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Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.
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Macaca fascicularis , Fibras Nerviosas , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Animales , Células Ganglionares de la Retina/citología , Masculino , Estudios Transversales , Tomografía de Coherencia Óptica/métodos , Femenino , Disco Óptico/anatomía & histología , Disco Óptico/diagnóstico por imagen , Longitud Axial del Ojo/anatomía & histología , Valores de Referencia , Biometría , Errores de Refracción/fisiopatologíaRESUMEN
OBJECTIVES: This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP). METHODS AND ANALYSIS: This cross-sectional study included 324 children with hyperopia aged 3-12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p<0.05) in the univariate analysis were included in a stepwise multiple linear regression. RESULTS: Overall, 324 children were included, 172 with low and 152 with moderate-to-high hyperopia. The median optic disc area and vessel diameter were 1.42 mm2 and 65.09 µm, respectively. Children with high hyperopia had larger superior neuroretinal rim (NRR) width and larger vessel diameter than those with low and moderate hyperopia. In the univariate analysis, axial length was significantly associated with smaller superior NRR width (ß=-3.030, p<0.001), smaller temporal NRR width (ß=-1.469, p=0.020) and smaller vessel diameter (ß=-0.076, p<0.001). A mild inverse correlation was observed between the optic disc area and vertical disc diameter with age. CONCLUSION: AI-based CFP analysis showed that children with high hyperopia had larger mean vessel diameter but smaller vertical cup-to-disc ratio than those with low hyperopia. This suggests that AI can provide quantitative data on fundus parameters in children with hyperopia.
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Inteligencia Artificial , Hiperopía , Disco Óptico , Fotograbar , Vasos Retinianos , Humanos , Hiperopía/diagnóstico , Hiperopía/fisiopatología , Estudios Transversales , Masculino , Niño , Femenino , Preescolar , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Disco Óptico/irrigación sanguínea , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Fotograbar/métodos , Fondo de Ojo , Agudeza Visual/fisiología , Refracción Ocular/fisiologíaRESUMEN
The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy, which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407, cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds. Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.
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Apoptosis , Carragenina , Ácido Eicosapentaenoico , Ferroptosis , Compuestos Ferrosos , Hidrogeles , Metalocenos , Ferroptosis/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Metalocenos/química , Metalocenos/farmacología , Apoptosis/efectos de los fármacos , Ratones , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Carragenina/farmacología , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/química , Humanos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Metástasis de la Neoplasia , Microambiente Tumoral/efectos de los fármacos , Femenino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacosRESUMEN
Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.
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Córnea , Estudio de Asociación del Genoma Completo , Glaucoma de Ángulo Abierto , Análisis de la Aleatorización Mendeliana , Glaucoma de Ángulo Abierto/genética , Humanos , Córnea/patología , Polimorfismo de Nucleótido Simple , Presión Intraocular/fisiología , Factores de Riesgo , Predisposición Genética a la Enfermedad , Paquimetría Corneal , Masculino , FemeninoRESUMEN
PURPOSE: Aztreonam/avibactam is effective against serious infections caused by Gram-negative bacteria including Enterobacterales harboring metallo-ß-lactamases. While the utility of this combination has been established in vitro and in clinical trials, the purpose of this study is to enhance our understanding of the underlying mechanism responsible for their activities through metabolomic profiling of a multidrug-resistant Escherichia coli clinical isolate. METHODS: Metabolomic analyses of time-dependent changes in endogenous bacterial metabolites in a clinical isolate of a multidrug-resistant E. coli treated with aztreonam and avibactam were performed. E. coli metabolomes were compared at 15 min, 1 h and 24 h following treatments with either avibactam (4 mg/L), aztreonam (4 mg/L), or aztreonam (4 mg/L) + avibactam (4 mg/L). RESULTS: Drug treatment affected 326 metabolites with magnitude changes of at least 2-fold, most of which are involved primarily in peptidoglycan biosynthesis, nucleotide metabolism, and lipid metabolism. The feedstocks for peptidoglycan synthesis were depleted by aztreonam/avibactam combination; a significant downstream increase in nucleotide metabolites and a release of lipids were observed at the three timepoints. CONCLUSION: The findings indicate that the aztreonam/avibactam combination accelerates structural damage to the bacterial membrane structure and their actions were immediate and sustained compared to aztreonam or avibactam alone. By inhibiting the production of crucial cell wall precursors, the combination may have inflicted damages on bacterial DNA.
