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OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.
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Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.
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AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/etiología , Reino Unido/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Adulto , Factores de Riesgo , Índice de Masa Corporal , Fumar/efectos adversos , Fumar/epidemiología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Ejercicio Físico , Estudios de Seguimiento , Presión Sanguínea , IncidenciaRESUMEN
BACKGROUND: This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns. METHODS AND RESULTS: We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow-up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257-0.365]; P<0.001). Elevated CVH scores were associated with a reduced risk of MACE across different sleep patterns. Similar trends were observed for individual MACE components, heart failure, and all-cause mortality. These findings remained robust in sensitivity analyses and across various subgroups. CONCLUSIONS: In individuals without known CVD, maintaining a favorable sleep pattern and achieving optimal CVH levels, as measured by traditional metrics, were associated with the lowest MACE risk. Enhanced CVH significantly reduced CVD risk, even in individuals with a poor sleep pattern. These results emphasize the importance of considering multiple dimensions of sleep health alongside CVH to mitigate CVD risk. REGISTRATION: URL: https://www.ukbiobank.ac.uk; Unique identifier: 91090.
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Enfermedades Cardiovasculares , Sueño , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Estudios Prospectivos , Persona de Mediana Edad , Reino Unido/epidemiología , Anciano , Incidencia , Factores de Riesgo , Medición de Riesgo/métodos , Adulto , Factores de Riesgo de Enfermedad Cardiaca , Calidad del Sueño , Estado de Salud , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.
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Aneurisma de la Aorta , Disección Aórtica , Ácido Ascórbico , Factores Protectores , Vitamina E , Humanos , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Femenino , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/efectos adversos , Vitamina E/administración & dosificación , Factores de Riesgo , Anciano , Incidencia , Disección Aórtica/epidemiología , Disección Aórtica/prevención & control , Aneurisma de la Aorta/epidemiología , Aneurisma de la Aorta/prevención & control , Medición de Riesgo , Reino Unido/epidemiología , Factores de Tiempo , Dieta/efectos adversos , AdultoRESUMEN
Lagomorpha coccidiosis, caused by coccidia, is a prevalent disease affecting rabbits, hares and pikas. This meta-analysis aimed to estimate the pooled prevalence of coccidia infection in lagomorphs and identify potential risk factors. A systematic search of six databases yielded 102 studies published between 1981 and 2023. The pooled prevalence of Eimeriidae, Sarcocystidae and Cryptosporidiidae in lagomorphs was 76.4%, 6.2% and 3.9%, respectively. Rabbits had the highest prevalence of Eimeriidae (76.8%) and Sarcocystidae (7.4%), while pikas had the highest prevalence of Cryptosporidiidae (6.2%). Juvenile rabbits exhibited the highest prevalence of Eimeriidae (84.6%) and Cryptosporidiidae (9.9%). Northwest China had the highest prevalence of Eimeriidae (87.8%). Over time, the prevalence of Eimeriidae declined (Coefficient: -0.0062; P<0.05), but remained high (65.0%) in the past five years. Our findings highlight the prevalence of Eimeriidae infection in lagomorphs and the need for further research on Sarcocystidae and Cryptosporidiidae infections. We emphasize the importance of developing lagomorpha coccidia vaccines and implementing vaccination schedules for juvenile rabbits to mitigate coccidia infections.
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Coccidiosis , Lagomorpha , Animales , China/epidemiología , Lagomorpha/parasitología , Prevalencia , Coccidiosis/epidemiología , Coccidiosis/veterinaria , Coccidiosis/parasitología , CoccidiosRESUMEN
BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.
