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1.
Nat Immunol ; 20(6): 711-723, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31061530

RESUMEN

Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease TRAB domain-containing protein 2A (TRABD2A) inhibited this production in resting CD4+ T cells by degrading the virion structural precursor polyprotein Gag at the plasma membrane. Depletion or inhibition of metalloprotease activity by TRABD2A profoundly enhanced HIV-1 production in resting CD4+ T cells. TRABD2A expression was much higher in resting CD4+ T cells than in activated CD4+ T cells and was considerably reduced by T cell activation. Moreover, reexpressing TRABD2A reinforced the resistance of activated CD4+ T cells to the production of HIV-1 progeny. Collectively, these results elucidate the molecular mechanism employed by resting CD4+ T cells to potently restrict the assembly and production of HIV-1 progeny.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/fisiología , Metaloproteasas/genética , Replicación Viral , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo , Animales , Linfocitos T CD4-Positivos/metabolismo , Cationes , Línea Celular , Activación Enzimática , Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Proteínas de la Membrana/metabolismo , Metaloproteasas/antagonistas & inhibidores , Metaloproteasas/metabolismo , Familia de Multigenes , Proteolisis , Proteína 1 que Contiene Dominios SAM y HD/genética , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Carga Viral
2.
Proc Natl Acad Sci U S A ; 120(3): e2212991120, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36638209

RESUMEN

The urokinase-type plasminogen activator (uPA) system consists of the proteinase uPA, its receptor (PLAUR/uPAR). Under physiological conditions, uPA and PLAUR are predominantly expressed by blood cells, including neutrophils, monocytes, and macrophages, and play important roles in cell activation, adhesion, migration, and extravasation. Here, we report that PLAUR, which is highly expressed in macrophages and dendritic cells (DCs) but hardly expressed in CD4+ T cells, inhibits the release of HIV-1 progeny virions from the cell membrane. Silencing PLAUR markedly enhanced the transmission of HIV-1 in macrophages and DCs. We further demonstrated that PLAUR is localized at the cell membrane to block the release of HIV-1 virions. Interestingly, we found that uPA compromises the PLAUR-mediated inhibition to slightly enhance HIV-1 production in primary macrophages and DCs. In the absence of PLAUR, this enhanced effect induced by uPA is abrogated. In conclusion, PLAUR is a new anti-HIV-1 protein produced in both macrophages and DCs where it inhibits HIV-1 transmission. This discovery may provide a novel therapeutic target for combating HIV.


Asunto(s)
VIH-1 , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Replicación Viral , Humanos , Membrana Celular/metabolismo , VIH-1/fisiología , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Virión/metabolismo
3.
Brief Bioinform ; 25(1)2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-38189536

RESUMEN

Accurate subgenome phasing is crucial for understanding the origin, evolution and adaptive potential of polyploid genomes. SubPhaser and WGDI software are two common methodologies for subgenome phasing in allopolyploids, particularly in scenarios lacking known diploid progenitors. Triggered by a recent debate over the subgenomic origins of the cultivated octoploid strawberry, we examined four well-documented complex allopolyploidy cases as benchmarks, to evaluate and compare the accuracy of the two software. Our analysis demonstrates that the subgenomic structure phased by both software is in line with prior research, effectively tracing complex allopolyploid evolutionary trajectories despite the limitations of each software. Furthermore, using these validated methodologies, we revisited the controversial issue regarding the progenitors of the octoploid strawberry. The results of both methodologies reaffirm Fragaria vesca and Fragaria iinumae as progenitors of the octoploid strawberry. Finally, we propose recommendations for enhancing the accuracy of subgenome phasing in future studies, recognizing the potential of integrated tools for advanced complex allopolyploidy research and offering a new roadmap for robust subgenome-based phylogenetic analysis.


