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The chemokine co-receptors CXCR4 and CCR5 mediate HIV entry and signal transduction necessary for viral infection. However, to date only the CCR5 antagonist maraviroc is approved for treating HIV-1 infection. Given that approximately 50% of late-stage HIV patients also develop CXCR4-tropic virus, clinical anti-HIV CXCR4 antagonists are needed. Here, we describe a novel allosteric CXCR4 antagonist TIQ-15 which inhibits CXCR4-tropic HIV-1 infection of primary and transformed CD4 T cells. TIQ-15 blocks HIV entry with an IC50 of 13 nM. TIQ-15 also inhibits SDF-1α/CXCR4-mediated cAMP production, cofilin activation, and chemotactic signaling. In addition, TIQ-15 induces CXCR4 receptor internalization without affecting the levels of the CD4 receptor, suggesting that TIQ-15 may act through a novel allosteric site on CXCR4 for blocking HIV entry. Furthermore, TIQ-15 did not inhibit VSV-G pseudotyped HIV-1 infection, demonstrating its specificity in blocking CXCR4-tropic virus entry, but not CXCR4-independent endocytosis or post-entry steps. When tested against a panel of clinical isolates, TIQ-15 showed potent inhibition against CXCR4-tropic and dual-tropic viruses, and moderate inhibition against CCR5-tropic isolates. This observation was followed by a co-dosing study with maraviroc, and TIQ-15 demonstrated synergistic activity. In summary, here we describe a novel HIV-1 entry inhibitor, TIQ-15, which potently inhibits CXCR4-tropic viruses while possessing low-level synergistic activities against CCR5-tropic viruses. TIQ-15 could potentially be co-dosed with the CCR5 inhibitor maraviroc to block viruses of mixed tropisms.
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Infecções por HIV , HIV-1 , Receptores CXCR4 , Internalização do Vírus , Humanos , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Internalização do Vírus/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Inibidores da Fusão de HIV/farmacologia , Maraviroc/farmacologia , Triazóis/farmacologia , Fármacos Anti-HIV/farmacologia , Células HEK293RESUMO
Persistence of human immunodeficiency virus (HIV) reservoirs prevents viral eradication, and consequently HIV-infected patients require lifetime treatment with antiretroviral therapy (ART) [1-5]. Currently, there are no effective therapeutics to prevent HIV rebound upon ART cessation. Here we describe an HIV/SIV Rev-dependent lentiviral particle that can be administered to inhibit viral rebound [6-9]. Using simian immunodeficiency virus (SIV)-infected rhesus macaques as a model, we demonstrate that the administration of pre-assembled SIV Rev-dependent lentiviral particles into SIVmac239-infected Indian rhesus macaques can lead to reduction of viral rebound upon ART termination. One of the injected animals, KC50, controlled plasma and CNS viremia to an undetectable level most of the time for over two years after ART termination. Surprisingly, detailed molecular and immunological characterization revealed that viremia control was concomitant with the induction of neutralizing antibodies (nAbs) following the administration of the Rev-dependent vectors. This study emphasizes the importance of neutralizing antibodies (nAbs) for viremia control [10-15], and also provides proof of concept that the Rev-dependent vector can be used to target viral reservoirs, including the CNS reservoirs, in vivo. However, future large-scale in vivo studies are needed to understand the potential mechanisms of viremia control induced by the Rev-dependent vector.
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The associations of arbuscular mycorrhizal (AM) or ectomycorrhiza (EcM) fungi with plants have sequentially evolved and significantly contributed to enhancing plant nutrition. Nonetheless, how evolutionary and ecological forces drive nutrient acquisition strategies of AM and EcM woody plants remains poorly understood. Our global analysis of woody species revealed that, over divergence time, AM woody plants evolved faster nitrogen mineralization rates without changes in nitrogen resorption. However, EcM woody plants exhibited an increase in nitrogen mineralization but a decrease in nitrogen resorption, indicating a shift towards a more inorganic nutrient economy. Despite this alteration, when evaluating present-day woody species, AM woody plants still display faster nitrogen mineralization and lower nitrogen resorption than EcM woody plants. This inorganic nutrient economy allows AM woody plants to thrive in warm environments with a faster litter decomposition rate. Our findings indicate that the global pattern of nutrient acquisition strategies in mycorrhizal plants is shaped by the interplay between phylogeny and climate.
