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The factors affecting the antibody responses to the ZF2001 vaccine remain unknown. To address this, we conducted a cross-sectional serological study in the real world. Adults with no prior SARS-CoV-2 infection history and received three doses of ZF2001 vaccine were invited to our study in the early stages of the COVID-19 epidemic in Chongqing between 7 April 2021 and 17 November 2021. A questionnaire survey was conducted to obtain demographic characteristics, health information, and the frequency of lifestyles at the time of enrollment. A total of 266 eligible subjects aged 18 to 86 years, with a median age of 56.00 (IQR: 34-66) participated. 68.80% of them were female. Hypertension (13.16%) and diabetes (6.02%) were common comorbidities. Serum samples were collected at one month after the third dose of ZF2001 vaccination, and serological testing was conducted using the Pseudovirus-Based Neutralization Assay. The chi-square test was employed to compare seropositivity rates, and the Mann-Whitney U test or the Kruskal-Wallis test was used to analyze the neutralizing antibodies level in stratified groups. Subsequently, univariate and multivariate linear regression analyses were conducted to identify the influencing factors. We observed that seropositivity rates was 76.32%, with 95% confidence interval (95%CI) 70.85%-81.03%, and geometric mean titer (GMT) was 120.26, with 95%CI 100.38-144.08. Age, diabetes, and frequently of alcohol were negative associations with antibody response (ß = -0.2021, 95% CI: -0.2507 to -0.1535, ß = -0.2873, 95% CI: -0.5590 to -0.0155, ß = -0.2082, 95% CI: -0.3419 to-0.0746, P < 0.0001, P = 0.0384, P = 0.0024). Conversely, the -interval between 1 and 2 dose and frequently of tea were positive associations with antibody response (ß = 0.1369, 95% CI: 0.0463 to 0.2275, ß = 0.0830, 95% CI: 0.0106 to 0.1554, P = 0.0032, P = 0.0247). Overall, the ZF2001 vaccine-induced antibody response was influenced by a multifactor that may provide a reference for the development of personalized antigen vaccines and vaccination strategies in the future.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Adulto , Anticuerpos Antivirales/sangre , China/epidemiología , Anciano , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Adulto Joven , Anciano de 80 o más Años , Adolescente , Vacunación , Formación de Anticuerpos , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Proteínas Recombinantes/inmunologíaRESUMEN
Odorant-binding proteins (OBPs) play key roles in host plant location by insects, and can accordingly serve as important targets for the development of attractants. In this study, we detected the high expression of SlitOBP34 in male antennae of Spodoptera litura. Subsequently, the fluorescence competitive binding experiments displayed that the SlitOBP34 protein has binding affinity for different ligands. Then, protein-ligand interaction analyses found the presence of six amino acid residues may serve as key recognition sites. Further electroantennographic and biobehavioral assessments revealed that the electrophysiological responses of male antennae were evoked in response to stimulation with the six identified host volatiles, and that these volatiles attracted male moths to varying extents. Notably, low concentrations of benzaldehyde, 1-hexanol, and cis-3-hexenyl acetate were found to have significant attractant effects on male moths, thereby identifying these three host volatiles as potential candidates for the development of male attractants. These findings advance our current understanding of the olfactory-encoded mechanisms of host plants selection in S. litura and have enabled us to develop novel adult attractants for controlling the pest in the future.