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Antibacterianos , Compuestos de Azabiciclo , Aztreonam , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Escherichia coli , Metabolómica , Aztreonam/farmacología , Compuestos de Azabiciclo/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Escherichia coli/genética , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Metaboloma/efectos de los fármacosRESUMEN
AIMS: Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assess the trends of the visual impairment burden attributable to high FPG levels globally, regionally, nationally, and by income level. METHODS: We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. RESULTS: The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). CONCLUSIONS: The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.
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Glucemia , Ayuno , Trastornos de la Visión , Humanos , Glucemia/metabolismo , Glucemia/análisis , Ayuno/sangre , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Masculino , Femenino , Años de Vida Ajustados por Discapacidad/tendencias , Carga Global de Enfermedades/tendencias , Persona de Mediana Edad , Adulto , Anciano , Salud GlobalRESUMEN
Investigating the relationship of soil aggregate stability with the organic carbon in the aggregate and its response to land use change is conducive to the estimation of soil carbon sink potential, improvement of rocky desertification, and rational land use in karst areas of Southwest China. In order to explore the effects of land use change on the composition and stability of soil aggregate stability as well as the content of aggregate organic carbon, the soil (0-30 cm) of five land use types (secondary forest, pomelo forest, paddy field, pepper forest, and dry land) was selected as the research object. The characteristics and correlation of soil aggregate components and organic carbon under different land use patterns were obtained, and the contribution of soil aggregates to the change in organic carbon after land use change was calculated. The results showed that the macroaggregates in the surface soil (0-15 cm) of the secondary forest, pomelo forest, and paddy field were 63.32%, 52.38%, and 47.77%, respectively, which were significantly higher than that of dry land (23.70%), as was also seen in the lower layer (15-30 cm). The geometric mean diameter (GMD) and mean weight diameter (MWD) of soil aggregates in the secondary forest, pomelo forest, and paddy field were significantly higher than those in dry land. In the surface soil, the organic carbon of the secondary forest and paddy field was significantly higher than that of other land use patterns. By contrast, in the lower soil layer, only the organic carbon of the paddy field was significantly higher than that of the others. Under different land use patterns, the organic carbon content of aggregates followed the same order of macroaggregates > microaggregates > silt and clay, indicating that macroaggregates allowed soil organic carbon to accumulate, whereas silt and clay did the opposite. According to correlation analysis, the content of soil macroaggregates was significantly positively correlated with GMD, MWD, and soil aggregate organic carbon, suggesting that the increase in soil macroaggregates could improve the stability of soil aggregates and store more soil organic carbon. Further, as land use change may have significantly affected the soil aggregate, moderate development of forestry and paddy cultivation is suggested to improve the soil carbon sequestration potential in the karst area of Southwest China.
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Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.
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Aprendizaje Profundo , Demencia Frontotemporal , Glaucoma , Miopía , Humanos , Estudios Transversales , Estudios Retrospectivos , Glaucoma/complicaciones , Glaucoma/diagnóstico , Miopía/complicaciones , Miopía/diagnóstico , Atrofia , CoroidesRESUMEN
BACKGROUND: Cataract, glaucoma and age-related macular degeneration (AMD) are major causes of visual impairment. As these are age-related conditions, the prevalence of associated visual impairment is anticipated to increase as the population ages. However, age-period-cohort effects on the disease burden have not been investigated. METHODS: This was a population-based study using aggregated data from the Global Burden of Disease Study 2019. Age-period-cohort analysis was conducted using age-standardised prevalence rates (ASPRs) of visual impairment caused by cataract, glaucoma and AMD as disease burden indicator. RESULTS: In 2019, the estimated global ASPRs of visual impairment due to cataract, glaucoma and AMD were 1207.9, 94.7 and 96.8 per 100 000 people, respectively. Between 1990 and 2019, the global visual impairment ASPRs for glaucoma and AMD declined by 15.4% and 2.0%, respectively, whereas that for cataract increased by 5.0%. Wide heterogeneity was observed in age-period-cohort effects on ASPRs across different Sociodemographic Index (SDI) regions. Low-middle SDI regions had the largest ASPR reductions for all three eye diseases and showed improvement in both period and cohort effects. In contrast, in high-middle SDI regions, visual impairment ASPRs significantly increased during the study period with unfavourable patterns. CONCLUSIONS: The wide heterogeneity in age-period-cohort effects reflects different stages of societal transition and vision health. The unfavourable trends in age-period-cohort effects on disease prevalence identified in specific groups provide key information that may be used to identify priority groups in need of treatment and prevention.