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Micorrizas , Raízes de Plantas/microbiologia , Nitrogênio , Plantas , Nutrientes , Solo , SimbioseRESUMO
Water use efficiency (WUE) represents the trade-off between carbon assimilation and water loss in plants. It remains unclear how leaf stomatal and photosynthetic traits regulate the spatial variation of leaf WUE in different natural forest ecosystems. We investigated 43 broad-leaf tree species spanning from cold-temperate to tropical forests in China. We quantified leaf WUE using leaf δ13C and measured stomatal traits, photosynthetic traits as well as maximum stomatal conductance ( G w max ) and maximum carboxylation capacity ( V c max ). We found that leaves in cold-temperate forests displayed 'fast' carbon economics, characterized by higher leaf nitrogen, Chl, specific leaf area, and V c max , as an adaptation to the shorter growing season. However, these leaves exhibited 'slow' hydraulic traits, with larger but fewer stomata and similar G w max , resulting in higher leaf WUE. By contrast, leaves in tropical forests had smaller and denser stomata, enabling swift response to heterogeneous light conditions. However, this stomatal configuration increased potential water loss, and coupled with their low photosynthetic capacity, led to lower WUE. Our findings contribute to understanding how plant photosynthetic and stomatal traits regulate carbon-water trade-offs across climatic gradients, advancing our ability to predict the impacts of climate changes on forest carbon and water cycles.
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Clima , Florestas , Fotossíntese , Estômatos de Plantas , Água , Fotossíntese/fisiologia , Água/metabolismo , Água/fisiologia , Estômatos de Plantas/fisiologia , Característica Quantitativa Herdável , Folhas de Planta/fisiologia , Isótopos de Carbono , Árvores/fisiologia , Carbono/metabolismo , Nitrogênio/metabolismoRESUMO
Multispectral imaging holds great promise for the detection of metameric materials. However, traditional multispectral imaging systems are characterized by their large volume, complex structure, and high computational requirements, limiting their practical application. We propose a jointly optimized deep optical architecture that combines the liquid crystal (LC) microlens array (MLA) characteristics and a multi-level perceptual spectral reconstruction network (MLP-SRN). The core of the architecture is to integrate the physical properties of the LC-MLA into the MLP-SRN using point spread function (PSF) optical convolution kernels, decoupling the light-field characteristic information collected by the LC-MLA at different voltages. Experimental results demonstrate that the incorporation of the physical properties of the LC-MLA not only reduces the system size and computational complexity but demonstrates excellent performance in identifying a metameric material.
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BACKGROUND: Arterial stiffness (AS) was associated with heart failure (HF) in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account. Whether AS was independently associated with new-onset HF in community dwellers has not been fully investigated to date. METHODS: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity (baPWV) screening in 2010 to 2019 were included. They were free of HF and atrial fibrillation at baseline. The participants were allocated to 3 groups according to their baPWV values. Normal AS was defined as baPWV <1400 cm/s, borderline AS was defined as 1400≤baPWV<1800 cm/s, and elevated AS was defined as baPWV ≥1800 cm/s. Cox proportional hazard regression was used to calculate hazard ratios with 95% CIs of new-onset HF across different AS groups. RESULTS: A total of 40 064 participants were enrolled with a mean age of 48.81±12.67 years. During a mean 5.53 years of follow-up, 411 participants developed HF. Compared with the normal AS group, the hazard ratio (95% CI) for incident HF was 1.97 (1.36-2.86) for the borderline AS group and 2.24 (1.49-3.38) for the elevated AS group in the multivariable-adjusted model. For each 1 SD (359 cm/s) increase in baPWV, the hazard ratio (95% CI) for new-onset HF was 1.10 (1.02-1.20). CONCLUSIONS: AS was positively associated with a higher risk of new-onset HF independently of traditional risk factors, with a dose-responsive effect.
