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1.
Proc Natl Acad Sci U S A ; 121(27): e2400230121, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38913902

RESUMEN

Climate influences near-surface biogeochemical processes and thereby determines the partitioning of carbon dioxide (CO2) in shale, and yet the controls on carbon (C) weathering fluxes remain poorly constrained. Using a dataset that characterizes biogeochemical responses to climate forcing in shale regolith, we implement a numerical model that describes the effects of water infiltration events, gas exchange, and temperature fluctuations on soil respiration and mineral weathering at a seasonal timescale. Our modeling approach allows us to quantitatively disentangle the controls of transient climate forcing and biogeochemical mechanisms on C partitioning. We find that ~3% of soil CO2 (1.02 mol C/m2/y) is exported to the subsurface during large infiltration events. Here, net atmospheric CO2 drawdown primarily occurs during spring snowmelt, governs the aqueous C exports (61%), and exceeds the CO2 flux generated by pyrite and petrogenic organic matter oxidation (~0.2 mol C/m2/y). We show that shale CO2 consumption results from the temporal coupling between soil microbial respiration and carbonate weathering. This coupling is driven by the impacts of hydrologic fluctuations on fresh organic matter availability and CO2 transport to the weathering front. Diffusion-limited transport of gases under transient hydrological conditions exerts an important control on CO2(g) egress patterns and thus must be considered when inferring soil CO2 drawdown from the gas phase composition. Our findings emphasize the importance of seasonal climate forcing in shaping the net contribution of shale weathering to terrestrial C fluxes and suggest that warmer conditions could reduce the potential for shale weathering to act as a CO2 sink.

2.
Plant J ; 116(5): 1248-1270, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37566437

RESUMEN

Dehydration response element binding (DREB) proteins are vital for plant abiotic stress responses, but the understanding of DREBs in bamboo, an important sustainable non-timber forest product, is limited. Here we conducted a comprehensive genome-wide analysis of the DREB gene family in Moso bamboo, representing the most important running bamboo species in Asia. In total, 44 PeDREBs were identified, and information on their gene structures, protein motifs, phylogenetic relationships, and stress-related cis-regulatory elements (CREs) was provided. Based on the bioinformatical analysis, we further analyzed PeDREBs from the A5 group and found that four of five PeDREB transcripts were induced by salt, drought, and cold stresses, and their proteins could bind to stress-related CREs. Among these, PeDREB28 was selected as a promising candidate for further functional characterization. PeDREB28 is localized in nucleus, has transcriptional activation activity, and could bind to the DRE- and coupling element 1- (CE1) CREs. Overexpression of PeDREB28 in Arabidopsis and bamboo improved plant abiotic stress tolerance. Transcriptomic analysis showed that broad changes due to the overexpression of PeDREB28. Furthermore, 628 genes that may act as the direct PeDREB28 downstream genes were identified by combining DAP-seq and RNA-seq analysis. Moreover, we confirmed that PeDREB28 could bind to the promoter of pyrabactin-resistance-like gene (DlaPYL3), which is a homolog of abscisic acid receptor in Arabidopsis, and activates its expression. In summary, our study provides important insights into the DREB gene family in Moso bamboo, and contributes to their functional verification and genetic engineering applications in the future.


Asunto(s)
Arabidopsis , Filogenia , Arabidopsis/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismo , Elementos de Respuesta , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas/genética
3.
Am Heart J ; 271: 1-11, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38336159

RESUMEN

BACKGROUND: Although previous risk models exist for advanced heart failure with reduced ejection fraction (HFrEF), few integrate invasive hemodynamics or support missing data. This study developed and validated a heart failure (HF) hemodynamic risk and phenotyping score for HFrEF, using Machine Learning (ML). METHODS: Prior to modeling, patients in training and validation HF cohorts were assigned to 1 of 5 risk categories based on the composite endpoint of death, left ventricular assist device (LVAD) implantation or transplantation (DeLvTx), and rehospitalization in 6 months of follow-up using unsupervised clustering. The goal of our novel interpretable ML modeling approach, which is robust to missing data, was to predict this risk category (1, 2, 3, 4, or 5) using either invasive hemodynamics alone or a rich and inclusive feature set that included noninvasive hemodynamics (all features). The models were trained using the ESCAPE trial and validated using 4 advanced HF patient cohorts collected from previous trials, then compared with traditional ML models. Prediction accuracy for each of these 5 categories was determined separately for each risk category to generate 5 areas under the curve (AUCs, or C-statistics) for belonging to risk category 1, 2, 3, 4, or 5, respectively. RESULTS: Across all outcomes, our models performed well for predicting the risk category for each patient. Accuracies of 5 separate models predicting a patient's risk category ranged from 0.896 +/- 0.074 to 0.969 +/- 0.081 for the invasive hemodynamics feature set and 0.858 +/- 0.067 to 0.997 +/- 0.070 for the all features feature set. CONCLUSION: Novel interpretable ML models predicted risk categories with a high degree of accuracy. This approach offers a new paradigm for risk stratification that differs from prediction of a binary outcome. Prospective clinical evaluation of this approach is indicated to determine utility for selecting the best treatment approach for patients based on risk and prognosis.


