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Purpose: Primary surgery failure of macular holes causes poor visual acuity outcomes. Several studies indicate that small-medium idiopathic full-thickness macular holes (iFTMH) have consistent and high anatomical closure rates after vitrectomy and internal limiting membrane (ILM) peeling, regardless of iFTMH diameters. However, there is no systematic analysis examining the relationship between iFTMH diameters and anatomical closure rates. Methods: In this systematic review and meta-regression, we searched PubMed, Embase, and Web of Science databases on October 24th, 2022. We included studies regarding iFTMH, with ILM peeling/inverted flap technique, long-lasting gas tamponade, and face-down position after surgery. Univariable meta-regression with a restricted cubic spline model and component-plus-residual plot after covariables adjustment were used to explore non-linear association. Results: A total of 7257 participants from 19 randomized controlled trials and 49 observational studies were included in this meta-analysis. In ILM peeling group, every 100-µm increment in diameter was associated with a 3.8 % (95 % confidence interval [CI], 1.8%-5.7 %, P < 0.001) relatively lower anatomical closure rate. Yet, among studies using the inverted flap technique, baseline iFTMH diameter was not associated with a lower anatomical closure rate (0.2 %, 95%CI, -4.2 %-4.5 %, P > 0.9). The restricted cubic spline model and component-plus-residual plot controlling for age, sex, and symptom duration prior to surgery showed no evident non-linearity in both surgical techniques. Conclusions: The iFTMH diameter is linear and inversely associated with the anatomical closure rate after the ILM peeling technique, but not with the inverted flap technique. The present study supports the use of advanced techniques, e.g., inverted flap technique, in small-medium iFTMH to improve anatomical closure rates.

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Alterations in the reward and cognitive control systems are commonly observed among adolescents with internet dependence (ID), and this impairment is often accompanied by social dysfunctions, such as academic burnout. However, the intercorrelations among ID, reward, cognitive control processing, and learning burnout remain unclear. We recruited 1074 Chinese adolescents to investigate the complex interrelationships among these variables using network analysis. The resulting network revealed patterns that connected ID to the behavioral inhibition/activation system (BIS/BAS), self-control, and learning burnout; these results exhibited reasonable stability and test-retest consistency. Throughout the network, the node of BAS-drive was the critical influencing factor, and the node of self-control was the protection factor. In addition, several symptoms of learning burnout and ID were positively associated with sensitivity to punishment. As revealed by the network comparison test, the network constructed among internet dependent (ID) group differed from the network constructed among internet nondependent (IND) group not only in the edges between BIS and learning burnout but also in terms of the edges associated with learning burnout. In conclusion, this study provides insights into the complex mechanisms underlying ID among adolescents from the perspective of the network relationships between core influencing factors and negative consequences. It validates the dual-system model of risky behavior among adolescents and offers a foundation for early warning and interventions for ID in this context.

Assuntos

Esgotamento Psicológico , Transtorno de Adição à Internet , Recompensa , Humanos , Adolescente , China , Transtorno de Adição à Internet/psicologia , Masculino , Feminino , Esgotamento Psicológico/psicologia , Autocontrole/psicologia , Comportamento do Adolescente/psicologia , Aprendizagem , Função Executiva , Cognição

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In recent years, carbon monoxide (CO) has garnered increased attention as a novel green therapy for hepatocellular carcinoma (HCC) treatment. However, the CO donor is still limited in clinical application due to its lack of targeted ability and unstable release rate. Here, self-assembled amphiphilic nanomicelles glucose-polyethylene glycol (PEG)-lipoic acid (LA)-Fe2(CO)6 (Glu-Fe2(CO)6) are first designed as a CO donor and synthesized via a chemical method, combining glucose with Fe2(CO)6 through PEG-LA. Some advantages of this tumor-targeted Glu-Fe2(CO)6 delivery system include (I) good water-solubility, (II) the glutathione responsive CO slow release, (III) the active tumor-targeted ability of glucose as targeted ligands, and (IV) outstanding efficacy of antitumor and safety of CO therapy of HCC both in vitro and in vivo. These findings suggest that Glu-Fe2(CO)6 nanomicelles hold promise for enhancing antitumor therapeutic capabilities, presenting a novel tumor-targeted delivery strategy in gas therapy for HCC treatment.