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Antenas de Artrópodos , Proteínas de Insectos , Receptores Odorantes , Spodoptera , Compuestos Orgánicos Volátiles , Animales , Spodoptera/efectos de los fármacos , Masculino , Receptores Odorantes/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/farmacología , Antenas de Artrópodos/metabolismo , Hexanoles/farmacología , Hexanoles/metabolismo , Acetatos/metabolismo , Acetatos/farmacología , BenzaldehídosRESUMEN
BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that seriously threatens human health. Rho GTPase-activating protein 4 (ARHGAP4) plays an important role in the occurrence and development of tumors. OBJECTIVE: The purpose of this study was to explore the role of ARHGAP4 in the progression of KIRC and its diagnostic and prognostic value. METHODS: Multiple analytical methods and in vitro cell assays were used to explore the expression of ARHGAP4 and its value in the progression, diagnosis and prognosis of KIRC. The biological function of ARHGAP4 was studied by GO analysis and KEGG pathway analysis, and then the relationship between ARHGAP4 and immune infiltration was analyzed. RESULTS: The expression of ARHGAP4 was significantly up-regulated in KIRC. We found that the high expression of ARHGAP4 was related to the progression of KIRC and suggested a poor prognosis. Compared with normal tissues, ARHGAP4 had a better diagnostic value in KIRC. The biological function of ARHGAP4 was related to immunity, and its expression was also closely related to tumor immune infiltration and immune checkpoints. CONCLUSIONS: Our study demonstrated that ARHGAP4 may be a biomarker, which is related to the progression, diagnosis and prognosis of KIRC. Its biological functions are related to tumor immune infiltration.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Proteínas Activadoras de GTPasa , Neoplasias Renales , Humanos , Pronóstico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/genética , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/inmunología , Neoplasias Renales/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Masculino , Femenino , Regulación hacia Arriba , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Línea Celular TumoralRESUMEN
Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.
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Conducta Alimentaria , Proteínas de Insectos , Larva , Spodoptera , Animales , Spodoptera/metabolismo , Spodoptera/fisiología , Spodoptera/genética , Spodoptera/crecimiento & desarrollo , Larva/metabolismo , Larva/crecimiento & desarrollo , Larva/fisiología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genéticaRESUMEN
Purpose: Circular RNAs (circRNAs) have been verified to participate in multiple biological processes and disease progression. Yet, the role of circRNAs in the pathogenesis of diabetic retinopathy (DR) is still poorly understood and deserves further study. This study aimed to investigate the role of circRNAs in the regulation of high glucose (HG)-induced apoptosis of retinal microvascular endothelial cells (RMECs). Methods: Epiretinal membranes from patients with DR and nondiabetic patients with idiopathic macular epiretinal membrane were collected for this study. The circRNA microarrays were performed using high-throughput sequencing. Hierarchical clustering, functional enrichment, and network regulation analyses were used to analyze the data generated by high-throughput sequencing. Next, RMECs were subjected to HG (25 mM) conditions to induce RMECs apoptosis in vitro. A series of experiments, such as Transwell, the Scratch wound, and tube formation, were conducted to explore the regulatory effect of circRNA on RMECs. Fluorescence in situ hybridization (FISH), immunofluorescence staining, and Western blot were used to study the mechanism underlying circRNA-mediated regulation. Results: A total of 53 differentially expressed circRNAs were found in patients with DR. Among these, hsa_circ_0000880 was significantly upregulated in both the diabetic epiretinal membranes and in an in vitro DR model of HG-treated RMECs. Hsa_circ_0000880 knockout facilitated RMECs vitality and decreased the paracellular permeability of RMECs under hyperglycemia. More importantly, silencing of hsa_circ_0000880 significantly inhibited HG-induced ROS production and RMECs apoptosis. Hsa_circ_0000880 acted as an endogenous sponge for eukaryotic initiation factor 4A-III (EIF4A3). Knockout of hsa_circ_0000880 reversed HG-induced decrease in EIF4A3 protein level. Conclusions: Our findings suggest that hsa_circ_0000880 is a novel circRNA can induce RMECs apoptosis in response to HG conditions by sponging EIF4A3, offering an innovative treatment approach against DR. Translational Relevance: The circRNAs participate in the dysregulation of microvascular endothelial function induced by HG conditions, indicating a promising therapeutic target for DR.