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Arritmias Cardíacas , Análisis de la Aleatorización Mendeliana , Sueño , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Femenino , Masculino , Estudios Prospectivos , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Incidencia , Persona de Mediana Edad , Sueño/fisiología , Reino Unido/epidemiología , Factores de Riesgo , Estudios de Seguimiento , AncianoRESUMEN
Micro- and nanoplastics (MNPs), emerging as pervasive environmental pollutants, present multifaceted threats to diverse ecosystems. This review critically examines the ability of MNPs to traverse biological barriers in fish, leading to their accumulation in gonadal tissues and subsequent reproductive toxicity. A focal concern is the potential transgenerational harm, where offspring not directly exposed to MNPs exhibit toxic effects. Characterized by extensive specific surface areas and marked surface hydrophobicity, MNPs readily adsorb and concentrate other environmental contaminants, potentially intensifying reproductive and transgenerational toxicity. This comprehensive analysis aims to provide profound insights into the repercussions of MNPs on fish reproductive health and progeny, highlighting the intricate interplay between MNPs and other pollutants. We delve into the mechanisms of MNPs-induced reproductive toxicity, including gonadal histopathologic alterations, oxidative stress, and disruptions in the hypothalamic-pituitary-gonadal axis. The review also underscores the urgency for future research to explore the size-specific toxic dynamics of MNPs and the long-term implications of chronic exposure. Understanding these aspects is crucial for assessing the ecological risks posed by MNPs and formulating strategies to safeguard aquatic life.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Animales , Ecosistema , Microplásticos , Peces , Gónadas , PlásticosRESUMEN
Objectives: Crohn's disease is a chronic gastrointestinal disease that belongs to inflammatory bowel disease. This systematic review aims to assess the level of evidence in randomized controlled trials (RCTs) on the effects of acupuncture for Crohn's disease. Methods: We searched 12 databases from the date of the establishment of each database up to May, 2023 for relevant RCTs. The risk of bias of each study was assessed independently by three reviewers. The level of evidence of meta-analysis was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Results: A total of 12 studies were included. The effective rate (odds ratio [OR] 3.23, 95% confidence interval [CI] 1.43, 7.30) for mild to moderate Crohn's disease patients showed a significant difference between the acupuncture with moxibustion group and the sham-acupuncture with sham-moxibustion group. CDAI change (mean difference [MD] -74.15, 95% CI -93.28, -55.01) for mild to moderate Crohn's disease showed a significant difference between the acupuncture with moxibustion group and the sham-acupuncture with sham-moxibustion group. Conclusion: Although acupuncture with moxibustion showed significant effects compared to sham-acupuncture with sham-moxibustion, the effect of acupuncture alone is inconclusive. Moreover, only the effect of acupuncture treatment on mild to moderate Crohn's disease patients was derived as a remarkable result. To confirm the effectiveness of acupuncture treatment for Crohn's disease, studies using only acupuncture for intervention or more RCTs targeting various Crohn's disease patients according to the CDAI are required.
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FGFR fusions retaining the FGFR kinase domain are active kinases that are either overexpressed or constitutively activated throughout diverse cancer types. The presence of FGFR translocations enhances tumor cell proliferation and contributes to significant sensitivity to FGFR kinase inhibitors. FGFR2 as an actionable target in intrahepatic cholangiocarcinoma (iCCA) has been tested in many clinical trials. FISH (fluorescence in situ hybridization) and NGS (next-generation sequence) are well-known tools to investigate the translocations of FGFR with multiple or unknown translocation partners. A rapid and robust FISH assay was developed and validated to detect FGFR2 translocations from FFPE specimens in iCCA. The analytical performance of the FISH assay was evaluated for probe localization, probe sensitivity and specificity, and assay precision. Twenty-five archival FFPE specimens from local iCCA patients were tested for FGFR2 translocations. FISH results were correlated with that of NGS on some samples. Biallelic translocations and a novel FGFR2 translocation involving the partner gene, SHROOM3, t(4;10) (q21;q26), were identified in a local iCCA patient.
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BACKGROUND & AIMS: Individuals with high blood pressure (BP) have varying risks of cardiovascular events due to other coexisting factors. We aimed to identify the predictors of long-term absence of coronary artery calcium (CAC) in individuals with high BP, which is an indicator of healthy arterial aging and can guide preventive strategies. METHODS: We analyzed data from participants with high BP (≥120/80 mm Hg) in the Multi-Ethnic Study of Atherosclerosis who had baseline CAC = 0 and underwent a second CAC scanning after 10 years. We used multivariable logistic regression to evaluate the association between various risk factors for atherosclerotic cardiovascular disease (ASCVD) and long-term CAC = 0. We also calculated the area under the receiver operating characteristic curve (AUC) to predict the phenotype of healthy arterial aging in this population. RESULTS: We included 830 participants (37.6% male, mean ± SD age of 59.4 ± 8.7 years). During follow-up, 46.5% of participants (n = 386) had CAC = 0, and they were younger and had fewer metabolic syndrome components. Adding ASCVD risk factors to the demographic model (age, sex, and ethnicity) moderately increased the predictive value for long-term CAC = 0 (AUC: demographic model + ASCVD risk factors vs. demographic model alone, 0.653 vs. 0.597, p < .001; category net reclassification improvement = 0.104, p = .044; integrated discrimination improvement = 0.040, p < .001). CONCLUSION: In individuals with high BP and initial CAC = 0, over 40% maintained CAC = 0 during a 10-year follow-up, which was associated with fewer ASCVD risk factors. These findings may have implications for preventive strategies in individuals with high BP.Clinical Trial registration number: The MESA was registered at clinical trials. gov as NCT00005487.KEY MESSAGESNearly half (46.5%) of individuals with high blood pressure (BP) maintained a long-term absence of coronary artery calcium (CAC) during a 10-year follow-up, and this was associated with a 66.6% lower risk of atherosclerotic cardiovascular disease (ASCVD) events compared to those who developed incident CAC.Individuals with high BP, who are usually assumed to have an increased risk of ASCVD, exhibit significant heterogeneity in their ASCVD risk; those who maintain CAC = 0 have a lower ASCVD risk.Adding overall ASCVD risk factors to demographic information resulted in a moderate improvement in predicting long-term CAC = 0.
