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Necroptosis is generally considered as an inflammatory cell death form. The core regulators of necroptotic signaling are receptor-interacting serine-threonine protein kinases 1 (RIPK1) and RIPK3, and the executioner, mixed lineage kinase domain-like pseudokinase (MLKL). Evidence demonstrates that necroptosis contributes profoundly to inflammatory respiratory diseases that are common public health problem. Necroptosis occurs in nearly all pulmonary cell types in the settings of inflammatory respiratory diseases. The influence of necroptosis on cells varies depending upon the type of cells, tissues, organs, etc., which is an important factor to consider. Thus, in this review, we briefly summarize the current state of knowledge regarding the biology of necroptosis, and focus on the key molecular mechanisms that define the necroptosis status of specific cell types in inflammatory respiratory diseases. We also discuss the clinical potential of small molecular inhibitors of necroptosis in treating inflammatory respiratory diseases, and describe the pathological processes that engage cross talk between necroptosis and other cell death pathways in the context of respiratory inflammation. The rapid advancement of single-cell technologies will help understand the key mechanisms underlying cell type-specific necroptosis that are critical to effectively treat pathogenic lung infections and inflammatory respiratory diseases.
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Proteínas Quinases , Doenças Respiratórias , Humanos , Proteínas Quinases/metabolismo , Necroptose/fisiologia , Morte Celular , Transdução de Sinais , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , ApoptoseRESUMO
Exciton-polaritons, hybrid quasiparticles from the strong coupling of excitons and cavity photons in semiconductor microcavities, offer a platform for exploring quantum coherence and nonlinear optical properties. The unique polariton parametric scattering (PPS) laser is of interest for its potential in quantum technologies and nonlinear devices. However, direct resonant excitation of polaritons in strong-coupling microcavities is challenging. This study proposes an innovative two-photon absorption (TPA) pump mechanism to address this. We observe TPA-driven PPS lasing in a strongly coupled microcavity at room temperature. High K-value exciton injections promote coherent stimulated emission of polariton scattering through intermode channels. Angle-resolved spectra confirm a TPA process, showing evolution from pump-state to signal-state. Hanbury Brown-Twiss measurement of second-order correlation g2(τ) of signal state indicates a phase transition from a classical thermal state to a quantum coherent state. Theoretical modeling provides insights into the physical mechanisms of PPS. Our work advances nonlinear phenomena exploration in strongly coupled light-matter systems, contributing to quantum polaritonics and nonlinear optics.
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The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.
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Carcinogênese , Hexoquinase , Proteínas Proto-Oncogênicas c-akt , Hexoquinase/metabolismo , Hexoquinase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Humanos , Animais , Fosforilação , Camundongos , Carcinogênese/metabolismo , Carcinogênese/genética , Metástase Neoplásica , Feminino , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Glucose/metabolismoRESUMO
Cas9 protein-mediated gene editing has revolutionized genetic manipulation in most organisms. There are many cases where multiplexed gene editing is needed. Cas9 is capable of multiplex gene editing when expressed with multiple guide RNAs. Conventional cloning methods for multiplexed gene editing vector is not efficient due to repeated use of a single-guide RNA scaffold and inefficient ligation. In this study, we conducted structure-guided mutagenesis and random mutagenesis on the original sgRNA scaffold and identified a large number of functional sgRNA scaffold variants. With these scaffold variants and different tRNAs, fusion polymerase chain reaction protocol was developed to rapidly synthesize spacer-scaffold-tRNA-spacer units with up to 9 targets. In conjunction with golden gate cloning, gene editing vectors with up to 24 target sites were efficiently cloned in one-step cloning. One such gene editing vector targeting 12 genes in tomato were tested in stable transformation and 10 out of the 12 genes were found mutated in a single transgenic line. To facilitate the application of multiplexed gene editing using these scaffold variants and tRNAs from different species, a webserver was created to generate primer sets and provide template sequences for the synthesis of large sgRNA expression units based on the user-supplied target sequences and species.