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Retinopatía Diabética , Membrana Epirretinal , Humanos , Células Endoteliales , ARN Circular/genética , Hibridación Fluorescente in Situ , Retinopatía Diabética/genética , Apoptosis/genética , Glucosa/toxicidad , Factor 4A Eucariótico de Iniciación , ARN Helicasas DEAD-boxRESUMEN
PURPOSE: To investigate the alterations in retinochoroidal parameters measured by optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with carotid artery stenosis (CAS) and assess their associations with digital subtraction angiography (DSA) data. METHOD: This study enrolled patients diagnosed with CAS and age-matched healthy controls. Both groups underwent OCT and OCTA examinations. DSA and assessment of carotid artery stenosis were performed only in the CAS group. The study evaluated various retinochoroidal parameters from OCT and OCTA, including linear vessel density (LVD), foveal avascular zone (FAZ), choroidal thickness (ChT), and retinal nerve fiber layer (RNFL) thickness. DSA-derived measures included cervical segment (C1) diameter, cavernous segment (C4) diameter, stenosis percentage, ophthalmic artery (OA) filling time, C1-OA filling time, and residual stenosis. RESULTS: A total of 42 eyes from 30 CAS patients and 60 eyes from 30 healthy controls were included. Patients with CAS displayed significantly decreased LVD compared to controls (p < 0.001). Additionally, the CAS group had thinner choroid and RNFL (p = 0.047 and p < 0.001, respectively). Macular LVD negatively correlated with both stenosis percentage and C1-OA filling time (p = 0.010 and p = 0.014, respectively). In patients who underwent carotid artery stenting, preoperative ChT significantly correlated with residual stenosis (Pearson r = -0.480, p = 0.020). CONCLUSION: OCT and OCTA provide a quantitative assessment of retinochoroidal microstructural changes associated with CAS, suggesting potential for noninvasive evaluation of the disease. This might contribute to the prevention of irreversible ocular complications and early detection of CAS. Furthermore, ChT may not only aid in diagnosing CAS more reliably but also offer prognostic information.
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Estenosis Carotídea , Coroides , Microvasos , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Estenosis Carotídea/diagnóstico por imagen , Femenino , Masculino , Anciano , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Coroides/patología , Persona de Mediana Edad , Microvasos/diagnóstico por imagen , Angiografía de Substracción Digital/métodos , Estudios de Casos y Controles , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patologíaRESUMEN
Splicing factor polyglutamine binding protein-1 (PQBP1) is abundantly expressed in the central nervous system during development, and mutations in the gene cause intellectual disability. However, the roles of PQBP1 in cancer progression remain largely unknown. Here, it is shown that PQBP1 overexpression promotes tumor progression and indicates worse prognosis in ovarian cancer. Integrative analysis of spyCLIP-seq and RNA-seq data reveals that PQBP1 preferentially binds to exon regions and modulates exon skipping. Mechanistically, it is shown that PQBP1 regulates the splicing of genes related to the apoptotic signaling pathway, including BAX. PQBP1 promotes BAX exon 2 skipping to generate a truncated isoform that undergoes degradation by nonsense-mediated mRNA decay, thus making cancer cells resistant to apoptosis. In contrast, PQBP1 depletion or splice-switching antisense oligonucleotides promote exon 2 inclusion and thus increase BAX expression, leading to inhibition of tumor growth. Together, the results demonstrate an oncogenic role of PQBP1 in ovarian cancer and suggest that targeting the aberrant splicing mediated by PQBP1 has therapeutic potential in cancer treatment.
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Discapacidad Intelectual , Neoplasias Ováricas , Femenino , Humanos , Proteína X Asociada a bcl-2/genética , Proteínas de Unión al ADN/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Neoplasias Ováricas/genética , Empalme del ARN/genética , Factores de Empalme de ARN/genéticaRESUMEN
Image quality variation is a prominent cause of performance degradation for intelligent disease diagnostic models in clinical applications. Image quality issues are particularly prominent in infantile fundus photography due to poor patient cooperation, which poses a high risk of misdiagnosis. Here, we developed a deep learning-based image quality assessment and enhancement system (DeepQuality) for infantile fundus images to improve infant retinopathy screening. DeepQuality can accurately detect various quality defects concerning integrity, illumination, and clarity with area under the curve (AUC) values ranging from 0.933 to 0.995. It can also comprehensively score the overall quality of each fundus photograph. By analyzing 2,015,758 infantile fundus photographs from real-world settings using DeepQuality, we found that 58.3% of them had varying degrees of quality defects, and large variations were observed among different regions and categories of hospitals. Additionally, DeepQuality provides quality enhancement based on the results of quality assessment. After quality enhancement, the performance of retinopathy of prematurity (ROP) diagnosis of clinicians was significantly improved. Moreover, the integration of DeepQuality and AI diagnostic models can effectively improve the model performance for detecting ROP. This study may be an important reference for the future development of other image-based intelligent disease screening systems.