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Aterosclerosis , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Hipertensión , Calcificación Vascular , Femenino , Humanos , Masculino , Calcio , Enfermedades Cardiovasculares/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Vasos Coronarios/diagnóstico por imagen , Hipertensión/epidemiología , Medición de Riesgo/métodos , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiologíaRESUMEN
BACKGROUND: Reduced lung function has been linked to cardiovascular disease, but population-based evidence on the relationship between lung function decline and coronary artery calcium (CAC) progression is rare. METHODS: A total of 2694 participants (44.7% men) with a mean ± standard deviation age of 40.4 ± 3.6 years from the Coronary Artery Risk Development in Young Adults (CARDIA) were included. The rates of decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over a 20-year period were calculated for each participant and categorized into quartiles. The primary outcome was CAC progression. RESULTS: During a mean follow-up of 8.9 years, 455 (16.9%) participants had CAC progression. After adjusting for traditional cardiovascular risk factors, the hazard ratios (95% confidence intervals [CIs]) for CAC progression were higher for participants in the 2nd (Q2), 3rd (Q3), and highest quartiles (Q4) of FVC decline compared with those in the lowest quartile (Q1): 1.366 (1.003-1.861), 1.412 (1.035-1.927), and 1.789 (1.318-2.428), respectively. Similar trends were observed for the association between FEV1 and CAC progression. The association remained robust across a series of sensitivity analyses and all subgroups. CONCLUSIONS: A faster decline in FVC or FEV1 during young adulthood is independently associated with an increased risk of CAC progression in midlife. Maintaining optimal lung function during young adulthood may improve future cardiovascular health.
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Calcio , Enfermedad de la Arteria Coronaria , Masculino , Adulto Joven , Humanos , Adulto , Femenino , Pulmón/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Capacidad Vital , Factores de Riesgo , Volumen Espiratorio ForzadoAsunto(s)
Quitosano , Factor Neurotrófico Ciliar , Ratas , Animales , Nervio Óptico/fisiología , Ratas Sprague-DawleyRESUMEN
Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI. Lipidomic analysis was used to determine the profile of CL alteration in the adult rat spinal cord following a moderate contusive SCI at the 10th thoracic (T10) level. Cellular, molecular, and genetic assessments were performed to determine whether CL alterations mediate mitochondrial dysfunction and neuronal death after SCI, and, if so, whether reversing CL alteration leads to neuroprotection after SCI. Using lipidomic analysis, we uncovered CL alterations at an early stage of SCI. Over 50 distinct CL species were identified, of which 50% showed significantly decreased abundance after SCI. The decreased CL species contained mainly polyunsaturated fatty acids that are highly susceptible to peroxidation. In parallel, 4-HNE, a lipid peroxidation marker, significantly increased after SCI. We found that mitochondrial oxidative stress not only induced CL oxidation, but also resulted in CL loss by activating cPLA2 to hydrolyze CL. CL alterations induced mitochondrial dysfunction and neuronal death. Remarkably, pharmacologic inhibition of CL alterations with XJB-5-131, a novel mitochondria-targeted electron and reactive oxygen species scavenger, reduced cell death, tissue damage and ameliorated motor deficits after SCI in adult rats. These findings suggest that CL alteration could be a novel mechanism that mediates injury-induced neuronal death, and a potential therapeutic target for ameliorating secondary SCI.
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Cardiolipinas , Traumatismos de la Médula Espinal , Ratas , Animales , Cardiolipinas/metabolismo , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Muerte Celular , Mitocondrias/metabolismo , Fosfolípidos/metabolismo , HomeostasisRESUMEN
BACKGROUND: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. METHODS: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. RESULTS: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369-2.264] to 2.047 [1.380-3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. CONCLUSIONS: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00005130.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Síndrome Metabólico , Obesidad Metabólica Benigna , Adulto , Índice de Masa Corporal , Calcio , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/epidemiología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad Metabólica Benigna/complicaciones , Obesidad Metabólica Benigna/diagnóstico , Obesidad Metabólica Benigna/epidemiología , Fenotipo , Factores de RiesgoRESUMEN
The direct usage of CO2 in the flue gas to produce fuels or chemicals is of great significance from energy-saving and low-cost perspectives, yet it is still underexplored. Herein, we report the photoreduction of CO2 from the simulated industrial exhaust by synergistic catalysis of TEOA and a metal-free composite (COF1-g-C3N4) fabricated via covalently grafting COF1 with g-C3N4. The hydrogen bond interaction between TEOA and hydrazine units on COF1 is detected in diluted CO2, which leads to significantly enhanced light absorption in the whole visible-light region. Also, the photo-induced electrons undergo fast transfer from COF1 to g-C3N4. This kind of dynamic interface with enhanced light absorption and electron transfer effects promotes the photosynthetic yield of syngas to 165.6 µmol·g-1·h-1 with the use of simulated exhaust gas as a raw material directly. The photosynthetic yield of syngas ranks among the highest of known metal-free catalysts in diluted CO2. This work provides a general rule for designing efficient catalysts via a controlled catalytic interface and new insights into the role of TEOA in photochemical CO2 reduction.
