RESUMEN
A broad range of enzymes are used to modify starch for various applications. Here, a thermophilic 4-α-glucanotransferase from Thermoproteus uzoniensis (TuαGT) is engineered by N-terminal fusion of the starch binding domains (SBDs) of carbohydrate binding module family 20 (CBM20) to enhance its affinity for granular starch. The SBDs are N-terminal tandem domains (SBDSt1 and SBDSt2) from Solanum tuberosum disproportionating enzyme 2 (StDPE2) and the C-terminal domain (SBDGA) of glucoamylase from Aspergillus niger (AnGA). In silico analysis of CBM20s revealed that SBDGA and copies one and two of GH77 DPE2s belong to well separated clusters in the evolutionary tree; the second copies being more closely related to non-CAZyme CBM20s. The activity of SBD-TuαGT fusions increased 1.2-2.4-fold on amylose and decreased 3-9 fold on maltotriose compared with TuαGT. The fusions showed similar disproportionation activity on gelatinised normal maize starch (NMS). Notably, hydrolytic activity was 1.3-1.7-fold elevated for the fusions leading to a reduced molecule weight and higher α-1,6/α-1,4-linkage ratio of the modified starch. Notably, SBDGA-TuαGT and-SBDSt2-TuαGT showed Kd of 0.7 and 1.5 mg/mL for waxy maize starch (WMS) granules, whereas TuαGT and SBDSt1-TuαGT had 3-5-fold lower affinity. SBDSt2 contributed more than SBDSt1 to activity, substrate binding, and the stability of TuαGT fusions.
Asunto(s)
Sistema de la Enzima Desramificadora del Glucógeno , Almidón , Almidón/química , Proteína 1 Similar al Receptor de Interleucina-1 , Sistema de la Enzima Desramificadora del Glucógeno/genética , AmilopectinaRESUMEN
China has put great efforts into air pollution control over the past years and recently committed to its most ambitious climate target. Cost and benefit analysis has been widely used to evaluate the control policies in terms of past performance, future reduction potential, and direct and indirect impacts. To understand the cost and benefit analysis for air pollution control in China, we conducted a bibliometric review of more than 100 studies published over the past two decades, including the current research progress, most commonly adopted methods, and core findings. The control target in cost and benefit analysis has shifted in three stages, from individual and primary pollution control, moving to joint prevention of multiple and secondary pollutants, and then towards synergistic control of air pollution and carbon. With the expansion of the research scope, the integrated assessment model has gradually demonstrated the necessity for long-term ex-anti policy simulation, especially for dealing with complex factors. To ensure long-term air quality, climate, public health, and sustainable economic development, substantial evidence from published studies has suggested that China needs to continue its efforts in the upstream adjustment of the energy system and industrial structure with multi-regional and -sector collaboration. This cost and benefit review paper provides decision-makers with the fundamental information and knowledge gaps in air pollution control strategies in China, and direction for facing future challenges.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Análisis Costo-Beneficio , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , China , PolíticasRESUMEN
Due to the lack of black carbon (BC) measurement data in some cases, elemental carbon (EC) is often used as a surrogate of BC, with a simple assumption that they are interchangeable. Such assumption will inevitably lead to uncertainties in radiative forcing estimation and health impact assessment. In order to quantitatively and systematically evaluate the relationship between BC and EC as well as factors responsible for their difference, 3-year collocated equivalent BC (eBC) and EC measurements with 1-h resolution were performed in Beijing, China continuously from 2016 to 2019. EBC concentration was measured by the multi-wavelength aethalometer (AE-33) based on optical analysis, while EC concentration was determined by semi-continuous OC/EC analyzer with thermal-optical method. The results showed that around 90% of eBC concentration was higher than that of EC, with average difference between eBC and EC as 1.21 µg m-3 (accounting for 33% of average eBC in Beijing). EBC and EC concentrations exhibited strong correlation (r = 0.90) during the whole study period, but the slopes (or eBC/EC ratio) and correlation coefficients varied across seasons (spring: 1.67 and 0.94; summer: 0.91 and 0.65; fall: 1.15 and 0.88; winter: 1.09 and 0.91, respectively). Based on the information from shell/core ratios by Single Particle Soot Photometer (SP2), source apportionment results by positive matrix factorization model, and chemical composition of PM2.5, the differences between eBC and EC concentrations were found to be primarily related to BC aging process and secondary components as evidenced by strong positive correlation with secondary species (e.g., secondary organic carbon and nitrate). This study provided seasonal specific conversion factors of eBC and EC in Beijing and helpful reference for other areas, which will contribute new knowledge of carbonaceous aerosol and reduce uncertainty in assessing future climate change and health studies of BC.