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Osteopontin is a crucial protein ingredient that has been applied in fortified dairy products and infant formula. It has great significance to infant gut health and brain development. However, current techniques including enzyme-linked immunosorbent assay and liquid chromatography coupled with mass spectrometry are still facing the bottleneck of low sensitivity and indirect quantification. Moreover, the unavailable certified commercial OPN standard hinders its accurate quantification. Herein, a novel method of anion-exchange chromatography was established to determine OPN concentration in several dairy matrices. The polarity-reversed capillary isoelectric focusing was utilized to measure the exact isoelectric point (pI) to support method development for OPN separation. Analytical ultracentrifugation was used to calibrate the purity of intact OPN to develop an in-house reference standard. The method showed the merits of limits of detection to 0.04 mg/100 g, relative standard deviation of reproducibility <5% for 13 out of 14 tested matrices, and an average recovery rate of 101.3%. This method has shown the potential to be adopted as an international standard method for the quantification of intact OPN in infant formula and dairy products.
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Fórmulas Infantiles , Osteopontina , Lactante , Humanos , Reproducibilidad de los Resultados , Cromatografía Liquida , Aniones , Productos Lácteos , UltracentrifugaciónRESUMEN
Riptortus pedestris (bean bug), a common soybean pest, has a highly developed olfactory system to find hosts for feeding and oviposition. Chemosensory proteins (CSPs) have been identified in many insect species; however, their functions in R. pedestris remain unknown. In this study, quantitative real time-polymerase chain reaction (qRT-PCR) revealed that the expression of RpedCSP12 in the adult antennae of R. pedestris increased with age. Moreover, a significant difference in the expression levels of RpedCSP12 was observed between male and female antennae at one and three days of age. We also investigated the binding ability of RpedCSP12 to different ligands using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP12 only bound to one aggregation pheromone, (E)-2-hexenyl (Z)-3-hexenoate, and its binding decreased with increasing pH. Furthermore, homology modelling, molecular docking, and site-directed mutagenesis revealed that the Y27A, L74A, and L85A mutants lost their binding ability to (E)-2-hexenyl (Z)-3-hexenoate. Our findings highlight the olfactory roles of RpedCSP12, providing insights into the mechanism by which RpedCSPs bind to aggregation pheromones. Therefore, our study can be used as a theoretical basis for the population control of R. pedestris in the future.
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Heterópteros , Feromonas , Animales , Femenino , Simulación del Acoplamiento Molecular , Heterópteros/genética , Glycine maxRESUMEN
BACKGROUND: The 24-h circadian rhythm is considered crucial for insect sexual communication. However, its molecular mechanisms and signaling pathways, particularly the roles of the clock gene period (Per), remain largely unclear. The sex pheromone communication behavior of Spodoptera litura displays typical circadian rhythm characteristics. Thus, it represents an excellent model for functional analyses of the clock gene Per. RESULTS: In this study, we investigated the potential roles of SlitPer in regulating sex pheromone communication in S. litura using RNA interference, quantitative real-time polymerase chain reactions (qPCR), gas chromatography, and behavioral assays. The qPCR results showed that the expression levels of SlitPer and two desaturase genes (SlitDes5 and SlitDes11) in the siPer group differed significantly at most time points from those in the siNC group. Dynamic variation in the three major sex pheromone titers and calling behavior of S. litura females in the siPer group was disordered. In addition, the mating rates of siPer S. litura females decreased significantly by 33.33%. Oviposition by mated siPer females was substantially reduced by 84.84%. CONCLUSION: These findings provide a fundamental basis for elucidating the molecular mechanism by which Per regulates sex pheromone communication behavior in lepidopteran species. © 2023 Society of Chemical Industry.