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Sistemas CRISPR-Cas , Edição de Genes , Edição de Genes/métodos , RNA Guia de Sistemas CRISPR-Cas , Proteína 9 Associada à CRISPR/genética , Clonagem MolecularRESUMO
Antibodies specifically bind to antigens and are an essential part of the immune system. Hence, antibodies are powerful tools in research and diagnostics. High-throughput sequencing technologies have promoted comprehensive profiling of the immune repertoire, which has resulted in large amounts of antibody sequences that remain to be further analyzed. In this study, antibodies were downloaded from IMGT/LIGM-DB and Sequence Read Archive databases. Contributing features from antibody heavy chains were formulated as numerical inputs and fed into an ensemble machine learning classifier to classify the antigen specificity of six classes of antibodies, namely anti-HIV-1, anti-influenza virus, anti-pneumococcal polysaccharide, anti-citrullinated protein, anti-tetanus toxoid and anti-hepatitis B virus. The classifier was validated using cross-validation and a testing dataset. The ensemble classifier achieved a macro-average area under the receiver operating characteristic curve (AUC) of 0.9246 from the 10-fold cross-validation, and 0.9264 for the testing dataset. Among the contributing features, the contribution of the complementarity-determining regions was 53.1% and that of framework regions was 46.9%, and the amino acid mutation rates occupied the first and second ranks among the top five contributing features. The classifier and insights provided in this study could promote the mechanistic study, isolation and utilization of potential therapeutic antibodies.
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Sequência de Aminoácidos , Anticorpos/química , Aprendizado de Máquina , Especificidade de Anticorpos , Regiões Determinantes de Complementaridade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Curva ROCRESUMO
Peptide ALW (ALWPPNLHAWVP) targeting anti-dsDNA antibodies has shown promising therapeutic effects in alleviating lupus nephritis, but is potentially limited by poor stability and non-kidney targeting. We recently developed a D-form modified ALW, called D-ALW, which has the capacity to widely inhibit pathogenic polyclonal anti-dsDNA antibody reactions. Further modification of D-ALW using PEG-PLGA nanoparticles to enhance good kidney-targeting ability and extend half-life. Here, we demonstrate that the D-form modified ALW maintains higher binding and inhibition efficiencies and achieves higher stability. Most importantly, D-ALW nanoparticles exhibit excellent kidney-targeting ability and prolong the half-life of the peptides in BALB/c mice. Additionally, compared to D-ALW, D-ALW nanoparticles significantly reduce the glomerular deposition of IgG and C3, improve renal histopathologies, such as glomerular proliferation and inflammatory cells infiltration, and markedly prolong lifespan in MRL/lpr lupus-prone mice. Overall, these results establish that the D-ALW nanoparticles offer synergistic benefits in both safety and efficacy, providing long-term renal preservation and treatment advantages in lupus nephritis.