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Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.
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Envejecimiento , Catequina , Senescencia Celular , Proantocianidinas , Retina , Animales , Retina/metabolismo , Retina/efectos de los fármacos , Ratones , Proantocianidinas/farmacología , Proantocianidinas/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Senescencia Celular/efectos de los fármacos , Catequina/farmacología , Catequina/metabolismo , Catequina/química , Biflavonoides/farmacología , Senoterapéuticos/farmacología , Ratones Endogámicos C57BL , Humanos , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patologíaRESUMEN
Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance. Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: ⢠Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. ⢠The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: ⢠The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. ⢠The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.
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Enfermedades del Recién Nacido , Retinopatía de la Prematuridad , Recién Nacido , Masculino , Lactante , Femenino , Humanos , Niño , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/epidemiología , Países en Desarrollo , Recien Nacido Extremadamente Prematuro , Prevalencia , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Edad GestacionalRESUMEN
The composition of soil organic carbon and its stability mechanism are the key to understanding the terrestrial carbon sink capacity. The stability of soil organic carbon in a karst ecosystem greatly affects the soil carbon fixation capacity. In order to understand the impact of human activities on the stability of soil organic carbon in karst areas, the karst valley area of Zhongliang Mountain in Chongqing was selected as an example, and soil samples of four typical land use modes (mixed forest, bamboo forest, grassland, and cultivated land) were collected in layers to analyze the total organic carbon (TOC) and heavy fraction organic carbon (HFOC). The distribution characteristics of light fraction organic carbon (LFOC), labile organic carbon (LOC), and recalcitrant organic carbon (ROC) were analyzed quantitatively by using a structural equation model to provide basic data for soil carbon sink assessment and soil quality protection in karst areas. The results showed that the organic carbon components under different land use patterns in karst areas had obvious surface accumulation, and the content of organic carbon components in the surface layer was 1.2 times that in the bottom layer. Except for LFOC, the content of other organic carbon components was the highest in the mixed forest, followed by that in the bamboo forest and wasteland, with the lowest in cultivated land. Mixed forest ω(TOC) content was the highest, 42.5 g·kg-1, followed by that of bamboo forest (36.6 g·kg-1) and grassland (18.7 g·kg-1), and cultivated land content was the lowest, 13.4 g·kg-1. The soil organic carbon content of cultivated land was 68.5%, 63.5%, and 28.3% lower than that of mixed forest, bamboo forest, and grassland, respectively. Mixed forest had the highest content of ω(HFOC), 21 g·kg-1, followed by those of bamboo forest (20.9 g·kg-1), grassland (18.2 g·kg-1), and cultivated land (13.5 g·kg-1). The mixed forest ω(LOC) content was the highest, 16.3 g·kg-1, followed by those of bamboo forest (14.9 g·kg-1), grassland (11.5 g·kg-1), and cultivated land (5.3 g·kg-1). Mixed forest ω (ROC) content was the highest, 25.7 g·kg-1, followed by those of bamboo forest (21.6 g·kg-1), grassland (15.9 g·kg-1), and cultivated land (10.3 g·kg-1). The bamboo forest land ω(LFOC) content was 15.9 g·kg-1, followed by those of mixed forest (13.9 g·kg-1), grassland (7.3 g·kg-1), and cultivated land (4.9 g·kg-1). The recalcitrant organic carbon index (ROCI) was used to indicate the stability of soil organic carbon. The variation range of ROCI was 33.9%-64.5%, of which the highest was mixed forest (64.5%-66.3%), and the lowest was cultivated land (33.8%-39.6%). The ROCI of mixed forest, bamboo forest, and grassland were 1.8 times, 1.6 times, and 1.4 times that of cultivated land, respectively. Karst area ω (inert organic carbon) content and ROCI showed that human agricultural activities caused the reduction in soil organic carbon content and the destruction of soil physical structure, resulting in the accelerated decomposition and turnover rate of soil organic matter. The most important factor affecting soil stability in karst areas was soil pH. Tillage activities caused soil pH to rise, reduced soil microbial activity, and were not conducive to the accumulation of the inert organic carbon and soil organic carbon pool in the soil.
