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1.
Nanoscale ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016256

RESUMO

Blackening (or enhancing the optical absorption in the visible region) of nano-sized white semiconducting oxides (N-WSOs) is of significant importance for solar utilization. Here, we present a novel Mars-van-Krevelen mechanism-based method for blackening the N-WSOs via facile one-step heating of the N-WSOs with alcohols. Taking n-butanol-induced blackening of TiO2 (anatase) as an example, the pristine TiO2 NP powders can be successfully blackened to form black TiO2 (B-TiO2) via heating with n-butanol at 300 °C for 20 min. Technical analyses demonstrate that the B-TiO2 nanocrystals are wrapped with a 2 nm thick disordered layer, which is rich in oxygen vacancies, Ti3+ and hydroxyl groups. Both theoretical and experimental results show that B-TiO2 has much stronger optical absorption in the visible region than pristine TiO2. Furthermore, the influence factors (including heating temperatures and alcohol types) and good universality of this blackening method are also demonstrated. A blackening principle based on Mars-van-Krevelen mechanism-induced oxygen vacancy generation and hydroxylation-anchoring of oxygen vacancies has been proposed, and the mechanism can well explain all the phenomena observed in experiments. Importantly, such B-TiO2 shows hugely enhanced activity in solar photodegradation of dye pollutants. Under simulated solar irradiation, the degradation rate constant achieved by the B-TiO2 catalyst is 2.3 times that of the pristine TiO2, showing an obvious enhancement. Further experiments reveal that the improved degradation activity is mainly attributed to the enhanced optical absorption in the visible region and the synergistic photothermal and photocatalytic effect. This study demonstrates a new and facile approach to blacken the N-WSOs for enhanced solar utilization.

2.
J Med Internet Res ; 22(2): e16715, 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32044751

RESUMO

BACKGROUND: People living with HIV (PLWH) have high rates of depressive symptoms. However, only a few effective mental health interventions exist for this vulnerable population. OBJECTIVE: The aim of this study was to assess the efficacy of a WeChat-based intervention, Run4Love, with a randomized controlled trial among 300 people living with HIV and depression (PLWHD) in China. METHODS: We recruited PLWH from the HIV outpatient clinic in South China. Participants were screened based on the Center for Epidemiologic Studies-Depression (CES-D) scale. Those who scored 16 or higher were eligible to participate. A total of 300 eligible patients were enrolled. After obtaining informed consent from the participants, completion of a baseline survey, and collection of participants' hair samples for measuring cortisol, the participants were randomly assigned to an intervention or a control group in a 1:1 ratio. The intervention group received the Run4Love program, delivered via the popular social media app WeChat. Cognitive behavioral stress management courses and weekly reminders of exercise were delivered in a multimedia format. Participants' progress was monitored with timely and tailored feedback. The control group received usual care and a brochure on nutrition for PLWH. Data were collected at 3, 6, and 9 months. The primary outcome was depression, which was measured by a validated instrument. RESULTS: Participants in the intervention and control groups were comparable at baseline; about 91.3% (139/150), 88.3% (132/150), and 86.7% (130/150) participants completed the 3-, 6-, and 9-month follow-ups, respectively. At the 3-month follow-up, a significant reduction in CES-D score was observed in the intervention group (from 23.9 to 17.7 vs from 24.3 to 23.8; mean difference=-5.77, 95% CI -7.82 to -3.71; P<.001; standard effect size d=0.66). The mean changes in CES-D score from baseline to the 6- and 9-month follow-ups between the two groups remained statistically significant. No adverse events were reported. CONCLUSIONS: The WeChat-based mobile health (mHealth) intervention Run4Love significantly reduced depressive symptoms among PLWHD, and the effect was sustained. An app-based mHealth intervention could provide a feasible therapeutic option for many PLWHD in resource-limited settings. Further research is needed to assess generalizability and cost-effectiveness of this intervention. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showproj.aspx?proj=21019 (Archived by WebCite at https://www.webcitation.org/78Bw2vouF).