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Atractivos Sexuales , Animales , Femenino , Spodoptera/fisiología , Atractivos Sexuales/farmacología , Atractivos Sexuales/metabolismo , Interferencia de ARN , Comunicación , Proteínas de Insectos/metabolismoRESUMEN
In moths, the interactions between chemosensory proteins (CSPs) and sex pheromones have yet to be comprehensively investigated. Here, we examined the function of AlepCSP2 in male Athetis lepigone based on protein expression, molecular docking, site-directed mutagenesis, fluorescence competitive binding analyses, and RNA interference (RNAi) experiments. We found that AlepCSP2 showed strong binding affinity for two sex pheromones and five maize volatiles and that binding was optimal under neutral conditions. Furthermore, we identified six amino acids as being key residues involved in the interaction between AlepCSP2 and multiple ligands. Further RNAi showed that siCSP2 males displayed consistently lower electroantennography responses to two sex pheromones and three maize volatiles at different dosages tested, and the mating rate also decreased significantly by 37.50%. These findings will contribute to characterizing the binding mechanisms of moth CSPs to sex pheromones and host volatiles and also identify unique targets for developing novel pest behavior disruptors.
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Mariposas Nocturnas , Atractivos Sexuales , Masculino , Animales , Atractivos Sexuales/metabolismo , Zea mays/genética , Zea mays/metabolismo , Simulación del Acoplamiento Molecular , Mariposas Nocturnas/metabolismo , Proteínas de Insectos/metabolismo , Percepción , Feromonas/metabolismoRESUMEN
[This corrects the article DOI: 10.3389/fphar.2022.996635.].
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The supramolecular self-assembly behavior of a pair of low-symmetry tetracarboxylic acid molecules (H4OBDB and H4ADDI) and their co-assembly behavior with TMA as a bridging molecule were studied at the liquid-solid interface. Scanning tunneling microscope (STM) observations revealed that H4OBDB and H4ADDI molecules both tend to form O-shaped dimers but end up forming different types of self-assembly structures. We also investigated the construction of two-component co-assembly structures by mixing H4OBDB or H4ADDI molecules with bridging molecules such as TMA. The two formed co-assembly structures are similar. Based on the analysis of the STM results and the density functional theory (DFT) calculations, the formation mechanism of the assembled structures was revealed.
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Scientific territorial spatial planning is of great significance in the realization of the sustainable development goals in China, especially in the context of China's ecological civilization construction and territorial spatial planning. However, limited research has been carried out to understand the spatio-temporal change in EEQ and territorial spatial planning. In this study, Changsha County and six districts of Changsha City were selected as the research objects. Based on the remote sensing ecological index (RSEI) model, the spatio-temporal changes in the EEQ and spatial planning response in the study area during 2003-2018 were analyzed. The results reveal that (1) the EEQ of Changsha declined and then rose between 2003 and 2018, showing an overall decreasing trend. The average RSEI declined from 0.532 in 2003 to 0.500 in 2014 and then increased to 0.523 in 2018, with an overall decrease of 1.7%. (2) In terms of spatial pattern changes, the Xingma Group, the Airport Group and the Huangli Group in the east of the Xiangjiang River had the most serious EEQ degradation. The EEQ degradation of Changsha showed an expanding and polycentric decentralized grouping pattern. (3) Massive construction land expansion during rapid urbanization caused significant EEQ degradation in Changsha. Particularly, the areas with low EEQ were concentrated in the areas with concentrated industrial land. Scientific territorial spatial planning and strict control were conducive to regional EEQ improvement. (4) The prediction using the urban ecological model demonstrates that every 0.549 unit increase in NDVI or 0.2 unit decrease in NDBSI can improve the RSEI of the study area by 0.1 unit, thus improving EEQ. In the future territorial spatial planning and construction of Changsha, it is necessary to promote the transformation and upgrading of low-end industries into high-end manufacturing industries and control the scale of inefficient industrial land. The EEQ degradation caused by industrial land expansion needs to be noted. All of these findings can provide valuable information for relevant decision-makers to formulate ecological environment protection strategies and conduct future territorial spatial planning.
