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OBJECTIVE: The purpose of this study was to explore the auxiliary diagnostic value of volumetric CT value in quantifying the activity of a pulmonary tuberculoma. METHODS: Chest CT image data of 112 patients with pulmonary tuberculomas who were diagnosed clinically between October 16, 2013 and March 21, 2023 were selected. With the shortest diameter axis>5 mm on the mediastinal window serving as the inclusion criterion, 108 active tuberculomas and 64 non-active tuberculomas were selected. The focused image was manually segmented using ITK-SNAP software, the volumetric CT value of the focus was calculated, and the ROC curve was analyzed. Using the final clinical diagnosis as the reference standard, the auxiliary diagnostic efficacy and consistency of the conventional CT film reading method and volumetric CT value in determining the activity of a pulmonary tuberculoma were compared. RESULTS: The volumetric CT value of 108 active pulmonary tuberculoma lesions (33.39 [28.17,36.23] HU) was significantly less than 64 inactive pulmonary tuberculoma lesions (78.91 [57.81,120.31] HU); the difference was statistically significant (Z = -10.888. P < 0.001). ROC curve analysis showed that at a maximum Yoden index value of 0.963, the optimal volumetric CT threshold value was 45.32 HU, the sensitivity and specificity of the volumetric CT value in determining the activity of a pulmonary tuberculoma were 97.2% and 100.0%, respectively, and the maximum area under the ROC curve was 0.998. Taking the final clinical diagnosis as the reference standard, the sensitivity, specificity, consistency, and kappa value of the conventional CT film reading method for determining the activity of a pulmonary tuberculoma were 72.2% (78/108), 70.3% (45/64), 71.5% (123/172), and 0.413, respectively, while the corresponding volumetric CT values were 97.2% (105/108), 100.0% (64/64), 98.3% (168/172), and 0.951, respectively. CONCLUSION: Accurately quantifying the volumetric CT value of a pulmonary tuberculoma focus determines the activity of a pulmonary tuberculoma, which has very important auxiliary diagnostic value.
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Curva ROC , Tuberculoma , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Tuberculosis Pulmonar/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Tuberculoma/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto Joven , Anciano , Adolescente , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: We present a novel method for detecting atrial fibrillation (AFib) by analyzing Lead II electrocardiograms (ECGs) using a unique set of features. METHODS: For this purpose, we used specific signal processing techniques, such as proper orthogonal decomposition, continuous wavelet transforms, discrete cosine transform, and standard cross-correlation, to extract 48 features from the ECGs. Thus, our approach aims to more effectively capture AFib signatures, such as beat-to-beat variability and fibrillatory waves, than traditional metrics. Moreover, our features were designed to be physiologically interpretable. Subsequently, we incorporated an XGBoost-based ECG classifier to train and evaluate it using the publicly available 'Training' dataset of the 2017 PhysioNet Challenge, which includes 'Normal,' 'AFib,' 'Other,' and 'Noisy' ECG categories. RESULTS: Our method achieved an accuracy of 96 % and an F1-score of 0.83 for 'AFib' detection and 80 % accuracy and 0.85 F1-score for 'Normal' ECGs. Finally, we compared our method's performance with the top-classifiers from the 2017 PhysioNet Challenge, namely ENCASE, Random Forest, and Cascaded Binary. As reported by Clifford et al., 2017, these three best performing models scored 0.80, 0.83, 0.82, in terms of F1-score for 'AFib' detection, respectively. CONCLUSION: Despite using significantly fewer features than the competition's state-of-the-art ECG detection algorithms (48 vs. 150-622), our model achieved a comparable F1-score of 0.83 for successful 'AFib' detection. SIGNIFICANCE: The interpretable features specifically designed for 'AFib' detection results in our method's adaptability in clinical settings for real-time arrhythmia detection and is even effective with short ECGs (<10 heartbeats).
