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1.
BMC Med ; 22(1): 171, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38649992

RESUMEN

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.


Asunto(s)
Stents , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Dalteparina/administración & dosificación , Dalteparina/uso terapéutico , Dalteparina/efectos adversos , Resultado del Tratamiento , Procedimientos Quirúrgicos Operativos/efectos adversos , Hemorragia/inducido químicamente , Placebos/administración & dosificación , Atención Perioperativa/métodos
2.
Small ; 20(30): e2309431, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38402425

RESUMEN

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) is a promising gene editing tool to treat diseases at the genetic level. Nonetheless, the challenge of the safe and efficient delivery of CRISPR/Cas9 to host cells constrains its clinical applicability. In the current study, a facile, redox-responsive CRISPR/Cas9-Ribonucleoprotein (RNP) delivery system by combining iron-coordinated aggregation with liposomes (Fe-RNP@L) is reported. The Fe-RNP is formed by the coordination of Fe3+ with amino and carboxyl groups of Cas9, which modifies the lipophilicity and surface charge of RNP and alters cellular uptake from primary endocytosis to endocytosis and cholesterol-dependent membrane fusion. RNP can be rapidly and reversibly released from Fe-RNP in response to glutathione without loss of structural integrity and enzymatic activity. In addition, iron coordination also improves the stability of RNP and substantially mitigates cytotoxicity. This construct enabled highly efficient cytoplasmic/nuclear delivery (≈90%) and gene-editing efficiency (≈70%) even at low concentrations. The high payload content, high editing efficiency, good stability, low immunogenicity, and ease of production and storage, highlight its potential for diverse genome editing and clinical applications.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Hierro , Oxidación-Reducción , Ribonucleoproteínas , Edición Génica/métodos , Hierro/química , Humanos , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/química , Liposomas/química , Técnicas de Transferencia de Gen , Proteína 9 Asociada a CRISPR/metabolismo
3.
Exp Eye Res ; : 110109, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39326774

RESUMEN

Keratoconus (KC) is a complex corneal disorder with a well-recognized genetic component. In this study, we aimed to expand the genetic spectrum of 200 Chinese patients with keratoconus and their unaffected parents. Trio-based whole-exome sequencing was performed in 200 patients with sporadic keratoconus and their unaffected parents. The variants identified in candidate genes for keratoconus were analyzed using multiple bioinformatics tools. Finally, we identified 7 variants in 5 candidate genes for keratoconus in 5 patients. The c.T464C variant in the IMPDH1 gene was defined as likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics, and the remaining variants in candidate genes (TRANK1, SLC4A11, CERKL, IFT172) were defined as uncertain significance. Our results expand the genetic spectrum in KC, highlight the genetic heterogeneity of this disease and provide important clues for future functional validation.

4.
Avian Pathol ; : 1-28, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39417776

RESUMEN

Avian leukosis virus subgroup J (ALV-J) is an alpharetrovirus that infects chickens, causing immunosuppression and a decrease in production performance, leading to substantial economic losses in the poultry industry. ALV-J is also well-known for its oncogenic properties, inducing tumors such as myelomas and hemangiomas in infected chickens. TRIM45 has been identified as a potential tumor suppressor, however, the relationship between TRIM45 expression and ALV-J infection remains to be elucidated.This study aimed to dissect the molecular characteristics of the chicken TRIM45 gene and its modulation during ALV-J infection, as well as its influence on viral replication. We found that the chicken TRIM45 RING domain is significantly different from that of humans and other mammals. TRIM45 is expressed in all chicken tissues, with the highest levels in the heart. Subcellular localization studies indicated a cytoplasmic distribution of TRIM45, forming aggregates within cells. Our findings demonstrate that ALV-J infection significantly upregulates TRIM45 expression in DF-1 cells. To assess the functional role of TRIM45 in ALV-J replication, we employed both gene silencing and overexpression strategies. Strikingly, the overexpression of TRIM45, including a mutant lacking the RING domain, was found to markedly suppress ALV-J replication. In contrast, TRIM45 knockdown via siRNA resulted in an enhanced viral replication, highlighting the importance of TRIM45 limiting ALV-J replication. Mechanistically, overexpression of TRIM45 induces apoptosis in infected cells, independent of its RING domain function. In conclusion, our study demonstrates that chicken TRIM45 acts as a negative regulator of ALV-J replication in vitro by promoting apoptosis in infected cells.