3.
Nanoscale Horiz ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073017

RESUMO

Detection of trace harmful small gaseous molecules (h-SGMs), based on surface enhanced Raman spectroscopy (SERS), has been expected to be a useful strategy but is challenging due to the extremely small Raman cross section (RCS) and weak metal affinity of the h-SGMs. Here, a new strategy, ultrathin layer solid transformation-enabled (ULSTE)-SERS, is proposed. It uses the chemical reaction between the target h-SGM and an ultrathin layer of solid sensing matter coated on a plasmonic metal SERS substrate. This reaction in situ produces a new solid matter with large RCS, which ensures the detection of trace h-SGMs via SERS. The validity of this strategy has been demonstrated by detecting trace H2S gas with an ultrathin CuO layer wrapped around Au nanoparticles. Furthermore, this strategy allows fast and ultrasensitive detection. The detection limit can be down to ppb (even ppt) levels with 10 min preprocessing. Importantly, this strategy has good universality for various other h-SGMs, such as SO2, CS2, CH3SH, and HCl, etc., using appropriate sensing matter. Additionally, the ULSTE-SERS is also suitable for unstable molecules and fast portable detection due to the stable solid layer. This work provides highly efficient SERS-based detection of trace h-SGMs, which is easily applied in practical situations.

4.
J Virol ; 94(2)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31666372

RESUMO

Follicular helper T (TFH) cells have been shown to support productive human immunodeficiency virus type 1 (HIV-1) replication and to serve as a key component of the latent viral reservoir. However, the viral characteristics of this latent reservoir and the clinical relevance of this reservoir remain unclear. In this study, we assessed the tropic composition of latent viruses from peripheral TFH (pTFH), non-TFH memory, and naive CD4+ T cells from individuals with HIV-1 infections on suppressive combined antiretroviral therapy (cART). X4-tropic latent HIV-1 was preferentially enriched in pTFH cells compared to levels in the other two subsets. Interestingly, the ratio of X4-tropic latent HIV-1 in pTFH cells not only was robustly and inversely correlated with blood CD4+ T cell counts across patients but also was prognostic of CD4+ T cell recovery in individuals on long-term cART. Moreover, patients with higher X4-tropic latent HIV-1 ratios in pTFH cells showed greater risks of opportunistic coinfections. These findings reveal the characteristics of latent HIV-1 in TFH cells and suggest that the ratio of X4-tropic latent HIV-1 in pTFH cells is a valuable indicator for disease progression and cART efficacy.IMPORTANCE TFH cells have been shown to harbor a significant amount of latent HIV-1; however, the viral characteristics of this reservoir and its clinical relevance remain largely unknown. In this study, we demonstrate that X4-tropic latent HIV-1 is preferentially enriched in pTFH cells, which also accurately reflects the viral tropism shift. The ratio of X4-tropic proviruses in pTFH cells but not in other memory CD4+ T cell subsets is inversely and closely correlated with blood CD4+ T cell counts and CD4+ T cell recovery rates with cART. Our data suggest that the ratio of X4-tropic provirus in peripheral TFH cells can be easily measured and reflects disease progression and treatment outcomes during cART.

5.
Nanotechnology ; 31(15): 155501, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31887726

RESUMO

Rapid, ultrasensitive and reliable detection of mercury ions (Hg2+) by surface enhanced Raman spectroscopy (SERS) is of importance, but is restricted by the extremely low Raman cross section of the Hg2+. Here, we report a facile methodology that can realize such detection based on the organometallic Cu(CH4N2S)Cl · 0.5H2O nanobelts and SERS. In the assay, Hg2+ react with the nanobelts coated on a SERS active gold nanoparticle (NP) film to form ultrafine HgS NPs in situ. Subsequently, solid HgS is SERS determined to mirror the presence of Hg2+. Importantly, such detection is rapid and ultrasensitive. Within 10 min, limit of detection (LoD) of ppt level can be realized. The high detection efficiency is attributed to the superhydrophilicity, rich micropores and ultrathin nature of the organometallic nanobelts besides the strong SERS effect of Au NP film. In addition, this detection is highly resistant to various metal ions (Cu2+, Fe3+, Bi3+, Cr3+, Na+, Ni2+, Cd2+, etc) and is highly reliable in actual water (lake and tap water). Finally, influences of some substrate parameters and detection conditions on the test results are revealed. The optimal thickness of the gold NP film is about 80 nm, and the optimal wavelength of excitation light is about 633 nm. A small amount of Cu(CH4N2S)Cl · 0.5H2O nanobelts or a large volume of Hg2+ contaminated solution contributes to low LoDs. We believe that this work provides a rapid and sensitive detection for Hg2+.