Asunto(s)
Insuficiencia Cardíaca , Hemodinámica , Aprendizaje Automático , Fenotipo , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Medición de Riesgo/métodos , Persona de Mediana Edad , Hemodinámica/fisiología , Volumen Sistólico/fisiología , Corazón Auxiliar , Anciano , Pronóstico
4.
Clin Exp Immunol ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651179

RESUMEN

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.

5.
Cancer Cell Int ; 24(1): 118, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553715

RESUMEN

BACKGROUND: Increasing evidence proves that RBP7 plays a significant role in breast cancer (BC). The present study was aimed to investigate the mechanism of RBP7. METHODS: Western Blotting and qRT-PCR were performed for evaluating the expression levels. CCK8, colony forming, xenograft mouse model, wound healing and transwell assays were conducted to examine cell ability of proliferation, invasion and migration. Nile red staining and Oil red O staining were used for testing the lipid. RESULTS: RBP7 was related to overall survival (OS) in patients with HR + BC. RBP7 protein was significantly decreased in HR + BC tissues and cells. RBP7 suppressed HR + BC cell proliferation in vitro and in vivo, and inhibited migration and invasion. RBP7 reduced fatty acid in HR + BC cells by inhibiting the AKT/SREBP1 pathway. CONCLUSIONS: RBP7 may function as a tumor suppressor in HR + BC by inhibiting the AKT/SREBP1 pathway and reducing fatty acid.

6.
J Org Chem ; 89(11): 7770-7779, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38738957

RESUMEN

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

7.
Epilepsy Behav ; 150: 109556, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38029661

RESUMEN

OBJECTIVE: The timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. METHODS: We retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. RESULTS: This study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. SIGNIFICANCE: ASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period.


Asunto(s)
Epilepsia , Síndrome de Abstinencia a Sustancias , Niño , Humanos , Estudios Retrospectivos , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Epilepsia/cirugía , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Electroencefalografía , Síndrome de Abstinencia a Sustancias/etiología , Recurrencia
8.
Epilepsy Behav ; 151: 109645, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38244419

RESUMEN

OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.


Asunto(s)
Epilepsia , Humanos , Epilepsia/terapia , Convulsiones , Certificación , China , Lenguaje
9.
Neurol Sci ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488928

RESUMEN

BACKGROUND: Observational studies have indicated that psychiatric disorders are the most common comorbidities in pediatric epilepsy. However, the existence and direction of a causal relationship between the two remains controversial. This study aims to investigate the association between common childhood psychiatric disorders and epilepsy using a two-sample, bidirectional Mendelian randomization (MR) approach. METHODS: Genetic instruments were obtained from the most recent and largest genome-wide association studies (GWAS), including datasets for epilepsy (N_case = 29,994, N_control = 52,538), attention deficit hyperactivity disorder (ADHD) (N_case = 38,691, N_control = 186,843), autism spectrum disorder (ASD) (N_case = 18,381, N_control = 27,969), and Tourette syndrome (TS) (N_case = 4,819, N_control = 9488). MR analyses were conducted using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression. RESULTS: No reliable evidence was found to suggest a causal effect of ADHD, ASD, or TS on epilepsy, nor was there any reliable evidence indicating that epilepsy increases the risk of these three psychiatric disorders. These findings remained consistent across various sensitivity analyses. CONCLUSION: Although observational studies have highlighted a high comorbidity rate between pediatric epilepsy and psychiatric disorders like ADHD and ASD, the MR analysis did not confirm a causal relationship between them. This suggests that previous studies might have been influenced by confounding biases or other biases, potentially overestimating the true relationship. A deeper understanding of the mechanisms underlying these comorbidities is crucial for refining the treatment of pediatric epilepsy.

