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An iron-catalyzed efficient C-H amination for the construction of imidazole-fused-ring systems was developed under aerobic conditions. Compared to previous studies, this work exhibited green features. The reaction was conducted in the green solvent anisole, with water as the only byproduct. Four C(sp3)-H bonds were cleaved and three C-N bonds were formed in this transformation. Imidazo[1,5-a]pyridine-, imidazo[5,1-b]oxazole-, imidazo[5,1-b]thiazole-, imidazo[1,5-a]pyrazine-, and imidazo[1,5-a]imidazole-related N-heterocycles were obtained in acceptable-to-excellent yield.
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PURPOSE: We aimed to develop and test a deep-learning system to perform image quality and diabetic macular ischemia (DMI) assessment on optical coherence tomography angiography (OCTA) images. METHODS: This study included 7,194 OCTA images with diabetes mellitus for training and primary validation and 960 images from three independent data sets for external testing. A trinary classification for image quality assessment and the presence or absence of DMI for DMI assessment were labeled on all OCTA images. Two DenseNet-161 models were built for both tasks for OCTA images of superficial and deep capillary plexuses, respectively. External testing was performed on three unseen data sets in which one data set using the same model of OCTA device as of the primary data set and two data sets using another brand of OCTA device. We assessed the performance by using the area under the receiver operating characteristic curves with sensitivities, specificities, and accuracies and the area under the precision-recall curves with precision. RESULTS: For the image quality assessment, analyses for gradability and measurability assessment were performed. Our deep-learning system achieved the area under the receiver operating characteristic curves >0.948 and area under the precision-recall curves >0.866 for the gradability assessment, area under the receiver operating characteristic curves >0.960 and area under the precision-recall curves >0.822 for the measurability assessment, and area under the receiver operating characteristic curves >0.939 and area under the precision-recall curves >0.899 for the DMI assessment across three external validation data sets. Grad-CAM demonstrated the capability of our deep-learning system paying attention to regions related to DMI identification. CONCLUSION: Our proposed multitask deep-learning system might facilitate the development of a simplified assessment of DMI on OCTA images among individuals with diabetes mellitus at high risk for visual loss.
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Aprendizado Profundo , Angiofluoresceinografia/métodos , Isquemia/diagnóstico , Doenças Retinianas/diagnóstico , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Retinopatia Diabética/diagnóstico , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Diabetic retinopathy (DR) has been considered to involve mitochondrial alterations and be related to the nucleotide-binding oligomerization domain-like receptors 3 (NLRP3) inflammasome activation. The voltage-dependent anion channel 1 (VDAC1) protein is one of the key proteins that regulates the metabolic and energetic functions of the mitochondria. To explore the involvement of VDAC1 in mitophagy regulation of NLRP3 inflammasome activation under high-glucose (HG) conditions, this study examined expressions of VDAC1, mitochondrial function and mitophagy-related proteins, and NLRP3 inflammasome-related proteins in human retinal capillary endothelial cells (HRCECs) cultured with 30 mM of glucose in the presence or absence of mitophagy inhibitor (Mdivi-1) using Western blot. Mitochondrial membrane potential and mitochondrial reactive oxygen species (mtROS) were detected using flow cytometry. GFP-tagged pAdTrack-VDAC1 adenovirus was used to overexpress VDAC1. Cell biological behaviors, including proliferation, migration, tubule formation, and apoptosis, were also observed. Our results showed that when compared to the normal glucose and high mannitol groups, increased amounts of mitochondrial fragments, reduced mitochondrial membrane potential, increased expression of mitochondrial fission protein Drp 1, decreased expression of mitochondrial fusion protein Mfn 2, accumulation of mtROS, and activation of the NLRP3 inflammasome were observed in the HG group. Meanwhile, HG markedly reduced the protein expressions of PINK1, Parkin and VDAC1. Inhibition of mitophagy reduced PINK1 expression, enhanced NLRP3 expression, but failed to alter VDAC1. VDAC1 overexpression promoted PINK1 expression, inhibited NLRP3 activation and changed the cell biological behaviors under HG conditions. These findings demonstrate that VDAC1-mediated mitophagy plays a crucial role in regulating NLRP3 inflammasome activation in retinal capillary endothelial cells under HG conditions, suggesting that VDAC1 may be a potential target for preventing or treating DR.