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Anticorpos Antinucleares , Modelos Animais de Doenças , Nefrite Lúpica , Camundongos Endogâmicos MRL lpr , Nanopartículas , Animais , Nefrite Lúpica/imunologia , Nefrite Lúpica/tratamento farmacológico , Camundongos , Anticorpos Antinucleares/imunologia , Nanopartículas/química , Feminino , Camundongos Endogâmicos BALB C , Rim/patologia , Rim/metabolismo , Peptídeos/química , Peptídeos/imunologia , Imunoglobulina G/imunologia , HumanosRESUMO
BACKGROUND: Azvudine has been approved for the treatment of coronavirus disease 2019 (COVID-19) patients in China, and this meta-analysis aims to illustrate the safety of azvudine and its effectiveness in reducing mortality. METHODS: PubMed, Embase, Web of science, Cochrane Library and the Epistemonikos COVID-19 Living Overview of Evidence database (L.OVE) were searched to aggregate currently published studies. Cochrane risk of bias tool and ROBINS-I tool were used to assess the risk of bias of randomized controlled study and cohort study respectively. Odds radios (ORs) with 95% confidence interval (CIs) were combined for dichotomous variables. Publication bias was assessed by Egger's test and funnel plots. RESULTS: A total of 184 articles were retrieved from the included databases and 17 studies were included into the final analysis. Pooled analysis showed that azvudine significantly reduced mortality risk in COVID-19 patients compared with controls (OR: 0.41, 95%CI 0.31-0.54, p < 0.001). Besides, either mild to moderate or severe COVID-19 patients could benefit from azvudine administration. There was no significant difference in the incidence of ICU admission (OR: 0.90, 95%CI 0.47-1.72, p = 0.74) and invasive ventilation (OR: 0.94, 95%CI 0.54-1.62, p = 0.82) between azvudine and control group. The incidence of adverse events was similar between azvudine and control (OR: 1.26, 95%CI 0.59-2.70, p = 0.56). CONCLUSIONS: This meta-analysis suggests that azvudine could reduce the mortality risk of COVID-19 patients, and the safety of administration is acceptable. TRIAL REGISTRATION: PROSPERO; No.: CRD42023462988; URL: https://www.crd.york.ac.uk/prospero/ .
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Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidade , Antivirais/uso terapêutico , Antivirais/efeitos adversos , SARS-CoV-2/efeitos dos fármacos , Resultado do TratamentoRESUMO
Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by traumatic brain injury, spinal cord injury, and burns. Despite a wide range of evidence underscoring the significance of neurogenic signals in proper bone remodeling, a clear understanding of HO induced by nerve injury remains rudimentary. Recent studies suggest that injury to the nervous system can activate various signaling pathways, such as TGF-ß, leading to neurogenic HO through the release of neurotrophins. These pathophysiological changes lay a robust groundwork for the prevention and treatment of HO. In this review, we collected evidence to elucidate the mechanisms underlying the pathogenesis of HO related to nerve injury, aiming to enhance our understanding of how neurological repair processes can culminate in HO.
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Ossificação Heterotópica , Ossificação Heterotópica/metabolismo , Humanos , Animais , Neurotransmissores/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Over the past decade, extreme temperature events have become more frequent and longer in duration. Previous studies on the association between extreme cold events (ECEs) and congenital heart defects (CHDs) are few and inconsistent. We conducted a national multicenter study in 1313 hospitals in 26 provinces in China and collected a total of 14â¯808 high CHD-risk participants from 2013 to 2021. We evaluated the ECEs experienced by each pregnant women during the embryonic period (3-8 weeks). The results indicated that ECEs experienced by pregnant women during the embryonic period were associated with the development of fetal CHD and were more strongly associated with some specific fetal CHD subtypes, such as pulmonary stenosis, pulmonary atresia, and tetralogy of Fallot. Of the CHD burden, 2.21% (95% CI: 1.43, 2.99%)-2.40% (95% CI: 1.26, 3.55%) of fetal CHD cases were attributable to ECEs during the embryonic period. Our findings emphasize the need to pay more attention to pregnant women whose embryonic period falls during the cold season to reduce cold spell detriments to newborns.