Asunto(s)
Contaminantes Atmosféricos , Hollín , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Beijing , Carbono/análisis , China , Monitoreo del Ambiente/métodos , Material Particulado/análisis , Estaciones del Año , Hollín/análisisRESUMEN
The coal-dominated electricity system poses major challenges for India to tackle air pollution and climate change. Although the government has issued a series of clean air policies and low-carbon energy targets, a key barrier remains enforcement. Here, we quantify the importance of policy implementation in India's electricity sector using an integrated assessment method based on emissions scenarios, air quality simulations, and health impact assessments. We find that limited enforcement of air pollution control policies leads to worse future air quality and health damages (e.g., 14â¯200 to 59â¯000 more PM2.5-related deaths in 2040) than when energy policies are not fully enforced (5900 to 8700 more PM2.5-related deaths in 2040), since coal power plants with end-of-pipe controls already emit little air pollution. However, substantially more carbon dioxide will be emitted if low-carbon and clean coal policies are not successfully implemented (e.g., 400 to 800 million tons more CO2 in 2040). Thus, our results underscore the important role of effectively implementing existing air pollution and energy policy to simultaneously achieve air pollution, health, and carbon mitigation goals in India.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/prevención & control , Electricidad , India , Material Particulado/análisis , PolíticasRESUMEN
Diabetic retinopathy (DR) is a devastating complication of diabetes. The aim of the present study is to investigate the exact role and mechanism of long noncoding RNA MALAT1 (MALAT1) in the progress of DR. An oxygen-induced retinopathy (OIR) mouse model and high glucose (HG) stimulated human retinal microvascular endothelial cells (HRMECs) were employed to mimic the pathological statues of DR. Quantitative real-time PCR (qRT-PCR) and Western blot results showed that MALAT1, VEGFA, and HIF-1α levels were increased in DR retinal tissues and HG-stimulated HRMECs, whereas the expression of miR-203a-3p was decreased. Knockdown of MALAT1 or upregulation of miR-203a-3p both suppressed HG-induced proliferation, migration, and tube formation of HRMECs. A dual-luciferase reporter assay showed that miR-203a-3p could bind to the predicted seed regions of MALAT1 as evidenced by the reduced luciferase activity. Furthermore, enforced downregulation of miR-203a-3p abolished the suppressive effect of MALAT1 silencing on HRMEC cell migration and tube formation. In conclusion, these data demonstrated that MALAT1 may affect angiogenesis by sponging miR-203a-3p in DR, suggesting that MALAT1 may act as a novel therapeutic target for the treatment of DR.
Asunto(s)
Retinopatía Diabética/inducido químicamente , Retinopatía Diabética/genética , MicroARNs/genética , Neovascularización Patológica/genética , Oxígeno/farmacología , ARN Largo no Codificante/genética , Animales , Línea Celular , Movimiento Celular/genética , Proliferación Celular/genética , Diabetes Mellitus/genética , Retinopatía Diabética/patología , Regulación hacia Abajo/genética , Células Endoteliales/patología , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Neovascularización Patológica/patología , Retina/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA-203-3p (miR-203-3p) was found to be down-regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR-203a-3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR-203a-3p agomir by intravitreal injection. The results showed that the level of miR-203a-3p was decreased in OIR rats, and forced over-expression of miR-203a-3p inhibited OIR-induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR-induced up-regulation of VEGFA, HIF-α, PCNA, and MMPs in the retina was also counteracted by miR-203a-3p. Additionally, high glucose (HG)-induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up-regulation of miR-203a-3p. Dual-luciferase reporter assay showed that miR-203a-3p could specifically bind to the 3'UTR of VEGFA and HIF-1α. Over-expression of VEGFA or HIF-1α restored the tube formation activity of HRMECs suppressed by miR-203a-3p. In conclusion, our findings demonstrate that up-regulation of miR-203a-3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF-1α.