Asunto(s)
Benchmarking , Fragaria , Filogenia , Fragaria/genética , Poliploidía , Programas Informáticos
4.
Proc Natl Acad Sci U S A ; 119(2)2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34987100

RESUMEN

Myeloid lineage cells such as macrophages and dendritic cells (DCs), targeted by HIV-1, are important vehicles for virus dissemination through the body as well as viral reservoirs. Compared to activated lymphocytes, myeloid cells are collectively more resistant to HIV-1 infection. Here we report that NRP-1, encoding transmembrane protein neuropilin-1, is highly expressed in macrophages and DCs but not CD4+ T cells, serving as an anti-HIV factor to inhibit the infectivity of HIV-1 progeny virions. Silencing NRP-1 enhanced the transmission of HIV-1 in macrophages and DCs significantly and increased the infectivity of the virions produced by these cells. We further demonstrated that NRP-1 was packaged into the progeny virions to inhibit their ability to attach to target cells, thus reducing the infectivity of the virions. These data indicate that NRP-1 is a newly identified antiviral protein highly produced in both macrophages and DCs that inhibit HIV-1 infectivity; thus, NRP-1 may be a novel therapeutic strategy for the treatment of HIV-1 infection.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Células Mieloides/metabolismo , Neuropilina-1/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Línea Celular , Células Dendríticas/metabolismo , VIH-1 , Humanos , Macrófagos/metabolismo , Macrófagos/virología , Virión/metabolismo , Replicación Viral/efectos de los fármacos
5.
J Infect Dis ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207199

RESUMEN

BACKGROUND: Shenzhen, a city with a substantial mobile population, was identified as the first discovered region of HIV-1 CRF55_01B and epicenter of its severe epidemic. During the implementation of venue-based behavioral interventions and the "treat-all" policy, discerning the spread patterns and transmission hotspots of CRF55_01B is imperative. METHODS: In this study, 1,450 partial pol sequences, with demographic information, were collected from all newly diagnosed CRF55_01B infections in Shenzhen from 2008 to 2020. Molecular networks were constructed using the maximum likelihood and time-resolve phylogenies. Transmission rates, effective reproduction numbers (Re) of clusters and viral dispersal were evaluated using Bayesian inference. RESULTS: In total, 526 sequences formed 114 clusters, including seven large clusters. The status and size of clusters were strongly correlated with age, ethnicity, occupation and CD4+ T cell counts. The transmission rates of clusters were significantly higher than the national epidemic estimate. Four large clusters had Re exceeding 1 at the end of sampling period. Immigrants from Guangdong and Hunan, along with local residents, were identified as the transmission hubs, with heterosexual men being the main source and MSM being the main destination. The virus exhibited a high movement frequency from individuals aged 30-49 years toward diverse age groups. CONCLUSIONS: This study demonstrated the hidden CRF55_01B transmissions continued despite current combined interventions in Shenzhen, and special at-risk individuals susceptible to infection or transmission were identified, potentially serving as targets for more effective prevention and control of the local epidemic, thereby mitigating cross-regional spread nationwide due to population migration.

6.
J Magn Reson Imaging ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980200

RESUMEN

BACKGROUND: Despite the advent of combination antiretroviral therapy, people living with human immunodeficiency virus (PLWH) are at an increased risk for cardiac disease. PURPOSE: To explore the presence and extent of diastolic atrial and left ventricular dysfunction in PLWH using cardiac MRI in correlation with clinical markers of disease activity. STUDY TYPE: Prospective. POPULATION: A total of 163 participants comprising 101 HIV-infected individuals (age: 52 years [42-62 years]; 92% male) and 62 age- and sex-matched healthy volunteers (age: 51 years [30-72 years]; 85% male). FIELD STRENGTH/SEQUENCE: 3.0 T, cardiac MRI including balanced steady-state free precession (SSFP) for the short-axis, two-, three-, and four-chamber views were performed. ASSESSMENT: Assessment of cardiac function and strain analysis were accomplished by CVI42 software. Blood samples for CD4+ T cells and cardiac risk factors were also collected before MRI. STATISTICAL TESTS: Independent t tests, Mann-Whitney U test, Pearson's correlation analysis, and multivariate linear analyses (significance level: P < 0.05). RESULTS: PLWH had a significantly larger left atrial volume maximum index (LAVImax: 32.6 ± 8.7 vs. 28.7 ± 8.1 mL/m2), minimum (LAVImin: 14.8 ± 5.5 vs. 11.5 ± 5.4 mL/m2,), and prior to atrial contraction (LAVIpre-a: 23.4 ± 6.7 vs. 19.7 ± 7.2 mL/m2) as compared to healthy volunteers. The LA reservoir (LAtEF: 55.0 ± 10.2 vs. 61.4 ± 10.4; Sls: 29.0 ± 8.1 vs. 33.8 ± 11.8), conduit (LApEF: 28.4 ± 8.2 vs. 32.3 ± 11.3, P = 0.01; Sle: 16.3 ± 6.5 vs. 18.9 ± 8.2), and booster pump function (LAaEF: 37.4 ± 12.4 vs. 42.7 ± 13.1, P = 0.01, Sla: 12.7 ± 5.1 vs. 14.9 ± 5.7) were all significant impaired in PLWH. Global circumferential left ventricular diastolic strain rate (LVGCS-d) was significantly lower in the HIV patients. Multivariate analysis results showed that Nadir CD4+ T cells had a significant adverse association with LVGCS-d (ß = 0.51). CONCLUSION: LA structure abnormalities and LV diastolic dysfunction were manifested in PLWH, with Nadir CD4+ T cell counts potentially serving as a risk factor for early cardiac diastolic dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