6.
Sci Total Environ ; 707: 136084, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31863980

RESUMO

Heavy metals in contaminated sites can affect plant responses to emerging contaminates such as engineered silver nanoparticles (AgNPs), but the underlying mechanisms are poorly understood. After 4-day exposure to 0-2.5 mg Cu L-1 hydroponically, Cu concentrations in roots of wheat seedlings (Triticum aestivum L.) increased from 20 ± 3 to 325 ± 58 mg kg-1. Meanwhile, the cell death in root tips, as measured by the uptake of Evans blue stain, increased 1.8-2.8 times in response to Cu exposure. Total thiol contents in roots (including glutathione, cysteine and phytochelatins), as measured by high performance liquid chromatography, increased 1.4 times upon low Cu exposure but decreased 2.2 times upon high Cu exposure. After those wheats were exposed to 10 mg L-1 AgNPs for 8 h, the Ag influx rates decreased 1.3-3.9 times in Cu pre-exposed plants. Together, the cell death in root tips and thiol levels in roots could explain the decreased Ag influx rates of Cu pre-exposed plants. These findings indicate that the bioavailability of AgNPs without consideration of pre-existing metals could be over-estimated.

7.
AIDS Care ; 32(1): 128-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31181956

RESUMO

Few studies have examined the relationship between inconsistent condom use and sexual partnership characteristics among people living with HIV (PLWH). The current study focused on such association and its gender differences. The study was conducted in a large hospital in South China in 2013. A total of 320 dyads (PLWH indexes and their sexual partners) were recruited from an outpatient clinic using convenience sampling. The proportion of inconsistent condom use in the last six months among female indexes was higher than that among male indexes (52.4% vs. 43.6%). Of sexual partnership characteristics, HIV seropositive status was a risk factor for inconsistent condom use for both male and female indexes (aOR = 2.32, 95%CI = 1.15∼4.66, aOR = 3.09, 95%CI = 1.10∼8.67, respectively). For male indexes, lower educational level was also a risk factor (aOR = 2.39, 95%CI = 1.23∼4.67); while having had emotionally intimate relationships was a protective factor (aOR = 0.40, 95%CI = 0.21∼0.77). For female indexes, receiving material support was a risk factor (aOR = 10.17, 95%CI = 2.13∼48.61) and receiving health-related advice was a protective factor (aOR = 0.11, 95%CI = 0.02∼0.55). Future HIV interventions for PLWH need to be gender-sensitive and include their sexual partners.

8.
J Med Internet Res ; 21(11): e14729, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774411

RESUMO

BACKGROUND: People living with HIV and depression have high rates of suicide. Studies of mobile health (mHealth) interventions have shown feasibility, acceptability, and efficacy in improving mental health in people living with HIV and depression. However, few studies have examined the mechanisms and effects of mHealth interventions on suicide. OBJECTIVE: This study was designed to examine the mechanisms and effects of a WeChat-based intervention, Run4Love, on suicide among people living with HIV and depression in China, while considering perceived stress and depressive symptoms as mediators. METHODS: A sample of 300 People living with HIV and depression was recruited from the outpatient clinic of a large HIV or AIDS treatment hospital and was randomized to the Run4Love group or a control group. Data were collected at baseline, 3-, 6-, and 9-month follow-ups. Path analysis modeling, with longitudinal data, was used in data analyses. RESULTS: The Run4Love mHealth intervention had a direct effect on reducing suicide rate at the 6-month follow-up (beta=-.18, P=.02) and indirect effect through reducing perceived stress and depressive symptoms at the 3-month follow-up (beta=-.09, P=.001). A partial mediating effect between perceived stress and depressive symptoms accounted for 33% (-0.09/-0.27) of the total effect. CONCLUSIONS: Through path analyses, we understood the mechanisms and effects of an mHealth intervention on suicide prevention. The findings underscored the importance of stress reduction and depression treatment in such a program. We call for more effective suicide prevention, especially mHealth interventions targeting the vulnerable population of people living with HIV and depression. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showprojen.aspx?proj=21019.