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Frio Extremo , Cardiopatias Congênitas , Gravidez , Humanos , Recém-Nascido , Feminino , Exposição Materna , Cardiopatias Congênitas/epidemiologia , Temperatura , China/epidemiologiaRESUMO
It is widely recognized that air pollution exerts substantial detrimental effects in human health and the economy. The potential for harm is closely linked to the concentrations of pollutants like nitrogen dioxide (NO2) and ozone (O3), as well as their collective oxidative potential (OX). Yet, due to the challenges of directly monitoring OX as an independent factor and the influences of different substances' varying ability to contain or convey OX, uncertainties persist regarding its actual impact. To provide further evidence to the association between short-term exposures to NO2, O3, and OX and mortality, this study conducted multi-county time-series analyses with over-dispersed generalized additive models and random-effects meta-analyses to estimate the mortality data from 2014 to 2020 in Jiangsu, China. The findings reveal that short-term exposures to these pollutants are linked to increased risks of all-cause, cardiovascular, and respiratory mortality, where NO2 demonstrates 2.11% (95% confidence interval: 1.79%, 2.42%), 2.28% (1.91%, 2.66%), and 2.91% (2.13%, 3.69%) respectively per every 10 ppb increase in concentration, and the effect of O3 is 1.11% (0.98%, 1.24%), 1.39% (1.19%, 1.59%), and 1.82% (1.39%, 2.26%), and OX is 1.77% (1.58%, 1.97%), 2.19% (1.90%, 2.48%), and 2.90% (2.29%, 3.52%). Notably, women and individuals aged over 75 years exhibit higher susceptibility to these pollutants, with NO2 showing a greater impact, especially during the warm seasons. The elevated mortality rates associated with NO2, O3, and OX underscore the significance of addressing air pollution as a pressing public health issue, especially in controlling NO2 and O3 together. Further research is needed to explore the underlying mechanisms and possible influential factors of these effects.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Ozônio , Humanos , Feminino , Idoso , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/toxicidade , Dióxido de Nitrogênio/análise , Fatores de Tempo , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Ozônio/toxicidade , Ozônio/análise , Poluentes Ambientais/análise , Estresse Oxidativo , Material Particulado/análiseRESUMO
BACKGROUND: Obesity is characterized by a chronic low-grade inflammatory condition. Two emerging inflammatory biomarkers, the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI), have gained attention. However, the relationships between obesity and SII/SRI remain unclear. METHODS: In this study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 among adults. SII-SIRI/SII/SIRI were categorized into three groups based on tertiles. The association between obesity and SII-SIRI/SII/SIRI was assessed by multivariable logistic regression models. Restricted cubic spline (RCS) plots were used to examine the nonlinear association between obesity and SII/SIRI. Finally, potential independent associations between obesity and SII/SIRI were further explored using subgroup analyses. RESULTS: The study included 20,011 adults, of whom 7,890 (39.32%) were obesity. In model 1, participants in the high (Q3) level of SII-SIRI had a significantly association with obesity than those in the low (Q1) level group. The high level of SII and SIRI were positively associated with obesity as compared to low levels. Model 2 revealed a positive association between obesity and high levels of SII-SIRI/SII/SIRI. Model 3 demonstrated a similar trend. RCS curves revealed a nonlinear association linking obesity to SII/SIRI. Subgroup analysis showed an interaction between SII/SIRI and age. CONCLUSIONS: Our research suggested that obesity was positively associated with SII-SIRI/SII/SIRI in U.S. adults. SII/SIRI may represent a cost-effective and direct approach to assessing obesity.
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Biomarcadores , Inflamação , Inquéritos Nutricionais , Obesidade , Humanos , Obesidade/imunologia , Obesidade/epidemiologia , Obesidade/complicações , Masculino , Inflamação/imunologia , Feminino , Adulto , Pessoa de Meia-Idade , Biomarcadores/sangue , Estados Unidos/epidemiologia , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Idoso , Modelos LogísticosRESUMO
BACKGROUND: The instrumental activities of daily living (IADL) among the elderly have been found to be heterogeneous, with different trajectories. However, the transition of the IADL over time remains unclear. We aimed to explore the transition probabilities and the predictors of IADL among the elderly. METHODS: Longitudinal data from the 2014 (T1) and 2018 (T2) waves of the Chinese Longitudinal Healthy Longevity Survey were extracted. A sample of 2,944 participants aged 65 years or older, with complete responses to the IADL scale, was included. Latent profile analysis (LPA) and latent transition analysis (LTA) were employed to identify latent profiles of IADL and investigate the transition probabilities between profiles from T1 to T2. The predictors of latent profiles and transition probabilities were examined using multinomial regression analysis. RESULTS: The results of LPA at both T1 and T2 supported a 4-profile model solution. They were labeled as the "Normal function profile," "Mildly impaired profile," "Moderately impaired profile," and "Highly impaired profile". The Normal function profile and Highly impaired profile were characterized by maintaining stability rather than transitioning over time, with transition probabilities of 0.71 and 0.68, respectively, for maintaining stability. The Mildly impaired profile and Moderately impaired profile were characterized by a stronger tendency towards transition rather than stability, with transition probabilities of 0.29 and 0.45, respectively, of transitioning to the Highly impaired profile. The transition probabilities from the three impaired function profiles to the Normal function profile ranged from 0.05 to 0.19. Age, gender, place of residence, and social participation were significant predictors of profile attribution at T1 and transition probabilities over time. CONCLUSIONS: This study employed the LTA to examine the transition probability of IADL among the Chinese elderly. By recognizing the different profiles of IADL and understanding the factors associated with transitions among the elderly, interventions can be tailored to improve their functional independence and successful reintegration into families and society.
