV/syphilis had smaller increases in CD4 + T cell counts and CD4/CD8 ratios than patients infected only with HIV. The rate of recurrence of syphilis or reinfection was 9% (n = 128) during seven years of ART. Conclusion: HIV/syphilis co-infection had a negative impact on immune recovery and antiretroviral effectiveness. RPR titer and HIV viral load should be monitored in patients coinfected with HIV/syphilis, especially in patients with high RPR titers.

The objective of this study was to assess the epidemiological trends among patients with AIDS in Tianjin, China. A long-term surveillance study was conducted from 2005 to 2016 in Tianjin, China. All patients with AIDS registered in Tianjin from 2005 to 2016 were recruited to this study. Demographic information and clinical features were recorded. A total of 3062 patients with AIDS who were treated with antiretroviral therapy were included in this study. Among AIDS patients, men were more likely to be younger than women (age, 37.84 years vs. 43.27 years; P < 0.001). The incidence of AIDS increased by 39.6% annually over the past 12 years overall. There was the greatest increase (by 44.7%) for homosexual route. Moreover, the proportion of patients aged < 30 years increased considerably over the 12-year study period, while there was a decrease in the proportion of patients aged ≥ 35 years. The frequency of homosexual transmission increased by 86% from before 2011 to 2016, but the frequency of heterosexual transmission decreased by 49%. The frequency of transmission through intravenous drug use decreased in men and patients aged 25–29 years. For those infected through homosexual transmission, there was a significant increase in the numbers of patients aged 20–24 years and 25–29 years. It is important for developing countries to effectively prevent and control the transmission of HIV/AIDS; in particular, it is crucial to promote disease education and sexual protection among young men.