9.
JMIR Mhealth Uhealth ; 7(11): e15489, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730042

RESUMO

BACKGROUND: Although several studies have investigated the effects of mobile health (mHealth) interventions on depression among people living with HIV, few studies have explored mediators of mHealth-based interventions to improve mental health in people living with HIV. Identifying influential mediators may enhance and refine effective components of mHealth interventions to improve mental health of people living with HIV. OBJECTIVE: This study aimed to examine mediating factors of the effects of a mHealth intervention, Run4Love, designed to reduce depression among people living with HIV using 4 time-point measurement data. METHODS: This study used data from a randomized controlled trial of a mHealth intervention among people living with HIV with elevated depressive symptoms in Guangzhou, China. A total of 300 patients were assigned to receive either the mHealth intervention (n=150) or a waitlist control group (n=150) through computer-generated block randomization. Depressive symptoms, coping, and HIV-related stigma were measured at baseline, 3-, 6-, and 9-month follow-ups. The latent growth curve model was used to examine the effects of the intervention on depressive symptoms via potential mediators. Mediating effects were estimated using bias-corrected 95% bootstrapped CIs (BCIs) with resampling of 5000. RESULTS: Enhanced positive coping and reduced HIV-related stigma served as effective treatment mediators in the mHealth intervention. Specially, there was a significant indirect effect of the mHealth intervention on the slope of depressive symptoms via the slope of positive coping (beta=-2.86; 95% BCI -4.78 to -0.94). The indirect effect of the mHealth intervention on the slope of depressive symptoms via the slope of HIV-related stigma was also statistically significant (beta=-1.71; 95% BCI -3.03 to -0.40). These findings indicated that enhancement of positive coping and reduction of HIV-related stigma were important mediating factors of the mHealth intervention in reducing depression among people living with HIV. CONCLUSIONS: This study revealed the underlying mediators of a mHealth intervention to reduce depression among people living with HIV using latent growth curve model and 4 time-point longitudinal measurement data. The study results underscored the importance of improving positive coping skills and mitigating HIV-related stigma in mHealth interventions to reduce depression among people living with HIV.

10.
BMC Infect Dis ; 19(1): 926, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675923

RESUMO

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients. METHODS: This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1-2, 3-4, 5-6, 7-8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis. RESULTS: The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = - 0.317, p < .001), CD8+ T cell number (rho = - 0.361, p < .001), "programmed cell death protein 1" (PD-1) (rho = - 0.347, p < .001), "T cell immunoglobulin domain and mucin domain-3" (Tim3) (rho = - 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and "regulated upon activation normal T-cell expressed and secreted" (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024). CONCLUSIONS: Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.


Assuntos
Dengue/etiologia , Células Supressoras Mieloides/patologia , Adolescente , Adulto , Arginase/sangue , Linfócitos T CD4-Positivos/patologia , Estudos de Casos e Controles , Estudos Transversais , Dengue/sangue , Feminino , Citometria de Fluxo , Humanos , Interferon-alfa/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Óxido Nítrico/sangue , Prognóstico , Fatores de Tempo , Carga Viral , Adulto Jovem
11.
Small ; 15(47): e1905171, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31617321

RESUMO

Li metal is the optimal choice as an anode due to its high theoretical capacity, but it suffers from severe dendrite growth, especially at high current rates. Here, an ionic gradient and lithiophilic inter-phase film is developed, which promises to produce a durable and high-rate Li-metal anode. The film, containing an ionic-conductive Li0.33 La0.56 TiO3 nanofiber (NF) layer on the top and a thin lithiophilic Al2 O3 NF layer on the bottom, is fabricated with a sol-gel electrospinning method followed by sintering. During cycling, the top layer forms a spatially homogenous ionic field distribution over the anode, while the bottom layer reduces the driving force of Li-dendrite formation by decreasing the nucleation barrier, enabling dendrite-free plating-stripping behavior over 1000 h at a high current density of 5 mA cm-2 . Remarkably, full cells of Li//LiNi0.8 Co0.15 Al0.05 O2 exhibit a high capacity of 133.3 mA h g-1 at 5 C over 150 cycles, contributing a step forward for high-rate Li-metal anodes.