Asunto(s)
Proliferación Celular/genética , Retinopatía Diabética/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , MicroARNs/genética , Oxígeno/metabolismo , Neovascularización Retiniana/genética , Factor A de Crecimiento Endotelial Vascular/genética , Regiones no Traducidas 3'/genética , Animales , Línea Celular , Movimiento Celular/genética , Diabetes Mellitus/genética , Retinopatía Diabética/patología , Modelos Animales de Enfermedad , Regulación hacia Abajo/genética , Células Endoteliales/patología , Células HEK293 , Humanos , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Ratas , Ratas Sprague-Dawley , Retina/patología , Neovascularización Retiniana/patología , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: To compare the efficiency of preloaded vs manually loaded IOL (P-IOL vs M-IOL, respectively) delivery systems in cataract surgery in the largest ambulatory surgery center of Northwestern China. METHODS: A total of 200 cases were included in this prospective, observational study. Time and motion data were collected in a one- or two-operating room (1-OR or 2-OR, respectively) scenario. A model of the efficiency and revenue implications of introducing a preloaded delivery system for IOLs in cataract surgery was used to estimate the changes in cataract throughput and hospital revenue through transitioning from the M-IOL delivery system to the P-IOL system. RESULTS: In the 1-OR scenario, the mean total case time was 16.9 min using P-IOL, which was a 7.7% reduction compared with M-IOL (P < 0.01). In the 2-OR scenario, the mean total surgeon time was 10.8 min using P-IOL, which was a 7.8% reduction compared with M-IOL (P < 0.05). By switching from M-IOL to P-IOL, annual throughput will increase by 5.2% (960 cases) in the 1-OR scenario and 7.7% (1440 cases) in the 2-OR scenario, accompany by an increase in revenue of approx. 284,352 USD in the 1-OR scenario and approx. 426,528 USD in the 2-OR scenario. CONCLUSION: This report is the first of a comparison of two IOL delivery systems in China using different settings in the scenario. IOL delivery with preloaded systems is time saving in both the 1-OR scenario and the 2-OR scenario. Moreover, switching from the M-IOL delivery system to the P-IOL system holds potential to increase cataract throughput and hospital revenue.
Asunto(s)
Extracción de Catarata , Catarata , Lentes Intraoculares , Procedimientos Quirúrgicos Ambulatorios , China , Humanos , Implantación de Lentes Intraoculares , Complicaciones Posoperatorias , Estudios ProspectivosRESUMEN
This paper employs statistical complexity measure (SCM) to investigate the occurrence of stochastic multiresonance (SMR) induced by noise and time delay in small-world neural networks coupled with FitzHugh-Nagumo (FHN) neurons. Our findings reveal that SCM exhibits four local maxima at four optimal noise levels, providing evidence for the occurrence of quadruple stochastic resonances. When time delay τ is taken into account in the information transmission, under moderate noise levels, SCM shows several local maxima when τ = n T e with n being a positive integer and T e being the period of subthreshold signal. This indicates the appearance of delay-induced SMR at the multiples of the period of subthreshold signal. Intriguingly, at low noise levels, a strong coherence between time delay and neuronal firing dynamics emerges at τ = n T e - 2 , as confirmed by a series of SCM maxima at these time delays. Furthermore, the study demonstrates that by adjusting the degrees and sizes of small-world networks, as well as the coupling strength, it is possible to optimize the strength of delay-induced SMR, thus maximizing the detection capability of subthreshold signal. The research results may provide us with an effective approach for understanding the role of time delay in signal detection and information transmission.