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Atividades Cotidianas , Nível de Saúde , Idoso , Humanos , Povo Asiático , Longevidade , China/epidemiologiaRESUMO
Cellular senescence is a complex multifactorial biological phenomenon that plays essential roles in aging, and aging-related diseases. During this process, the senescent cells undergo gene expression altering and chromatin structure remodeling. However, studies on the epigenetic landscape of senescence using integrated multi-omics approaches are limited. In this research, we performed ATAC-seq, RNA-seq and ChIP-seq on different senescent types to reveal the landscape of senescence and identify the prime regulatory elements. We also obtained 34 key genes and deduced that NAT1, PBX1 and RRM2, which interacted with each other, could be the potential markers of aging and aging-related diseases. In summary, our work provides the landscape to study accessibility dynamics and transcriptional regulations in cellular senescence. The application of this technique in different types of senescence allows us to identify the regulatory elements responsible for the substantial regulation of transcription, providing the insights into molecular mechanisms of senescence.
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Senescência Celular , Regulação da Expressão Gênica , Senescência Celular/genética , Montagem e Desmontagem da Cromatina , Sequências Reguladoras de Ácido Nucleico , Cromatina/genéticaRESUMO
BACKGROUND: Caregiver self-efficacy is crucial in improving patient outcomes and caregiver well-being, but there is a lack of suitable scales to assess this concept within the context of Chinese culture. This study aimed to cross-culturally translate the Caregiver Self-Efficacy in Contributing to Patient Self-Care (CSE-CSC) Scale and evaluate its psychometric properties using classical test theory and item response theory. METHODS: The CSE-CSC scale was adapted using Brislin's translation model after obtaining authorization from the original author. A multicenter, cross-sectional study was conducted to assess the psychometric properties of this scale. Classical test theory was used to evaluate reliability (internal consistency, test-retest reliability), validity (content validity, structural validity, convergent validity), and floor and ceiling effects. Item response theory was employed to assess the fit of the rating scale model, reliability, item difficulties, and measurement invariance. RESULTS: The translation and cultural adaptation process was completed. Classical test theory demonstrated good internal consistency (Cronbach's α = 0.935) and test-retest reliability (ICC from 0.784 to 0.829, p<0.001). The I-CVI and K* of each item ranged from 0.875 to 1.00 and 0.871 to 1.00. The first-order 2-factor model fit well (χ2/df = 3.71, RMSEA = 0.082, SRMR = 0.032, CFI = 0.973, TLI = 0.60). Convergent validity showed that the CSE-CSC scores had a strong positive correlation with three separate scales of the CC-SC-CII. There was no floor and ceiling effect in this scale. Rasch analysis showed that the CSE-CSC scale demonstrated a good fit to the rating scale model and exhibited excellent reliability (person/item separation index>2, person/item reliability coefficients>0.8). The Wright map showed that item difficulty matched the respondents' measured abilities. The analysis of differential item functioning (DIF) showed that all items were comparable in gender. CONCLUSIONS: This study indicated that the CSE-CSC scale had good reliability, validity, difficulty degree, and measurement invariance. The CSE-CSC scale can be used to measure caregiver self-efficacy of Chinese patients with multiple chronic conditions.