12.
mBio ; 10(5)2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594817

RESUMO

The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4+ T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161+ CD4+ T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161+ CD4+ T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency.IMPORTANCE The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161+ CD4+ T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.

13.
Front Immunol ; 10: 2151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572371

RESUMO

Current combined antiretroviral therapy (cART) mainly targets 3 of the 15 HIV proteins leaving many potential viral vulnerabilities unexploited. To purge the HIV-1 latent reservoir, various strategies including "shock and kill" have been developed. A key question is how to restore impaired immune surveillance. HIV-1 protein Nef has long been known to mediate the downregulation of cell-surface MHC-I and assist HIV-1 to evade the immune system. Through high throughput screening of Food and Drug Administration (FDA) approved drugs, we identified lovastatin, a statin drug, to significantly antagonize Nef to downregulate MHC-I, CD4, and SERINC5, and inhibit the intrinsic infectivity of virions. In addition, lovastatin boosted autologous CTLs to eradicate the infected cells and effectively inhibit the subsequent viral rebound in CD4+ T-lymphocytes isolated from HIV-1-infected individuals receiving suppressive cART. Furthermore, we found that lovastatin inhibits Nef-induced MHC-I downregulation by directly binding with Nef and disrupting the Nef-AP-1 complex. These results demonstrate that lovastatin is a promising agent for counteracting Nef-mediated downregulation of MHC-I, CD4, and SERINC5. Lovastatin could potentially be used in the clinic to enhance anti-HIV-1 immune surveillance.

14.
Elife ; 82019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397674

RESUMO

The antiviral activity of host factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) and its degradation mediated by human immunodeficiency virus type 1 (HIV-1) Vif protein are important topics. Although accumulating evidence indicates the importance of deubiquitination enzymes (DUBs) in innate immunity, it is unknown if they participate in A3G stability. Here, we found that USP49 directly interacts with A3G and efficiently removes ubiquitin, consequently increasing A3G protein expression and significantly enhancing its anti-HIV-1 activity. Unexpectedly, A3G degradation was also mediated by a Vif- and cullin-ring-independent pathway, which was effectively counteracted by USP49. Furthermore, clinical data suggested that USP49 is correlated with A3G protein expression and hypermutations in Vif-positive proviruses, and inversely with the intact provirus ratio in the HIV-1 latent reservoir. Our studies demonstrated a mechanism to effectively stabilize A3G expression, which could comprise a target to control HIV-1 infection and eradicate the latent reservoir.


Assuntos
Desaminase APOBEC-3G/metabolismo , HIV-1/crescimento & desenvolvimento , HIV-1/imunologia , Fatores Imunológicos/metabolismo , Ubiquitina Tiolesterase/metabolismo , Ubiquitina/metabolismo , Replicação Viral , Células HEK293 , Células HeLa , Humanos , Imunidade Inata
15.
Front Immunol ; 10: 1647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379845

RESUMO

Background: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in human immunodeficiency virus type-1 (HIV-1) disease progression. However, the potential mechanisms that affecting NK-mediated ADCC response are still not well-elucidated. Methods: Antigen-antibody complex model of Ab-opsonized P815 cells was adopted to induce a typical non-specific ADCC response. The capacities of HIV-1 specific NK-ADCC were measured by using the combination model of gp120 protein and plasma of HIV-1 elite controllers. The levels of plasma cytokine were measured by ELISA. Anti-IL-2 blocking antibody was used to analyze the impact of activated CD56+ T cells on NK-ADCC response. Results: IL-2, IL-15, IFN-α, and IFN-ß could effectively enhance the non-specific and HIV-1-specific NK-ADCC responses. Compared with healthy controls, HIV-1-infected patients showed decreased plasma IL-2 levels, while no differences of plasma IFN-α, IL-15, and IFN-ß were presented. IL-2 production was detected from CD56+ T cells activated through antibody-dependent manner. The capability of NK-ADCC could be weakened by blocking IL-2 secretion from activated CD56+ T cells. Although no difference of frequencies of CD56+ T cells was found between HIV-1-infected patients and healthy controls, deficient IL-2 secretion from activated CD56+ T were found in chronic HIV-1 infection. Conclusions: The impaired ability of activated CD56+ T cells to secreting IL-2 might contribute to the attenuated NK cell-mediated ADCC function in HIV-1 infection.