7.
Fish Shellfish Immunol ; 154: 109906, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278379

RESUMEN

Interferon-inducible double-stranded RNA-dependent protein kinase (PKR) is one of the key antiviral arms in the innate immune system. The activated PKR performs its antiviral function by inhibiting protein translation and inducing apoptosis. In our previous study, we identified grass carp TARBP2 as an inhibitor of PKR activity, thereby suppressing cell apoptosis. This study aimed to explore the effects of grass carp TARBP2 on PKR activity and cell apoptosis. Grass carp TARBP2 comprises two N-terminal dsRBDs and a C-terminal C4 domain. Subcellular localization analysis conducted in CIK cells revealed that TARBP2-FL (full-length TARBP2), TARBP2-Δ1 (lack of the first dsRBD), and TARBP2-Δ2 (lack of the second dsRBD) are predominantly located in the cytoplasm, while TARBP2-Δ3 (lack of the two dsRBDs) is distributed both in the nucleus and cytoplasm. Colocalization and immunoprecipitation assays confirmed the interaction of TARBP2-FL, TARBP2-Δ1, and TARBP2-Δ2 with PKR, while TARBP2-Δ3 showed no binding. Furthermore, our findings suggested that the inhibitory effect of TARBP2-Δ1 or TARBP2-Δ2 on the PKR-eIF2α pathway is depressed compared to TARBP2-FL. In cell apoptosis assays, it was observed that TARBP2-FL inhibits PKR-mediated cell apoptosis. TARBP2-Δ1 or TARBP2-Δ2 exhibits decreased inhibition to PKR-mediated cell apoptosis, whereas TARBP2-Δ3 nearly completely loses this inhibitory effect. These findings highlight the critical importance of two dsRBDs of TARBP2 in interaction with PKR, as well as in the inhibition of PKR activity, resulting in the suppression of cell apoptosis triggered by prolonged PKR activation.

8.
Int J Environ Health Res ; 34(10): 3615-3633, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38339769

RESUMEN

This study aimed to determine dust-phase phthalate levels in 112 dormitories of 14 universities during autumn and winter, investigate their potential sources, and estimate phthalate exposure via dust ingestion. Twelve phthalates were detected, among which di-(2-ethylhexyl) phthalate (DEHP) and dicyclohexyl phthalate (DCHP) were the most abundant, followed by di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP). The median concentrations and contributions of DCHP and DEHP were the highest. The contributions of di-n-octyl phthalate and di-nonyl phthalate were higher in winter than in autumn. Potential sources included iron furniture, chemical fiber textiles, clothes, and personal care products. Medium-density fiberboard furniture is a potential sink for phthalates. In two seasons, DEHP, DCHP, DiBP, and DnBP were the main phthalates ingested by college students . The median oral exposure of ten phthalates was higher in females than in males. College students have a high risk of exposure to DEHP in dormitories.


