Search

In this paper, we introduce the notion of state maps from a semihoop H1 to another semihoop H2, which is a generalization of internal states (or state operators) on a semihoop H. Also we give a type of special state maps from a semihoop H1 to H1, which is called internal state maps (or IS-maps). Then we give some examples and basic properties of (internal) state maps on semihoops. Moreover, we discuss the relations between state maps and internal states on other algebras. Then we introduce several kinds of filters by state maps on semihoops, called SM-filters, state filters and dual state filters, respectively, and discuss the relations among them. Furthermore we introduce and study the notion of prime SM-filters on semihoops. Finally, using SM-filter, we characterize two kinds of state semihoops.

Background: Targeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8+ T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8+ T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8+ T-cell subsets in chronic HIV-1 infection remain poorly understood. Methods: This study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8+ T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8+ T cells. Results: The proportions of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1+CD39+ CD8+ T cells were negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39+CD8+ T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39- counterparts. In vitro , a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8+ T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells. Conclusion: In patients with chronic HIV-1 infection there are increased frequencies of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells. In treatment naïve patients, the frequencies of PD-1+CD39+ CD8+ T cells are negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling in vitro may exert a synergistic effect in restoring CD8+ T-cell function in HIV-1-infected patients. [ABSTRACT FROM AUTHOR]

Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (T CM ) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (T EMRA ). Moreover, a virtual memory CD8+ T cell (T VM ) subset was enriched in CCL4-CCL5+ T EMRA cells and phenotypically distinctive from CCL4+ T CM subset, supported by single-cell RNA-Seq data. Specifically, T VM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ T CM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, T VM cells inhibited HIV-1 reactivation more effectively than non-T VM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting T VM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Li, Zhen, Wang, Huang, Zou, Zheng, Huang, Meng, Jin, Li, Zhou, Fu, Zhang, Li, Yang, Wang, Yang, Song, Fan, Jiao, Xu, Zhang, Zhou, Yuan, Huang, Qin, Wu, Shi, Wang and Zhang.)

Background: Targeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8 + T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8 + T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8 + T-cell subsets in chronic HIV-1 infection remain poorly understood., Methods: This study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8 + T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8 + T cells., Results: The proportions of PD-1 + , CD39 + , and PD-1 + CD39 + CD8 + T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1 + CD39 + CD8 + T cells were negatively correlated with CD4 + T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39 + CD8 + T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39 - counterparts. In vitro , a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8 + T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells., Conclusion: In patients with chronic HIV-1 infection there are increased frequencies of PD-1 + , CD39 + , and PD-1 + CD39 + CD8 + T cells. In treatment naïve patients, the frequencies of PD-1 + CD39 + CD8 + T cells are negatively correlated with CD4 + T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling in vitro may exert a synergistic effect in restoring CD8 + T-cell function in HIV-1-infected patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Huang, Tu, Zhou, Hu, Fu, Li, Yang, Song, Fan, Jiao, Xu, Zhang, Zhou, Yuan, Zhen, Shi, Wang and Zhang.)

CAR-T cell-based immunotherapy has shown great promise in clinical trials for the treatment of hematological malignancies. The majority of these trials utilize retroviral and lentiviral vectors to introduce CAR transgene. In spite of its satisfactory efficiency, the concerns about the potential carcinogenicity and complicated synthesis procedure restrict widespread clinical applications of viral vectors. Recent studies show that transposon-based gene transfer is a safer and simpler non-viral approach for stable transgene expression. Here, we developed an in house made polymeric nanomicelles carrier for piggyBac (PB) transposon delivery to primary T lymphocytes. The properties, transfection efficiency and toxicity of this carrier was analyzed. Results indicated that nanomicelles produced in our study were stable and reduction-sensitive. These micelles can completely condense DNA and mediate transfection with efficiency of average 30.2% with high cell viability (> 80%). Furthermore, incorporating piggyBac transposase elements into polyplexes promoted persistent expression of the transgene (up to 55%). At the end of culture, CAR-T cells mainly exhibited memory phenotype and consisted of CD3 + CD8 + T cells. The cytotoxicity of these CAR-T cells was average 17% at 20:1 ratio. In conclusion, polymeric nanomicelles provide a flexible and safe method for gene delivery to T lymphocytes., Competing Interests: None., (AJTR Copyright © 2019.)

The security of protocol implementation is important and hard to be verified. Since the penetration testing is usually based on the experience of the security tester and the specific protocol specifications, a formal and automatic verification method is always required. In this paper, we propose an extended model of IOLTS to describe the legal roles and intruders of security protocol implementations, and then combine them together to generate the suitable test cases to verify the security of protocol implementation.

Aim: PKHDL1 (the gene for Polycystic Kidney and Hepatic Disease Like-1) had been recently identified, but characteristics of the gene product, Fibrocystin-L (FPC-L), still remain unknown. We therefore produced a rabbit polyclonal antibody hFL-Np to explore the cellular characteristics of this novel protein., Methods: Based on the hydrophobic/hydrophilic analyses, chose a cDNA fragment which encodes 633L-768K amino acids of the FPC-L and amplified it by RT-PCR. The PCR product was then cloned into a prokaryotic expression vector pGEX-GST. With IPTG induction, the antigen hFL-N was produced and further purified. A rabbit was immunized with the antigen and its antiserum was collected. Applied Western blot with the polyclonal antiserum hFL-Np and validated the antibody specific for FPC-L protein. In addition, also used immunofluorescence staining with hFL-Np to detect the subcellular distribution in cultured HEK293 cells., Results: The prokaryotic expression vector pGEX-hFL-N was successfully constructed and a hFL-N antigen was produced in E.coli Rossetta cells. Using the antigen, a polyclonal antibody hFL-Np was produced and the specificity for FPC-L was also proved by biochemistry and cellular assays. Using the antibody, the cellular staining reveals that FPC-L was a cytosolic protein., Conclusion: We produced an anti-FPC-L polyclonal antibody hFL-Np. By biochemistry and cellular characterization, proved that the polyclonal antibody hFL-Np is specific for FPC-L and demonstrated FPC-L is a cytosolic protein. The finding provides a platform for further dissecting FPC-L functions in mammalian development.