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BACKGROUND: Blindness and vision loss (BVL) is a major global health issue affecting older adults, but its burden in transition countries has received limited attention. Therefore, we aimed to assess the trends in the burden of BVL among older adults between 1990 and 2019 across Brazil, Russia, India, China, and South Africa (BRICS), and predict the burden by 2040. METHODS: Data on BVL and its related causes were obtained from the Global Burden of Disease 2019 study. We investigated the temporal trends by calculating the average annual percentage change using joinpoint regression analysis. Subsequently, we performed Bayesian age-period-cohort modeling to estimate the burden of BVL and its related causes by 2040. RESULTS: Most BRICS countries experienced a significant decline (p < 0.05) in age-standardized prevalence rates, and the decreasing trends tend to continue. However, by 2040, the number of BVL cases is expected to increase by approximately 50% across BRICS, with an estimated approximately 192, 170, 25, 17, and 7 million cases in China, India, Russia, Brazil, and South Africa, respectively. The related ranks of BVL causes are also estimated to change in the future, particularly in India. CONCLUSIONS: The different burdens and trends of BVL across BRICS reflected the different stages of population health transition. Effective eye disease prevention requires appropriate public health interventions. Developing effective health policies and services for older adults is urgently needed in BRICS countries.
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Ceguera , Atención a la Salud , Humanos , Anciano , Prevalencia , Teorema de Bayes , Ceguera/epidemiología , Ceguera/etiología , China/epidemiología , India/epidemiología , Sudáfrica/epidemiología , Brasil/epidemiologíaRESUMEN
Importance: Visual impairment in working-age individuals can affect their general health and employment prospects, leading to decreased social and economic productivity and increased poverty rates. Nonetheless, investigations in this population appear to be limited. Objective: To investigate the trends of visual impairment prevalence and disability-adjusted life-years (DALYs) in working-age individuals from 1990 to 2019. Design, Setting, and Participants: This cross-sectional, population-based study used data for individuals of working age (15-64 years) from 204 countries and territories obtained from the Global Burden of Disease 2019 study. The data analysis was performed between May 1 and 10, 2023. Exposure: Visual impairment, defined as visual acuity of less than 6/18 (20/60) or near visual acuity of less than 6/12 (20/40) distance equivalent as determined by Snellen chart. Main Outcomes and Measures: Trends of visual impairment prevalence, DALYs, and corresponding estimated annual percent changes (EAPCs) from 1990 to 2019 were stratified according to region, nation, and sociodemographic index (SDI). Results: There were 437â¯539â¯484 (95% uncertainty interval [UI], 325â¯463â¯851-575â¯573â¯588) prevalent cases of visual impairment globally (53.12% female and 46.88% male) in 2019, representing an increase of 91.46% from 1990 (prevalent cases, 228â¯530â¯964; 95% UI, 172â¯515â¯833-297â¯118â¯596). Over 3 decades, visual impairment-associated DALYs increased from 7â¯601â¯852 (95% UI, 5â¯047â¯030-11â¯107â¯897) to 12â¯563â¯276 (95% UI, 8â¯278â¯866-18â¯961â¯723). Among the 5 SDI groups, the low-SDI group had the largest increase in DALYs (898 167 [95% UI, 597 161-1 301 931] in 1990 to 1 634 122 [95% UI, 1 079 102-2 444 381] in 2019). Regionally, the greatest increase in prevalence was observed in Eastern Europe (EAPC, 0.10; 95% CI, 0.02-0.19). Among all countries and territories, Nepal had the highest national prevalence of visual impairment per 100â¯000 population in 2019 (26â¯008.45; 95% UI, 19â¯987.35-32â¯482.09), while South Sudan had the highest DALY rate per 100â¯000 population (480.59; 95% UI, 316.06-697.06). Conclusions and Relevance: Despite the mild decrease in visual impairment prevalence rates in less-developed countries, these findings suggest that the number of prevalent cases globally has increased substantially, with discernible unfavorable patterns in developed regions. The findings support the notion that visual impairment in working-age individuals is a growing global health challenge. A better understanding of its epidemiology may facilitate the development of appropriate measures for prevention and treatment from both medical and social perspectives.