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Cuidadores , Psicometria , Autocuidado , Autoeficácia , Humanos , China , Cuidadores/psicologia , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Autocuidado/psicologia , Reprodutibilidade dos Testes , Adulto , Inquéritos e Questionários/normas , Traduções , Comparação Transcultural , IdosoRESUMO
BACKGROUND: Delirium is common among elderly patients in the intensive care unit (ICU) and is associated with prolonged hospitalization, increased healthcare costs, and increased risk of death. Understanding the potential risk factors and early prevention of delirium is critical to facilitate timely intervention that may reverse or mitigate the harmful consequences of delirium. AIM: To clarify the effects of pre-admission falls on ICU outcomes, primarily delirium, and secondarily pressure injuries and urinary tract infections. METHODS: The study relied on data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Statistical tests (Wilcoxon rank-sum or chi-squared) compared cohort characteristics. Logistic regression was employed to investigate the association between a history of falls and delirium, as well as secondary outcomes, while Kaplan-Meier survival curves were used to assess short-term survival in delirium and non-delirium patients. RESULTS: Study encompassed 22,547 participants. Delirium incidence was 40%, significantly higher in patients with a history of falls (54.4% vs. 34.5%, p < 0.001). Logistic regression, controlling for confounders, not only confirmed that a history of falls elevates the odds of delirium (OR: 2.11; 95% CI: 1.97-2.26; p < 0.001) but also showed it increases the incidence of urinary tract infections (OR:1.50; 95% CI:1.40-1.62; p < 0.001) and pressure injuries (OR:1.36; 95% CI:1.26-1.47; p < 0.001). Elderly delirium patients exhibited lower 30-, 180-, and 360-day survival rates than non-delirium counterparts (all p < 0.001). CONCLUSIONS: The study reveals that history of falls significantly heighten the risk of delirium and other adverse outcomes in elderly ICU patients, leading to decreased short-term survival rates. This emphasizes the critical need for early interventions and could inform future strategies to manage and prevent these conditions in ICU settings.
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Acidentes por Quedas , Estado Terminal , Delírio , Unidades de Terapia Intensiva , Humanos , Delírio/epidemiologia , Idoso , Acidentes por Quedas/estatística & dados numéricos , Feminino , Masculino , Idoso de 80 Anos ou mais , Estudos de Coortes , Fatores de Risco , Hospitalização , Incidência , Infecções Urinárias/epidemiologiaRESUMO
BACKGROUND: Evidence linking nitrogen dioxide (NO2) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This study seeks to quantify mortality risk, excess deaths, and loss of life expectancy (LLE) associated with long-term exposure to NO2 among elderly individuals in China. METHODS: A nationwide dynamic cohort of 20352 respondents ≥65 years old were enrolled from the China Longitudinal Health and Longevity Survey during 2005-2018. Residential exposures to NO2 and co-pollutants were assessed by well-validated spatiotemporal prediction models. A Cox regression model with time-dependent covariates was utilized to quantify the association of all-cause mortality with NO2 exposure, controlling for confounders such as demographics, lifestyle, health status, and ambient temperature. NO2-attributable deaths and LLE were evaluated for the years 2010 and 2020 based on the pooled NO2-mortality relation derived from multi-national cohort investigations. Decomposition analyses were conducted to dissociate net shift in NO2-related deaths between 2010 and 2020 into four primary contributing factors. RESULTS: A total of 14313 deaths were recorded during follow-up of approximately 100 hundred person-years (median 3.6 years). We observed an approximately linear relationship (nonlinear P = 0.882) of NO2 exposure with all-cause death across a broad range from 6.6 to 95.7⯵g/m3. Every 10-µg/m3 rise in yearly average NO2 concentration was linked to a hazard ratio (HR) of 1.045 (95% confidence interval [CI]: 1.031-1.059). In the updated meta-analysis of this study and 9 existing cohorts, we estimated a pooled HR of 1.043 (95% CI: 1.023-1.063) for each 10-µg/m3 growth in NO2. Reaching a 10-µg/m3 counterfactual target of NO2 concentration in China could avoid 0.33 (95% empirical CI: 0.19-0.49) million premature deaths and an LLE of 0.40 (95% empirical CI: 0.23-0.59) years in 2010, which