16.
Adv Sci (Weinh) ; 6(13): 1900319, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31380187

RESUMO

The latent viral reservoir is the source of viral rebound after interruption of antiretroviral therapy (ART) and is the major obstacle in eradicating the latent human immunodeficiency virus-1 (HIV-1). In this study, arsenic class of mineral, arsenic trioxide, clinically approved for treating acute promyelocytic leukemia, is demonstrated to reactivate latent provirus in CD4+ T cells from HIV-1 patients and Simian immunodeficiency virus (SIV)-infected macaques, without significant systemic T cell activation and inflammatory responses. In a proof-of-concept study using chronically SIVmac239-infected macaques, arsenic trioxide combined with ART delays viral rebound after ART termination, reduces the integrated SIV DNA copies in CD4+ T cells, and restores CD4+ T cells counts in vivo. Most importantly, half of arsenic trioxide-treated macaques show no detectable viral rebound in the plasma for at least 80 days after ART discontinuation. Mechanistically, the study reveals that CD4 receptors and CCR5 co-receptors of CD4+ T cells are significantly downregulated by arsenic trioxide treatment, which reduces susceptibility to infection after provirus reactivation. Furthermore, an increase in SIV-specific immune responses after arsenic trioxide treatment may contribute to suppression of viral rebound. This work suggests that arsenic trioxide in combination with ART is a novel regimen in down-sizing or even eradicating latent HIV-1 reservoir.

17.
Small ; 15(35): e1902373, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31304683

RESUMO

Monodentate adsorption of oxygen intermediates results in a theoretical overpotential limit of ≈0.35 V for oxygen evolution reaction (OER), which causes the sluggish kinetics of the OER process. In this work, nonprecious chromium dopant is introduced into the self-supported CoFe layered double hydroxides (LDHs) on nickel foam (Cr-CoFe LDHs/NF) via a facile one-step hydrothermal method, which exhibits a preeminent electrocatalytic activity toward the OER with an ultralow overpotential of 238 mV to obtain 10 mA cm-2 and a high stability after cyclic voltammetry for 5000 cycles in alkaline solution (1 m KOH). Density functional theory (DFT) calculations unveil that Cr dopants as new active sites could improve the electron-donation ability of the resultant Cr-CoFe LDHs due to the smaller electronegativity of Cr in comparison with Fe and Co. Therefore, the scaling relation of adsorption energy among four oxygen intermediates is broken and consequently the OER performance is further promoted. This work provides a strategy to develop efficient metal layered double hydroxide OER catalysts.

18.
ACS Appl Mater Interfaces ; 11(31): 28145-28153, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290313

RESUMO

A facile and general strategy is presented for homogenous and ultrathin metal sulfide wrapping on plasmonic metal (PM) nanoparticles (NPs) based on a thiourea-induced isotropic shell growth. This strategy is typically implemented just via adding the thiourea into pre-formed PM colloidal solutions containing target metal ions. The validity of this strategy is demonstrated by taking the wrapped NPs with Au core and CuS shell or Au@CuS NPs as an example. They are successfully fabricated via adding the thiourea and Cu2+ solutions into pre-formed Au NP colloidal solution. The CuS shell layer is highly homogenous (<10% in relative standard deviation of shell thickness), regardless of the NPs' shape or curvature. The shell thickness can be controlled from tens down to 0.5 nm just by the addition of different amounts of shell precursors. The formation of the shell layer on the Au NPs can be attributed to the alternative deposition of Cu2+ and S2- ions on the thiourea-modified surface of Au NPs in the solution, which induces the isotropic shell growth. Further, this strategy is of good universality. Many other sulfide-wrapped PM NPs, such as Ag@CuS, Au@PtS2, Au@HgS, Ag@Ag2S NPs, and Ag@CuS nanorods, have been successfully obtained with homogeneous and ultrathin shells. Importantly, such ultrathin sulfide-wrapped PM NPs can be used for surface enhanced Raman scattering (SERS)-based detection of trace heavy-metal ions with strong anti-interference via the ion exchange process between the metal sulfide shell and heavy-metal ions. This study provides a simple and controllable route for wrapping the homogenous and ultrathin sulfide layers on the PM NPs, and such wrapped NPs have good practical applications in the SERS-based detection of trace heavy-metal ions.