Asunto(s)
Polvo , Exposición a Riesgos Ambientales , Ácidos Ftálicos , Ácidos Ftálicos/análisis , Polvo/análisis , Universidades , Humanos , Femenino , Masculino , Exposición a Riesgos Ambientales/análisis , Beijing , Vivienda , Contaminantes Ambientales/análisis , Monitoreo del Ambiente , Estaciones del Año , Contaminación del Aire Interior/análisis , Adulto Joven , Adulto
9.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2841-2852, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-39041143

RESUMEN

The discipline development is the pillar for the development of traditional Chinese medicine( TCM). The academic progress in TCM is the commanding height of the discipline development of TCM. To lead and promote the development and academic progress of TCM, the China Association of Chinese Medicine has summarized the Top Ten Academic Achievements in Traditional Chinese Medicine during 2020-2022, the Major Scientific Problems, Engineering Technical Problems, and Industrial Technical Problems in Traditional Chinese Medicine during 2019-2023, and the Remarkable Research Achievements of Traditional Chinese Medicine during 2012-2022. Based on the above research reports and the research achievements awarded the national science and technology prizes in TCM in the last 20 years and according to the current situation and layout of TCM discipline development, this paper reviews the major research achievements of TCM in the last two decades and the latest research progress in TCM during 2020-2023. The major scientific, engineering technical, and industrial technical problems in TCM are analyzed and the emerging trends of TCM are prospected in accordance with the development laws and characteristics of TCM. This review provides new ideas and reference for the high-quality development of TCM in the new era.


Asunto(s)
Medicina Tradicional China , Medicina Tradicional China/tendencias , China , Humanos , Medicamentos Herbarios Chinos
10.
J Transl Med ; 21(1): 869, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037074

RESUMEN

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.


Asunto(s)
Infecciones por VIH , Receptor Toll-Like 7 , Humanos , Antígeno CD47 , Quinasas Janus/metabolismo , Células Asesinas Naturales/metabolismo , Leucocitos Mononucleares/metabolismo , Ligandos , Factor de Transcripción STAT3/metabolismo , Interferón gamma/metabolismo
11.
PLoS Pathog ; 17(2): e1009258, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33577588

RESUMEN

Human immunodeficiency virus type 1 (HIV-1) recombinants in the world are believed to be generated through recombination between distinct HIV-1 strains among coinfection or superinfection cases. However, direct evidence to support transmission of HIV-1 recombinants from a coinfected/superinfected donor to putative recipient is lacking. Here, we report on the origin and evolutionary relationship between a set of recombinants from a CRF01_AE/CRF07_BC superinfected putative donor and diverse CRF01_AE/CRF07_BC recombinants from five putative recipients. Interviews on sociodemographic characteristics and sexual behaviors for these six HIV-1-infected men who have sex with men showed that they had similar ways of partner seeking: online dating sites and social circles. Phylogenetic and recombination analyses demonstrated that the near-full-length genome sequences from six patients formed a monophyletic cluster different from known HIV-1 genotypes in maximum likelihood phylogenetic trees, were all composed of CRF01_AE and CRF07_BC fragments with two common breakpoints on env, and shared 4-7 breakpoints with each other. Moreover, 3' half-genomes of recombinant strains from five recipients had identical/similar recombinant structures with strains at longitudinal samples from the superinfected donor. Recombinants from the donor were paraphyletic, whereas five recipients were monophyletic or polyphyletic in the maximum clade credibility tree. Bayesian analyses confirmed that the estimated time to the most recent common ancestor (tMRCA) of CRF01_AE and CRF07_BC strains of the donor was 2009.2 and 2010.7, respectively, and all were earlier than the emergence of recombinants from five recipients. Our results demonstrated that the closely related unique recombinant forms of HIV-1 might be the descendent of a series of recombinants generated gradually in a superinfected patient. This finding highlights the importance of early initiation of antiretroviral therapy as well as tracing and testing of partners in patients with multiple HIV-1 infection.


Asunto(s)
Genoma Viral , Infecciones por VIH/transmisión , VIH-1/genética , Homosexualidad Masculina , Recombinación Genética , Conducta Sexual , Sobreinfección/transmisión , Estudios de Cohortes , Evolución Molecular , Genotipo , Infecciones por VIH/genética , Infecciones por VIH/virología , Humanos , Masculino , Filogenia , Sobreinfección/genética , Sobreinfección/virología
12.
J Magn Reson Imaging ; 58(6): 1815-1823, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36988474