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Coronary heart disease (CHD) is one of the leading causes of mortality and morbidity in the United States. Accurate time-to-event CHD prediction models with high-dimensional DNA methylation and clinical features may assist with early prediction and intervention strategies. We developed a state-of-the-art deep learning autoencoder survival analysis model (AESurv) to effectively analyze high-dimensional blood DNA methylation features and traditional clinical risk factors by learning low-dimensional representation of participants for time-to-event CHD prediction. We demonstrated the utility of our model in two cohort studies: the Strong Heart Study cohort (SHS), a prospective cohort studying cardiovascular disease and its risk factors among American Indians adults; the Women's Health Initiative (WHI), a prospective cohort study including randomized clinical trials and observational study to improve postmenopausal women's health with one of the main focuses on cardiovascular disease. Our AESurv model effectively learned participant representations in low-dimensional latent space and achieved better model performance (concordance index-C index of 0.864 ± 0.009 and time-to-event mean area under the receiver operating characteristic curve-AUROC of 0.905 ± 0.009) than other survival analysis models (Cox proportional hazard, Cox proportional hazard deep neural network survival analysis, random survival forest, and gradient boosting survival analysis models) in the SHS. We further validated the AESurv model in WHI and also achieved the best model performance. The AESurv model can be used for accurate CHD prediction and assist health care professionals and patients to perform early intervention strategies. We suggest using AESurv model for future time-to-event CHD prediction based on DNA methylation features.

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Doença das Coronárias , Metilação de DNA , Humanos , Doença das Coronárias/mortalidade , Feminino , Análise de Sobrevida , Aprendizado Profundo , Fatores de Risco , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos

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AIMS: To quantitatively measure retinal curvature (RC) in children with myopia and explore its association with refractive status. METHODS: This cross-sectional study included participants aged 5-18 years who underwent comprehensive ocular examinations, including cycloplegic refraction and macula 24×20 mm optical coherence tomography (OCT) scans. RC was derived from OCT data using a three-dimensional reconstruction system. Mean RC was assessed in concentric circles (RC I-VI) with diameters of 1, 3, 6, 9, 12 and 15 mm around the fovea, as well as in four orientations (RC S/I/N/T). RESULTS: A total of 443 eyes were included in the analysis. The values from RC I to RC VI were 0.51±0.19, 0.53±0.19, 0.62±0.19, 0.76±0.23, 0.86±0.23 and 0.81±0.18 10-2mm-2, respectively. RC I exhibited the smallest curvature, while RC V displayed the highest (p<0.001). High myopia (HM) group demonstrated larger RC I and smaller RC III/IV/V/VI compared with low myopia (LM) group (p<0.01). Significant differences among RC S/I/N/T were observed in HM group (pairwise comparison, p<0.001), but not in LM group. Multiple regression analysis revealed that age, sex, corneal curvature radius and subfoveal choroidal thickness (SFCT) were associated factors with foveal RC, while age, SFCT and axial length (AL) were associated factors of peripheral RC. CONCLUSION: RC can quantitatively characterise retinal shape and the morphological changes induced by myopia. Myopia progression results in a bulging macular retina accompanied by a flattening peripheral retina in children, and also increases the irregularity among the four quadrants. Age, AL and SFCT are associated factors of RC.