10.
Neurosurg Rev ; 47(1): 283, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904885

RESUMEN

This study examined the risk factors for short-term outcomes, focusing particularly on the associations among molecular subgroups. The analysis focused on the data of pediatric patients with medulloblastoma between 2013 and 2023, as well as operative complications, length of stay from surgery to adjuvant treatment, 30-day unplanned reoperation, unplanned readmission, and mortality. 148 patients were included. Patients with the SHH TP53-wildtype exhibited a lower incidence of complications (45.2% vs. 66.0%, odds ratio [OR] 0.358, 95% confidence interval [CI] 0.160 - 0.802). Female sex (0.437, 0.207 - 0.919) was identified as an independent protective factor for complications, and brainstem involvement (1.900, 1.297 - 2.784) was identified as a risk factor. Surgical time was associated with an increased risk of complications (1.004, 1.001 - 1.008), duration of hospitalization (1.006, 1.003 - 1.010), and reoperation (1.003, 1.001 - 1.006). Age was found to be a predictor of improved outcomes, as each additional year was associated with a 14.1% decrease in the likelihood of experiencing a prolonged length of stay (0.859, 0.772 - 0.956). Patients without metastasis exhibited a reduced risk of reoperation (0.322, 0.133 - 0.784) and readmission (0.208, 0.074 - 0.581). There is a significant degree of variability in the occurrence of operative complications in pediatric patients with medulloblastoma. SHH TP53-wildtype medulloblastoma is commonly correlated with a decreased incidence of complications. The short-term outcomes of patients are influenced by various unmodifiable endogenous factors. These findings could enhance the knowledge of onconeurosurgeons and alleviate the challenges associated with patient/parent education through personalized risk communication. However, the importance of a dedicated center with expertise surgical team and experienced neurosurgeon in improving neurosurgical outcomes appears self-evident.


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Procedimientos Neuroquirúrgicos , Complicaciones Posoperatorias , Humanos , Meduloblastoma/cirugía , Femenino , Masculino , Niño , Neoplasias Cerebelosas/cirugía , Procedimientos Neuroquirúrgicos/métodos , Preescolar , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Adolescente , Estudios de Cohortes , Tiempo de Internación , Reoperación , Proteínas Hedgehog/genética , Factores de Riesgo , Proteína p53 Supresora de Tumor/genética
11.
Int J Mol Sci ; 25(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38791511

RESUMEN

G protein-coupled receptors (GPCRs) are relevant targets for health and disease as they regulate various aspects of metabolism, proliferation, differentiation, and immune pathways. They are implicated in several disease areas, including cancer, diabetes, cardiovascular diseases, and mental disorders. It is worth noting that about a third of all marketed drugs target GPCRs, making them prime pharmacological targets for drug discovery. Numerous functional assays have been developed to assess GPCR activity and GPCR signaling in living cells. Here, we review the current literature of genetically encoded cell-based assays to measure GPCR activation and downstream signaling at different hierarchical levels of signaling, from the receptor to transcription, via transducers, effectors, and second messengers. Singleplex assay formats provide one data point per experimental condition. Typical examples are bioluminescence resonance energy transfer (BRET) assays and protease cleavage assays (e.g., Tango or split TEV). By contrast, multiplex assay formats allow for the parallel measurement of multiple receptors and pathways and typically use molecular barcodes as transcriptional reporters in barcoded assays. This enables the efficient identification of desired on-target and on-pathway effects as well as detrimental off-target and off-pathway effects. Multiplex assays are anticipated to accelerate drug discovery for GPCRs as they provide a comprehensive and broad identification of compound effects.


Asunto(s)
Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/metabolismo , Humanos , Transducción de Señal/efectos de los fármacos , Desarrollo de Medicamentos/métodos , Descubrimiento de Drogas/métodos , Animales , Transferencia de Energía por Resonancia de Bioluminiscencia/métodos , Bioensayo/métodos
12.
Cancer Immunol Immunother ; 72(8): 2741-2755, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37119260

RESUMEN

Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+ T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Humanos , Epítopos de Linfocito T , Nitratos , Antígenos de Neoplasias , Neoplasias/tratamiento farmacológico , Linfocitos T Colaboradores-Inductores , Adyuvantes Inmunológicos , ADN , Inmunoterapia
13.
J Neurosci Res ; 101(7): 1044-1057, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36827444

