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1.
ACS Omega ; 9(11): 12789-12800, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38524481

RESUMO

The current research on fracture conductivity ignores the placement of the proppant in fractures and relies on single-fracture conductivity testing and calculation, which cannot represent the overall conductivity of complex fracture systems. This research proposes a calculation method for the long-term conductivity of complex fractures based on proppant placement. This method considers fracture morphology, proppant placement, proppant embedment, and deformation under high closing pressure. The research results show that fracture conductivity decreases with increasing time, which can be divided into three stages: the embedding stage, the creep stage, and the stabilization stage. The long-term conductivity of the main fracture is higher than that of the branching fracture. With increasing closing pressure, the conductivities of both the main fracture and the branching fracture decrease. This is because increasing closure stress accelerates proppant embedment and creep, compressing the fluid flow space and further reducing fracture conductivity. Fracture conductivity is related to the placement of the proppant and sand concentration. Increasing the sand ratio can significantly increase the placement of the proppant in the main fracture and branching fractures, thereby improving fracture conductivity. Increasing the fracturing fluid viscosity can increase its proppant migration capacity. The proppant does not easily settle prematurely in high-viscosity fracturing fluid and can enter more into branching fractures, thereby improving their conductivity.

2.
Small ; 20(3): e2306524, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37697691

RESUMO

Photonic crystal hydrogels (PCHs), with smart stimulus-responsive abilities, have been widely exploited as colorimetric sensors for years. However, the current fabrication technologies are mostly applicable to produce PCHs with simple geometries at the sub-millimeter scale, limiting the introduction of structural design into PCH sensors as well as the accompanied advanced applications. This paper reports the microfabrication of three-dimensional (3D) PCHs with the help of supramolecular agarose PCH as a sacrificial scaffold by two-photon lithography (TPL). The supramolecular PCHs, formulated with SiO2 colloidal nanoparticles and agarose aqueous solutions, show bright structural color and are degradable upon short-time dimethyl sulfoxide treatment. Leveraging the supramolecular PCH as a sacrificial scaffold, PCHs with precise 3D geometries can be fabricated in an economical and efficient way. This work demonstrates the application of such a strategy in the creation of structural-designed PCH mechanical microsensors that have not been explored before.

3.
Altern Ther Health Med ; 30(1): 44-50, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37773677

RESUMO

This study employs network pharmacology to uncover the pharmacological mechanisms underlying Shen-qi-di-huang decoction's efficacy in treating uremia. We identified a total of 927 differentially expressed genes (DEGs) through differential expression analysis and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform, of which 607 were downregulated and 320 were upregulated. We also obtained the effective biological components and related target gene information of Chinese herbal medicines such as Renshen, Huangqi, shudihuang, Shanyao, Fuling, Mudanpi, and Shanzhuyu in Shen-qi-di-huang decoction and constructed a regulatory relationship network between molecular components and target genes in Shen-qi-di-huang decoction. We then constructed a protein-protein interaction (PPI) network of 15 targeted genes (RXRA, ND6, CYP1B1, SLPI, CDKN1A, RB1, HIF1A, MYC, HSPB1, IFNGR1, NQO1, IRF1, RASA1, PSMG1 and MAP2K4) using the STRING database and visualized the PPI network using the software Cytoscape. In addition, we revealed the key molecular functions of uremia through Gene Ontology (GO) enrichment analysis, mainly including neuron apoptotic process, cellular response to oxidative stress, regulation of neuron apoptotic process, neuron projection cytoplasm, RNA polymerase II transcription regulator complex, plasma membrane bounded cell projection cytoplasm, NADH and NADPH dehydrogenase (quinone) activity, protein kinase inhibitor and ubiquitin protein ligase binding, etc. Finally, we identified important biological pathways in uremia through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which mainly concentrated in Kaposi sarcoma-associated, small cell lung cancer, Gastric cancer, Hepatitis B and C, Hepatocellular carcinoma, Thyroid cancer, Bladder cancer, MAPK signaling pathway, ErbB signaling pathway, Th17 cell differentiation, HIF-1 signaling pathway, Thyroid hormone signaling pathway and Cell cycle, etc. Using integrated bioinformatical analysis, we elucidated key pharmacological mechanisms based on targeted genes, which was enable early identification of patients with uremia and would contribute to early clinical diagnosis and treatment of patients.


Assuntos
Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Humanos , Farmacologia em Rede , Transdução de Sinais , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Proteína p120 Ativadora de GTPase
4.
J Transl Med ; 21(1): 869, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037074

RESUMO

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.