5.
Epilepsy Behav ; 155: 109786, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653175

RESUMEN

BACKGROUND: Although there are models predicting epilepsy recurrence under different clinical conditions, few studies have examined blood biomarkers. Inflammation plays a crucial role in the occurrence and development of epilepsy. We analyzed inflammatory mediators in a regional hospital-based epilepsy cohort and investigated their relationship with subsequent epilepsy recurrence. METHODS: Interictal inflammatory mediators were measured in 128 patients diagnosed with epilepsy participating in a prospective study. Inflammatory mediators were compared during the follow-up period between patients who experienced epilepsy recurrence and those who did not. We also assessed the correlation between inflammatory mediators and the time interval until the next recurrence. RESULTS: Over a median 4-month follow-up period, 41 patients experienced seizure recurrence. Differences in interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels were observed between seizure recurrence and non-recurrence groups. After adjusting for covariates through multivariate Cox regression analysis, the patients in the third IL-6 tertile (>2.31 pg/mL; HR: 2.49; 95 % CI: 1.00-6.16; P = 0.049) and in the third TNF-α tertile (>0.74 pg/mL; HR: 2.80; 95 % CI: 1.13-6.92; P = 0.026) had higher risk of seizure recurrence. The time until the next recurrence was negatively correlated with IL-6 level (ρ =  - 0.392, P = 0.011). CONCLUSION: High levels of IL-6 and TNF-α are associated with a higher possibility of seizure recurrence. Future predictive models should also include inflammatory mediators in addition to clinical variables.


Asunto(s)
Epilepsia , Interleucina-6 , Recurrencia , Convulsiones , Factor de Necrosis Tumoral alfa , Humanos , Femenino , Masculino , Interleucina-6/sangre , Adulto , Factor de Necrosis Tumoral alfa/sangre , Epilepsia/sangre , Persona de Mediana Edad , Convulsiones/sangre , Adulto Joven , Estudios Prospectivos , Estudios de Seguimiento , Biomarcadores/sangre
6.
Bioorg Chem ; 150: 107588, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38936051

RESUMEN

With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.


Asunto(s)
Antineoplásicos , Apoptosis , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Potencial de la Membrana Mitocondrial , Mitocondrias , Especies Reactivas de Oxígeno , Tiazoles , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Relación Estructura-Actividad , Tiazoles/farmacología , Tiazoles/química , Tiazoles/síntesis química , Estructura Molecular , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/química , Compuestos Organofosforados/síntesis química
7.
Environ Res ; 256: 119252, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38815716

RESUMEN

Bio-ingestion of microplastics poses a global threat to ecosystems, yet studies within nature reserves, crucial habitats for birds, remain scarce despite the well-documented ingestion of microplastics by avian species. Located in Jiangsu Province, China, the Yancheng Wetland Rare Birds Nature Reserve is home to diverse bird species, including many rare ones. This study aimed to assess the abundance and characteristics of microplastics in common bird species within the reserve, investigate microplastic enrichment across different species, and establish links between birds' habitat types and microplastic ingestion. Microplastics were extracted from the feces of 110 birds, with 84 particles identified from 37.27% of samples. Among 8 species studied, the average microplastic abundance ranged from 0.97 ± 0.47 to 43.43 ± 61.98 items per gram of feces, or 1.5 ± 0.87 to 3.4 ± 1.50 items per individual. The Swan goose (Anser cygnoides) exhibited the highest microplastic abundance per gram of feces, while the black-billed gull (Larus saundersi) had the highest abundance per individual. The predominant form of ingested microplastics among birds in the reserve was fibers, with polyethylene being the most common polymer type. Significant variations in plastic exposure were observed among species and between aquatic and terrestrial birds. This study represents the first quantitative assessment of microplastic concentrations in birds within the reserve, filling a crucial gap in research and providing insights for assessing microplastic pollution and guiding bird conservation efforts in aquatic and terrestrial environments.


