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RNA sequencing (RNA-seq) has become a standard method for profiling gene expression, yet genomic DNA (gDNA) contamination carried over to the sequencing library poses a significant challenge to data integrity. Detecting and correcting this contamination is vital for accurate downstream analyses. Particularly, when RNA samples are scarce and invaluable, it becomes essential not only to identify but also to correct gDNA contamination to maximize the data's utility. However, existing tools capable of correcting gDNA contamination are limited and lack thorough evaluation. To fill the gap, we developed CleanUpRNAseq, which offers a comprehensive set of functionalities for identifying and correcting gDNA-contaminated RNA-seq data. Our package offers three correction methods for unstranded RNA-seq data and a dedicated approach for stranded data. Through rigorous validation on published RNA-seq datasets with known levels of gDNA contamination and real-world RNA-seq data, we demonstrate CleanUpRNAseq's efficacy in detecting and correcting detrimental levels of gDNA contamination across diverse library protocols. CleanUpRNAseq thus serves as a valuable tool for post-alignment quality assessment of RNA-seq data and should be integrated into routine workflows for RNA-seq data analysis. Its incorporation into OneStopRNAseq should significantly bolster the accuracy of gene expression quantification and differential expression analysis of RNA-seq data.
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Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people's living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients' well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.
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The simultaneous removal of heavy metal complexes (HMCs) and heavy metal ions presents a significant challenge in treating wastewater. To address this, we propose a Calcite/Peroxymonosulfate (Calcite/PMS) system aimed at simultaneously decomplexing Cu-EDTA and removing Cu ions. Calcite/PMS system could achieve 99.5 % Cu-EDTA decomplexation and 61.9 % Cu ions removal within 60 min under initial conditions of Cu-EDTA (10 mg/L), Calcite (3 g/L), and PMS (2 mM). Singlet oxygen (1O2) emerged as the predominant reactive species responsible for Cu-EDTA decomplexation, which selectively targeted the N-C bonds in the Cu-EDTA structure to produce intermediates with lower biotoxicity than EDTA. Interestingly, solid phase Cu(III) (≡Cu(III)) promoted the generation of superoxide radicals (O2â¢-) with a contribution of up to 72.8 %. Subsequently, nascent ≡Cu(III) and O2â¢- accelerated the degradation of intermediates. Besides, coexisting organic substances inhibited Cu-EDTA decomplexation, whereas inorganic ions had a weak impact. After five cycles of use, the Calcite/PMS system retained 99.3 % efficiency in decomplexing Cu-EDTA. This investigation provides valuable insights into using calcite to remove HMCs and enhances our comprehension of the decomplexation intermediates accelerating HMCs degradation.
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OBJECTIVE: To develop and validate a nomogram for quantitively predicting lymphovascular invasion (LVI) of breast cancer (BC) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomics and morphological features. METHODS: We retrospectively divided 238 patients with BC into training and validation cohorts. Radiomic features from DCE-MRI were subdivided into A1 and A2, representing the first and second post-contrast images respectively. We utilized the minimal redundancy maximal relevance filter to extract radiomic features, then we employed the least absolute shrinkage and selection operator regression to screen these features and calculate individualized radiomics score (Rad score). Through the application of multivariate logistic regression, we built a prediction nomogram that integrated DCE-MRI radiomics and MR morphological features (MR-MF). The diagnostic capabilities were evaluated by comparing C-indices and calibration curves. RESULTS: The diagnostic efficiency of the A1/A2 radiomics model surpassed that of the A1 and A2 alone. Furthermore, we incorporated the MR-MF (diffusion-weighted imaging rim sign, peritumoral edema) and optimized Radiomics into a hybrid nomogram. The C-indices for the training and validation cohorts were 0.868 (95% CI: 0.839-0.898) and 0.847 (95% CI: 0.787-0.907), respectively, indicating a good level of discrimination. Moreover, the calibration plots demonstrated excellent agreement in the training and validation cohorts, confirming the effectiveness of the calibration. CONCLUSION: This nomogram combined MR-MF and A1/A2 Radiomics has the potential to preoperatively predict LVI in patients with BC.