19.
BMJ ; 366: l4179, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285198

RESUMO

OBJECTIVE: To evaluate the effects of four drug (quadruple) versus three drug (triple) combination antiretroviral therapies in treatment naive people with HIV, and explore the implications of existing trials for clinical practice and research. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: PubMed, EMBASE, CENTRAL, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature from March 2001 to December 2016 (updated search in PubMed and EMBASE up to June 2018); and reference lists of eligible studies and related reviews. STUDY SELECTION: Randomised controlled trials comparing quadruple with triple combination antiretroviral therapies in treatment naive people with HIV and evaluating at least one effectiveness or safety outcome. REVIEW METHODS: Outcomes of interest included undetectable HIV-1 RNA, CD4 T cell count, virological failure, new AIDS defining events, death, and severe adverse effects. Random effects meta-analyses were conducted. RESULTS: Twelve trials (including 4251 people with HIV) were eligible. Quadruple and triple combination antiretroviral therapies had similar effects on all relevant effectiveness and safety outcomes, with no point estimates favouring quadruple therapy. With the triple therapy as the reference group, the risk ratio was 0.99 (95% confidence interval 0.93 to 1.05) for undetectable HIV-1 RNA, 1.00 (0.90 to 1.11) for virological failure, 1.17 (0.84 to 1.63) for new AIDS defining events, 1.23 (0.74 to 2.05) for death, and 1.09 (0.89 to 1.33) for severe adverse effects. The mean difference in CD4 T cell count increase between the two groups was -19.55 cells/µL (-43.02 to 3.92). In general, the results were similar, regardless of the specific regimens of combination antiretroviral therapies, and were robust in all subgroup and sensitivity analyses. CONCLUSION: In this study, effects of quadruple combination antiretroviral therapy were not better than triple combination antiretroviral therapy in treatment naive people with HIV. This finding lends support to current guidelines recommending the triple regimen as first line treatment. Further trials on this topic should be conducted only when new research is justified by adequate systematic reviews of the existing evidence. However, this study cannot exclude the possibility that quadruple cART would be better than triple cART when new classes of antiretroviral drugs are made available.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
J Immunol Res ; 2019: 1801560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183385

RESUMO

Due to the existence of viral reservoirs, the rebound of human immunodeficiency virus type 1 (HIV-1) viremia can occur within weeks after discontinuing combined antiretroviral therapy. Immunotherapy could potentially be applied to eradicate reactivated HIV-1 in latently infected CD4+ T lymphocytes. Although the existence of HIV-1-specific CD8+ T memory stem cells (TSCMs) is well established, there are currently no reports regarding methods using CD8+ TSCMs to treat HIV-1 infection. In this study, we quantified peripheral blood antigen-specific CD8+ TSCMs and then expanded HIV-1-specific TSCMs that targeted optimal antigen epitopes (SL9, IL9, and TL9) in the presence of interleukin- (IL-) 21 or IL-15. The suppressive capacity of the expanded CD8+ TSCMs on HIV-1 production was measured by assessing cell-associated viral RNA and performing viral outgrowth assays. We found that the number of unmutated TL9-specific CD8+ TSCMs positively correlated with the abundance of CD4+ T cells and that the expression of IFN-γ was higher in TL9-specific CD8+ TSCMs than that in non-TL9-specific CD8+ TSCMs. Moreover, the antiviral capacities of IL-21-stimulated CD8+ TSCMs exceeded those of conventional CD8+ memory T cells and IL-15-stimulated CD8+ TSCMs. Thus, we demonstrated that IL-21 could efficiently expand HIV-1-specific CD8+ TSCMs to suppress HIV-1 replication. Our study provides new insight into the function of IL-21 in the in vitro suppression of HIV-1 replication.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Interleucinas/metabolismo , Células Cultivadas , Estudos de Coortes , Epitopos/imunologia , Antígenos HIV/imunologia , Humanos , Memória Imunológica , Interferon gama/metabolismo , Interleucina-15/metabolismo , Ativação Linfocitária , Replicação Viral
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