RESUMEN

The maintenance of vigilance relies on the activation of the cerebral cortex by the arousal system centered on the brainstem. Previous studies have suggested that both objective and subjective vigilance are susceptible to sleep deprivation. This study aims to explore the alterations in brainstem arousal system functional connectivity (FC) and its involvement in these two types of vigilance decline following total sleep deprivation (TSD). Thirty-seven healthy male subjects underwent two counterbalanced resting-state fMRI scans, once in rested wakefulness (RW) and once after 36 h of TSD. The pontine tegmental area and caudal midbrain (PTA-cMidbrain), the core regions of the brainstem arousal system, were chosen as the seeds for FC analysis. The difference in PTA-cMidbrain FC between RW and TSD conditions was then investigated, as well as its associations with objective vigilance measured by psychomotor vigilance task (PVT) and subjective vigilance measured by Stanford Sleepiness Scale. The sleep-deprived subjects showed increased PTA-cMidbrain FC with the thalamus and cerebellum and decreased PTA-cMidbrain FC with the occipital, parietal, and sensorimotor regions. TSD-induced increases in PVT reaction time were negatively correlated with altered PTA-cMidbrain FC in the dorsolateral prefrontal cortex, extrastriate visual cortex, and precuneus. TSD-induced increases in subjective sleepiness were positively correlated with altered PTA-cMidbrain FC in default mode regions including the medial prefrontal cortex and precuneus. Our results suggest that different brainstem FC patterns underlie the objective and subjective vigilance declines induced by TSD.


Asunto(s)
Privación de Sueño , Vigilia , Humanos , Masculino , Privación de Sueño/diagnóstico por imagen , Vigilia/fisiología , Somnolencia , Sueño , Tronco Encefálico/diagnóstico por imagen , Imagen por Resonancia Magnética , Desempeño Psicomotor/fisiología
14.
Respir Res ; 24(1): 142, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37259066

RESUMEN

BACKGROUND: While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. METHODS: In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. RESULTS: We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are "hot tumors" with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. CONCLUSIONS: Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Muerte Celular Inmunogénica , Inmunoterapia , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Algoritmos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Pronóstico , Microambiente Tumoral/genética
15.
Pediatr Res ; 94(6): 1935-1941, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37460708

RESUMEN

BACKGROUND: Hirschsprung disease (HSCR) is a congenital intestinal malformation. Previous HSCR animal model needs invasive operation on adult animal. The aim of this study is to establish an early-onset animal model which is consistent with the clinical manifestation of HSCR patients. METHODS: The neonatal mice were randomly divided into the benzalkonium chloride (BAC) group, treated with BAC via enema, and the control group, treated with saline. Weight changes, excretion time of carmine, CT scan, hematoxylin-eosin staining and immunofluorescence staining were used to evaluate the effect of the model. Differentially expressed genes (DEGs) in the HSCR mice were analyzed by using DAVID 6.8 database and compared with DEGs from HSCR patients. RESULTS: The weight of mice was lower and the excretion time of carmine was longer in the BAC group. Moreover, distal colon stenosis and proximal colon enlargement appeared in the BAC group. Neurons in the distal colon decreased significantly after 4 weeks of BAC treatment and almost disappeared completely after 12 weeks. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression. CONCLUSIONS: An economical and reliable HSCR animal model which has similar clinical characteristics to HSCR patients was successfully established. IMPACT: The animal model of Hirschsprung disease was first established in BALB/c mice. This model is an animal model of early-onset HSCR that is easy to operate and consistent with clinical manifestations. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression.


Asunto(s)
Enfermedad de Hirschsprung , Humanos , Ratones , Animales , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/metabolismo , Carmín , Intestinos , Modelos Animales de Enfermedad
16.
Fish Shellfish Immunol ; 136: 108700, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36966895