RESUMEN

BACKGROUND: There are known cardiac manifestations of HIV, but the findings in asymptomatic subjects are still not fully explored. PURPOSE: To evaluate for the presence of subclinical myocardial injury in asymptomatic people living with human immunodeficiency virus (PLWH) by cardiac MRI and to explore the possible association between subclinical myocardial injury and HIV-related clinical characteristics. STUDY TYPE: Cross-sectional. POPULATION: A total of 80 asymptomatic PLWH (age: 53 years [47-56 years]; 90% male) and 50 age- and sex-matched healthy participants. FIELD STRENGTH/SEQUENCE: A 3-T, cine sequence, T1, T2, and T2* mapping. ASSESSMENT: Function analysis was derived from short axis, two-, three-, and four-chamber cine images by feature tracking. Regions of interest were manually selected in the midventricular septum T1, T2, and T2* mapping sequences. PLWH were evaluated for T1 increment (△T1 mapping = native T1 - cutoff values) and HIV-related clinical characteristics, particularly the nadir CD4 count. And PLWH were stratified into two groups according to the cutoff value of native T1: elevated native T1 and normal. STATISTICAL TESTS: T test, Wilcoxon rank-sum test, Chi-square test, Spearman rank correlation, and logistic regression. P <0.05 indicated statistical significance. RESULTS: Asymptomatic PLWH revealed significantly higher native myocardial T1 values (1241 ± 29 msec vs. 1189 ± 21 msec), T2 values (40.7 ± 1.5 msec vs. 37.9 ± 1.4 msec), and lower LVGRS (30.2% ± 6.2% vs. 35.8% ± 6.4%), LVGCS (-18.0% ± 2.5% vs. -19.5% ± 2.0%), and LVGLS (-16.0% ± 3.8% vs. -17.9% ± 2.6%) but showed no difference in T2* values (17.3 msec [16.3-19.1 msec] vs. 18.3 msec [16.5-19.3 msec], P = 0.201). A negative correlation between the native T1 increment in PLWH with subclinical myocardial injury and the nadir CD4 count (u = -0.316). Nadir CD4 count <500 cells/mm3 was associated with higher odds of elevated native T1 myocardial values (odds ratio, 6.12 [95% CI, 1.07-34.91]) in PLWH. DATA CONCLUSION: Subclinical myocardial inflammation and dysfunction were present in asymptomatic PLWH, and a lower nadir CD4 count may be a risk factor for subclinical myocardial injury. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Infecciones por VIH , Lesiones Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Femenino , VIH , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Corazón/diagnóstico por imagen , Miocardio , Infecciones por VIH/complicaciones , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas
13.
Arch Sex Behav ; 52(2): 679-687, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36539633

RESUMEN

In the "treat all" era, the high rate of late HIV diagnosis (LHD) worldwide remains an impediment to ending the HIV epidemic. In this study, we analyzed LHD in newly diagnosed people living with HIV (PLWH) and its impact on HIV transmission in Northeast China. Sociodemographic information, baseline clinical data, and plasma samples obtained from all newly diagnosed PLWH in Shenyang, the largest city in Northeast China, between 2016 and 2019 were evaluated. Multivariate logistic regression analysis was performed to identify risk factors associated with LHD. A molecular network based on the HIV pol gene was constructed to assess the risk of HIV transmission with LHD. A total of 2882 PLWH, including 882 (30.6%) patients with LHD and 1390 (48.2%) patients with non-LHD, were enrolled. The risk factors for LHD were older age (≥ 30 years: p < .01) and diagnosis in the general population through physical examination (p < .0001). Moreover, the molecular network analysis revealed that the clustering rate (p < .0001), the fraction of individuals with ≥ 4 links (p = .0847), and the fraction of individuals linked to recent HIV infection (p < .0001) for LHD were significantly or marginally significantly lower than those recorded for non-LHD. Our study indicates the major risk factors associated with LHD in Shenyang and their limited contribution to HIV transmission, revealing that the peak of HIV transmission of LHD at diagnosis may have been missed. Early detection, diagnosis, and timely intervention for LHD may prevent HIV transmission.