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Insuficiência Cardíaca , Rigidez Vascular , Humanos , Adulto , Pessoa de Meia-Idade , Índice Tornozelo-Braço , Rigidez Vascular/fisiologia , Análise de Onda de Pulso , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Pressão SanguíneaRESUMO
OBJECTIVES: This study aimed to evaluate the association between different levels of physical activity and risk of developing type 2 diabetes (T2D) mellitus among adults with prediabetes in Chinese population. METHODS: This prospective population-based cohort study included 12,424 participants (mean [SD] age, 52.8 [16.8] years; 82.2% men) with prediabetes at 2014 survey of the Kailuan study. Physical activity information was collected through the International Physical Activity Questionnaire-Short Form and categorized by metabolic equivalent (MET) of task as low, moderate, and high. Cox regression models were built to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between physical activity levels and incident T2D. RESULTS: During a median follow-up of 3.6 years, 2,207 (17.8%) participants developed T2D. The incident rate of T2D were 55.83/1000, 35.14/1000, and 39.61/1000 person-years in the low, moderate, and high physical activity level group, respectively. Both moderate (HR 0.57, 95% CI 0.49 to 0.67) and high (HR 0.76, 95% CI 0.66 to 0.89) physical activity levels were associated with lower risks of developing T2D compared to low physical activity level (P for trend < 0.001). The association between high physical activity level and T2D was primarily observed in participants without metabolic syndrome (P for interaction < 0.001). Moreover, participants with moderate or high levels of physical activity had significantly decreased fasting blood glucose levels during follow-up when compared to those with low level (P group*time < 0.001). CONCLUSION: This study suggested that individuals with prediabetes might benefit from moderate and high levels of physical activity.
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Diabetes Mellitus Tipo 2 , Exercício Físico , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Estado Pré-Diabético/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Exercício Físico/fisiologia , Estudos Prospectivos , Adulto , Fatores de Risco , China/epidemiologia , Idoso , Estudos de Coortes , Incidência , Inquéritos e Questionários , Glicemia/metabolismo , SeguimentosRESUMO
Bio-cement is a green and energy-saving building material that has attracted much attention in the field of ecological environment and geotechnical engineering in recent years. The aim of this study is to investigate the use of bio-cement (enzyme-induced calcium carbonate precipitation-EICP) in combination with admixtures for the improvement of desert sands, which can effectively improve the mechanical properties of desert sands and is particularly suitable for sand-rich countries. In addition, the suitability of tap water in bio-cement was elucidated and the optimum ratio of each influencing factor when tap water is used as a solvent was derived. The results showed that peak values of unconfined compressive strength (maximum increase of about 130 times), shear strength (increase of 27.09%), calcium carbonate precipitation value (increase of about 4.39 times), and permeability (decrease of about 93.72 times) were obtained in the specimens modified by EICP combined with admixture as compared to the specimens modified by EICP only. The incorporation of skimmed milk powder, though significantly increasing the strength, is not conducive to cost control. The microscopic tests show that the incorporation of admixtures can provide nucleation sites for EICP, thus improving the properties of desert sand. This work can provide new research ideas for cross-fertilization between the disciplines of bio-engineering, ecology, and civil engineering.
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Carbonato de Cálcio , Areia , Areia/química , Carbonato de Cálcio/química , Materiais de Construção , Clima Desértico , Força CompressivaRESUMO
INTRODUCTION: We delineated the associations among long-term blood pressure variability (BPV), brain structure, and cognitive function. METHODS: We included 1254 adult participants from the Kailuan study. BPV was calculated from 2006 to 2020. Brain magnetic resonance imaging (MRI) and Montreal Cognitive Assessment (MoCA) were conducted in 2020. RESULTS: Higher systolic BPV (SBPV) and diastolic BPV (DBPV) were associated with lower total and frontal gray matter (GM) volume, and higher SBPV was associated with lower temporal GM volume. Elevated DBPV was associated with lower volume of total brain and parietal GM, and higher white matter hyperintensity (WMH) volume. Higher SBPV and DBPV were associated with lower MoCA scores. Decreased total and regional GM volume and increased WMH volume were associated with lower MoCA scores. The association between SBPV and cognitive function was mediated by total, frontal, and temporal GM volume. DISCUSSION: GM volume may play key roles in the association between SBPV and cognitive function. HIGHLIGHTS: SBPV and DBPV were negatively associated with total and regional brain volume. SBPV and DBPV were negatively associated with cognitive function. Decreased brain volume was associated with cognitive decline. GM volume mediated the negative association between SBPV and cognitive function.