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Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Inflamassomos/genética , Mitofagia/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Canal de Ânion 1 Dependente de Voltagem/biossíntese , Canal de Ânion 1 Dependente de Voltagem/genética , Apoptose , Capilares/metabolismo , Capilares/ultraestrutura , Células Cultivadas , Células Endoteliais/ultraestrutura , Endotélio Vascular/metabolismo , Endotélio Vascular/ultraestrutura , Humanos , Inflamassomos/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteína 3 que Contém Domínio de Pirina da Família NLR/biossíntese , RNA/genética , Vasos Retinianos/metabolismo , Vasos Retinianos/ultraestruturaRESUMO
BACKGROUND: To analyze the distribution of manifest lesions of diabetic retinopathy (DR) by fundus fluorescein angiography (FFA) and color fundus photography (FP). METHODS: A total of 566 eyes of 324 Chinese patients diagnosed with DR were included in this retrospective study. DR severity was graded by the international grading criterion. The distributions of microaneurysms (MA), intraretinal hemorrhages/exudates (He/Ex), intraretinal microvascular abnormality (IRMA), capillary nonperfusion areas (NPA), and neovascularization (NV) were estimated by multiple logistic regression analyse based on nine-field FFA and FP images. RESULTS: In mild nonproliferative diabetic retinopathy (NPDR), the highest frequency of MA was found in the posterior pole (67.7%), followed by the inferior nasal (59.4%), and the nasal (55.4%) fields. In moderate NPDR, MA frequently distributed in the posterior pole (98.0%), nasal (97.0%), superior (96.0%), inferior nasal (94.9%), and inferior (92.9%) fields, whereas He/Ex were most prevalent in the posterior pole (69.7%). In severe NPDR and proliferative DR, IRMA, NPA, and NV were more frequent in the nasal field, particularly in the inferior nasal field (60.3, 38.7, and 76.0%, respectively). All lesions were more observed in the combined posterior pole, nasal, and inferior nasal fields than in the posterior pole or combined two fields in the early and severe stages of DR (P < 0.05). CONCLUSIONS: The manifest lesions of DR were common in the nasal field besides the posterior pole in Chinese patients. A combined examination of the posterior pole, nasal, and inferior nasal mid-peripheral retina would help to detect different retinal lesions of DR. TRIAL REGISTRATION: ClinicalTrial. gov, NCT03528720 . Registered 18 May 2018 - Retrospectively registered.
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Diabetes Mellitus , Retinopatia Diabética , Retinopatia Diabética/diagnóstico , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Fotografação , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Over the past 40 years, research has addressed the impact of the aging process on various aspects of visual function. Most studies have focused on age-related visual impairment in low-level local features of visual objects, such as orientation, contrast sensitivity and spatial frequency. However, whether there are lifespan changes in global visual perception is still unclear. To suitably frame this question, we defined global visual patterns by a topological approach, and local visual patterns were manipulated with different levels of geometrical invariants in descending order of structural stability from projective, affine, and then Euclidean features. Using the Configural Superiority Effect, we investigated the influence of aging on local and global visual perception through a comparison of young and old adults in Experiment 1; moreover, we provided continuous-aging data from 21 to 78 years of age to investigate age-related changes in visual perception in Experiment 2. We found a large perceptual decline across increasing age groups in local geometrical perception: for example, Euclidean (orientation), affine (parallelism), and projective (collinearity) discrimination. Moreover, the study provides a counterintuitive finding that global topological perception resists the aging process and remains constant throughout adult lifespan. These findings highlight the possibility that for humans, global topology may be a stable and fundamental component by which visual systems represent and characterize objects.