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Carga Global de Enfermedades , Salud Global , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Estudios Transversales , Prevalencia , Trastornos de la Visión/epidemiología , IncidenciaRESUMEN
The treatment of Pseudomonas aeruginosa infection often involves the combined use of ß-lactam and aminoglycoside antibiotics. In this study, we employed metabolomic analysis to investigate the mechanism responsible for the synergistic activities of meropenem/amikacin combination therapy against multidrug-resistant P. aeruginosa strains harboring OXA-50 and PAO genes. Antibiotic concentrations for meropenem (2 mg/L) monotherapy, amikacin (16 mg/L) monotherapy, and meropenem/amikacin (2/16 mg/L) combination therapy were selected based on clinical breakpoint considerations. Metabolomic analysis revealed significant alterations in relevant metabolites involved in bacterial cell membrane and cell wall synthesis within 15 min of combined drug administration. These alterations encompassed various metabolic pathways, including fatty acid metabolism, peptidoglycan synthesis, and lipopolysaccharide metabolism. Furthermore, at 1 h and 4 h, the combination therapy exhibited significant interference with amino acid metabolism, nucleotide metabolism, and central carbon metabolism pathways, including the tricarboxylic acid cycle and pentose phosphate pathway. In contrast, the substances affected by single drug administration at 1 h and 4 h demonstrated a noticeable reduction. Meropenem/amikacin combination resulted in notable perturbations of metabolic pathways essential for survival of P. aeruginosa, whereas monotherapies had comparatively diminished impacts.
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Amicacina , Infecciones por Pseudomonas , Humanos , Meropenem/farmacología , Meropenem/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad MicrobianaRESUMEN
Methanol-to-olefin (MTO) is a typical new coal chemical industry example. Due to the large volume of generated wastewater, complex composition including catalysts, aromatics and various oxygen-containing compounds, and serious environmental hazard, wastewater recycling is critical for sustainable industrial development and ecological protection. Herein, a swirl regenerating micro-channel separation (SRMS) technology was proposed to integrate deep filtration and hydrocyclone-enhanced regeneration. A small-scale experimental investigation was first conducted to verify the feasibility of the MTO wastewater treatment. A pilot SRMS device with a treatment capacity of 20 m3/h was constructed, and the device's continuous operation effect and stability were comprehensively evaluated. The separation performance of the SRMS device at different solution pH values and the impact of the hydrocyclone-enhanced regeneration of separation media were discussed in detail. At low solution pH values (<7), the SRMS device exhibits an average separation efficiency of 92.0% for fine particulate matter in wastewater, and the median particle size, d50, decreases from 1.55 to 0.6 µm. As the solution pH increases, the repulsive energy barrier for the medium-contaminant and contaminant-contaminant increases, inhibiting the deposition behavior of particulate pollutants. In addition, hydrocyclone desorbs contaminants deposited on the separation media and the average contaminant residual rate decreases from 3.3 to 0.2 wt%. We propose an industrial application for treating and reusing MTO wastewater (200 m3/h) using the SRMS technology based on the experimental results. The costs of the wastewater treatment process are as low as 0.25 CNY/m3, and the wastewater reuse rate is over 97% without chemical consumption. This work can provide an environmentally friendly and economically sustainable approach to the source management of MTO wastewater.
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Metanol , Aguas Residuales , Alquenos , Carbón Mineral , PolvoRESUMEN
AIMS: Diabetic retinopathy (DR) is the leading cause of blindness in patients with diabetes mellitus (DM). We investigated its trends in high-income countries to gain insights into preventing DR-related blindness in diabetes-epidemic areas. METHODS: For joinpoint regression analysis, we extracted data from the Global Burden of Disease 2019 study and analysed the prevalence trends of DR-related blindness according to DM type, patients' sex and age, region, and nation. RESULTS: Overall, the age-standardised prevalence rate (ASPR) of DR-related blindness has decreased. The prevalence rates of blindness decreased more sharply for Type 1 DM than for Type 2 DM. The ASPR was higher and the decreasing trend was less pronounced in women than in men. Southern Latin America had the highest ASPR, whereas Australasia had the lowest ASPR. Singapore experienced the greatest decline, whereas unfavourable trends were observed in the USA. CONCLUSIONS: Despite decrease in the overall ASPR of DR-related blindness during the study period, large improvement opportunities were identified. As DM prevalence increases and the population ages rapidly in high-income countries, novel effective screening, treatment, and prevention strategies are urgently needed to improve the visual outcomes of individuals with DM or at risk of DM.