greatly dropped to 0.24 (95% empirical CI: 0.14-0.36) million deaths and 0.21 (95% empirical CI: 0.12-0.31) years of LLE in 2020. The net fall in NO2-attributable deaths (-26.8%) between 2010 and 2020 was primarily driven by the declines in both NO2 concentration (-41.6%) and mortality rate (-27.1%) under population growth (+41.0%) and age structure transition (+0.9%). CONCLUSIONS: Our findings provide national evidence for increased risk of premature death and loss of life expectancy attributed to later-life NO2 exposure among the elderly in China. In an accelerated aging society, strengthened clean air actions should be formulated to minimize the health burden and regional inequality in NO2-attributable mortality.
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Poluentes Atmosféricos , Exposição Ambiental , Expectativa de Vida , Dióxido de Nitrogênio , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Poluentes Atmosféricos/efeitos adversos , China/epidemiologia , Estudos de Coortes , População do Leste Asiático , Exposição Ambiental/efeitos adversos , Estudos Longitudinais , Mortalidade/tendências , Dióxido de Nitrogênio/efeitos adversos , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Cohort evidence linking long-term ozone (O3) exposure to mortality remained largely mixed worldwide and was extensively deficient in densely-populated Asia. This study aimed to assess the long-term effects of O3 exposure on all-cause mortality among Chinese adults, as well as to examine potential regional heterogeneity across the globe. METHODS: A national dynamic cohort of 42153 adults aged 16+ years were recruited from 25 provinces across Chinese mainland and followed up during 2010-2018. Annual warm-season (April-September) O3 and year-round co-pollutants (i.e., nitrogen dioxide [NO2] and fine particulate matter [PM2.5]) were simulated through validated spatial-temporal prediction models and were assigned to each enrollee in each calendar year. Cox proportional hazards models with time-varying exposures were employed to assess the O3-mortality association. Concentration-response (C-R) curves were fitted by natural cubic spline function to investigate the potential nonlinear association. Both single-pollutant model and co-pollutant models additionally adjusting for PM2.5 and/or NO2 were employed to examine the robustness of the estimated association. The random-effect meta-analysis was adopted to pool effect estimates from the current and prior population-based cohorts (n = 29), and pooled C-R curves were fitted through the meta-smoothing approach by regions. RESULTS: The study population comprised of 42153 participants who contributed 258921.5 person-years at risk (median 6.4 years), of whom 2382 death events occurred during study period. Participants were exposed to an annual average of 51.4 ppb (range: 22.7-74.4 ppb) of warm-season O3 concentration. In the single-pollutant model, a significantly increased hazard ratio (HR) of 1.098 (95% confidence interval [CI]: 1.023-1.179) was associated with a 10-ppb rise in O3 exposure. Associations remained robust to additional adjustments of co-pollutants, with HRs of 1.099 (95% CI: 1.023-1.180) in bi-pollutant model (+PM2.5) and 1.093 (95% CI: 1.018-1.174) in tri-pollutant model (+PM2.5+NO2), respectively. A J-shaped C-R relationship was identified among Chinese general population, suggesting significant excess mortality risk at high ozone exposure only. The combined C-R curves from Asia (n = 4) and North America (n = 17) demonstrated an overall increased risk of all-cause mortality with O3 exposure, with pooled HRs of 1.124 (95% CI: 0.966-1.307) and 1.023 (95% CI: 1.007-1.039) per 10-ppb rise, respectively. Conversely, an opposite association was observed in Europe (n = 8, HR: 0.914 [95% CI: 0.860-0.972]), suggesting significant heterogeneity across regions (P < 0.01). CONCLUSIONS: This study provided national evidence that high O3 exposure may curtail long-term survival of Chinese general population. Great between-region heterogeneity of pooled O3-mortality was identified across North America, Europe, and Asia.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Ozônio , Adulto , Humanos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Ozônio/toxicidade , Material Particulado/toxicidade , Estações do Ano , China/epidemiologia , Poluentes Ambientais/análiseRESUMO
BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10⯵g/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10⯵g/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.