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Fibrilación Atrial , Electrocardiografía , Procesamiento de Señales Asistido por Computador , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Humanos , Electrocardiografía/métodos , AlgoritmosRESUMEN
OBJECTIVE: To comprehensively assess the global, regional and national burden of polycystic ovary syndrome (PCOS) in incidence, prevalence, and years lived with disability (DLYs) based on the Global Burden of Disease Study (GBD) 2019. METHODS: This was a cross-sectional descriptive study. Data on PCOS incidence, prevalence, and DLYs from 1990 to 2019 were obtained from the GBD study 2019. According to the commonwealth income, WHO region, and the sociodemographic index, the estimates were demonstrated along with the estimated annual percentage change (EAPC). The EAPC data were analyzed by four levels of hierarchical clustering and displayed in the world map. The Autoregressive Integrated Moving Average (ARIMA) and Bayesian age-period-cohort (BAPC) model was used to predict the PCOS burden in the next 20 years. RESULTS: From 1990 to 2019, the number of PCOS incidence in one year increased from 1.4 million in 1990 to 2.1 million in 2019 (54.3%). Only the EAPC estimates of incidence in the Region of the Americas decreased, and their aged-standardized incidence rate (ASIR) values were the highest in 1990 and 2019. There was no significant correlation between human development index (HDI) and EAPC. However, when HDI < 0.7, EAPC of incidence and prevalence was positively correlated with HDI, and when HDI > 0.7, EAPC of incidence and prevalence was negatively correlated with HDI. Countries with the middle level HDI have the highest increasing trend of ASIR and age-standardized prevalence rate (ASPR). The 10 to 19 years old group had the highest incidence counts of PCOS globally. Besides, the ARIMA and BAPC model showed the consistent increasing trend of the burden of PCOS. CONCLUSION: In order to better promote the early diagnosis and treatment, expert consensus and diagnosis criteria should be formulated according to the characteristics of different ethnic groups or regions. It is necessary to emphasize the early screening and actively develop targeted drugs for PCOS.
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Carga Global de Enfermedades , Síndrome del Ovario Poliquístico , Síndrome del Ovario Poliquístico/epidemiología , Humanos , Femenino , Incidencia , Estudios Transversales , Prevalencia , Adulto , Adulto Joven , Teorema de Bayes , AdolescenteRESUMEN
The escalating threat of malachite green (MG) pollution poses significant risks to ecosystems. Saturation mutation targeting Tyr230 of small laccase (SLAC) from Streptomyces coelicolor yielded Y230R, exhibiting a remarkable 104 % increase in specific activity. Notably, this mutation achieved dual enhancements in both activity and pH stability. Molecular dynamics simulation revealed higher structural stability of Y230R compared to wild-type (WT) across varying pH levels. The increased count of hydrogen bonds in Y230R compared to WT may be contribute to its stability. Y230R demonstrated superior catalytic efficiency (67.0 %) in MG decolorization, maintaining over 90 % activity after 30 min incubation in MG solution (500 mg/L), highlighting enhanced tolerance compared to WT. Molecular docking analysis attributed the differential catalytic effects on MG and ABTS to structural disparities and hydrogen bonding. Y230R stands as a promising composite mutant for future laccase engineering and industrial applications.
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Estabilidad de Enzimas , Lacasa , Simulación del Acoplamiento Molecular , Colorantes de Rosanilina , Lacasa/química , Lacasa/genética , Lacasa/metabolismo , Colorantes de Rosanilina/química , Colorantes de Rosanilina/metabolismo , Concentración de Iones de Hidrógeno , Streptomyces/enzimología , Streptomyces/genética , Simulación de Dinámica Molecular , Enlace de Hidrógeno , Mutación , Cinética , Biocatálisis , CatálisisRESUMEN
Developing cost-effective, durable bifunctional electrocatalysts is crucial but remains challenging due to slow hydrogen/oxygen evolution reaction (HER/OER) kinetics in water electrolysis. Herein, a combined engineering strategy of phosphorous vacancy (Vp) and spontaneous built-in electric field (BIEF) is proposed to design novel highly-conductive Co-doped MoP@MXene heterostructures with phosphorous vacancy (Vp-Co-MoP@MXene). Wherein, Co doping regulates the surface electronic structure and charge re-distribution of MoP, Vp induces more defects and active sites, while BIEF accelerates the interfacial charge transfer rate between Vp-Co-MoP and MXene. Therefore, the synergistic integration of Vp-Co-MoP/MXene efficiently decreases activation energy and kinetic barrier, thus promoting its intrinsically catalytic activity and structural stability. Consequently, the Vp-Co-MoP@MXene catalyst displays low overpotentials of 102.3/196.5 and 265.0/320.0 mV at 10/50 mA cm-2 for HER and OER, respectively. Notably, two-electrode electrolyzers with the Vp-Co-MoP@MXene bifunctional catalysts to achieve 10/50 mA cm-2, only need low-cell voltages of 1.57/1.64 V in alkaline media. Besides, experimental and theoretical results confirm that the hetero-structure effectively reduces hydrogen adsorption free energy and rate-determining-step energy barrier of OER intermediates, thereby greatly boosting its intrinsically catalytic activity. This work verifies an effective strategy to fabricate efficient non-precious bifunctional electro-catalysts for water splitting via combination engineering of phosphorous vacancy, cation doping, and BIEF.