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Pressão Sanguínea , Cognição , Substância Cinzenta , Imageamento por Ressonância Magnética , Humanos , Masculino , Substância Cinzenta/diagnóstico por imagem , Feminino , Pressão Sanguínea/fisiologia , Cognição/fisiologia , Pessoa de Meia-Idade , Idoso , Disfunção Cognitiva/fisiopatologia , Adulto , Testes de Estado Mental e Demência , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , ChinaRESUMO
The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regulatory T cells (T(reg) cells). We identify two transforming growth factor-ß1 (TGF-ß1)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3(-/-) CD4(+) T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3(-/-) T cells showed greater differentiation into the T(H)17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-ß-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.
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Asma/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Inibidoras de Diferenciação/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Animais , Asma/induzido quimicamente , Asma/genética , Asma/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Deleção de Sequência/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia , Ativação Transcricional/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Understanding how plants adapt to spatially heterogeneous phosphorus (P) supply is important to elucidate the effect of environmental changes on ecosystem productivity. Plant P supply is concurrently controlled by plant internal conservation and external acquisition. However, it is unclear how climate, soil, and microbes influence the contributions and interactions of the internal and external pathways for plant P supply. Here, we measured P and nitrogen (N) resorption efficiency, litter and soil acid phosphatase (AP) catalytic parameters (Vmax(s) and Km ), and soil physicochemical properties at four sites spanning from cold temperate to tropical forests. We found that the relative P limitation to plants was generally higher in tropical forests than temperate forests, but varied greatly among species and within sites. In P-impoverished habitats, plants resorbed more P than N during litterfall to maintain their N : P stoichiometric balance. In addition, once ecosystems shifted from N-limited to P-limited, litter- and soil-specific AP catalytic efficiency (Vmax(s) /Km ) increased rapidly, thereby enhancing organic P mineralization. Our findings suggested that ecosystems develop a coupled aboveground-belowground strategy to maintain P supply and N : P stoichiometric balance under P-limitation. We also highlighted that N cycle moderates P cycles and together shape plant P acquisition in forest ecosystems.
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Ecossistema , Fósforo , Fósforo/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Florestas , Plantas/metabolismo , Solo/química , Fosfatase Ácida/metabolismo , Nitrogênio/metabolismo , Folhas de Planta/metabolismoRESUMO
The miniaturized imaging spectrometers face bottlenecks in reconstructing the high-resolution spectral image. In this study, we have proposed an optoelectronic hybrid neural network based on zinc oxide (ZnO) nematic liquid crystal (LC) microlens array (MLA). This architecture optimizes the parameters of the neural network by constructing the TV-L1-L2 objective function and using mean square error as a loss function, giving full play to the advantages of ZnO LC MLA. It adopts the ZnO LC-MLA as optical convolution to reduce the volume of the network. Experimental results show that the proposed architecture has reconstructed a 1536 × 1536 pixels resolution enhancement hyperspectral image in the wavelength range of [400â nm, 700â nm] in a relatively short time, and the spectral accuracy of reconstruction has reached just 1â nm.
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OBJECTIVE: We aimed to examine the association of triglyceride-glucose index (TyG) with risk for cardiovascular disease (CVD) among postmenopausal women. METHODS: A total of 7741 participants met the inclusion criteria, and were included in the analysis. The TyG index was calculated as ln (triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2). The participants were classified into four groups by the quartiles of TyG index, and the Q1 group was used as the reference group. The cumulative incidence of CVD for the groups were compared using the Kaplan-Meier curves. The association between the TyG index and risk of CVD among postmenopausal women was assessed by the Cox proportional hazards models (hazard ratio [HR], 95% confidence intervals [CI]). RESULTS: During a median follow-up of 12 years, a total of 383 (4.95%) participants developed incident CVD. After adjusting for potential confounding factors, a high baseline TyG index (Q4 group) was associated with higher future risk of CVD, the HR (95% CI) of CVD risk was 1.70 (1.21-2.38) in Q4 group compared with the Q1 group. Subgroup analyses showed the Q4 group was significantly associated with the risk of CVD, regardless of age at menopause (younger than 50 years; 50 years and older) and obesity status. CONCLUSIONS: Higher TyG index at baseline as a marker of insulin resistance (IR), is associated with higher risk of future CVD among postmenopausal women. The TyG index may serve as a simple and easy marker for early identification of high-risk individuals in the postmenopausal women.