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We prepare a novel COF for CO2 photoreduction with 99.9% CO selectivity in aqueous solution without a cocatalyst. DFT shows that the preferential adsorption of H+ on the COF results in increased CO2 adsorption energy providing an anchoring site of CO2, and with the cooperation of an ethylene group, CO2 reduction is triggered.
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BACKGROUND: Prodrugs are medications or compounds that, after administration, can be converted into pharmacologically active drugs through metabolism. Unlike conventional drugs, prodrugs have reduced adverse or unintended effects, which could become critical limitations in treatments such as chemotherapy. Previously through computer-aided drug design and chemical synthesis, we have obtained and examined a prodrug N-benzyloxycarbonyl-Ala-Asn-Doxorubicin (CBZ-AAN-DOX). CBZ-AAN-DOX is essentially Doxorubicin that is chemically-modified with tripeptides to target Legumain, a highly expressed protein in cancer cells and is involved in tumor metastasis and tumor microvessel formation. The difficulty to test the safety and efficacy of the prodrug (including the pharmacodynamic parameters of CBZ-AAN-DOX on metastasis and invasion of tumors, as well as cardiac and vascular toxicity) primarily comes from the lack of appropriate experimental models. METHODS: Human cervical cancer cell lines CaSki under hypoxic conditions were used to evaluate the cell viability by CCK-8 assay after the prodrug treatment. Western blotting method was performed for Legumain protein determination in the cell culture. Wound healing and transwell invasion assays were performed to determine the effects of the prodrug on tumor metastasis and invasion, respectively. Zebrafish models were constructed for toxicity and angiogenesis visual analysis after in vivo treatment with the prodrug. RESULTS: The CCK-8 results showed that CBZ-AAN-DOX exhibits an IC50 of 28.7 µM in 48 h on CaSki cells that had a lower cell inhibition rate than DOX 80.3 µM for 24 h. Legumain expression was significantly increased in a time-dependent manner in 48 h under hypoxia conditions. The results also showed that 13.9 µM of the prodrug significantly inhibited the migration and invasion of cells and the effects were significantly stronger than that of 41.8 µM of DOX under hypoxia conditions after 48 h. The effects of 160 µM of the prodrug on the survival rate of zebrafish after 72 h and heart-toxicity showed no obvious abnormalities. Cell metastasis and angiogenesis were also inhibited in tumor-bearing zebrafish model. CONCLUSION: The findings in this study demonstrated that CBZ-AAN-DOX is a promising chemotherapy candidate with low toxicity and high efficiency for cervical cancer. Remarkably, the hypoxic culture model together with the zebrafish model serve as a good system for the evaluation of the toxicity, targeting and impact of the prodrug on tumor invasion and metastasis.
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Antibióticos Antineoplásicos/farmacología , Cisteína Endopeptidasas/genética , Doxorrubicina/análogos & derivados , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica/prevención & control , Oligopéptidos/farmacología , Profármacos/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Animales , Antibióticos Antineoplásicos/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular , Cisteína Endopeptidasas/metabolismo , Modelos Animales de Enfermedad , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Femenino , Humanos , Hipoxia/diagnóstico , Hipoxia/tratamiento farmacológico , Hipoxia/genética , Hipoxia/mortalidad , Neovascularización Patológica/diagnóstico , Neovascularización Patológica/genética , Neovascularización Patológica/mortalidad , Oligopéptidos/metabolismo , Profármacos/metabolismo , Análisis de Supervivencia , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/mortalidad , Ensayos Antitumor por Modelo de Xenoinjerto , Pez CebraRESUMEN
A system containing polyoxometalate ([Co-POM]2-) and [Ru(bpy)3]2+ as constructed for visible-light-induced CO2 conversion to syngas. In diluted CO2, high efficiency of 56.8 mmol g-1 h-1 in syngas production was gained, exceeding that of reported systems with [Ru(bpy)3]2+ participation in similar conditions. Mechanism studies revealed efficient photo-induced charge separation is achieved in the system and CO2 reduction tends to occur on [Ru(bpy)3]2+.