RESUMEN

In recent years, the widespread use of antibiotics in intensive grouper mariculture has resulted in the ineffectiveness of antibiotic treatment, leading to an increasing incidence of diseases caused by bacteria, viruses, and parasites, causing serious economic losses. Hence, it is crucial to develop alternative strategies to antibiotics for healthy and sustainable development of the mariculture industry. Here, we aimed to screen host gut-derived probiotics and evaluate its effects on growth and immunity of grouper. In this study, 43 bacterial strains were isolated from the intestine of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), and a potential probiotic strain G1-26, which can efficiently secrete amylase, protease, and lipase, was obtained using different screening mediums. Based on 16S rDNA sequencing, the potential probiotic strain G1-26 was identified as Vibrio fluvialis. The results of a biological characteristic evaluation showed that V. fluvialis G1-26 could grow at 25-45 °C, pH 5.5-7.5, salinity 10-40, and bile salt concentration 0-0.030%, and produce amylase, lipase, and protease under different culture conditions. Additionally, V. fluvialis G1-26 is sensitive to many antibiotics and does not exhibit aquatic biotoxicity. Subsequently, hybrid groupers were fed diets containing V. fluvialis G1-26 at different concentrations (0, 106, 108, and 1010 CFU/g) for 60 d. The results showed that V. fluvialis G1-26 at 108 CFU/g did not significantly affect the growth performance of the hybrid grouper (P > 0.05). V. fluvialis G1-26 supplementation at 108 and 1010 CFU/g significantly promoted the relative expression of immune-related genes in hybrid groupers (TLR3, TLR5, IL-1ß, IL-8, IL-10, CTL, LysC, TNF-2, and MHC-2) and improved the activities of alkaline phosphatase, acid phosphatase, total superoxide dismutase, and total protein in the liver. In conclusion, V. fluvialis G1-26, a potential probiotic strain isolated from the intestine of the hybrid grouper, can be used as an effective immunopotentiator at an optimal dose of 108 CFU/g diet. Our results provide a scientific basis for the development and utilization of probiotics in the grouper mariculture industry.


Asunto(s)
Lubina , Probióticos , Animales , Antioxidantes/metabolismo , Dieta/veterinaria , Probióticos/farmacología , Péptido Hidrolasas , Amilasas , Lipasa , Alimentación Animal/análisis
17.
Virus Genes ; 59(4): 613-623, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37170002

RESUMEN

As the problem of bacterial resistance becomes serious day by day, bacteriophage as a potential antibiotic substitute attracts more and more researchers' interest. In this study, Escherichia phage Kayfunavirus CY1 was isolated from sewage samples of swine farms and identified by biological characteristics and genomic analysis. One-step growth curve showed that the latent period of phage CY1 was about 10 min, the outbreak period was about 40 min and the burst size was 35 PFU/cell. Analysis of the electron microscopy and whole-genome sequence showed that the phage should be classified as a member of the Autographiviridae family, Studiervirinae subfamily. Genomic analysis of phage CY1 (GenBank accession no. OM937123) revealed a genome size of 39,173 bp with an average GC content of 50.51% and 46 coding domain sequences (CDSs). Eight CDSs encoding proteins involved in the replication and regulation of phage DNA, 2 CDSs encoded lysis proteins, 14 CDSs encoded packing and morphogenesis proteins. Genomic and proteomic analysis identified no sequence that encoded for virulence factor, integration-related proteins or antibiotic resistance genes. In summary, morphological and genomics suggest that phage CY1 is more likely a novel Escherichia phage.


Asunto(s)
Bacteriófagos , Caudovirales , Porcinos , Animales , Proteómica , Genoma Viral/genética , Genómica , Bacteriófagos/genética , Caudovirales/genética , Escherichia/genética
18.
Environ Sci Technol ; 57(24): 9055-9063, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37285149

RESUMEN

The ultraviolet (UV)/chlorine process has attracted increasing attention for micropollutant abatement. However, the limited hydroxyl radical (HO•) generation and the formation of undesired disinfection byproducts (DBPs) are the two major issues in this process. This study investigated the roles of activated carbon (AC) in the UV/chlorine/AC-TiO2 process for micropollutant abatement and DBP control. The degradation rate constant of metronidazole by UV/chlorine/AC-TiO2 was 3.44, 2.45, and 1.58 times higher than those by UV/AC-TiO2, UV/chlorine, and UV/chlorine/TiO2, respectively. AC acted as an electron conductor and dissolved oxygen (DO) adsorbent, resulting in the steady-state concentration of HO• that was ∼2.5 times that of UV/chlorine. Compared with UV/chlorine, the formation of total organic chlorine (TOCl) and known DBPs in UV/chlorine/AC-TiO2 was reduced by 62.3 and 75.7%, respectively. DBP could be controlled via adsorption on AC, and the increased HO• and decreased chlorine radical (Cl•) and chlorine exposure reduced DBP formation. UV/chlorine/AC-TiO2 efficiently abated 16 structurally different micropollutants under environmentally relevant conditions owing to the enhanced generation of HO•. This study provides a new strategy for designing catalysts with photocatalytic and adsorption properties for UV/chlorine to promote micropollutant abatement and DBP control.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Cloro , Carbón Orgánico , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Rayos Ultravioleta , Desinfección , Halogenación , Cloruros
19.
Childs Nerv Syst ; 39(8): 2115-2122, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37081233