Asunto(s)
Aves , Monitoreo del Ambiente , Heces , Microplásticos , Humedales , Animales , China , Microplásticos/análisis , Heces/química , Contaminantes Químicos del Agua/análisis , Conservación de los Recursos Naturales
8.
Lipids Health Dis ; 23(1): 100, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600516

RESUMEN

BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.


Asunto(s)
Producto de la Acumulación de Lípidos , Apnea Obstructiva del Sueño , Humanos , Encuestas Nutricionales , Adiposidad , Estudios Transversales , Índice de Masa Corporal , Obesidad Abdominal/metabolismo
9.
Psychol Res ; 88(2): 389-403, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37815675

RESUMEN

The interval timing can be distorted by emotions. Previous studies indicated that anticipated fear stimuli can lead to temporal overestimation, similar to the effects observed from direct exposure to fear stimuli. However, this time distortion may not always manifest when anticipated. This study aimed to systematically examine the effect of the reinforcement probability of anticipated fear stimuli on time perception in predictable emotional scenarios. The experiment established 100% fear conditioning by associating a conditioned stimulus (CS+) with an aversive unconditioned stimulus (US), electrical stimulation. Participants completed a temporal bisection task under different cues (threat CS+ and safe CS-) expectations. Participants were explicitly informed that an aversive electrical stimulus would always follow the threat cues (CS+) with 100% probability, though in reality, different blocks presented the threat cue with probability manipulation of 50 and 100%. Results showed that only in the 50% reinforcement probability, participants overestimated the duration when anticipating aversive electrical stimulation, while no significant differences were observed in the 100% reinforcement probability. Additionally, the effect of anxiety on temporal judgment failed to capture the overall trend as fixed effects but only contributed to the individual variations as random effects. The findings suggest that the anticipated aversive electrical stimulation may lead to temporal overestimation. Furthermore, the results indicate that a reliable approach for manipulating the effect of anticipated aversive electrical stimulation on temporal overestimation is to establish 100% fear conditioning and use a reinforcement probability like 50%.


Asunto(s)
Miedo , Refuerzo en Psicología , Humanos , Miedo/psicología , Emociones , Condicionamiento Clásico/fisiología , Probabilidad
10.
Int J Mol Sci ; 25(15)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39125712

RESUMEN

Liver lipid metabolism disruption significantly contributes to excessive fat buildup in waterfowl. Research suggests that the supplementation of Threonine (Thr) in the diet can improve liver lipid metabolism disorder, while Thr deficiency can lead to such metabolic disorders in the liver. The mechanisms through which Thr regulates lipid metabolism remain unclear. STAT3 (signal transducer and activator of transcription 3), a crucial transcription factor in the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway, participates in various biological processes, including lipid and energy metabolism. This research investigates the potential involvement of STAT3 in the increased lipid storage seen in primary duck hepatocytes as a result of a lack of Thr. Using small interfering RNA and Stattic, a specific STAT3 phosphorylation inhibitor, we explored the impact of STAT3 expression patterns on Thr-regulated lipid synthesis metabolism in hepatocytes. Through transcriptome sequencing, we uncovered pathways related to lipid synthesis and metabolism jointly regulated by Thr and STAT3. The results showed that Thr deficiency increases lipid deposition in primary duck hepatocytes (p < 0.01). The decrease in protein and phosphorylation levels of STAT3 directly caused this deposition (p < 0.01). Transcriptomic analysis revealed that Thr deficiency and STAT3 knockdown jointly altered the mRNA expression levels of pathways related to long-chain fatty acid synthesis and energy metabolism (p < 0.05). Thr deficiency, through mediating STAT3 inactivation, upregulated ELOVL7, PPARG, MMP1, MMP13, and TIMP4 mRNA levels, and downregulated PTGS2 mRNA levels (p < 0.01). In summary, these results suggest that Thr deficiency promotes lipid synthesis, reduces lipid breakdown, and leads to lipid metabolism disorders and triglyceride deposition by downregulating STAT3 activity in primary duck hepatocytes.