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Envelhecimento/fisiologia , Visão Ocular/fisiologia , Percepção Visual/fisiologia , Adulto , Idoso , Análise de Variância , Sensibilidades de Contraste/fisiologia , Discriminação Psicológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orientação Espacial/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos , Adulto JovemRESUMO
A novel route for the synthesis of unsymmetrical benzo-fused BODIPYs is reported using 4,5,6,7-tetrafluoroisoindole as a precursor. The reactivity of the 3,5-dibromo tetrafluorobenzo-fused BODIPY was investigated under nucleophilic substitution and Pd(0)-catalyzed cross-coupling reaction conditions. In addition to the 3,5-bromines, one α-fluoro group on the benzo-fused ring can also be functionalized, and an unusual homocoupling with formation of a bisBODIPY was observed. This new class of fluorinated BODIPYs could find various applications in medicine and materials.
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Compostos de Boro/química , Corantes Fluorescentes/síntese química , Catálise , Espectroscopia de Ressonância Magnética/métodos , Modelos Moleculares , Paládio/química , Espectrofotometria UltravioletaRESUMO
Object substitution masking (OSM) is said to occur on an object level without a close spatiotemporal proximity of target and mask. An influential account for OSM is "object updating," which espouses that OSM occurs when the target is updated by the mask as they share a single object representation. However, it is unclear what attribute determines whether the mask shares the same object representation as the target. We hypothesize that topological property determines whether a new object representation is built, and hence topological perception modulates object-level masking. We systematically manipulated the similarity between the target and the mask by changing a topological property (number of holes), color, shape, and orientation. We found that the topological change between the target and the mask reduced masking effects of all the other properties. Changing color, shape, or orientation, however, did not affect the masking effect of any other property. The global effect of the topological change remained across a variety of temporal and spatial distances between the target and the mask and was not limited to masking paradigms. Thus, our results suggest that the object representation, constrained by its topological properties, serves as a higher and global level of OSM, influencing the ongoing visual processing of features that are at a lower and local level.
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Mascaramento Perceptivo/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Atenção , Cognição , Feminino , Humanos , Masculino , Máscaras , Orientação , Orientação Espacial , Adulto JovemRESUMO
Superior colliculus-pulvinar-amygdala pathway is one of the subcortical visual pathways in mammalian brain. Some recent studies suggest that this pathway is involved in processing emotion-related visual information. This review discusses the possibility that this pathway is more related to visual alert rather than simply the early visual information processing. The biological significance of this pathway is also discussed. Instead of detecting "where" or "what" the visual target is, the task of this early visual stage is to send out a warning signal, i.e., "something appears", so that the brain can be set up in a state of alert, which is important for the survival of animals. Thus, in the early visual information process, detection of new object "emerging" or "disappearing" takes priority over the acquisition of its feature information of "texture" and "shape", etc. The subcortical pathway may provide the neural basis of early visual warning in topological perception, a biological significance critical for animal survival.
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Tonsila do Cerebelo/fisiologia , Encéfalo/fisiologia , Pulvinar/fisiologia , Colículos Superiores/fisiologia , Vias Visuais , Animais , Emoções , Humanos , PercepçãoRESUMO
BACKGROUND: To describe the study design, methodology and baseline characteristics of the Dongguan Eye Study. DESIGN: Population-based, cross-sectional study PARTICIPANTS: A total of 8952 rural-dwelling residents aged 40 years or older in Hengli, Dongguan. METHODS: The Dongguan Eye Study was conducted from September 2011 to February 2012. The interview covered demographic data, socio-economic status and health- and vision-related quality of life. Physical measurements included height, weight, waist and hip circumference, heart rate and blood pressure. Laboratory tests included fasting blood glucose, haemoglobin A1c, oral glucose tolerance, serum total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, serum creatinine, blood urea nitrogen and uric acid. Ophthalmic examinations included visual acuity and autorefraction testing, intraocular pressure measurement, slit-lamp examination, ocular biometry, gonioscopy, fundus photography, retinal nerve fibre layer imaging and visual field testing. MAIN OUTCOME MEASURES: Prevalence and risk factors for visual impairment, blindness, eye diseases and their associations with systemic medical indicators or health-related lifestyles, as well as epidemiological data on diabetic subjects. Methodology, response rates and baseline characteristics are presented. RESULTS: Of the 11 357 individuals eligible for the Dongguan Eye Study, 8952 (78.82%) subjects participated. All participants were self-identified Han Chinese. The average age was 54.0 years, 59.9% were female, 48.4% were farmers and 77.2% had elementary or junior middle school educational levels. The average body mass index and waist-hip ratio were 24.6 ± 3.9 kg/m(2) and 0.9 ± 0.2. CONCLUSIONS: Data from the Dongguan Eye Study provide information concerning the prevalence, risk factors and impacts of eye diseases in rural residents undergoing urbanization in southern China.