RESUMEN
Simvastatin is a cholesterol-lowering drug which exhibits numerous pleiotropic effects including anti-cancer activity. Yet, the anti-cancer effects in choroidal melanoma remain poorly characterized. Therefore, in this study, we investigated the effects of simvastatin on OCM-1 cells growth, apoptosis and cycle. Simvastatin showed an inhibitory effects on OCM-1 cells viability in dose-dependent (2-10 µM) and time-dependent (24-72 h) manner. Further study suggested that simvastatin-induced inhibition OCM-1 cells proliferation was associated with G1 phase arrest, decreased protein and mRNA expression of proliferation marker cyclin D1, cyclin E, cyclin dependent kinase (CDK)2 and increased expression of CDK inhibitory protein P21. In addition, simvastatin resulted in an increase in levels of reactive oxygen species (ROS) in OCM-1 cells and simvastatin significantly triggered apoptosis in OCM-1 cells, which was characterized by increased chromatin condensation, activation of caspase-9 and cleaved-caspase-3, increased expression mitochondrion-related apoptosis protein of P53, Bax and decreased expression of Bcl2 and iASPP. Collectively, our study demonstrated that simvastatin can efficiently inhibit proliferation and induce apoptosis in OCM-1 cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Neoplasias de la Coroides/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Melanoma/patología , Simvastatina/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Western Blotting , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias de la Coroides/enzimología , Ciclina E/metabolismo , Ciclina E/farmacología , Quinasa 2 Dependiente de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Fase G1/efectos de los fármacos , Humanos , Melanoma/enzimología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Oncogénicas , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales Cultivadas , Proteína X Asociada a bcl-2/metabolismoRESUMEN
How to improve the solubility of linear dextrins (LD) and retain their characteristic helix amphiphilic cavities with flexible embedding capability, is a question worth exploring without adding new chemical groups. The strategy presented in this study is to attach a highly flexible (α-1 â 6) glucochain at the reducing end of LD by preparing a new type of dextrin, referred to as single-arm linear dextrin (SLD). In the actual synthesis, an (α-1 â 6) linked oligosaccharide of DP¯ 10.7 (PDI = 1.28) was formed by extension of glucose units onto sucrose (2 M) by using L940W mutant of the glucansucrase GTF180-ΔN firstly. Next using γ-CD as glucosylation donor γ-CGTase extended this (α-1 â 6) glucochain with (α-1 â 4) bonds. SLD is a chimeric glucosaccharide comprising an (α-1 â 4) linked part (DP¯ 10.5) attached to the nonreducing end of an (α-1 â 6) glucochain as verified by enzyme fingerprinting and 1H NMR. Furthermore, SLD was validated to show greatly improved solubility and dispersibility of resveratrol in water, as indicated by a 3.12-fold enhancement over the solubility in the presence of 0.014 M SLD. This study provided a new strategy for solving the solubility problem of LD and opens possibilities for new design of the fine structure of starch-like materials.
Asunto(s)
Dextrinas , Limosilactobacillus reuteri , Glucosa , Almidón , Oligosacáridos/químicaRESUMEN
PURPOSE: To retrospectively analyze the clinical data of large samples of YAG laser posterior capsulotomy, and to explore the influencing factors of time from cataract surgery to YAG laser capsulotomy (TFCSTLC), so as to provide reference for the occurrence and treatment of real-world posterior capsular opacification (PCO). METHODS: 1093 patients (1093 eyes) with PCO who underwent YAG laser posterior capsulotomy from 2014 to 2019 in the largest eye center of northwest China were analyzed retrospectively. The gender, age, systemic complications, material, and design of intraocular lens (IOL) and TFCSTLC were recorded. The test and Wilcoxon rank sum test were applied to analyze and compare the average TFCSTLC values under different factors, and the relationship between each factor and TFCSTLC was analyzed by multiple linear regression. RESULTS: The average TFCSTLC was 19.2 (range, 7.9 â¼ 31.2) months. There were significant statistical differences in TFCSTLC among the implanted single focus versus multifocal IOLs (P < 0.001), diabetic versus non-diabetic patients (P < 0.001), high myopia versus non-high myopia patients (P = 0.003). Multiple linear regression analysis demonstrated that TFCSTLC was negatively correlated in patients with diabetes mellitus versus with no history of diabetes mellitus (coefficient, -5.36; 95% confidence interval [CI], -8.30 to -2.41; P < 0 .001), and multifocal IOL versus a single focus IOL implanted (coefficient, -5.56 ; 95% CI, -9.01 to -2.11; P = 0.002). CONCLUSIONS: TFCSTLC may be affected by many factors in the real world. The YAG laser posterior capsulotomy time was sooner in patients with a history of diabetes mellitus and multifocal IOL implanted.