Asunto(s)
Patos , Hepatocitos , Factor de Transcripción STAT3 , Treonina , Triglicéridos , Animales , Factor de Transcripción STAT3/metabolismo , Hepatocitos/metabolismo , Fosforilación , Treonina/metabolismo , Triglicéridos/metabolismo , Metabolismo de los Lípidos , Células Cultivadas
11.
BMC Nurs ; 23(1): 296, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684975

RESUMEN

BACKGROUND: Intrahospital transport of critically ill patients is a common practice in intensive care units (ICUs), where patients' safety is constantly challenged in high-intensity and dynamic environments. While Intrahospital Transport Safety Scale (IHTSS) is widely used internationally to evaluate the intrahospital transport safety, it has not been introduced in China. OBJECTIVES: This study aimed to assess the reliability and validity of the Chinese version of the IHTSS scale among critical care nurses in China. METHODS: A cross-sectional study was conducted using a cluster sampling method. A total of 544 critical care nurses from 25 ICUs in 10 tertiary hospitals were recruited. We employed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to examine the questionnaire's underlying factor structure, ensuring construct validity. Additionally, internal consistency was assessed using Cronbach's alpha coefficient, test-retest reliability, and corrected item-total correlation. RESULTS: The Chinese version of the scale displayed robust psychometric properties, with a Cronbach's α coefficient of 0.976, a split-half reliability of 0.906, and a test-retest reliability of 0.856. EFA revealed a robust four-factor model that accounted for 75.970% of the variance, with the factor loadings of the items ranging from 0.433 to 0.951. CFA indicated a strong model fit, with a chi-square to degrees of freedom ratio (CMIN/DF) of 2.765, comparative fit index (CFI) of 0.943, incremental fit index (IFI) of 0.943, and goodness-of-fit index (GFI) of 0.845, supporting the efficacy of the four-factor model in assessing intrahospital transport safety for critically ill patients. CONCLUSION: The Chinese version of the IHTSS demonstrated favourable reliability and validity among critical care nurses in China, making it a suitable tool for measuring the level of intrahospital transport safety for critically ill patients.

12.
Angew Chem Int Ed Engl ; 63(12): e202318756, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38289020

RESUMEN

The simultaneous improvement of efficiency and stability of organic solar cells (OSCs) for commercialization remains a challenging task. Herein, we designed asymmetric acceptors DT-C8Cl and DT-C8BTz with functional haloalkyl chains, in which the halogen atoms could induce noncovalent interactions with heteroatoms like O, S, and Se, etc., thus leading to appropriately manipulated film morphology. Consequently, binary devices based on D18: DT-C8Cl achieved a champion power conversion efficiency (PCE) of 19.40 %. The higher PCE of D18: DT-C8Cl could be attributed to the enhanced π-π stacking, improved charge transport, and reduced recombination losses. In addition, the noncovalent interactions induced by haloalkyl chains could effectively suppress unfavorable morphology evolutions and thereby reduce trap density of states, leading to improved thermal and storage stability. Overall, our findings reveal that the rational design of asymmetric acceptors with functional haloalkyl chains is a novel and powerful strategy for simultaneously enhancing the efficiency and stability of OSCs.