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Lysosomes play a crucial role in various intracellular pathways as their final destination. Various stressors, whether mild or severe, can induce lysosomal membrane permeabilization (LMP), resulting in the release of lysosomal enzymes into the cytoplasm. LMP not only plays a pivotal role in various cellular events but also significantly contributes to programmed cell death (PCD). Previous research has demonstrated the participation of LMP in central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid hemorrhage (SAH), and hypoxic-ischemic encephalopathy (HIE). However, the mechanisms underlying LMP in CNS injuries are poorly understood. The occurrence of LMP leads to the activation of inflammatory pathways, increased levels of oxidative stress, and PCD. Herein, we present a comprehensive overview of the latest findings regarding LMP and highlight its functions in cellular events and PCDs (lysosome-dependent cell death, apoptosis, pyroptosis, ferroptosis, and autophagy). In addition, we consolidate the most recent insights into LMP in CNS injury by summarizing and exploring the latest advances. We also review potential therapeutic strategies that aim to preserve LMP or inhibit the release of enzymes from lysosomes to alleviate the consequences of LMP in CNS injury. A better understanding of the role that LMP plays in CNS injury may facilitate the development of strategic treatment options for CNS injury.
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We examined the occurrence and levels of 19 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in 7 species of marine bivalve molluscs collected from four coastal cities of Shandong Province, China. Perfluorooctanoic acid (PFOA) was the most prevalent component, accounting for 68.1 % of total PFASs. The total PFASs in bivalve molluscs ranged from 0.86 to 6.55 ng/g wet weight, with the highest concentration found in Meretrix meretrix L. The concentration of total PFASs in bivalve molluscs showed the following trend: clams > scallops > oysters > mussels. Estimation on the human intake of PFASs from consumption of bivalve molluscs resulted in hazard ratios (HR) ranging from 0.12 to 6.40. Five of the seven species had HR >1, indicating high exposure risks associated with PFASs. Therefore, the occurrence of PFASs in marine biota is particularly concerning and further investigations on the sources of PFASs in Shandong are warranted.
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Bivalvos , Monitoreo del Ambiente , Fluorocarburos , Contaminantes Químicos del Agua , Animales , China , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisis , Humanos , Caprilatos/análisisRESUMEN
BACKGROUND: Central nervous system (CNS) injury causes severe organ damage due to both damage resulting from the injury and subsequent cell death. However, there are currently no effective treatments for countering the irreversible loss of cell function. Parthanatos is a poly (ADP-ribose) polymerase 1 (PARP-1)-dependent form of programmed cell death that is partly responsible for neural cell death. Consequently, the mechanism by which parthanatos promotes CNS injury has attracted significant scientific interest. AIM OF REVIEW: Our review aims to summarize the potential role of parthanatos in CNS injury and its molecular and pathophysiological mechanisms. Understanding the role of parthanatos and related molecules in CNS injury is crucial for developing effective treatment strategies and identifying important directions for future in-depth research. KEY SCIENTIFIC CONCEPTS OF REVIEW: Parthanatos (from Thanatos, the personification of death according to Greek mythology) is a type of programmed cell death that is initiated by the overactivation of PARP-1. This process triggers a cascade of reactions, including the accumulation of poly(ADP-ribose) (PAR), the nuclear translocation of apoptosis-inducing factor (AIF) after its release from mitochondria, and subsequent massive DNA fragmentation caused by migration inhibitory factor (MIF) forming a complex with AIF. Secondary molecular mechanisms, such as excitotoxicity and oxidative stress-induced overactivation of PARP-1, significantly exacerbate neuronal damage following initial mechanical injury to the CNS. Furthermore, parthanatos is not only associated with neuronal damage but also interacts with various other types of cell death. This review focuses on the latest research concerning the parthanatos cell death pathway, particularly considering its regulatory mechanisms and functions in CNS damage. We highlight the associations between parthanatos and different cell types involved in CNS damage and discuss potential therapeutic agents targeting the parthanatos pathway.