Asunto(s)
Opacificación Capsular , Catarata , Terapia por Láser , Cápsula del Cristalino , Lentes Intraoculares , Humanos , Implantación de Lentes Intraoculares/efectos adversos , Cápsula del Cristalino/cirugía , Estudios Retrospectivos , Capsulotomía Posterior/efectos adversos , Opacificación Capsular/etiología , Opacificación Capsular/cirugía , Lentes Intraoculares/efectos adversos , Terapia por Láser/efectos adversos , Complicaciones Posoperatorias/cirugía , Catarata/complicacionesRESUMEN
Isomalto/malto-polysaccharides (IMMPs) derived from malto-oligosaccharides such as maltoheptaose (G7) are elongated non-branched gluco-oligosaccharides produced by 4,6-α-glucanotransferase (GtfB). However, G7 is expensive and cumbersome to produce commercially. In this study, a cost-effective enzymatic process for IMMPs synthesis is developed that utilizes the combined action of cyclodextrinase from Palaeococcus pacificus (PpCD) and GtfB-ΔN from Limosilactobacillus reuteri 121 to convert ß-cyclodextrin into IMMPs with a maximum yield (16.19 %, w/w). The purified IMMPs synthesized by simultaneous or sequential treatments, designated as IMMP-Sim and IMMP-Seq, possess relatively high contents of α-(1 â 6) glucosidic linkages. By controlling the release of G7 and smaller malto-oligosaccharides by PpCD, IMMP-Seq was obtained of DP varying from 12.9 to 29.5. Enzymatic fingerprinting revealed different linkage-type distribution of α-(1 â 6) linked segments with α-(1 â 4) segments embedded at the reducing end and middle part. The proportion of α-(1 â 6) segments containing the non-reducing end was 56.76 % for IMMP-Sim but 28.98 % for IMMP-Seq. Addition of G3 or G4 as specific acceptors resulted in IMMPs exhibiting low polydispersity. This procedure can be applied as a novel bioprocess that does not require costy high-purity malto-oligosaccharides and with control of the average DP of IMMPs by adjusting the substrate composition.
Asunto(s)
Polisacáridos , beta-Ciclodextrinas , Análisis Costo-Beneficio , Polisacáridos/química , Oligosacáridos/químicaRESUMEN
Bioenergy with carbon capture and storage, among other negative-emission technologies, is required for China to achieve carbon neutrality-yet it may hinder land-based Sustainable Development Goals. Using modelling and scenario analysis, we investigate how to mitigate the potential adverse impacts on the food system of ambitious bioenergy deployment in China and its trading partners. We find that producing bioenergy domestically while sticking to the food self-sufficiency ratio redlines would lower China's daily per capita calorie intake by 8% and increase domestic food prices by 23% by 2060. Removing China's food self-sufficiency ratio restrictions could halve the domestic food dilemma but risks transferring environmental burdens to other countries, whereas halving food loss and waste, shifting to healthier diets and narrowing crop yield gaps could effectively mitigate these external effects. Our results show that simultaneously achieving carbon neutrality, food security and global sustainability requires a careful combination of these measures.
Asunto(s)
Carbono , Tecnología , Carbono/análisis , Condiciones Sociales , ChinaRESUMEN
INTRODUCTION: Establishing the reference interval for pulse oxygen saturation (SpO2) is essential for sensitively identifying neonatal hypoxaemia due to various causes. However, the reference interval for high altitudes has not yet been established, and existing studies have many limitations. This study will aim to establish the reference interval for various high altitudes and determine whether preductal and postductal measurements at the same altitude vary. METHODS AND ANALYSIS: This is a multicentre, open, cross-sectional study, which will begin in February 2022. Approximately 2000 healthy full-term singleton neonates will be recruited from six hospitals (altitude ≥2000 m) in Qinghai Province, China. The participating hospitals will use a uniform pulse oximeter type. The measurements will be performed between 24 hours after birth and discharge. During the measurement, the neonate will be awake and quiet. Preductal and postductal measurements will be performed. The measurement time, site and results will be recorded and input, along with the collected basic information, into the perinatal cloud database. We will carry out strict quality control for basic information collection, measurement and data filing. We will perform descriptive statistics on the distribution range of the collected data, determine the lower limit value of the reference interval for each hospital and the corresponding altitude, perform curve fitting for the lower limit value, use the altitude as a covariate for the function corresponding to the fitted curve, establish the prediction equation and ultimately determine the reference intervals of each high altitude location. ETHICS AND DISSEMINATION: Our protocol has been approved by the Medical Ethics Committee of all participating hospitals. We will publish our study results in academic conferences and peer-reviewed public journals. TRIAL REGISTRATION NUMBER: NCT05115721.