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BACKGROUND: To examine if pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and to assess if PBT has any subsequent impact on pregnancy outcomes. METHODS: A retrospective, single-center study was carried out at Beijing Tongren Hospital, focusing on women of childbearing age diagnosed with UM and treated with iodine-125 plaque brachytherapy. Both the outcomes of pregnancies and the health status of the fetuses were monitored. Survival analyses were conducted using the Kaplan-Meier method, with endpoints being metastasis and death. RESULTS: A total of 13 patients who had full-term pregnancies and 96 non-pregnant women matched by age and tumor size were included. The mean follow-up time was 67.0 ± 27.7 months (median:66.0 months, range:21.0 to 116.0 months). In the pregnant group, two patients developed metastases, one of whom died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15-2.86; P = 0.576) and overall survival (HR: 0.48, 95% CI: 0.06-3.66; P = 0.464). All pregnant patients carried the pregnancy to term and delivered healthy children with no report of placental or infant metastases to date. CONCLUSION: Pregnancy does not appear to negatively impact the prognosis of UM patients undergoing PBT. PBT showed no observable detriment to maternal fertility and exhibited no teratogenic effects on the fetus. However, the long-term implications of PBT on pregnancy remain uncertain, necessitating additional, prolonged follow-up studies.

Assuntos

Braquiterapia , Melanoma , Resultado da Gravidez , Neoplasias Uveais , Humanos , Feminino , Braquiterapia/métodos , Neoplasias Uveais/radioterapia , Neoplasias Uveais/mortalidade , Gravidez , Melanoma/radioterapia , Melanoma/mortalidade , Estudos Retrospectivos , Adulto , Seguimentos , Radioisótopos do Iodo/uso terapêutico , Adulto Jovem , Complicações Neoplásicas na Gravidez/radioterapia , Complicações Neoplásicas na Gravidez/mortalidade , Taxa de Sobrevida/tendências , Prognóstico , Pessoa de Meia-Idade

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Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8+ T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC.

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The remediation of soil pollution by heavy metals (HMs) presents a significant challenge in environmental restoration. Stabilization remediation technology has proven effective in treating HMs contaminated soil. However, its development is constrained by drawbacks such as slow reaction kinetics and low adsorption capacity. This research synthesized a nano-SiO2@iron­phosphorus (FPOH) material by SiO32- encapsulating the iron-phosphate precipitate obtained from Fe ion and phosphate. In addition, this research applied this material to ferrallisols, calcareous soils and organic soils with three different levels of high pollution by Cd, Pb, Cu and Zn. The experimental results indicate that all experimental soils stabilized rapidly within 1 day and met the requirements of remediation engineering standards (ChinaMEE HJ 1282-2023). Analysis of the possible mechanisms suggests that the FPOH material effectively fills voids with phosphate mineral formation, preventing the secondary release of HMs. During the stabilization process, FPOH involves the adsorption of free ions and small organic molecules in the soil, which does not affect its high reactivity. The development and utilization of FPOH offer valuable insights for soil stabilization remediation.

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The potential effects of probiotics on lowering lipid accumulation and alleviating gut microbiota perturbation have been extensively substantiated, but whether Lactobacillus rhamnoses-fermented oyster mushroom (FOM) could more pronouncedly attenuate obesity remains unclear. In this study, the anti-obesity effect of FOM was estimated based on the gut microbiota profile and analysis of hepatic lipid metabolic characteristics. The results revealed that FOM intervention dramatically improved hepatic lipid accumulation, characterized by reduction in fat-related factor metabolism levels and liver lesion enzymatic activities and down-regulation of the expression of genes associated with glycolipid metabolism (Foxo1, Gck, G6pd, Il6r and IL-ß). Metabolomics analysis indicated HFD-induced dysglycaemia and disturbed amino acid metabolism, characterized by significant enrichment of pathways (butanoate metabolism, arginine biosynthesis, etc.) and elevated levels of D-mannose, succinate and ß-D-fructose, followed by a decreased galactitol content. Furthermore, FOM intervention showed significant enrichment of specific pathways, particularly transcriptional misregulation in cancer and FoxO signaling pathways, while the MAPK signaling pathway demonstrated consistent enrichment across all experimental groups. FOM intervention reshaped the gut microbiota structure by facilitating the proliferation of SCFA producers (Romboutsia, Ruminococcaceae and Allobaculum), together with the depletion of Lachnospiraceae population. The current study strengthened our understanding of FOM prebiotic activities and obesity alleviation mechanisms.