13.
BMC Genomics ; 24(1): 675, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37946105

RESUMEN

BACKGROUND: Epilepsy is a prevalent neurological disorder, and while its precise mechanism remains elusive, a connection to ferroptosis has been established. This study investigates the potential clinical diagnostic significance of ferroptosis-related genes (FRGs) during the acute phase of temporal lobe epilepsy. METHODS: To identify differentially expressed genes (DEGs), we accessed data from the GEO database and performed an intersection analysis with the FerrDB database to pinpoint FRGs. A protein-protein interaction (PPI) network was constructed. To assess the diagnostic utility of the discovered feature genes for the disease, ROC curve analysis was conducted. Subsequently, qRT-PCR was employed to validate the expression levels of these feature genes. RESULTS: This study identified a total of 25 FRGs. PPI network analysis revealed six feature genes: IL6, PTGS2, HMOX1, NFE2L2, TLR4, and JUN. ROC curve analysis demonstrated that the combination of these six feature genes exhibited the highest diagnostic potential. qRT-PCR validation confirmed the expression of these feature genes. CONCLUSION: We have identified six feature genes (IL6, PTGS2, HMOX1, NFE2L2, TLR4, and JUN) strongly associated with ferroptosis in epilepsy, suggesting their potential as biomarkers for the diagnosis of temporal lobe epilepsy.


Asunto(s)
Epilepsia del Lóbulo Temporal , Ferroptosis , Humanos , Epilepsia del Lóbulo Temporal/genética , Ciclooxigenasa 2 , Ferroptosis/genética , Interleucina-6 , Receptor Toll-Like 4 , Biología Computacional
14.
BMC Ophthalmol ; 23(1): 446, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37932670

RESUMEN

INTRODUCTION: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare genetic disease with diverse ocular malformations. This study aimed to investigate the disease-causing gene in members of a BPES pedigree presenting with the rare features of anisometropia, unilateral pathologic myopia (PM), and congenital cataracts. METHODS: The related BPES patients underwent a comprehensive ocular examination. Next, whole-exome sequencing (WES) was performed to screen for the disease-causing genetic variants. A step-wise variant filtering was performed to select candidate variants combined with the annotation of the variant's pathogenicity, which was assessed using several bioinformatic approaches. Co-segregation analysis and Sanger sequencing were then conducted to validate the candidate variant. RESULTS: The variant c.672_701dup in FOXL2 was identified to be the disease-causing variant in this rare BPES family. Combined with clinical manifestations, the two affected individuals were diagnosed with type II BPES. CONCLUSION: This study uncovered the variant c.672_701dup in FOXL2 as a disease causal variant in a rare-presenting BPES family with anisometropia, unilateral pathogenic myopia, and/or congenital cataracts, thus expanding the phenotypic spectrum of FOXL2.


Asunto(s)
Anisometropía , Blefarofimosis , Catarata , Miopía , Humanos , Mutación , Secuenciación del Exoma , Linaje , Síndrome , Proteína Forkhead Box L2/genética
15.
Molecules ; 28(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37049834

RESUMEN

(1) Background: The extraction parameters can dramatically alter the extraction rate and biological activity of polysaccharides. (2) Methods: Here, an enzyme-assisted extraction (EAE) was employed to extract D. officinale polysaccharides (DOPs), and its optimal extraction conditions were established by single-factor and Box-Behnken design (BBD) experiments. Further, on the basis of in vitro antioxidant capacity, the paraquat (PQ)-induced oxidative stress of Caenorhabditis elegans (C. elegans) was chosen as a research model to explore the antioxidant activity of DOPs. (3) Results: The results showed that the extraction yield of DOPs reached 48.66% ± 1.04% under the optimal condition. In vitro experiments had shown that DOPs have considerable ABTS+ radical scavenging capacity (EC50 = 7.27 mg/mL), hydroxyl radical scavenging capacity (EC50 = 1.61 mg/mL), and metal chelating power (EC50 = 8.31 mg/mL). Furthermore, in vivo experiments indicated that DOPs (0.25 mg/mL) significantly prolonged the lifespan, increased antioxidant enzyme activity, and upregulated the expression of daf-16 (>5.6-fold), skn-1 (>5.2-fold), and sir-2.1 (>2.3-fold) of C. elegans. (4) Conclusions: DOPs can be efficiently extracted by EAE and are effective in the reduction of oxidative stress levels in C. elegans.