Asunto(s)
Infecciones por VIH , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Factores de Riesgo , Diagnóstico Precoz , China/epidemiología
14.
BMC Public Health ; 23(1): 2494, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38093204

RESUMEN

INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Estudios Transversales , Aceptación de la Atención de Salud , Fármacos Anti-VIH/uso terapéutico
15.
Proc Natl Acad Sci U S A ; 117(17): 9537-9545, 2020 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-32273392

RESUMEN

P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-like, 120-kDa glycoprotein that binds to P-, E-, and L-selectins. PSGL-1 is expressed primarily on the surface of lymphoid and myeloid cells and is up-regulated during inflammation to mediate leukocyte tethering and rolling on the surface of endothelium for migration into inflamed tissues. Although it has been reported that PSGL-1 expression inhibits HIV-1 replication, the mechanism of PSGL-1-mediated anti-HIV activity remains to be elucidated. Here we report that PSGL-1 in virions blocks the infectivity of HIV-1 particles by preventing the binding of particles to target cells. This inhibitory activity is independent of the viral glycoprotein present on the virus particle; the binding of particles bearing the HIV-1 envelope glycoprotein or vesicular stomatitis virus G glycoprotein or even lacking a viral glycoprotein is impaired by PSGL-1. Mapping studies show that the extracellular N-terminal domain of PSGL-1 is necessary for its anti-HIV-1 activity, and that the PSGL-1 cytoplasmic tail contributes to inhibition. In addition, we demonstrate that the PSGL-1-related monomeric E-selectin-binding glycoprotein CD43 also effectively blocks HIV-1 infectivity. HIV-1 infection, or expression of either Vpu or Nef, down-regulates PSGL-1 from the cell surface; expression of Vpu appears to be primarily responsible for enabling the virus to partially escape PSGL-1-mediated restriction. Finally, we show that PSGL-1 inhibits the infectivity of other viruses, such as murine leukemia virus and influenza A virus. These findings demonstrate that PSGL-1 is a broad-spectrum antiviral host factor with a unique mechanism of action.


Asunto(s)
VIH-1/fisiología , Glicoproteínas de Membrana/metabolismo , Acoplamiento Viral , Capa Leucocitaria de la Sangre , Linfocitos T CD4-Positivos , Regulación de la Expresión Génica , Células HeLa , Humanos
16.
Int J Mol Sci ; 24(23)2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38069136

RESUMEN

Electrocatalysts with high efficiency and low cost are always urgently needed for oxygen reduction reaction (ORR). As a new carbon allotrope, graphdiyne (GDY) has received much attention due to its unique chemical structure containing sp- and sp2-hybridized carbons, and intrinsic electrochemical activity ascribed to its inherent conductivity. Herein, we prepared two graphdiyne materials named GDY nanotube and nitrogen-doped GDY (NGDY) nanotube via cross-coupling reactions on the surface of Cu nanowires. As metal-free catalysts, their electrocatalytic activities for ORR were demonstrated. The results showed that the NGDY nanotube presents more excellent electrochemical performance than that of the GDY nanotube, including more positive potential and faster kinetics and charge transfer process. The improvement can be ascribed to the greater number of structural electrocatalytic active sites from nitrogen atoms as well as the hollow nanotube morphology, which is beneficial to the adsorption of oxygen and acceleration of the catalytic reaction. This work helps develop high-quality graphdiyne-based electrocatalysts with well-defined chemical structures and morphologies for various electrochemical reactions.


Asunto(s)
Grafito , Nanotubos , Humanos , Hipoxia , Carbono , Oxígeno , Nitrógeno
17.
Molecules ; 28(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36677884

RESUMEN

The well-defined heterostructure of the photocathode is desirable for photoelectrochemically producing hydrogen from aqueous solutions. Herein, enhanced heterostructures were fabricated based on typical stable covalent organic framework (TpPa-1) films and TiO2 nanotube arrays (NTAs) as a proof-of-concept model to tune the photoelectrochemical (PEC) hydrogen generation by tailoring the photoelectrode microstructure and interfacial charge transport. Ultrathin TpPa-1 films were uniformly grown on the surface of TiO2 NTAs via a solvothermal condensation of building blocks by tuning the monomer concentration. The Pt1@TpPa-1/TiO2-NTAs photoelectrode with single-atom Pt1 as a co-catalyst demonstrated improved visible-light response, enhanced photoconductance, lower onset potential, and decreased Tafel slope value for hydrogen evolution. The hydrogen evolution rate of the Pt1@TpPa-1/TiO2-NTAs photoelectrode was five times that of Pt1@TpPa-1 under AM 1.5 simulated sunlight irradiation and the bias voltage of 0 V. A lower overpotential was recorded as 77 mV@10 mA cm-2 and a higher photocurrent density as 1.63 mA cm-2. The hydrogen evolution performance of Pt1@TpPa-1/TiO2-NTAs photoelectrodes may benefit from the well-matched band structures, effective charge separation, lower interfacial resistance, abundant interfacial microstructural sites, and surficial hydrophilicity. This work may raise a promising way to design an efficient PEC system for hydrogen evolution by tuning well-defined heterojunctions and interfacial microstructures.