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Importance: Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations. Objective: To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth. Design, Setting, and Participants: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023. Exposures: A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure. Main Outcomes and Measures: Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes. Results: This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (ß, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (ß, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA. Conclusions and Relevance: The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

Assuntos

Experiências Adversas da Infância , Envelhecimento , Humanos , Feminino , Experiências Adversas da Infância/estatística & dados numéricos , Gravidez , Adulto , Recém-Nascido , Estudos Transversais , Envelhecimento/genética , Envelhecimento/fisiologia , Envelhecimento/psicologia , Epigênese Genética , Estudos Longitudinais , Mães/psicologia , Mães/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Masculino , Metilação de DNA , Reino Unido/epidemiologia

RESUMO

OBJECTIVE: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on first transfer live birth rate (LBR) and cumulative LBR (CLBR) in donor oocyte in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study of the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. SETTING: Fertility centers reporting to Society for Assisted Reproductive Technology. PATIENT(S): A total of 11,348 fresh and 7,214 frozen-thawed donor oocyte IVF cycles were analyzed. INTERVENTION(S): The first reported donor stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. MAIN OUTCOME MEASURE(S): Live birth rate was compared for patients using fresh and frozen-thawed donor oocytes, with or without PGT-A. Logistic regression models were adjusted for age, body mass index, gravidity, infertility etiology, and prior IVF cycles. RESULT(S): Among patients who had blastocysts available for transfer or PGT-A, the use of PGT-A was associated with a decreased first transfer LBR (46.9 vs. 53.2%) and CLBR (58.4 vs. 66.6%) in fresh oocyte donor cycles compared with no PGT-A. Live birth rate in frozen-thawed oocyte donor cycles with PGT-A were nominally higher than those without PGT-A (48.3% vs. 40.5%) but were not statistically significant in multivariable logistic regression models. Early pregnancy loss was not significantly different with and without PGT-A. Multiple gestation, preterm birth, and low birth weight infants were all reduced with the addition of PGT-A in fresh donor oocyte cycles, although these outcomes were not significantly different when comparing single embryo transfers in fresh oocyte cycles and also not significantly different among frozen-thawed donor oocyte cycles. CONCLUSION(S): Preimplantation genetic testing for aneuploidy in fresh oocyte donor cycles was associated with decreased LBR and CLBR, whereas effects on frozen-thawed oocyte donor cycles were clinically negligible. Obstetric benefits associated with PGT-A in fresh donor cycles appear linked to increased single embryo transfer.

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BACKGROUND: The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. METHODS: We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. RESULTS: 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p < 0.0001). Patients with greater SII-PNI scores had a poorer prognosis (p < 0.0001). The SII-PNI score was found to be an independent predictor of both overall survival (HR = 4.982, 95%CI: 1.890-10.234, p = 0.001) and disease-free survival (HR = 4.763, 95%CI: 1.994-13.903, p = 0.001) in a multivariate analysis. CONCLUSION: The clinical potential and accuracy of low-cost stratification based on SII-PNI score in forecasting tumor response and prognosis in LAGC is satisfactory.

Assuntos

Terapia Neoadjuvante , Avaliação Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/imunologia , Masculino , Feminino , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inflamação , Estado Nutricional , Estudos Prospectivos , Quimioterapia Adjuvante/métodos

RESUMO

OBJECTIVE: To determine whether industry payments to physicians are associated with a difference in assisted reproductive technology practices and outcomes. DESIGN: Retrospective cohort. SETTING: Assisted reproductive technology centers. PATIENT(S): Patients undergoing asissted reproduction. INTERVENTION(S): Industry payments reported to the Open Payments 2020 database. MAIN OUTCOME MEASURE(S): The live birth rate, frozen embryo transfer (FET) rate, intracytoplasmic sperm injection (ICSI) rate, preimplantation genetic testing (PGT) rate, and percentage of patients aged >40 years were obtained from the Centers for Disease Control and Prevention 2020 database. Linear regression analysis was performed comparing the percentage of physicians per center receiving industry payments to clinic-level outcomes. RESULT(S): A total of 873 reproductive endocrinology and infertility physicians received payments in the 2020 database. At least one physician received a payment in 80.5% (437/543) of in vitro fertilization centers. Of 1,724 reproductive endocrinology and infertility physicians, 873 (50.6%) received at least one payment in 2020. The live birth, ICSI, FET, and PGT rates and percentage of patients aged >40 years did not significantly differ between centers by percentage of physicians receiving industry payments. However, in the subanalysis of 99 large centers (defined as ≥5 physicians), each increase in the percentage of physicians receiving industry payments was associated with increases of 0.20% (95% confidence interval, 0.02-0.39) and 0.14% (95% confidence interval, 0.05-0.24) in the PGT and FET rates, respectively. The live birth, ICSI rates and percentage of patients aged >40 years were not associated with increased industry payment rates to physicians. CONCLUSION(S): Industry payments were not associated with differences in in vitro fertilization center outcomes overall. However, large centers with more physicians receiving industry payments may be more likely to use additional procedures such as PGT and FET, without improvement in the final outcomes such as the live birth rate. Further research is needed to determine whether these differences reflect the industry payment influence vs. individual center/provider practice habits in larger practices.