Asunto(s)
Antioxidantes , Dendrobium , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Dendrobium/metabolismo , Caenorhabditis elegans , Estrés Oxidativo , Polisacáridos/farmacología , Polisacáridos/metabolismo
16.
Angew Chem Int Ed Engl ; 62(1): e202213869, 2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36333961

RESUMEN

The elaborate control of the vertical phase distribution within an active layer is critical to ensuring the high performance of organic solar cells (OSCs), but is challenging. Herein, a self-stratification active layer is realised by adding a novel polyfluoroalkyl-containing non-fullerene small-molecule acceptor (NFSMA), EH-C8 F17 , as the guest into PM6:BTP-eC9 blend. A favourable vertical morphology was obtained with an upper acceptor-enriched thin layer and a lower undisturbed bulk heterojunction layer. Consequently, a power conversion efficiency of 18.03 % was achieved, higher than the efficiency of 17.40 % for the device without EH-C8 F17 . Additionally, benefiting from the improved charge transport and collection realised by this self-stratification strategy, the OSC with a thickness of 350 nm had an impressive PCE of 16.89 %. The results of the study indicate that polyfluoroalkyl-containing NFSMA-assisted self-stratification within the active layer is effective for realising an ideal morphology for high-performance OSCs.

17.
BMC Gastroenterol ; 22(1): 482, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36419007

RESUMEN

BACKGROUND: Previous studies have reported that the tumor heterogeneity and complex oncogenic mechanisms of proximal and distal colon cancer (CRC) are divergent. Therefore, we aim to analyze the differences between left-sided CRC (L_cancer) and right-sided CRC (R_cancer), as well as constructing respective nomograms. METHODS: We enrolled 335 colon cancer patients (146 L_cancer patients and 189 R_cancer patients) from The Cancer Genome Atlas (TCGA) data sets, and 102 pairs of color cancer tissue and adjacent normal tissue (51 L_cancer patients and 51 R_cancer patients) from our hospital. Firstly, we analyzed the differences between the L_cancer patients and R_cancer patients, and then established the L_cancer and R_cancer prognostic models using LASSO Cox. RESULTS: R_cancer patients had lower survival than L_cancer patients. R_cancer patients had higher ESTIMATE and immune scores and lower tumor purity. These patterns of expression of immune checkpoint-related genes and TMB level were higher in R_cancer than in L_cancer patients. Finally, we using Lasso Cox regression analyses established a prognostic model for L_cancer patients and a prognostic model for R_cancer patients. The AUC values of the risk score for OS in L_cancer were 0.862 in the training set and 0.914 in the testing set, while those in R_cancer were 0.835 in the training set and 0.857 in the testing set. The AUC values in fivefold cross-validation were between 0.727 and 0.978, proving that the two prognostic models have great stability. The nomogram of L_cancer included prognostic genes, age, pathological M, pathological stage, and gender, the AUC values of which were 0.800 in the training set and 0.905 in the testing set. Meanwhile, the nomogram of R_cancer comprised prognostic genes, pathological N, pathological T, and age, the AUC values of which were 0.836 in the training set and 0.850 in the testing set. In the R_cancer patients, high-risk patients had a lower proportion of 'B cells memory', 'Dendritic cells resting', immune score, ESTIMATE score, immune checkpoint-related genes, and HLA-family genes, and a higher proportion of 'T cells follicular helper', 'Dendritic cells activated', and 'Mast cells activated'. CONCLUSIONS: We found significant differences between L_cancer and R_cancer patients and established a clinical predictive nomogram for L_cancer patients and a nomogram for R_cancer patients. Additionally, R_cancer patients in low-risk groups may be more beneficial from immunotherapy.