Assuntos
Infecções por HIV , Receptor 7 Toll-Like , Humanos , Antígeno CD47 , Janus Quinases/metabolismo , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/metabolismo , Ligantes , Fator de Transcrição STAT3/metabolismo , Interferon gama/metabolismo
5.
Nat Commun ; 14(1): 7369, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37963911

RESUMO

Current techniques for visualizing and quantifying cellular forces have limitations in live cell imaging, throughput, and multi-scale analysis, which impede progress in cell force research and its practical applications. We developed a photonic crystal cellular force microscopy (PCCFM) to image vertical cell forces over a wide field of view (1.3 mm ⨯ 1.0 mm, a 10 ⨯ objective image) at high speed (about 20 frames per second) without references. The photonic crystal hydrogel substrate (PCS) converts micro-nano deformations into perceivable color changes, enabling in situ visualization and quantification of tiny vertical cell forces with high throughput. It enabled long-term, cross-scale monitoring from subcellular focal adhesions to tissue-level cell sheets and aggregates.


Assuntos
Adesões Focais , Fótons , Microscopia de Força Atômica/métodos
6.
Lancet Reg Health West Pac ; 36: 100772, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37547042

RESUMO

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

7.
Neurogastroenterol Motil ; 35(9): e14633, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37427541

RESUMO

BACKGROUND: This study aimed to compare the prevalence and symptoms of fecal incontinence (FI) in relation to irritable bowel syndrome (IBS-associated FI), constipation (constipation-associated FI), and isolation (isolated FI). METHODS: Data were analyzed from 3145 respondents without organic comorbidities known to influence defecation function from the general Chinese population who filled in the online Groningen Defecation and Fecal Continence questionnaire. FI, IBS, and constipation were evaluated with the Rome IV criteria. KEY RESULTS: The prevalence of FI was 10.5% (n = 329) in the non-comorbidity group. After multivariable logistic regression analysis, IBS (odds ratio [OR]: 12.55, 95% confidence interval [CI]: 9.06-17.36) and constipation (OR: 4.38, 95% CI: 3.27-5.85) were the most significant factors contributing to FI. Based on this finding, 106/329 (32.2%) had IBS-associated FI, 119/329 (36.2%) had constipation-associated FI, and 104/329 (31.6%) had isolated FI. Among the 329 FI respondents, there was a high prevalence of IBS and constipation-related symptoms, including abdominal pain (81.5%) and abdominal bloating (77.8%) for IBS and straining during defecation (75.4%), incomplete defecation (72.3%), defecation blockage (63.2%), anal pain during defecation (59.3%), and hard stools (24%) for constipation. The patients with IBS-associated FI asked for specialists' help less frequently than those with isolated FI. Interestingly, among the patients with constipation-associated FI, 56.3% used anti-diarrhea medicine. CONCLUSIONS AND INFERENCES: The prevalence of IBS-associated FI, constipation-associated FI, and isolated FI is comparably high. It is important to diagnose and target the cause of FI to provide personalized and cause-targeting care instead of treating only the FI symptoms.


Assuntos
Incontinência Fecal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/diagnóstico , Medicina de Precisão , Constipação Intestinal , Defecação
8.
Ann Palliat Med ; 12(3): 507-515, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37038059

RESUMO

BACKGROUND: Currently, the diagnosis of defecation disorders in China is usually based on varied and ambiguous criteria. We aimed to translate the Groningen Defecation and Fecal Continence (DeFeC) questionnaire to Chinese and test its reproducibility and feasibility in the general Chinese population. METHODS: The Groningen Defecation Questionnaire was translated into Chinese according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). The feasibility and reproducibility were evaluated by performing a test-retest online survey and calculating the Cohen's kappa (κ) coefficient [or intraclass correlation coefficient (ICC)], with 0.01-0.20 considered slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement; and 0.81-1.00, almost perfect agreement. RESULTS: In total, 130 respondents completed the questionnaire twice, with a mean age of 47.08±12.46 years. No remarks were made that indicted that the questions were difficult to understand. The median time to complete the questionnaire was 20.78 min [interquartile range (IQR), 14.83-29.20 min] for the first time. The κ coefficient of all defecation function-related domains ranged between 0.25 and 0.71, with an average value of 0.53. The constipation and fecal incontinence-related domains showed a substantial and moderate agreement level, as indicated by κ of 0.65 and 0.52, respectively. The Agachan constipation score and Wexner incontinence score showed perfect and substantial agreement, as indicated by an ICC of 0.88 and 0.74, respectively. CONCLUSIONS: The Chinese version of the Groningen DeFeC questionnaire is highly feasible and reproducible and can be applied in clinical and research activities for the Chinese population.


Assuntos
Constipação Intestinal , Incontinência Fecal , Inquéritos e Questionários , Adulto , Humanos , Pessoa de Meia-Idade , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Incontinência Fecal/complicações , Incontinência Fecal/diagnóstico , Reprodutibilidade dos Testes , População do Leste Asiático , China
9.
J Magn Reson Imaging ; 58(6): 1815-1823, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36988474

RESUMO

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.