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A novel sandwich-type electrochemical immunosensor for the detection of the liver cancer marker alpha-fetoprotein (AFP) in human serum is proposed. The two-dimensional MXene material Ti3C2Tx was first prepared using etching and ultrasonic stripping, and then Ti3C2Tx was used to reduce chloroauric acid to form Ti3C2Tx/AuNP composites which were modified on the surface of the glassy carbon electrodes to form probe-type sensors. The Ti3C2Tx/AuNPs provide a large number of binding sites for the AFP capture antibody (Ab1) and increase the electrochemical reaction active site. The Ti3C2Tx/copper metal-organic frameworks HKUST-1 composite was also prepared by solvothermal method and combined with toluidine blue (TB) and AFP detection antibody (Ab2) to form a labeled sandwich-type electrochemical immunosensor. The sensor achieved trace detection of AFP from 0.1 to 100 ng/mL with a detection limit of 0.073 pg/mL and possesses good selectivity, stability, and reproducibility. The sensor performs well in clinical samples and has good potential for clinical applications.

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Anticorpos Imobilizados , Técnicas Biossensoriais , Técnicas Eletroquímicas , Ouro , Limite de Detecção , Neoplasias Hepáticas , Nanopartículas Metálicas , Estruturas Metalorgânicas , Titânio , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Técnicas Eletroquímicas/métodos , Ouro/química , Nanopartículas Metálicas/química , Imunoensaio/métodos , Estruturas Metalorgânicas/química , Anticorpos Imobilizados/imunologia , Titânio/química , Técnicas Biossensoriais/métodos , Cloreto de Tolônio/química , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Eletrodos , Cobre/química

RESUMO

BACKGROUND: American Indian populations have experienced marked disparities in respiratory disease burden. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) are a novel class of biomarkers that may improve recognition of lung damage in indigenous populations. RESEARCH QUESTION: Are plasma EV-miRNAs viable biomarkers of respiratory health in American Indian populations? STUDY DESIGN AND METHODS: The Strong Heart Study (SHS) is a prospective cohort study that enrolled American Indians aged 45 to 74 years. EV-miRNA expression was measured in plasma (1993-1995). Respiratory health outcomes, including pre-bronchodilator FEV1, FVC, and respiratory symptom burden, were ascertained in the same study visit. Club cell secretory protein (CC-16), an antiinflammatory pneumoprotein implicated in COPD pathogenesis, was measured in serum. Linear and logistic regression were used for statistical analyses. Biological pathway analyses were used to elucidate gene targets of significant EV-miRNAs. RESULTS: Among 853 American Indian adults, three EV-miRNAs were associated with FEV1, four EV-miRNAs were associated with FVC, and one EV-miRNA was associated with FEV1/FVC (P < .05). Increased miR-1294 expression was associated with higher odds of airflow limitation (OR, 1.29; 95% CI, 1.07-1.55), whereas increased expression of miR-1294 (OR, 1.32; 95% CI, 1.07-1.63) and miR-532-5p (OR, 1.57; 95% CI, 1.02-2.40) was associated with higher odds of restriction. Increased miR-451a expression was associated with lower odds of exertional dyspnea (OR, 0.71; 95% CI, 0.59-0.85). Twenty-two EV-miRNAs were associated with serum CC-16 levels (q < 0.05), suggesting that EV-miRNAs may play a role in the pathway linking CC-16 to COPD pathogenesis. A pathway analysis showed key EV-miRNAs targeted biological pathways that modulate inflammation, immunity, and structural integrity in the lungs. INTERPRETATION: Circulating EV-miRNAs are novel mechanistic biomarkers of respiratory health and may facilitate the early detection and treatment of lung damage in American Indian populations that have been disproportionately affected by chronic lung diseases.