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Povo Asiático/etnologia , Cegueira/etnologia , Oftalmopatias/etnologia , População Rural/estatística & dados numéricos , Pessoas com Deficiência Visual/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Constituição Corporal , China/epidemiologia , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Nível de Saúde , Humanos , Pressão Intraocular/fisiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Projetos de Pesquisa , Fatores de Risco , Classe Social , Acuidade Visual/fisiologiaRESUMO
PURPOSE: Recent studies revealed that immunological mechanisms play a prominent role in the pathogenesis of proliferative diabetic retinopathy (PDR). Given the importance of the immune response in PDR and the significance of the programmed death 1 (PD-1) pathway as an immune regulatory pathway, the aim of this study is to determine the expression and functional characteristics of the PD-1 pathway in peripheral blood lymphocytes from patients with PDR. METHODS: Peripheral blood lymphocytes were obtained from patients with PDR, age-matched patients with diabetes mellitus and no diabetic retinopathy (DM-NDR), and controls. The mRNA expression of PD-1 and its ligands were determined using real-time PCR. The frequencies of PD-1 and its ligands, activation-induced apoptosis, IFN-γ, and IL-4 were determined by flow cytometry. RESULTS: The PD-1 mRNA expression markedly decreased, while the frequency of PD-1(+) cells increased in the PDR group compared with the DM-NDR and control groups. The expression of PD-ligand 1 (PD-L1) mRNA and PD-L1(+) cells in the PDR group was lower than that in the other two groups. In the PDR group, the frequency of Annexin V(+)PI(-) and Annexin V(+)PI(-)PD-1(+) cells increased, while the frequency of Annexin V(+)PI(-)PD-L1(+) cells decreased. Although their expression was upregulated, the ratio of PD-1(+) IFN-γ(+) to PD-1(+)IL-4(+) cells in the PDR group was not significantly different to that in the DM-NDR and control groups. CONCLUSIONS: These results suggest that PD-1 is involved in the development of PDR by mediating activation-induced apoptosis.
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Retinopatia Diabética/imunologia , Receptor de Morte Celular Programada 1/genética , Adulto , Idoso , Apoptose/genética , Apoptose/imunologia , Estudos de Casos e Controles , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Feminino , Humanos , Ligantes , Ativação Linfocitária , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/sangue , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Novel aza-BODIPYs with significant bathochromic shifts were designed and synthesized by installation of strong electron-withdrawing groups on the para-positions of 1,7-phenyls and electron-donating groups on the para-positions of 3,4-phenyls. These dyes show strong NIR fluorescence emissions up to 756 nm, and absorptions up to 720 nm.