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Diabetes Mellitus , Retinopatía Diabética , Masculino , Humanos , Femenino , Retinopatía Diabética/diagnóstico , Prevalencia , Países Desarrollados , Factores de Riesgo , Ceguera/epidemiología , Ceguera/etiología , Ceguera/prevención & controlRESUMEN
Multi-modal skin lesion diagnosis (MSLD) has achieved remarkable success by modern computer-aided diagnosis (CAD) technology based on deep convolutions. However, the information aggregation across modalities in MSLD remains challenging due to severity unaligned spatial resolution (e.g., dermoscopic image and clinical image) and heterogeneous data (e.g., dermoscopic image and patients' meta-data). Limited by the intrinsic local attention, most recent MSLD pipelines using pure convolutions struggle to capture representative features in shallow layers, thus the fusion across different modalities is usually done at the end of the pipelines, even at the last layer, leading to an insufficient information aggregation. To tackle the issue, we introduce a pure transformer-based method, which we refer to as "Throughout Fusion Transformer (TFormer)", for sufficient information integration in MSLD. Different from the existing approaches with convolutions, the proposed network leverages transformer as feature extraction backbone, bringing more representative shallow features. We then carefully design a stack of dual-branch hierarchical multi-modal transformer (HMT) blocks to fuse information across different image modalities in a stage-by-stage way. With the aggregated information of image modalities, a multi-modal transformer post-fusion (MTP) block is designed to integrate features across image and non-image data. Such a strategy that information of the image modalities is firstly fused then the heterogeneous ones enables us to better divide and conquer the two major challenges while ensuring inter-modality dynamics are effectively modeled. Experiments conducted on the public Derm7pt dataset validate the superiority of the proposed method. Our TFormer achieves an average accuracy of 77.99% and diagnostic accuracy of 80.03% , which outperforms other state-of-the-art methods. Ablation experiments also suggest the effectiveness of our designs. The codes can be publicly available from https://github.com/zylbuaa/TFormer.git.
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Enfermedades de la Piel , Humanos , Diagnóstico por Computador , Procesamiento de Imagen Asistido por Computador , Enfermedades de la Piel/diagnóstico por imagenRESUMEN
Silica is one of the most widely used ceramics due to its excellent chemical stability and dielectric property. However, its destructive brittle nature inhabits it from wider application as a functional ceramic. An improvement in toughness is a challenging topic for silica ceramic, as well as other ceramics. In the paper, silica ceramic with different types of boron nitride powders and alumina platelets was fabricated by hot-pressing. Introduction of the additives had great influence on the composites' mechanical properties and microstructure. The silica matrix composite containing micro-sized boron nitride powders possessed the best mechanical properties, including the bending strength (134.5 MPa) and the fracture toughness (1.85 Mpa·m1/2). Meanwhile, the introduction of alumina platelets combined with boron nitride nanosheets achieved an effective enhancement of fracture toughness while maintaining the bending strength. Compared with the monolithic silica, the composite with simultaneous addition of alumina platelets and boron nitride nanosheets had a fracture toughness of 2.23 Mpa·m1/2, increased by approximately 27% (1.75 Mpa·m1/2). The crack deflection and platelet pullout were contributing to enhancement of the fracture toughness. The improved mechanical properties, combined with the intrinsic excellent dielectric and chemical properties, make the silica matrix composites promising wave transparent and thermal protection materials.
RESUMEN
Alumina is one of the most commonly used and researched structural ceramic because of its excellent properties. However, its intrinsic brittleness is the fatal drawback, which hinders it from wider applications. How to improve its fracture toughness as well as the bending strength is always challenging for material researchers. In this paper, alumina matrix composites were fabricated by hot-pressing, in which some additives, including zirconia, alumina platelets, and MXene, were incorporated. The influence of the introduced additives on their microstructure and mechanical properties was investigated. Compare with the monolithic alumina, both bending strength and fracture toughness of all samples were improved greatly. Incorporation of zirconia was beneficial to the mechanical properties due to the phase-transformation strengthening and toughening mechanism. While alumina platelets resulted in high fracture toughness because of the self-toughening of elongated grains. The synergistic effect of alumina platelets and MXene enormously improved the fracture toughness from 2.9 ± 0.3 MPa·m1/2 for monolithic alumina to 7.5 ± 0.4 MPa·m1/2 for the composite, which was increased by 159%. This work will provide useful references for the fabrication of high-strength and high-toughness alumina ceramics by introducing additives properly.