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Neoplasias de la Mama , Medios de Contraste , Imagen por Resonancia Magnética , Invasividad Neoplásica , Nomogramas , Radiómica , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Metástasis Linfática/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Invasividad Neoplásica/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
The association between the triglyceride-glucose (TyG) index and impaired fasting glucose (IFG) in elderly individuals remains uncertain. Our study aimed to explore the association between the TyG index and the risk of future IFG in this population. This retrospective cohort study included 17,746 elderly individuals over 60. In this population, Cox regression models proportional to hazards, along with smooth curve fitting and cubic spline functions, were employed to examine the association between the baseline TyG index and the risk of IFG. Subgroup analyses and sensitivity were also performed to ensure the robustness of the study findings. After adjusting for covariates, a positive association between the TyG index and the risk of IFG was found (HR = 1.43, 95% CI 1.27-1.60, P < 0.0001). The likelihood of IFG rose steadily as the TyG index quartiles (from Q1 to Q4) increased, with Q4 demonstrating a 62% elevated risk compared to Q1 (adjusted HR = 1.62, 95% CI 1.37-1.90). Additionally, we found the association between TyG index and risk of IFG was a linear. Sensitivity and subgroup analyses confirmed the stability of the results. Our study observed a linear association between the TyG index and the development of IFG in elderly Chinese individuals. Recognizing this association can help clinicians identify high-risk individuals and implement targeted interventions to reduce their risk of progressing to diabetes.
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Glucemia , Ayuno , Triglicéridos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/análisis , China/epidemiología , Pueblos del Este de Asia , Ayuno/sangre , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Objective: The concept of substances of medicine food homology (SMFH) has garnered significant attention in recent years. This study conducts a systematic analysis of patent literature related to SMFH, and elucidates the development trends, technical hotspots, and the overall patent protection landscape of SMFH in China over the past two decades. Methods: The patent search focused on the SMFH varieties as the objects of inquiry, with retrieval conducted in patent databases. Subsequently, the acquired data underwent processing, analysis, and visualization. Results: While the technical threshold for pharmaceutical applications surpasses that of the food service sector, the former may assume a prominent role in the future. Research and development (R&D) activities in the southeast of China demonstrate robust activity than other regions. Colleges and scientific research institutions exhibit substantial advantages in patent applications compared with individuals and hold greater potential for future development. Conclusion: The findings of this patent analysis indicate that China's SMFH industry are presently undergoing a transition from an extensive model to a high-quality model. The quality and technical standards of SMFH products are consistently improving. Consequently, there is a need for more stringent patent application requirements to align with the evolving development needs.
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Currently, three expanded polytetrafluoroethylene (ePTFE) prosthetic graft types are most commonly used for patients with end-stage kidney disease (ESKD) who require long-term vascular access for hemodialysis. However, studies comparing the three ePTFE grafts are limited. This study compared the clinical efficacy and postoperative complications of three ePTFE prosthetic graft types used for upper limb arteriovenous graft (AVG) surgery among patients with ESKD. Patients with ESKD requiring upper limb AVG surgery admitted to our center between January 2016 and September 2019 were enrolled. Overall, 282 patients who completed the 2-year follow-up were included and classified into the following three groups according to the ePTFE graft type: the GPVG group with the PROPATEN® graft, the GAVG group with the straight-type GORE® ACUSEAL, and the BVVG group with the VENAFLO® II. The patency rate and incidence of access-related complications were analyzed and compared between groups. The patients were followed up postoperatively, and data were collected at 6, 12, 18, and 24 months postoperatively. Respective to these follow-up time points, in the GPVG group, the primary patency rates were 74.29%, 65.71%, 51.43%, and 42.86%; the assisted primary patency rates were 85.71%, 74.29%, 60.00%, and 48.57%; and the secondary patency rates were 85.71%, 80.00%, 71.43%, and 60.00%. In the GAVG group, the primary patency rates were 73.03%, 53.93%, 59.42%, and 38.20%; the assisted primary patency rates were 83.15%, 68.54%, 59.55%, and 53.93%; and the secondary patency rates were 85.39%, 77.53%, 68.54%, and 62.92%, respectively. In the BVVG group, the primary patency rates were 67.24%, 53.45%, 41.38%, and 29.31%; the assisted primary patency rates were 84.48%, 67.24%, 55.17%, and 44.83%; and the secondary patency rates were 86.21%, 81.03%, 68.97%, and 60.34%, respectively. The differences in patency rates across the three grafts were not statistically significant. Overall, 18, 4, and 12 patients in the GPVG, GAVG, and BVVG groups, respectively, experienced seroma. Among the three grafts, GORE® ACUSEAL had the shortest anastomosis hemostatic time. The first cannulation times for the three grafts were GPVG at 16 (±8.2), GAVG at 4 (±4.9), and BVVG at 18 (±12.7) days. No significant difference was found in the postoperative swelling rate between the GPVG group and the other two groups. Furthermore, no statistically significant differences were found across the three graft types regarding postoperative vascular access stenosis and thrombosis, ischemic steal syndrome, pseudoaneurysm, or infection. In conclusion, no statistically significant differences in the postoperative primary, assisted primary, or secondary graft patency rates were observed among the three groups. A shorter anastomosis hemostatic time, first cannulation time, and seroma occurrence were observed with the ACUSEAL® graft than with its counterparts. The incidence of upper extremity swelling postoperatively was greater with the PROPATEN® graft than with the other grafts. No statistically significant differences were observed among the three grafts regarding the remaining complications.