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Compostos Aza/química , Boratos/química , Compostos de Boro/química , Corantes Fluorescentes/química , Porfobilinogênio/análogos & derivados , Porfobilinogênio/química , Elétrons , Estrutura Molecular , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
PURPOSE: Microglia-related inflammation is closely linked to the pathogenesis of retinal diseases. The primary objective of this research was to investigate the impact and mechanism of M1 phenotype microglia on the barrier function of retina microvascular endothelial cells. METHODS: Quantitative polymerase chain reactions and western blot techniques were utilized to analysis the mRNA and protein expressions of M1 and M2 markers of human microglial clone 3 cell line (HMC3), as well as the levels of Notch ligands and receptors under the intervention of lipopolysaccharide (LPS) or interleukin (IL)-4. ELISA was utilized to detect the pro-inflammatory and anti-inflammatory cytokines from HMC3 cells. The cellular tight junction and apoptosis of human retinal microvascular endothelial cells (HRMECs) were assessed by western blot and fluorescein isothiocyanate-dextran permeability assay. The inhibitors of Notch1 and RNA interference (RNAi) targeting Jagged1 were used to assess their contribution to the barrier function of vascular endothelial cells. RESULTS: Inducible nitric oxide synthase (iNOS) and IL-1ß were considerably elevated in LPS-treated HMC3, while CD206 and Arg-1 markedly elevated under IL-4 stimulation. The conditioned medium derived from LPS-treated HMC3 cells promoted permeability, diminished the expression of zonula occludens-1 and Occludin, and elevated the expression of Cleaved caspase-3 in HRMECs. RNAi targeting Jagged1 or Notch1 inhibitor could block M1 HMC3 polarization and maintain barrier function of HRMECs. CONCLUSION: Our findings suggest that Jagged1-Notch1 signaling pathway induces M1 microglial cells to disrupt the barrier function of HRMECs, which may lead to retinal diseases.
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BACKGROUND: To apply machine learning (ML) algorithms to perform multiclass diabetic retinopathy (DR) classification using both clinical data and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional observational study, clinical data and OCTA parameters from 203 diabetic patients (203 eye) were used to establish the ML models, and those from 169 diabetic patients (169 eye) were used for independent external validation. The random forest, gradient boosting machine (GBM), deep learning and logistic regression algorithms were used to identify the presence of DR, referable DR (RDR) and vision-threatening DR (VTDR). Four different variable patterns based on clinical data and OCTA variables were examined. The algorithms' performance were evaluated using receiver operating characteristic curves and the area under the curve (AUC) was used to assess predictive accuracy. RESULTS: The random forest algorithm on OCTA+clinical data-based variables and OCTA+non-laboratory factor-based variables provided the higher AUC values for DR, RDR and VTDR. The GBM algorithm produced similar results, albeit with slightly lower AUC values. Leading predictors of DR status included vessel density, retinal thickness and GCC thickness, as well as the body mass index, waist-to-hip ratio and glucose-lowering treatment. CONCLUSIONS: ML-based multiclass DR classification using OCTA and clinical data can provide reliable assistance for screening, referral, and management DR populations.
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Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.
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Doenças Autoimunes , Colangite , Cirrose Hepática Biliar , Camundongos , Animais , Cirrose Hepática Biliar/terapia , Imunoterapia Adotiva , Receptor de Morte Celular Programada 1 , Linfócitos T CD8-Positivos , Colangite/terapia , Doenças Autoimunes/genéticaRESUMO
BACKGROUND: Post-cataract surgery fibrosis in the lens capsule is caused by epithelial to mesenchymal transition (EMT) of the lens epithelium. Mammalian target of rapamycin (mTOR) has been demonstrated to be a key regulator of EMT. The aim of this study was to investigate the role of mTOR in transforming growth factor ß2 (TGF-ß2)-induced EMT in human lens epithelial cells (HLECs). METHODS: Human lens epithelial B-3 (HLEB-3) cells were cultured with 10 ng/ml TGF-ß2 for different periods of time. The expression of E-cadherin, connexin 43, fibronectin and α-smooth muscle actin (α-SMA), and activation of mTOR were determined by Western blots. Cell migration was assessed by wound healing assay. An inhibition test was performed using two kinds of mTOR inhibitors. RESULTS: E-cadherin and connexin 43 expressions were suppressed, whereas fibronectin and α-SMA expressions were increased in HLEB-3 cells after treatment with TGF-ß2. mTOR was activated during the TGF-ß2-induced EMT in a time-dependent manner. Rapamycin or Ku-0063794 with 100 nM was able to inhibit the phosphorylation of mTOR and impaired EMT induced by TGF-ß2. Cell motility enhanced by TGF-ß2 for 24 h was attenuated by both rapamycin and Ku-0063794. CONCLUSIONS: mTOR is activated during TGF-ß2-induced EMT in HLECs, suggesting that it is involved in the regulation of TGF-ß2-induced EMT and may contribute to the development of posterior capsule opacification.