Asunto(s)
Altitud , Saturación de Oxígeno , Estudios Transversales , Femenino , Humanos , Recién Nacido , Estudios Multicéntricos como Asunto , Oximetría/métodos , Oxígeno , EmbarazoRESUMEN
Proliferative diabetic retinopathy, the primary cause of vision loss in adults, is one of serious microvascular complications caused by diabetes. Both poly-ADP-ribose-polymerase (PARP) and nuclear factor (NF)-κB signaling are involved in the injury process. Injury activates PARP, which in turn potentiates NF-κB activation and causes cell apoptosis. Like the NF-κB pathway, Notch1 signaling plays a key role in the regulation of cell proliferation, differentiation, and apoptosis. However, the connections between these signaling pathways are not well understood. In this study, we used both streptozotocin (STZ)-induced diabetic mice and human retinal vascular endothelial cells (HRVECs) cultured in high glucose to detect these relationships. We found that apoptosis was increased in both STZ-induced diabetic mice and high-glucose-treated HRVECs, which was due to increased activation of PARP, cleaved caspase3, and reduced expression of Notch1 and p-Akt. The results of Notch1 overexpression and knockdown indicated that Notch1 signaling participated in the interaction of PARP and p50, and inhibited PARP- and p50-mediated apoptosis directly. These phenomena could be blocked by pretreatment with the PI3K inhibitor wortmannin via reducing p-Akt levels. Thus, our study demonstrated that Notch1 signaling protects cells from PARP- and NF-κB-induced apoptosis under high glucose through the activation of Akt.
Asunto(s)
Apoptosis/efectos de los fármacos , Glucosa/farmacología , FN-kappa B/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Receptor Notch1/metabolismo , Retina/metabolismo , Androstadienos/farmacología , Animales , Western Blotting , Caspasa 3/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , FN-kappa B/genética , Subunidad p50 de NF-kappa B/genética , Subunidad p50 de NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Poli(ADP-Ribosa) Polimerasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Receptor Notch1/genética , Retina/patología , WortmaninaRESUMEN
Gene therapy emerged as important approach in treatment for many inborn disorders caused by genetic defects, as well as other diseases. This manuscript focused on Adeno-associated virus (AAV) based gene therapy to eye diseases. The paper firstly introduced the AAV vectors and the techniques of eye delivery, then summarized some tested genes that were used in past treatment to retinal degeneration disorders. Finally the paper discussed the updated optogenetics and its roles in AAV based gene therapy for eye diseases.
Asunto(s)
Dependovirus/genética , Oftalmopatías/terapia , Terapia Genética/métodos , Animales , Ojo/metabolismo , Ojo/patología , Oftalmopatías/genética , Oftalmopatías/patología , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , HumanosRESUMEN
Introduction: The reference interval for pulse oxygen saturation (SpO2) in neonates born at high altitudes has not been defined to date. The purpose of this study was to systematically review published studies and determine the reference interval of SpO2 in neonates at different altitudes. Methods: Databases of PubMed, Embase, Cochrane Library, Clinicaltrials.Gov, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science Technology Journals Database, and Chinese Clinical Trial Registry were searched for studies reporting SpO2 in healthy neonates at different altitudes. Retrieval time was from inception of the database to August 16, 2021. The Agency for Healthcare Research and Quality checklist was used to evaluate the quality of studies. Python v3.8 was used to analyze the data. This systematic review was drafted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Seven cross-sectional studies, published between 1991 and 2020, were identified. They were from US, Mexico, Israel, Ecuador, and China. Three studies were rated as high quality and four as moderate quality. The mean SpO2 (with standard deviation or standard error) of neonates born in 40 different altitudes (ranging from 25 meters to 3,100 meters) were obtained. The prediction equation for calculation of the lower limit of the reference interval was established, and the reference intervals for SpO2 at different altitudes were determined. Conclusions: In healthy neonates, the lower limit of the reference interval of SpO2 decreases with increase in altitude. High-quality prospective studies are need to confirm our findings.