18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(6): 929-933, 2023 Dec 30.
Artículo en Zh | MEDLINE | ID: mdl-38173103

RESUMEN

Objective To investigate the influencing factors of Bethesda Ⅲ results in fine-needle aspiration biopsy of thyroid nodules.Methods A total of 300 thyroid nodules with cytological diagnosis results were analyzed retrospectively,including 100 Bethesda Ⅲ nodules and 50 nodules of Bethesda Ⅱ,Ⅳ,Ⅴ,and Ⅵ categories,respectively.Univariate analysis and Logistic regression analysis were performed on the clinical data of patients and the ultrasound signs of thyroid nodules to clarify the factors influencing the diagnosis of Bethesda Ⅲ nodules.Results Univariate analysis showed that Bethesda Ⅲ nodules were mostly adjacent to the capsule(P<0.001),with no blood flow in the color Doppler assessment(P=0.011)and lack of blood supply(P=0.033)and maximum diameter ≤0.9 cm(P=0.038)as revealed by the contrast-enhanced ultrasound.Logistic regression showed that the position close to the capsule(OR=5.110,95%CI=2.153-12.130,P<0.001)and color Doppler without blood flow signal(OR=3.015,95%CI=1.094-8.311,P=0.033)were independent risk factors for the diagnosis of Bethesda Ⅲ nodules.Conclusions The puncture difficulty caused by the dangerous position of thyroid nodules close to the capsule and the aspiration difficulty caused by the absence of blood flow signal in color Doppler are the main factors influencing the diagnosis of Bethesda Ⅲ nodules.Therefore,corresponding avoidance measures should be taken during the aspiration process to reduce the diagnosis results of Bethesda Ⅲ nodules.


Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Neoplasias de la Tiroides/diagnóstico , Biopsia con Aguja Fina/métodos , Estudios Retrospectivos , Ultrasonografía/métodos
19.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6324-6333, 2023 Dec.
Artículo en Zh | MEDLINE | ID: mdl-38211989

RESUMEN

Chronic heart failure(CHF) is a comprehensive clinical syndrome caused by multiple factors that result in structural and/or functional abnormalities of the heart, leading to impaired ventricular contraction and/or relaxation functions. This medical condition represents the final stage of various cardiovascular diseases. In the treatment of CHF, multiple clinical studies have demonstrated the benefits of using traditional Chinese medicine(TCM) to control oxidative stress, inflammation, and apoptosis, thereby delaying ventricular remodeling and reducing myocardial fibrosis. In this study, common TCM syndromes in the diagnosis and treatment of CHF in recent years were reviewed and summarized. Five common treatment methods including benefiting Qi and activating blood circulation, enhancing Qi and nourishing Yin, warming Yang for diuresis, eliminating phlegm and dampness, rescuing from collapse by restoring Yang, and corresponding classic prescriptions in prevention and treatment of CHF were concluded under the guidance of TCM syndrome differentiation thinking. Meanwhile, research progress on the modern pharmacological effects of these classic prescriptions was systematically discussed, so as to establish a unique treatment system for CHF by classic prescriptions under the guidance of TCM syndrome differentiation theory and provide innovative diagnosis and treatment strategies for clinical CHF.


Asunto(s)
Insuficiencia Cardíaca , Medicina Tradicional China , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Enfermedad Crónica , Síndrome
20.
Zhongguo Zhong Yao Za Zhi ; 48(3): 614-624, 2023 Feb.
Artículo en Zh | MEDLINE | ID: mdl-36872224

RESUMEN

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.


Asunto(s)
Cardiopatías , Insuficiencia Cardíaca , Animales , Medicina Tradicional China , Enfermedad Crónica , Modelos Animales
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