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Granulation of juice sacs is a physiological disorder, which affects pomelo fruit quality. Here, the transcriptome and ubiquitinome of the granulated juice sacs were analyzed in Guanxi pomelo. We found that lignin accumulation in the granulated juice sacs was regulated at transcription and protein modification levels. In transcriptome data, we found that the genes in lignin biosynthesis pathway and antioxidant enzyme system of the granulated juice sacs were significantly upregulated. However, in ubiquitinome data, we found that ubiquitinated antioxidant enzymes increased in abundance but the enzyme activities decreased after the modification, which gave rise to reactive oxygen species (ROS) contents in granulated juice sacs. This finding suggests that ubiquitination level of the antioxidant enzymes is negatively correlated with the enzyme activities. Increased H2O2 is considered to be a signaling molecule to activate the key gene expressions in lignin biosynthesis pathway, which leads to the lignification in granulated juice sacs of pomelo. This regulatory mechanism in juice sac granulation of pomelo was further confirmed through the verification experiment using tissue culture by adding H2O2 or dimethylthiourea (DMTU). Our findings suggest that scavenging H2O2 and other ROS are important for reducing lignin accumulation, alleviating juice sac granulation and improving pomelo fruit quality.
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Citrus , Lignina , Lignina/metabolismo , Citrus/metabolismo , Citrus/genética , Jugos de Frutas y Vegetales/análisis , Especies Reactivas de Oxígeno/metabolismo , Transcriptoma , Peróxido de Hidrógeno/metabolismo , Regulación de la Expresión Génica de las Plantas , Frutas/metabolismo , Frutas/genética , Antioxidantes/metabolismoRESUMEN
Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.
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Mastitis , Infecciones Estafilocócicas , Femenino , Humanos , Ratas , Animales , Staphylococcus aureus/fisiología , Proteómica , Ácido Araquidónico/metabolismo , Mastitis/microbiología , Mastitis/patología , Mastitis/veterinaria , Inflamación/metabolismo , Redes y Vías Metabólicas , Glándulas Mamarias Animales/metabolismo , Infecciones Estafilocócicas/metabolismoRESUMEN
Plants that grow in extreme environments represent unique sources of stress-resistance genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic evergreen broadleaf shrub native to semi-arid and desert regions; however, its drought-tolerance mechanisms remain poorly understood. Here, we report the assembly of a reference-grade genome for A. mongolicus, describe its evolutionary history within the legume family, and examine its drought-tolerance mechanisms. The assembled genome is 843.07 Mb in length, with 98.7% of the sequences successfully anchored to the nine chromosomes of A. mongolicus. The genome is predicted to contain 47 611 protein-coding genes, and 70.71% of the genome is composed of repetitive sequences; these are dominated by transposable elements, particularly long-terminal-repeat retrotransposons. Evolutionary analyses revealed two whole-genome duplication (WGD) events at 130 and 58 million years ago (mya) that are shared by the genus Ammopiptanthus and other legumes, but no species-specific WGDs were found within this genus. Ancestral genome reconstruction revealed that the A. mongolicus genome has undergone fewer rearrangements than other genomes in the legume family, confirming its status as a "relict plant". Transcriptomic analyses demonstrated that genes involved in cuticular wax biosynthesis and transport are highly expressed, both under normal conditions and in response to polyethylene glycol-induced dehydration. Significant induction of genes related to ethylene biosynthesis and signaling was also observed in leaves under dehydration stress, suggesting that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Ectopic expression of AmERF2, an ethylene response factor unique to A. mongolicus, can markedly increase the drought tolerance of transgenic Arabidopsis thaliana plants, demonstrating the potential for application of A. mongolicus genes in crop improvement.