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Earlier studies have revealed microRNAs (miRNAs) as potential biomarkers for neurological conditions, however, such evidence on psychiatric outcomes is limited. We utilized the Normative Aging Study (NAS) cohort to investigate the associations between extracellular miRNAs (ex-miRNA) and psychiatric symptoms among a group of older male adults, along with the targeted genes and biological pathways. We studied 569 participants with miRNA profile primarily measured in extracellular vesicles isolated from plasma, and psychiatric symptoms reported over 1996-2014 with repeated measures. Global and dimension scales of psychiatric symptoms were measured via the administration of Brief Symptom Inventory (BSI) per visit covering nine aspects of psychiatric health, such as anxiety, depression, hostility, psychoticism, etc. Ex-miRNAs were profiled using small RNA sequencing. Associations of expression of 395 ex-miRNAs (present in >70% samples) with current mental status were assessed using single-miRNA as well as Least Absolute Shrinkage and Selection Operator (LASSO)-based multi-miRNAs linear mixed effects models adjusting for key demographic and behavioral factors. Biological functions were explored using pathway analyses. We identified ex-miRNAs associated with each BSI scale. In particular, hsa-miR-320d was consistently identified for two global scales. Similar overlapping miRNAs across global and dimension scores included hsa-miR-379-3p, hsa-miR-1976, hsa-miR-151a-5p, hsa-miR-151b, hsa-miR-144-3p, etc. Top KEGG pathways for identified miRNAs included p53 signaling, Hippo signaling, FoxO signaling, protein processing in endoplasmic reticulum and several pathways related with cancer and neurological diseases. This study provided early evidence supporting the associations between extracellular miRNAs and psychiatric conditions. MiRNAs may serve as biomarkers of subclinical psychiatric illness in older adults.

Assuntos

Envelhecimento , MicroRNAs , Humanos , Masculino , Idoso , MicroRNAs/genética , MicroRNAs/sangue , Envelhecimento/fisiologia , Transtornos Mentais/genética , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Vesículas Extracelulares/metabolismo , Pessoa de Meia-Idade , Estudos de Coortes

RESUMO

BACKGROUND: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression. METHODS: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses. We looked at associations between measured toenail metals: arsenic, cadmium, lead, manganese, and mercury and 282 ex-miRNAs in this population using canonical correlation analyses (CCAs) and longitudinal median regression. We adjusted for covariates such as age, education, body mass index, drinking and smoking behaviors, diabetes, and where available, seafood consumption. The p-values obtained from regression analyses were corrected for multiple comparisons. Ex-miRNAs identified to be associated with toenail metal levels were further examined using pathway analyses. RESULTS: Our dataset included 937 observations from 589 men with an average age of 72.9 years at baseline. Both our correlation and regression analyses identified lead and cadmium as exposures most strongly associated with ex-miRNA expression. Numerous ex-miRNAs were identified as being associated with toenail metal levels. miR-27b-3p, in particular, was found to have high correlation with the first canonical dimension in the CCA and was significantly associated with cadmium in the regression analysis. Pathway analyses revealed messenger RNA (mRNA) targets for the ex-miRNAs that were associated with a number of clinical disorders including cancer, cardiovascular disease, and neurological disorders, etc. CONCLUSION: Toenail metals were associated with changes in ex-miRNA levels in both correlational and regression analyses. The ex-miRNAs identified can be linked to a variety of clinical disorders. Further studies are required to validate these findings.