RESUMEN

BACKGROUND: Neonatal posthemorrhagic hydrocephalus remains a common complication in preterm infants, with high rates of mortality and morbidity, placing parents at high risk of anxiety and depression. We sought to investigate the neurodevelopmental outcomes of infants with posthemorrhagic hydrocephalus who underwent surgery and the psychological effect on their parents. METHODS: We retrospectively analysed all infants with posthemorrhagic hydrocephalus born between 2014 and 2020 in the Children's Hospital of Chongqing Medical University, China. The neurodevelopmental outcomes of 28 patients were evaluated by the Pediatric Stroke Outcome Measure score, and the psychological states of the parents of survivors were assessed by the Hospital Anxiety and Depression Scale. RESULTS: The families of the 28 patients were followed up for a median duration of 3 years; 6 (21.4%) patients died within 6 months after discharge, 12 (42.9%) patients had moderate to severe dysfunction, and only 10 (35.7%) patients had good outcomes. Regarding the 22 parents of the survivors, 5 (22.7%) and 4 (18.2%) had borderline anxiety and depression symptoms, respectively. Two (9.1%) caregivers had exact anxiety and depression symptoms. Leukomalacia after intraventricular haemorrhage was associated with adverse neurological outcomes. The infants' histories of epileptic seizures during the neonatal period were associated with the anxiety of their parents. CONCLUSION: The overall outcome of posthemorrhagic hydrocephalus patients is unsatisfactory, and children with leukomalacia after haemorrhage tend to have poor outcomes. A history of epileptic seizures during the course of the disease may exacerbate the anxiety of the caregivers.


Asunto(s)
Hidrocefalia , Recien Nacido Prematuro , Lactante , Recién Nacido , Humanos , Niño , Estudios Retrospectivos , Hidrocefalia/cirugía , Hidrocefalia/complicaciones , Hemorragia Cerebral/complicaciones , Convulsiones/complicaciones
20.
Neurosurg Rev ; 46(1): 170, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37433938

RESUMEN

An external ventricular drain (EVD) is used to facilitate cerebrospinal fluid (CSF) removal in medulloblastoma patients suffering from hydrocephalus. It is essential to recognize that EVD management plays a crucial role in influencing the incidence of drain-related complications. However, the ideal method for EVD management remains undetermined. Our research sought to examine the safety of EVD placement and the impact of EVD on the incidences of intracranial infections, postresection hydrocephalus, and posterior fossa syndrome (PFS). We conducted a single-center observational study involving a cohort of 120 pediatric medulloblastoma patients who were treated from 2017 to 2020. The rates of intracranial infection, postresection hydrocephalus, and PFS were 9.2%, 18.3%, and 16.7%, respectively. EVD did not influence the occurrence of intracranial infection (p = 0.466), postresection hydrocephalus (p = 0.298), or PFS (p = 0.212). A gradual EVD weaning protocol correlated with an elevated incidence of postresection hydrocephalus (p = 0.033), whereas a rapid weaning approach resulted in 4.09 ± 0.44 fewer drainage days (p < 0.001) than the gradual weaning strategy. EVD placement (p = 0.010) and intracranial infection (p = 0.002) were linked to delayed speech return, whereas a longer duration of drainage was conducive to the recovery of language function (p = 0.010). EVD insertion was not correlated with the incidence of intracranial infection, postoperative hydrocephalus, or PFS. The optimal EVD management method should encompass a rapid EVD weaning strategy, followed by prompt drain closure. We have presented additional evidence to improve the safety of EVD insertion and management in neurosurgical patients to ultimately facilitate the establishment of standardized institutional/national implementation and management protocols.


Asunto(s)
Neoplasias Cerebelosas , Pérdida de Líquido Cefalorraquídeo , Hidrocefalia , Meduloblastoma , Humanos , Niño , Hidrocefalia/cirugía , Meduloblastoma/complicaciones , Meduloblastoma/cirugía , Neoplasias Cerebelosas/complicaciones , Neoplasias Cerebelosas/cirugía , Resultado del Tratamiento
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