Assuntos
Infecções por HIV , Traumatismos Cardíacos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , HIV , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Coração/diagnóstico por imagem , Miocárdio , Infecções por HIV/complicações , Imagem Cinética por Ressonância Magnética , Valor Preditivo dos Testes
10.
Front Immunol ; 14: 1106881, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875092

RESUMO

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected "rapid progressors" (RPs) have severe damage to the immune system early in HIV infection, which provides a "magnified" opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 "normal progressors" (NPs; CD4+ T-cell count > 500 cells/µl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.


Assuntos
Linfócitos T CD8-Positivos , Infecções por HIV , Humanos , Espécies Reativas de Oxigênio , Proteína Supressora de Tumor p53 , Mitocôndrias , Ácidos Graxos
12.
Arch Sex Behav ; 52(2): 679-687, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36539633

RESUMO

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.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Fatores de Risco , Diagnóstico Precoce , China/epidemiologia
13.
ACS Nano ; 16(12): 21334-21344, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36482510

RESUMO

Plant photosynthesis is considered to be an environmentally friendly and effective measure for reducing carbon dioxide levels to meet the global objective of carbon neutrality. However, the light energy utilization of photosynthetic pigments is insufficient. Begonia pavonine (B. pavonina) with blue leaves exhibits a photosynthetic quantum yield 10% higher than those of other plants by virtue of their photonic crystal (PC) thylakoids. Inspired by this property, we prepared non-angle-dependent PC hydrogels and assembled them with algae Chlorella pyrenoidosa (C. pyre). The band edge of PC hydrogels matched the absorption peaks of C. pyre, and the resulting slow photon effect increased the interaction time between incident light and photosynthetic pigments, which in turn induced the expression of light-harvesting proteins and the synthesis of pigments, thereby improving the light energy utilization. Further, we introduced an artificial antenna into the assembly, which assisted the slow photon effect in increasing the oxygen evolution and carbon sequestration rate by more than 200%. This method avoids the photobleaching problems faced by methods of synthesizing artificial antenna pigments and the biosafety problems faced by genetically engineered methods of editing pigments or proteins.


Assuntos
Begoniaceae , Chlorella , Chlorella/metabolismo , Begoniaceae/metabolismo , Fotossíntese , Plantas/metabolismo , Tilacoides/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo
14.
Materials (Basel) ; 15(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36431732

RESUMO

For a better understanding of the changing trend in crystalline components of asphalt binders, asphalt binders originating from the SHRP Materials Reference Library with different oxidation degrees (unaged, 20 h PAV, and 60 h PAV) were prepared. The native asphalt binders and their oxidized residues were characterized by liquid-state nuclear magnetic resonance (NMR) spectroscopy and high-temperature gas chromatography (HTGC). The results showed that, compared with other carbon types, the content of internal methylene carbons of long paraffinic chains between different SHRP binders was quite different. The NMR average length of a long paraffinic internal methylene chain showed a good correlation with the wax content obtained at -20 °C using the methyl ethyl ketone (MEK) precipitation method and also the recently developed variable-temperature Fourier-transform infrared spectroscopy (VT-FTIR) method. In most cases, the average length of straight internal methylene carbons of a long paraffinic chain terminated by a methyl group increased with the oxidation of the asphalt binder. However, the difference caused by oxidation was significantly smaller than the difference caused by the source of the asphalt binder. In general, oxidation will make the n-alkanes distributed in asphalt binder fall within a narrower range. The carbon number of n-alkanes in the asphalt binder generally grew with oxidation.

15.
Front Immunol ; 13: 946871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268017

RESUMO

The ectonucleotidases CD38 and CD39 have a critical regulatory effect on tumors and viral infections via the adenosine axis. Natural killer (NK) cells produce cytokines, induce cytotoxic responses against viral infection, and acquire immunoregulatory properties. However, the roles of CD38 and CD39 expressed NK cells in HIV disease require elucidation. Our study showed that the proportions of CD38+CD39+ NK cells in HIV-infected individuals were positively associated with HIV viral loads and negatively associated with the CD4+ T cell count. Furthermore, CD38+CD39+ NK cells expressed additional inhibitory receptors, TIM-3 and LAG-3, and produced more TGF-ß. Moreover, autologous NK cells suppressed the proliferation of CD8+ T and CD4+ T cells of HIV-infected individuals, and inhibiting CD38 and CD39 on NK cells restored CD8+ T and CD4+ T cell proliferation in vitro. In conclusion, these data support a critical role for CD38 and CD39 on NK cells in HIV infection and targeting CD38 and CD39 on NK cells may be a potential therapeutic strategy against HIV infection.