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Ecosistema , Ambiente , Ciudades , Urbanización , Tecnología de Sensores Remotos , China , Conservación de los Recursos NaturalesRESUMEN
Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.
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Inteligencia Artificial , Citometría de Flujo , Curva ROC , Área Bajo la CurvaRESUMEN
PURPOSE: This study sought to assess the predictive performance of optical coherence tomography (OCT) images for the response of diabetic macular edema (DME) patients to anti-vascular endothelial growth factor (VEGF) therapy generated from baseline images using generative adversarial networks (GANs). METHODS: Patient information, including clinical and imaging data, was obtained from inpatients at the Ophthalmology Department of Qilu Hospital. 715 and 103 pairs of pre-and post-treatment OCT images of DME patients were included in the training and validation sets, respectively. The post-treatment OCT images were used to assess the validity of the generated images. Six different GAN models (CycleGAN, PairGAN, Pix2pixHD, RegGAN, SPADE, UNIT) were applied to predict the efficacy of anti-VEGF treatment by generating OCT images. Independent screening and evaluation experiments were conducted to validate the quality and comparability of images generated by different GAN models. RESULTS: OCT images generated f GAN models exhibited high comparability to the real images, especially for edema absorption. RegGAN exhibited the highest prediction accuracy over the CycleGAN, PairGAN, Pix2pixHD, SPADE, and UNIT models. Further analyses were conducted based on the RegGAN. Most post-therapeutic OCT images (95/103) were difficult to differentiate from the real OCT images by retinal specialists. A mean absolute error of 26.74 ± 21.28 µm was observed for central macular thickness (CMT) between the synthetic and real OCT images. CONCLUSION: Different generative adversarial networks have different prognostic efficacy for DME, and RegGAN yielded the best performance in our study. Different GAN models yielded good accuracy in predicting the OCT-based response to anti-VEGF treatment at one month. Overall, the application of GAN models can assist clinicians in prognosis prediction of patients with DME to design better treatment strategies and follow-up schedules.
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Fotoquimioterapia , Humanos , Edema Macular/diagnóstico por imagen , Edema Macular/tratamiento farmacológico , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/tratamiento farmacológico , Tomografía de Coherencia Óptica/métodos , Estudios Retrospectivos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Factores de Crecimiento Endotelial Vascular , Inhibidores de la Angiogénesis/uso terapéuticoRESUMEN
PURPOSE: To determine the proteomic profiles of exosomes derived from vitreous humour (VH) obtained from proliferative diabetic retinopathy (PDR) patients and non-diabetic controls with idiopathic macular hole/epiretinal membrane. METHODS: Vitreal exosomes were isolated using differential ultracentrifugation, followed by characterisation performed using different techniques. A label-free proteomic analysis was conducted to determine the protein profiles of the exosomes. A parallel reaction monitoring (PRM) analysis was performed to verify the identified proteins and associated functional annotations were derived by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Receiver operating characteristic (ROC) analysis was utilised to evaluate the diagnostic value of target proteins in distinguishing PDR from controls. RESULTS: Exosomes were successfully isolated from VH, and were well characterised by various techniques. The results of proteomic analysis showed that a total of 758 proteins were identified and 10 proteins were screened as differentially expressed proteins, significantly changed in the PDR group containing 4 elevated proteins and 6 reduced proteins. GO analysis indicated that these differential proteins were mainly involved in many metabolic pathways, including nicotinamide adenine dinucleotide metabolism, adenosine diphosphate metabolic process and glycolytic process. The KEGG analysis enriched the top five pathways including glycolysis/gluconeogenesis, fructose and mannose metabolism, biosynthesis of amino acids, hypoxia-inducible factor 1 signalling pathway and carbon metabolism. The differential proteins, namely, lactate dehydrogenase A, ficolin 3, apolipoprotein B and apolipoprotein M, were further verified by PRM and showed a consistent trend with label-free proteomic analysis. The ROC analysis identified these proteins as promising biomarkers for PDR diagnosis. CONCLUSIONS: Vitreal exosomes from patients with PDR contained few proteins unique to PDR; thus, exosomal proteins have great potential as disease biomarkers and therapeutic targets for PDR.