Assuntos

MicroRNAs , Unhas , Humanos , Unhas/química , Masculino , MicroRNAs/análise , Idoso , Exposição Ambiental/análise , Idoso de 80 Anos ou mais , Envelhecimento , Metais/análise , Poluentes Ambientais/análise , Pessoa de Meia-Idade , Metais Pesados/análise

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An advanced biodegradable packaging film with antimicrobial and fresh-maintaining functions was constructed by incorporating berberine and L-arginine into the starch/polyvinyl alcohol (PVA) film matrix. The film was endowed with a dual antibacterial capacity thanks to the intrinsic antibacterial capability of berberine and cascaded photodynamic sterilization. The aggregated berberine presents an excellent photodynamic activity to generate reactive oxygen species (ROS), which further triggers the NO release from L-arginine. Under the synergetic action of ROS and NO, the as-prepared film not only has an antibacterial efficiency of over 99 % against both S. aureus and E. coli but also delays fruit ripening through antagonistic effects on ethylene to extend the shelf life of food. Meanwhile, the as-prepared film presents UV-shielding properties, thermal stability, and considerable mechanical properties. Specifically, the packaging film exhibits good biocompatibility and is biodegradable, with a degradation rate of 56 % within 16 days, which has great potential for improving food safety and environmental events.

Assuntos

Embalagem de Alimentos , Conservação de Alimentos , Álcool de Polivinil , Amido , Esterilização , Álcool de Polivinil/química , Amido/química , Conservação de Alimentos/métodos , Esterilização/métodos , Embalagem de Alimentos/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Berberina/química , Berberina/farmacologia

RESUMO

Indicators of male fertility are in decline globally, but the underlying causes, including the role of environmental exposures, are unclear. This study aimed to examine organic chemical pollutants in seminal plasma, including both known priority environmental chemicals and less studied chemicals, to identify uncharacterized male reproductive environmental toxicants. Semen samples were collected from 100 individuals and assessed for sperm concentration, percent motility, and total motile sperm. Targeted and nontargeted organic pollutant exposures were measured from seminal plasma using gas chromatography, which showed widespread detection of organic pollutants in seminal plasma across all exposure classes. We used principal component pursuit (PCP) on our targeted panel and derived one component (driven by etriadizole) associated with total motile sperm (p < 0.001) and concentration (p = 0.03). This was confirmed by the exposome-wide association models using individual chemicals, where etriadizole was negatively associated with total motile sperm (FDR q = 0.01) and concentration (q = 0.07). Using PCP on 814 nontargeted spectral peaks identified a component that was associated with total motile sperm (p = 0.001). Bayesian kernel machine regression identified one principal driver of this association, which was analytically confirmed to be N-nitrosodiethylamine. These findings are promising and consistent with experimental evidence showing that etridiazole and N-nitrosodiethylamine may be reproductive toxicants.

Assuntos

Poluentes Ambientais , Sêmen , Sêmen/química , Sêmen/efeitos dos fármacos , Masculino , Humanos , Expossoma , Adulto , Exposição Ambiental

RESUMO

In engineered photonic lattices, topological photonic (TP) modes present a promising avenue for designing waveguides with suppressed backscattering. However, the integration of the TP modes in electromagnetic systems has faced longstanding challenges. The primary obstacle is the insufficient development of high-efficiency coupling technologies between the TP modes and the conventional transmission modes. This dilemma leads to significant scattering at waveguide terminals when attempting to connect the TP waveguides with other waveguides. In this study, a topological photonic substrate-integrated waveguide (TPSIW) is proposed that can seamlessly integrate into traditional microstrip line systems. It successfully addresses the matching problem and demonstrates efficient coupling of both even and odd TP modes with the quasi-transverse electromagnetic modes of microstrip lines, resulting in minimal energy losses. In addition, topological leaky states are introduced through designed slots on the TPSIW top surface. These slots enable the creation of TP leaky-wave antennas with beam steering capabilities. A wireless link based on TPSIWs are further established that enables the transmission of distinct signals toward different directions. This work is an important step toward the integration of TP modes in microwave systems, unlocking the possibilities for the development of high-performance wireless devices.