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Derivación Arteriovenosa Quirúrgica , Prótesis Vascular , Fallo Renal Crónico , Politetrafluoroetileno , Diálisis Renal , Extremidad Superior , Grado de Desobstrucción Vascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Extremidad Superior/irrigación sanguínea , Prótesis Vascular/efectos adversos , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/métodos , Fallo Renal Crónico/terapia , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Diseño de Prótesis , Adulto , Resultado del Tratamiento , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/epidemiologíaRESUMEN
Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.
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Aminopeptidasas , Proteínas Bacterianas , Ésteres , Simulación del Acoplamiento Molecular , Pseudomonas aeruginosa , Hidrólisis , Ésteres/metabolismo , Ésteres/química , Aminopeptidasas/metabolismo , Aminopeptidasas/química , Aminopeptidasas/genética , Especificidad por Sustrato , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Pseudomonas aeruginosa/enzimología , Biodegradación Ambiental , Cinética , Bacillus subtilis/enzimología , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismoRESUMEN
Functionalized imidazo[1,2-α]pyridines are important scaffolds in pharmaceuticals. Herein, we present an efficient 3-sulfonylmethylation protocol for imidazo[1,2-α]pyridines by sodium sulfinates in DMA and H2O (2:1) via an FeCl3-catalyzed three-component coupling reaction. Various sulfonylmethyl imidazo[1,2-α]pyridines were thus afforded in high yields with excellent functional group tolerance. A plausible oxidation-addition mechanism was proposed.
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Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, and disulfidptosis is a newly discovered mechanism of programmed cell death. However, the effects of disulfidptosis-related lncRNAs (DR-lncRNAs) in LUAD have yet to be fully elucidated. The aim of the present study was to identify and validate a novel lncRNA-based prognostic marker that was associated with disulfidptosis. RNA-sequencing and associated clinical data were obtained from The Cancer Genome Atlas database. Univariate Cox regression and lasso algorithm analyses were used to identify DR-lncRNAs and to establish a prognostic model. Kaplan-Meier curves, receiver operating characteristic curves, principal component analysis, Cox regression, nomograms and calibration curves were used to assess the reliability of the prognostic model. Functional enrichment analysis, immune infiltration analysis, somatic mutation analysis, tumor microenvironment and drug predictions were applied to the risk model. Reverse transcription-quantitative PCR was subsequently performed to validate the mRNA expression levels of the lncRNAs in normal cells and tumor cells. These analyses enabled a DR-lncRNA prognosis signature to be constructed, consisting of nine lncRNAs; U91328.1, LINC00426, MIR1915HG, TMPO-AS1, TDRKH-AS1, AL157895.1, AL512363.1, AC010615.2 and GCC2-AS1. This risk model could serve as an independent prognostic tool for patients with LUAD. Numerous immune evaluation algorithms indicated that the low-risk group may exhibit a more robust and active immune response against the tumor. Moreover, the tumor immune dysfunction exclusion algorithm suggested that immunotherapy would be more effective in patients in the low-risk group. The drug-sensitivity results showed that patients in the high-risk group were more sensitive to treatment with crizotinib, erlotinib or savolitinib. Finally, the expression levels of AL157895.1 were found to be lower in A549. In summary, a novel DR-lncRNA signature was constructed, which provided a new index to predict the efficacy of therapeutic interventions and the prognosis of patients with LUAD.