Asunto(s)
Neoplasias del Colon , Inmunoterapia , Humanos , Pronóstico , Oncogenes , Nomogramas , Neoplasias del Colon/genética
18.
Support Care Cancer ; 30(6): 5449-5458, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35305161

RESUMEN

PURPOSE: To examine the level of stigma and identify its influencing factors among postoperative oral cancer patients in China. METHODS: In total, 274 postoperative oral cancer patients were recruited from a Grade A Tertiary Hospital in China using convenience sampling methods. Patients completed the Social Impact Scale (SIS), Medical Coping Mode Questionnaire (MCMQ), Social Support Rating Scale (SSRS), and General Self-efficacy Scale (GSE). RESULTS: Stigma reported by postoperative oral cancer patients was moderate (50.17 ± 21.24). Stepped multiple linear regression showed that the related factors influencing their feelings of stigma were educational level (ß = - 0.110, P = 0.001), smoking (ß = - 0.152, P < 0.001), betel quid (ß = - 0.120, P = 0.001), tumor location (ß = - 0.390, P < 0.001), tumor stage (ß = 0.219, P < 0.001), self-efficacy (ß = - 0.253, P < 0.001), and confrontation (ß = - 0.117, P = 0.001) and avoidance (ß = 0.123, P < 0.001), which explained 74.2% of the total variation in stigma (F = 99.378, P < 0.001). CONCLUSIONS: Stigma was positively predicted by tumor stage and avoidance but negatively predicted by education level, smoking, betel quid, tumor location, confrontation, and self-efficacy. Further work should focus on developing interventions to reduce stigma by improving protective factors and decreasing risk factors.


Asunto(s)
Neoplasias de la Boca , Estigma Social , Adaptación Psicológica , China/epidemiología , Estudios Transversales , Humanos , Neoplasias de la Boca/cirugía , Encuestas y Cuestionarios
19.
BMC Ophthalmol ; 22(1): 70, 2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35148715

RESUMEN

BACKGROUND: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. PURPOSE: To unravel the genetic cause of autosomal dominant family with CCMC. METHODS: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. RESULTS: Four CCMC patients from a Chinese family and five unaffected family members were enrolled in this study. Using whole-exome sequencing, a missense mutation c.295G > T (p.A99S, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level. CONCLUSIONS: A novel missense mutation (c.295G > T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.


Asunto(s)
Catarata , Catarata/genética , Enfermedades de la Córnea , Análisis Mutacional de ADN , Humanos , Mutación , Mutación Missense , Linaje , Fenotipo , Factores de Transcripción SOXB1/genética
20.
Sensors (Basel) ; 22(24)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36560307

RESUMEN

This paper presents a straightforward method to develop a nanoporous graphene oxide (NGO)-functionalized quartz crystal microbalance (QCM) gas sensor for the detection of trimethylamine (TMA), aiming to form a reliable monitoring mechanism strategy for low-concentration TMA that can still cause serious odor nuisance. The synthesized NGO material was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy to verify its structure and morphology. Compared with the bare and GO-based QCM sensors, the NGO-based QCM sensor exhibited ultra-high sensitivity (65.23 Hz/µL), excellent linearity (R2 = 0.98), high response/recovery capability (3 s/20 s) and excellent repeatability (RSD = 0.02, n = 3) toward TMA with frequency shift and resistance. Furthermore, the selectivity of the proposed NGO-based sensor to TMA was verified by analysis of the dual-signal responses. It is also proved that increasing the conductivity did not improve the resistance signal. This work confirms that the proposed NGO-based sensor with dual signals provides a new avenue for TMA sensing, and the sensor is expected to become a potential candidate for gas detection.


Asunto(s)
Grafito , Nanoporos , Tecnicas de Microbalanza del Cristal de Cuarzo , Grafito/química , Cuarzo
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