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Sequías , Fabaceae , Genoma de Planta , Fabaceae/genética , Fabaceae/fisiología , Estrés Fisiológico/genética , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , FilogeniaRESUMEN
Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.
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Betaína-Homocisteína S-Metiltransferasa , Carcinogénesis , Carcinoma Hepatocelular , Glucosafosfato Deshidrogenasa , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Animales , Humanos , Metilación , Betaína-Homocisteína S-Metiltransferasa/metabolismo , Betaína-Homocisteína S-Metiltransferasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Glucosafosfato Deshidrogenasa/genética , Ratones , Carcinogénesis/genética , Carcinogénesis/metabolismo , Arginina/metabolismo , Masculino , Línea Celular Tumoral , Ratones Noqueados , Regulación Neoplásica de la Expresión GénicaRESUMEN
Introduction: With improvements in living conditions, modern individuals exhibit a pronounced inclination towards a high-fat diet, largely because of its distinctive gustatory appeal. However, the association between high-fat diets and metabolic complications has largely been ignored, and metabolic diseases such as obesity and non-alcoholic fatty liver disease now constitute a major public health concern. Because high-fat diets increase the risk of metabolic diseases, a thorough investigation into the impact of high-fat diets on gut microbiota and metabolism is required. Methods: We utilize 16S rRNA sequencing and untargeted metabolomics analysis to demonstrate that SD rats fed a high-fat diet exhibited marked alterations in gut microbiota and plasma, intestinal metabolism. Results: Changes in gut microbiota included a decreased abundance at phylum level for Verrucomicrobiota, and a decreased abundance at genus level for Akkermansia, Ralstonia, Bacteroides, and Faecalibacterium. Additionally, significant changes were observed in both intestinal and plasma metabolite levels, including an upregulation of bile acid metabolism, an upregulation of glucose-lipid metabolism, and increased levels of metabolites such as norlithocholic acid, cholic acid, D-fructose, D-mannose, fructose lactate, and glycerophosphocholine. We also investigated the correlations between microbial communities and metabolites, revealing a significant negative correlation between Akkermansia bacteria and cholic acid. Discussion: Overall, our findings shed light on the relationship between symbiotic bacteria associated with high-fat diets and metabolic biomarkers, and they provide insights for identifying novel therapeutic approaches to mitigate disease risks associated with a high-fat diet.
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RNA molecules often play critical roles in assisting the formation of membraneless organelles in eukaryotic cells. Yet, little is known about the organization of RNAs within membraneless organelles. Here, using super-resolution imaging and nuclear speckles as a model system, we demonstrate that different sequence domains of RNA transcripts exhibit differential spatial distributions within speckles. Specifically, we image transcripts containing a region enriched in binding motifs of serine/arginine-rich (SR) proteins and another region enriched in binding motifs of heterogeneous nuclear ribonucleoproteins (hnRNPs). We show that these transcripts localize to the outer shell of speckles, with the SR motif-rich region localizing closer to the speckle center relative to the hnRNP motif-rich region. Further, we identify that this intra-speckle RNA organization is driven by the strength of RNA-protein interactions inside and outside speckles. Our results hint at novel functional roles of nuclear speckles and likely other membraneless organelles in organizing RNA substrates for biochemical reactions.
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Malachite green (MG) poses a formidable threat to ecosystems and human health. Laccase emerges as a promising candidate for MG degradation, prompting an investigation into the catalytic activity modulation of a small laccase (SLAC) from Streptomyces coelicolor, with a focus on amino acid position 228. Through saturation mutagenesis, five mutants with a 50% increase in the specific activity were generated. Characterization revealed notable properties, Km of E228F was 8.8% of the wild type (WT), and E288T exhibited a 133% kcat compared to WT. Structural analyses indicated improved hydrophobicity and electrostatic potential on the mutants' surfaces, with the stable E228F-ABTS complex exhibiting reduced flexibility, possibly contributing to the observed decrease in turnover rate. Mutants demonstrated enhanced MG decolorization, particularly E228G. Site 228 acts as a crucial functional control switch, suggesting its potential role in SLAC engineering. This study provides insights into laccase modulation and offers promising avenues for enzymatic bioremediation applications.