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Células Epiteliais/citologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Cristalino/citologia , Serina-Treonina Quinases TOR/fisiologia , Fator de Crescimento Transformador beta2/farmacologia , Actinas/metabolismo , Western Blotting , Caderinas/metabolismo , Movimento Celular , Células Cultivadas , Conexina 43/metabolismo , Células Epiteliais/metabolismo , Fibronectinas/metabolismo , Humanos , Morfolinas/farmacologia , Fosforilação , Pirimidinas/farmacologia , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the interaction effects between retinopathy and depression on mortality risks in genral population and subpopulation with diabetes. METHODS: Prospective analyses were conducted on data from the National Health and Nutrition Examination Surveys study. Associations of retinopathy, depression and their interaction with all-cause, cardiovascular disease (CVD)-specific, cancer-specific and other-specific mortality risk were estimated using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: Among 5367 participants, the weighted prevalence of retinopathy and depression was 9.6 % and 7.1 %, respectively. After a follow-up period of 12.1 years, 1295 deaths (17.3 %) occurred. Retinopathy was associated with an increased risk of all-cause (hazard ratio [HR]; 95 % confidence interval [CI]) (1.47; 1.27-1.71), CVD-specific (1.87; 1.45-2.41), and other-specific (1.43; 1.14-1.79) mortality. Similar relationship was observed between depression and all-cause mortality (1.24; 1.02-1.52). Retinopathy and depression had a positive multiplicative and additive interaction effect on all-cause (Pinteraction = 0.015; relative excess risk of interaction [RERI] 1.30; 95 % CI 0.15-2.45) and CVD-specific mortality (Pinteraction = 0.042; RERI 2.65; 95 % CI -0.12-5.42). Concomitant retinopathy and depression was more markedly associated with all-cause (2.86; 1.91-4.28), CVD-specific (4.70; 2.57-8.62), and other-specific mortality risks (2.18; 1.14-4.15) compared to those without retinopathy and depression. These associations were more pronounced in the diabetic participants. CONCLUSIONS: The co-occurrence of retinopathy and depression increases the risk of all-cause and CVD-specific mortality among middle-aged and older adults in the United States, especially in population with diabetes. Focus on diabetic patients and active evaluation and intervention of retinopathy with depression may improve their quality of life and mortality outcomes.
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Doenças Cardiovasculares , Diabetes Mellitus , Doenças Retinianas , Pessoa de Meia-Idade , Humanos , Estados Unidos/epidemiologia , Idoso , Estudos Prospectivos , Qualidade de Vida , Depressão , Doenças Cardiovasculares/epidemiologia , Doenças Retinianas/epidemiologia , Doenças Retinianas/complicações , Diabetes Mellitus/epidemiologia , Inquéritos Nutricionais , Fatores de RiscoRESUMO
We test the hypothesis that there exists a generalized magnocellular system in the brain optimized for temporal processing. In the visual system, it is well known that the magnocellular layers in the lateral geniculate nucleus (LGN) are strongly activated by transients and quickly habituate. However, little is known about the perhaps analogous magnocellular division of the medial geniculate nucleus (MGN), the auditory relay in the thalamus. We measured the functional responses of the MGN in 11 subjects who passively listened to sustained and transient nonlinguistic sounds, using functional MRI. We observed that voxels in the ventromedial portion of the MGN, corresponding to the magnocellular division, exhibited a robust preference to transient sounds, consistently across subjects, whereas the remainder of the MGN did not discriminate between sustained and transient sounds. We conclude that the magnocellular neurons in the MGN parallel the magnocellular neurons in its visual counterpart, LGN, and constitute an information stream specialized for encoding auditory dynamics.
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Corpos Geniculados , Tálamo , Corpos Geniculados/fisiologia , Humanos , Neurônios , Tálamo/fisiologiaRESUMO
Target identification of bioactive compounds is important for understanding their mechanisms of action and provides critical insights into their therapeutic utility. While it remains a challenge, unbiased chemoproteomics strategy using clickable photoaffinity probes is a useful and validated approach for target identification. One major limitation of this approach is the efficient synthesis of appropriately substituted clickable photoaffinity probes. Herein, we describe an efficient and consistent method to prepare such probes. We further employed this method to prepare a highly stereo-congested probe based on naturally occurring triterpenoid betulinic acid. With this photoaffinity probe, we identified tropomyosin as a novel target for betulinic acid that can account for the unique biological phenotype on cellular cytoskeleton induced by betulinic acid.