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Doenças Cardiovasculares , Glucose , Humanos , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Triglicerídeos , Pós-Menopausa , Glicemia , Medição de Risco , BiomarcadoresRESUMO
BACKGROUND: A few studies have reported the association between famine exposure during fetal development and risk of CVD, but no mechanisms have been explored. OBJECTIVES: The objective of this study was to examine risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. METHODS: A total of 59,416 participants of the Kailuan Study without CVD were included. All participants were divided into 3 groups based on date of birth, including the unexposed group (1963-1974), the fetal-exposed group (1959-1962), and the childhood-exposed group (1949-1958). Systemic immune-inflammation index (SII) (neutrophils × platelets / lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocytes / lymphocytes) are 2 novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. RESULTS: During a median follow-up period of 12.36 (12.69, 13.16) y, a total of 3772 cases of CVD were documented. Compared with unexposed participants, the fetal-exposed group had an increased risk of CVD (HR: 1.19; 95% CI: 1.04, 1.38) and stroke (HR: 1.28; 95% CI: 1.09, 1.51) but not MI. No association was observed in the childhood-exposed group. In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke and 31.25% of MI). CONCLUSIONS: Fetal exposure to famine may increase risk of CVD in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.
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Doenças Cardiovasculares , Efeitos Tardios da Exposição Pré-Natal , Inanição , Feminino , Humanos , Adulto , Criança , Fome Epidêmica , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Inanição/complicações , Inflamação , China , Fatores de RiscoRESUMO
Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Galphai-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.
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Actinas/metabolismo , Linfócitos T CD4-Positivos/virologia , Cofilina 1/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Receptores CXCR4/metabolismo , Sequência de Aminoácidos , Antígenos CD4 , Células Cultivadas , Cofilina 1/química , HIV , Infecções por HIV , Humanos , Dados de Sequência Molecular , Transdução de SinaisRESUMO
BACKGROUND: The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. METHODS: This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006-2007, 2010-2011, and 2014-2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 - 10) and late (cumCVAI10 - 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. RESULTS: During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13-1.61) in the highest quartile of cumCVAI, 1.35 (1.14-1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12-1.43) in those with a cumulative burden > 0, and 1.43 (1.14-1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11-1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03-1.46) for cumCVAI ≥ median with a positive slope. CONCLUSIONS: In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life.
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Adiposidade , Hipertensão , Humanos , População do Leste Asiático , Hipertensão/complicações , Estudos ProspectivosRESUMO
BACKGROUND: The triglyceride-glucose index (TyG index), an alternative indicator of peripheral insulin resistance (IR), is associated with cardiovascular disease (CVD) in the general population. The aim of this research was to determine the correlation between early-onset stroke and the TyG index among young Chinese adults. METHODS: Participants (age ≤ 40 years) who attended their first physical examination in Kailuan General Hospital or its 11 subsidiary hospitals between 2006 and 2012 were enrolled. The subjects were divided into four equal points according to the quartile of the TyG index, with the lowest quartile (Q1) as the reference group. A Cox proportional hazard model was employed to assess the correlation between early-onset stroke incidence and the TyG index. Restricted cubic spline analysis was further conducted to examine nonlinear associations. The TyG index was calculated as Ln [Triglyceride (TG, mg/dL) × Fasting Blood Glucose (FBG, mg/dL)/2]. RESULTS: Overall, 35,999 subjects met the inclusion criteria. Their mean age was 30.8 ± 5.7 years, and 77.1% of subjects were males. During a median observation period of 11 years, 281 stroke events occurred (62 hemorrhagic strokes and 219 ischemic strokes). Compared to the Q1 group (as the lowest group), subjects in groups Q2-Q4 had significantly higher risks of early-onset stroke (P < 0.05) after adjustment for relevant confounders in the Cox proportional hazards model. Similar results were consistent with ischemic stroke. However, no significant associations were observed between the risk of hemorrhage and the baseline TyG index. The restricted cubic splines revealed that the risk of stroke progressively increased with a high TyG index ≥ 8.41. CONCLUSIONS: The TyG index may be a major risk factor for early-onset stroke among young Chinese adults. A TyG index ≥ 8.41 can be used as an indicator for screening high-risk stroke groups.