Assuntos
Poluentes Atmosféricos , Cardiopatias Congênitas , Exposição Materna , Ozônio , Ozônio/toxicidade , Feminino , Humanos , Gravidez , Exposição Materna/efeitos adversos , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/epidemiologia , Adulto , China , Poluentes Atmosféricos/toxicidade , Estudos de Coortes , Adulto JovemRESUMO
OBJECTIVES: The built environment is increasingly recognized as being associated with late-life loneliness. However, the pathway remains understudied. This study investigated the mediating effects of productive engagement in relationships between the built environment and loneliness. METHODS: We conducted a cross-sectional analysis of data from 4,409 community-dwelling people aged 65 years and above in China. We employed the Chinese version of the De Jong Gierveld Loneliness Scale to assess loneliness. The built environment comprises residential density, street connectivity, park-based and vegetation-based green space, land use mix, and the number of and distance to the nearest recreational, health, shopping and community services within 300-meter and 500-meter buffer areas. Structural equation modeling was used. RESULTS: Only green space (parks) had a direct effect on loneliness. Residential density and green space (parks) had an indirect effect on loneliness through volunteering. The number of recreational services had an indirect effect on loneliness through recreational and sporting activities, although distance to the nearest recreational services did not. All the significant results were only found within 300-meter rather than 500-meter buffers. CONCLUSIONS: Our findings have implications for environmental gerontology theory and practice. Providing more green space and recreational services can significantly improve older adults' helping behavior, social activities and sporting activities, which can further reduce older adults' loneliness.
Assuntos
Ambiente Construído , Solidão , Humanos , Solidão/psicologia , Idoso , Masculino , Feminino , Estudos Transversais , China , Idoso de 80 Anos ou mais , Vida Independente , Características de Residência , Parques Recreativos , Recreação/psicologiaRESUMO
INTRODUCTION: Organoids are three-dimensional cellular aggregates derived from stem cells or primary tissues that can self-organize into organotypic structures and showcase the physiological functions of that organ. Organoids typically comprise multiple organ-specific cell types that are responsible for organ function in vivo. They may also incorporate various cellular and molecular stromal components to recapitulate the in vivo microenvironment of the target organ. METHODS: All articles related to thyroid-like organs were synthesized. Articles published between 1959 and 2023 were assessed, categorized, and analyzed using relevant keywords. RESULTS: As such, organoids provide a model of greater physiological relevance than 2D cell culture for basic and translational research. Murine and human organoids of the thyroid have been established from embryonic stem cells (ESCs), pluripotent stem cells (PSCs) and from various healthy or diseased thyroid tissues. These thyroid organoids have been used in basic and translation research on thyroid-related diseases including hyperthyroidism, Graves' disease, and Hashimoto's thyroiditis. In addition, organoids derived from patients with thyroid cancer retain histopathological features and mutational profile of the original tumor. These patient-derived organoids have been successfully used in in vitro evaluation of drug response of individual patients, demonstrating their potential application in personalized treatment of thyroid cancer. CONCLUSION: In this review article, we have discussed various techniques for establishing thyroid organoids and their applications in thyroid-related diseases as disease models, regenerative medicines, or a tool for drug testing.