Assuntos
Infecções por HIV , Humanos , Receptor Celular 2 do Vírus da Hepatite A , Células Matadoras Naturais , Adenosina , Proliferação de Células , Progressão da Doença , Citocinas , Contagem de Células , Fator de Crescimento Transformador beta
16.
Viruses ; 14(9)2022 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-36146701

RESUMO

Universal antiretroviral therapy (ART, "treat all") was recommended by the World Health Organization in 2015; however, HIV-1 transmission is still ongoing. This study characterizes the drivers of HIV transmission in the "treat all" era. Demographic and clinical information and HIV pol gene were collected from all newly diagnosed cases in Shenyang, the largest city in Northeast China, during 2016 to 2019. Molecular networks were constructed based on genetic distance and logistic regression analysis was used to assess potential transmission source characteristics. The cumulative ART coverage in Shenyang increased significantly from 77.0% (485/630) in 2016 to 93.0% (2598/2794) in 2019 (p < 0.001). Molecular networks showed that recent HIV infections linked to untreated individuals decreased from 61.6% in 2017 to 28.9% in 2019, while linking to individuals with viral suppression (VS) increased from 9.0% to 49.0% during the same time frame (p < 0.001). Undiagnosed people living with HIV (PLWH) hidden behind the links between index cases and individuals with VS were likely to be male, younger than 25 years of age, with Manchu nationality (p < 0.05). HIV transmission has declined significantly in the era of "treat all". Undiagnosed PLWH may drive HIV transmission and should be the target for early detection and intervention.


Assuntos
Infecções por HIV , HIV-1 , China/epidemiologia , Feminino , Genes pol , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Masculino , Manejo de Espécimes
17.
Front Immunol ; 13: 854432, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110864

RESUMO

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+ NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-ß1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.


Assuntos
Antígenos CD , Infecções por HIV , Antígenos CD/metabolismo , Progressão da Doença , Proteínas Ligadas por GPI/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Células Matadoras Naturais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Imunológicos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
18.
Proteomics Clin Appl ; 16(6): e2100099, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35920599

RESUMO

PURPOSE: Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV)-1 onward transmission and disease progression, leading to excellent prognosis in people living with HIV-1 (PWH). However, side effects, complications, and impaired immune reconstitution persist in some patients treated with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART. EXPERIMENTAL DESIGN: Quantitative proteomics analysis based on tandem mass tag (TMT) labeling was used to profile proteome changes of paired plasma samples from HIV-1 patients before receiving ART and after ART treatment. RESULTS: A total of 1398 protein groups (PGs) were identified, in which 18 proteins were downregulated and 50 were upregulated in plasma from ART treated patients. Based on Ingenuity Pathway analysis (IPA), gap junction signaling and actin cytoskeleton signaling were enriched among upregulated proteins, while downregulated proteins were mainly participated in IL-15 signaling pathway. Patients with the low level of CSF1R and the high levels of MINPP1 and TGM3 showed better CD4+ T-cell recovery. CONCLUSIONS: The present study provided plasma proteome changes after ART to elucidate the underlying mechanistic pathways in response to ART, and also identified potential targets to prompt immune reconstitution.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Proteoma/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/tratamento farmacológico , Proteômica , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Transglutaminases/metabolismo , Transglutaminases/uso terapêutico
19.
Nat Commun ; 13(1): 4563, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931721

RESUMO

The orderly arrangement of nanomaterials' tiny units at the nanometer-scale accounts for a substantial part of their remarkable properties. Maintaining this orderness and meanwhile endowing the nanomaterials with highly precise and free-designed 3D micro architectures will open an exciting prospect for various novel applications. In this paper, we developed a sacrificial-scaffold-mediated two-photon lithography (TPL) strategy that enables the fabrication of complex 3D colloidal crystal microstructures with orderly-arranged nanoparticles inside. We show that, with the help of a degradable hydrogel scaffold, the disturbance effect of the femtosecond laser to the nanoparticle self-assembling could be overcome. Therefore, hydrogel-state and solid-state colloidal crystal microstructures with diverse compositions, free-designed geometries and variable structural colors could be easily fabricated. This enables the possibility to create novel colloidal crystal microsensing systems that have not been achieved before.

20.
AIDS ; 36(12): 1741-1743, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35866529

RESUMO

We estimated the optimum time to initiate antiretroviral therapy (ART) in a retrospective observational cohort. We observed that ART initiation 7 days or less ( n  = 817) and 8-30 days ( n  = 1009) were the most important factors with viral suppression, and had similar viral suppression rate, CD4 + T-cell count increase and fractions of individuals with links at least 4 and individuals linked to recent HIV infection in HIV molecular networks. This study provides real-world evidence on the benefits of rapid ART initiation in resource-limited setting.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Retrospectivos , Carga Viral
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