RESUMEN
BACKGROUND: Pathological retinal neovascularization is a disease characterized by abnormal angiogenesis in retina that is a major cause of blindness in humans. Previous reports have highlighted the involvement of microRNAs (miRNAs) in retinal angiogenesis. Therefore, we aimed at exploring the mechanism underlying miR-203 regulating the progression of pathological retinal neovascularization. METHODS: Initially, the mouse model of pathological retinal neovascularization disease was established and the hypoxia-induced human retinal microvascular endothelial cells (HRMECs) were generated. Then, miR-203 and SNAI2 expression in HRMECs and retinal tissues was examined. Subsequently, the effects of miR-203 and SNAI2 on viability, migration, apoptosis and angiogenesis of HRMECs were investigated, with the expression of Bax, Ki-67, MMP-2, MMP-9, VEGF and CD34 measured. Finally, the regulation of miR-203 or SNAI2 on GSK-3ß/ß-catenin pathway was determined through examining the levels of phosphorylated p-GSK-3ß and ß-catenin. RESULTS: Poorly expressed miR-203 and highly expressed SNAI2 were found in HRMECs and retinal tissues of pathological retinal neovascularization. Importantly, overexpressed miR-203 or silencing SNAI2 inhibited viability, migration and angiogenesis but promoted apoptosis of HRMECs, evidenced by elevated Bax expression but reduced expression of Ki-67, MMP-2, MMP-9, VEGF and CD34. Moreover, overexpression of miR-203 was found to repress the GSK-3ß/ß-catenin pathway by downregulating SNAI2. CONCLUSION: Collectively, this study demonstrated that overexpression of miR-203 suppressed the angiogenesis in mice with pathological retinal neovascularization disease via the inactivation of GSK-3ß/ß-catenin pathway by inhibiting SNAI2, which provided a novel therapeutic insight for pathological retinal neovascularization disease.
Asunto(s)
Regulación hacia Abajo/genética , MicroARNs/metabolismo , Neovascularización Retiniana/genética , Factores de Transcripción de la Familia Snail/genética , Animales , Apoptosis/genética , Secuencia de Bases , Hipoxia de la Célula/genética , Movimiento Celular/genética , Supervivencia Celular/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Ratones Endogámicos C57BL , MicroARNs/genética , Microvasos/metabolismo , Retina/patología , Transducción de Señal , Factores de Transcripción de la Familia Snail/metabolismo , Regulación hacia Arriba/genética , beta Catenina/metabolismoRESUMEN
Many studies have reported associations between air pollution and health impacts, but few studies have explicitly differentiated the economic effects of PM2.5 and ozone at China's regional level. This study compares the PM2.5 and ozone pollution-related health impacts based on an integrated approach. The research framework combines an air pollutant emission projection model (GAINS), an air quality model (GEOS-Chem), a health model using the latest exposure-response functions, medical prices and value of statistical life (VSL), and a general equilibrium model (CGE). Results show that eastern provinces in China encounter severer loss from PM2.5 and more benefit from mitigation policy, whereas the lower income western provinces encounter severer health impacts and economic burdens due to ozone pollution, and the impact in southern and central provinces is relatively lower. In 2030, without control policies, PM 2.5 pollution could lead to losses of 2.0% in Gross Domestic Production (GDP), 210 billion Chinese Yuan (CNY) in health expenditure and a life loss of around 10,000 billion, while ozone pollution could contribute to GDP loss by 0.09% (equivalent to 78 billion CNY), 310 billion CNY in health expenditure, and a life loss of 2300 billion CNY (equivalent to 2.7% of GDP). By contrast, with control policies, the GDP and VSLs loss in 2030 attributable to ambient air pollution could be reduced significantly. We also find that the health and economic impacts of ozone pollution are significantly lower than PM2.5, but are much more difficult to mitigate. The Chinese government should promote air pollution control policies that could jointly reduce PM2.5 and ozone pollution.