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OBJECTIVES: To investigate the relationship between serum lipids and pterygium in a large-scale rural population aged 40 years or older from Southern China. STUDY DESIGN: The Dongguan Eye Study was a cross-sectional population-based study from September 2011 to February 2012. SETTING: The area was set in the rural area of Dongguan, Southern China. PARTICIPANTS: Adult rural population aged 40 or older. METHODS: Participants underwent physical, haematological and ophthalmic examinations. PRIMARY AND SECONDARY OUTCOME MEASURES: The frequency and risk factors of pterygium. RESULTS: A total of 11 357 participants were eligible for inclusion and 8952 (78.8%) participants were enrolled for the systemic and ophthalmic examinations. The prevalence of pterygium was 17.3% after adjusting the sex and age distribution, 22.0% in participants with hypercholesterolaemia (total cholesterol ≥6.22 mmol/L (240 mg/dL)) and 21.8% in those with low-density lipoprotein-cholesterol (LDL-C) ≥4.14 mmol/L (160 mg/dL), respectively. After adjusting for multiple confounding factors, higher level of high-density lipoprotein-cholesterol (HDL-C) (OR: 1.23, 95% CI: 1.06 to 1.41) and LDL-C (OR: 1.13, 95% CI: 1.06 to 1.20) were positively associated with the risk of pterygium. The ORs for HDL-C or LDL-C with pterygium were significantly greater in participants aged 40-49 years than those aged 50 years or above (P for interaction <0.001). Furthermore, increased HDL-C showed greater association with pterygium in normal body mass index (BMI) group compared with overweight group (P for interaction=0.002). CONCLUSION: Increased HDL-C and LDL-C are risk factors of pterygium, especially in people <50 years or those with normal BMI level. Strict control of HDL-C and LDL-C may be a new prevention method in reducing the risk of pterygium.
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Pterígio , Adulto , Humanos , HDL-Colesterol , LDL-Colesterol , Estudos Transversais , Fatores de Risco , China/epidemiologia , TriglicerídeosRESUMO
Purpose: To development and validation of machine learning-based classifiers based on simple non-ocular metrics for detecting referable diabetic retinopathy (RDR) in a large-scale Chinese population-based survey. Methods: The 1,418 patients with diabetes mellitus from 8,952 rural residents screened in the population-based Dongguan Eye Study were used for model development and validation. Eight algorithms [extreme gradient boosting (XGBoost), random forest, naïve Bayes, k-nearest neighbor (KNN), AdaBoost, Light GBM, artificial neural network (ANN), and logistic regression] were used for modeling to detect RDR in individuals with diabetes. The area under the receiver operating characteristic curve (AUC) and their 95% confidential interval (95% CI) were estimated using five-fold cross-validation as well as an 80:20 ratio of training and validation. Results: The 10 most important features in machine learning models were duration of diabetes, HbA1c, systolic blood pressure, triglyceride, body mass index, serum creatine, age, educational level, duration of hypertension, and income level. Based on these top 10 variables, the XGBoost model achieved the best discriminative performance, with an AUC of 0.816 (95%CI: 0.812, 0.820). The AUCs for logistic regression, AdaBoost, naïve Bayes, and Random forest were 0.766 (95%CI: 0.756, 0.776), 0.754 (95%CI: 0.744, 0.764), 0.753 (95%CI: 0.743, 0.763), and 0.705 (95%CI: 0.697, 0.713), respectively. Conclusions: A machine learning-based classifier that used 10 easily obtained non-ocular variables was able to effectively detect RDR patients. The importance scores of the variables provide insight to prevent the occurrence of RDR. Screening RDR with machine learning provides a useful complementary tool for clinical practice in resource-poor areas with limited ophthalmic infrastructure.