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Glicemia , Acidente Vascular Cerebral , Triglicerídeos , Feminino , Humanos , Masculino , Idade de Início , Biomarcadores/sangue , Glicemia/análise , População do Leste Asiático , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Triglicerídeos/sangue , Adulto Jovem , China/epidemiologiaRESUMO
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.
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HIV-1/fisiologia , Glicoproteínas de Membrana/metabolismo , Ligação Viral , Buffy Coat , Linfócitos T CD4-Positivos , Regulação da Expressão Gênica , Células HeLa , HumanosRESUMO
Objective: This cohort study investigated the association between cardiovascular health index scores and pregnancy-induced hypertension (PIH). Methods: A total of 1466 first-time pregnant women who delivered a single child between 2006 and 2016 were included in the study. All participants underwent a physical examination before delivery, and seven cardiovascular health indexes were collected and scored. Three groups were created based on the tri-sectional quantiles of the total score to observe whether PIH occurred among the groups. A dichotomous logistic regression analysis was carried out to investigate the relationship between cardiovascular health index scores and the occurrence of PIH. Results: During the observation of 1150 subjects, 103 cases of PIH were identified, resulting in an incidence rate of 8.96%. The study found that the incidence of PIH in the three groups was 17.5% in the first group, 6.7% in the second, and 5.8% in the third group. These rates showed a sequential decrease with statistically significant differences (P < .001). The multifactorial regression analysis revealed that after adjusting for various factors, there was a significant inverse relationship between cardiovascular health index scores and the risk of PIH. Specifically, for every one-point increase in the seven cardiovascular health index scores, the risk of PIH decreased by 29% (OR = 0.71, 95% CI 0.59-0.86). Conclusions: The study found an inverse correlation between cardiovascular health index scores and PIH, with higher scores associated with lower incidences of PIH. Each cardiovascular health indicator helps to lower the risk of PIH, and optimum cardiovascular health behaviors and variables are protective factors against PIH.
Assuntos
Hipertensão Induzida pela Gravidez , Hipertensão , Criança , Gravidez , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Estudos de Coortes , Fatores de RiscoRESUMO
BACKGROUND: Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and cardiovascular disease (CVD). However, the long-term effect of TyG index and incident CVD remains uncertain. This study aimed to investigate the association between cumulative TyG index and the risk of CVD. METHOD: In this study, we recruited individuals participating in Kailuan Study from 2006 to 2013 without stroke, myocardial infarction, and cancer in the four consecutive examinations. Cumulative TyG index was calculated by multiplying the average TyG index and the time between the two consecutive examinations. Cumulative TyG index levels were categorized into four quartile groups: Q1 group, ≤ 50.65 (as reference group), Q2 group, 50.65-53.86, Q3 group, 53.86-57.44, Q4 group, > 57.44. The association between cumulative TyG index and the risk of CVD was estimated by multivariable Cox proportional hazard models. RESULT: A total of 44,064 individuals participated in the final analysis. After a mean follow-up of 6.52 ± 1.14 years, incident CVD, MI and stroke occurred in 2057, 395 and 1695, respectively. The risk of developing CVD increased with the quartile of cumulative in TyG index, after adjustment for multiple potential confounders, the HR for CVD events were 1.25 (1.08-1.44) in Q2, 1.22 (1.05-1.40) in Q3 and 1.39 (1.21-1.61) in Q4, compared to Q1 group. The longer duration of higher TyG index exposure was significantly associated with increased CVD risk. Similar results were obtained in the subgroup and sensitivity analysis. CONCLUSION: Cumulative TyG index was associated with increased risk of CVD. Maintaining an appropriate level of TG and FBG within the desirable range and better control of cumulative TyG index are important for prevention of CVD.