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Diabetes Mellitus , Retinopatía Diabética , Exosomas , Humanos , Retinopatía Diabética/metabolismo , Proteómica/métodos , Exosomas/metabolismo , Cuerpo Vítreo/metabolismo , Biomarcadores/metabolismoRESUMEN
Transdifferentiation of keratocytes into fibroblasts or further into myofibroblasts, which produced denser and more disorganized extracellular matrix, is the major cause of corneal fibrosis and scarring, leading to corneal blindness. TGF-ß1 is the critical cytokine for the myofibroblast's transdifferentiation and survival. Hypoxia Inducible Factor (HIF) was found to play an important role in promoting fibrosis in lung, kidney, and dermal tissues recently. Our preliminary study demonstrated that topical administration of the acriflavine (ACF), a drug inhibiting HIF dimerization, delayed corneal opacity and neovascularization after the alkali burn. To know whether ACF could prevent corneal fibrosis and improve corneal transparency, we created a mouse mechanical corneal injury model and found that topical administration of ACF significantly inhibited corneal fibrosis at day 14 post-injury. The reduction of myofibroblast marker α-SMA, and fibronectin, one of the disorganized extracellular matrix molecules, in the corneal stroma were confirmed by the examination of immunohistochemistry and real-time PCR. Furthermore, the ACF inhibited the expression of α-SMA and fibronectin in both TGF-ß1 stimulated or unstimulated fibroblasts in vitro. This effect was based on the inhibition of HIF signal pathways since the levels of the HIF-1α downstream genes including Slc2a1, Bnip3 and VEGFA were downregulated. To our knowledge, this is the first time to implicate that HIFs might be a new treatment target for controlling corneal fibrosis in mechanical corneal injuries.
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Purpose: To identify the differential profiles of lipids in aqueous humor (AH) between control and diabetic cataract patients. Methods: The lipidomic profiles of 19 samples from patients with diabetic cataract (diabetic group) and 32 controls (control group) were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Differentially expressed lipids between the two groups were determined through partial least-squares-discriminant analysis and principal component analysis. Receiver operating characteristic curve was calculated to evaluate the diagnostic value of differentially expressed lipids in distinguishing diabetic cataract patients from the control subjects. The correlations of the target lipids with the serum lipids were determined by Pearson correlation. Results: The results of LC-MS/MS analysis revealed a remarkable variation in lipid class composition. As compared with the control group, the percentage of triglycerides (TGs) was higher and that of Ceramide-1-phosphates was significantly lower in the AH of the diabetic group. A multivariate analysis of the lipid species showed that the expression levels of 16 of 639 lipids significantly changed in the diabetic group as compared to the control group. Among them, TG (42:6) (area under curve [AUC] = 0.985, P < 0.0001) and diacylglycerol (DG) (24:2) (AUC = 0.944, P < 0.0001) exhibited high prediction capability for diabetic cataract. The results of Pearson correlation revealed that the concentrations of TG (42:6) in AH were positively correlated with serum TG levels in diabetic patients. Conclusions: The lipid composition of AH of diabetic cataract patients showed a significant difference from that of the healthy subjects. Lipid changes, especially the high AH levels of TG (42:6) and DG (24:2), might contribute to cataractogenesis and possibly be involved in the development of diabetic cataract. Translational Relevance: Changes in the lipid profile of AH may partly account for the pathogenesis of diabetic cataracts and lead to a novel therapeutic strategy for diabetic cataract.