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Lacasa , Streptomyces coelicolor , Humanos , Lacasa/química , Streptomyces coelicolor/genética , Streptomyces coelicolor/metabolismo , Ecosistema , Biodegradación AmbientalRESUMEN
BACKGROUND: 4D flow magnetic resonance imaging (4D flow MRI) can assess and measure the complex flow patterns of the right ventricle (RV) in congenital heart diseases, but its limited availability makes the broad application of intracardiac flow assessment challenging. Color Doppler imaging velocity reconstruction from conventional echocardiography is an emerging alternative, but its validity against 4D flow MRI needs to be established. OBJECTIVE: To compare intracardiac flow parameters measured by color Doppler velocity reconstruction (DoVeR) against parameters measured from 4D flow MRI. METHODS: We analyzed 20 subjects, including 7 normal RVs and 13 abnormal RVs (10 with repaired Tetralogy of Fallot, and 3 with atrial-level shunts). Intracardiac flow parameters such as relative pressure difference, vortex strength, total kinetic energy, and viscous energy loss were quantified using DoVeR and 4D flow MRI. The agreement between the two methods was determined by comparing the spatial fields and quantifying the cross-correlation and normalized difference between time-series measurements. RESULTS: The hemodynamic parameters obtained from DoVeR and 4D flow MRI showed similar flow characteristics and spatial distributions. The time evolutions of the parameters were also in good agreement between the two methods. The median correlation coefficient between the time-series of any parameter was between 0.87 and 0.92, and the median L2-norm deviation was between 10% to 14%. CONCLUSIONS: Our study shows that DoVeR is a reliable alternative to 4D flow MRI for quantifying intracardiac hemodynamic parameters in the RV.
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Cardiopatías Congénitas , Tetralogía de Fallot , Humanos , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Cardiopatías Congénitas/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Ecocardiografía , Velocidad del Flujo SanguíneoRESUMEN
Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, the asymmetric construction of two nonadjacent stereocenters is of significant importance but is challenging because of the lack of remote chiral induction models. Herein, based on a CâC bond relay strategy, we report a synergistic Pd/Cu-catalyzed 1,5-double chiral induction model. All four stereoisomers of the target products bearing 1,5-nonadjacent stereocenters involving both allenyl axial and central chirality could be obtained divergently by simply changing the combination of two chiral catalysts with different configurations. Control experiments and DFT calculations reveal a novel mechanism involving 1,5-oxidative addition, contra-thermodynamic η3-allyl palladium shift, and conjugate nucleophilic substitution, which play crucial roles in the control of reactivity, regio-, enantio-, and diastereoselectivity. It is expected that this CâC bond relay strategy may provide a general protocol for the asymmetric synthesis of structural motifs bearing two distant stereocenters.
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OBJECTIVE: This study aims to investigate the effects of natural products on animal models of premature ovarian failure (POF). METHODS: We conducted comprehensive literature searches and identified relevant studies that examined the protective effects of natural products on experimental POF. We extracted quantitative data on various aspects such as follicular development, ovarian function, physical indicators, oxidative stress markers, inflammatory factors, and protein changes. The data was analyzed using random-effects meta-analyses, calculating pooled standardized mean differences and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic, and bias was estimated using the SYRCLE tool. RESULTS: Among the 879 reviewed records, 25 articles met our inclusion criteria. These findings demonstrate that treatment with different phytochemicals and marine natural products (flavonoids, phenols, peptides, and alkaloids, etc.) significantly improved various aspects of ovarian function compared to control groups. The treatment led to an increase in follicle count at different stages, elevated levels of key hormones, and a decrease in atretic follicles and hormone levels associated with POF. This therapy also reduced oxidative stress (specifically polyphenols, resveratrol) and apoptotic cell death (particularly flavonoids, chrysin) in ovarian granulosa cells, although it showed no significant impact on inflammatory responses. The certainty of evidence supporting these findings ranged from low to moderate. CONCLUSIONS: Phytochemicals and marine natural product therapy (explicitly flavonoids, phenols, peptides, and alkaloids) has shown potential in enhancing folliculogenesis and improving ovarian function in animal models of POF. These findings provide promising strategies to protect ovarian reserve and reproductive health. Targeting oxidative stress and apoptosis pathways may be the underlying mechanism.