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Balanitis , Humanos , Balanitis/diagnóstico , Balanitis/terapia , Consenso , Pueblos del Este de AsiaRESUMEN
An organic-inorganic hybrid nanoprobe, namely LML-D-SBA@Eu3+-Gd3+, was constructed, with SBA-15 acting as the carrier material, and luminol and Eu3+ acting as fluorescence channels to achieve ratiometric signals that eliminate external interference (accurate detection). Gd3+ was used as a sensitizer to amplify the red emission of Eu3+ (ultrasensitive detection). In TCs detection, the luminol emission at 428 nm was quenched due to the photoinduced electron transfer mechanism, and the Eu3+ emission at 617 nm was sensitized due to the synergistic energy transfer from TCs and Gd3+ to Eu3+. The fluorescence intensity at 617 and 428 nm showed ratiometric changes as indicated by notable color changes from blue to red. The detection limits for TC and OTC were 0.21 and 0.08 ng/mL, respectively. To realize a facile, rapid, and cost-effective detection, we constructed a portable intelligent sensing platform based on smartphones, and it demonstrated great potential for on-site detection of TCs.
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Antibacterianos , Europio , Luminol , Dióxido de Silicio , Teléfono Inteligente , Tetraciclina , Luminol/química , Dióxido de Silicio/química , Europio/química , Antibacterianos/análisis , Tetraciclina/análisis , Tetraciclina/química , Gadolinio/química , Contaminación de Alimentos/análisis , Límite de Detección , Espectrometría de Fluorescencia/métodos , PorosidadRESUMEN
BACKGROUND: Observational studies have elucidated the associations between dietary factors and hypertension. Nevertheless, the exploration of these relationships using Mendelian randomization remains scarce currently. METHODS: The Mendelian randomization approach investigated the potential causal relationships between 16 dietary factors and hypertension. To achieve this, we identified genetic variants associated with these dietary factors by utilizing data from European-descent genome-wide association studies with a stringent significance threshold (P < 5 × 10 - 8). Subsequently, we obtained genetic associations with hypertension from the extensive FinnGen Study, encompassing 92,462 cases and 265,626 controls. Our primary analytical method was the inverse variance weighted method, and we also conducted assessments for heterogeneity and pleiotropy to ensure the robustness and reliability of our findings. RESULTS: The study revealed significant associations with hypertension risk for various dietary factors. Specifically, higher weekly alcohol consumption (OR: 1.53, 95% CI: 1.19-1.96) and more frequent alcohol intake (OR: 1.20, 95% CI: 1.08-1.33) were positively correlated with an increased risk of hypertension. Likewise, increased poultry intake (OR: 3.25, 95% CI: 1.83-5.78) and beef intake (OR: 1.80, 95% CI: 1.09-2.97) were also linked to a higher risk of hypertension. Conversely, there were protective factors associated with a decreased risk of hypertension. These included consuming salad and raw vegetables, dried fruits, cheese, and cereals. It is important to note that no evidence of pleiotropy was detected, underscoring the robustness of these findings. CONCLUSIONS: This study uncovered causal relationships between various dietary factors and hypertension risk. Specifically, alcohol consumption in terms of drinks per week and intake frequency, as well as poultry and beef intake, were causally associated with an elevated risk of hypertension. In contrast, consuming salad/raw vegetables, dried fruits, cheese, and cereals demonstrated an inverse causal association with hypertension, suggesting a potential protective effect.
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Dieta , Estudio de Asociación del Genoma Completo , Hipertensión , Análisis de la Aleatorización Mendeliana , Humanos , Hipertensión/epidemiología , Hipertensión/genética , Dieta/estadística & datos numéricos , Consumo de Bebidas Alcohólicas/epidemiología , Factores de Riesgo , Masculino , Polimorfismo de Nucleótido Simple , Animales , Femenino , Verduras , Frutas , Aves de CorralRESUMEN
Objective: In this study, we aimed to utilize computed tomography (CT)-derived radiomics and various machine learning approaches to differentiate between invasive mucinous adenocarcinoma (IMA) and invasive non-mucinous adenocarcinoma (INMA) preoperatively in solitary pulmonary nodules (SPN) ≤3 cm. Methods: A total of 538 patients with SPNs measuring ≤3 cm were enrolled, categorized into either the IMA group (n = 50) or INMA group (n = 488) based on postoperative pathology. Radiomic features were extracted from non-contrast-enhanced CT scans and identified using the least absolute shrinkage and selection operator (LASSO) algorithm. In constructing radiomics-based models, logistic regression, support vector machines, classification and regression trees, and k-nearest neighbors were employed. Additionally, a clinical model was developed, focusing on CT radiological features. Subsequently, this clinical model was integrated with the most effective radiomic model to create a combined model. Performance assessments of these models were conducted, utilizing metrics such as the area under the receiver operating characteristic curve (AUC), DeLong's test, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: The support vector machine approach showed superior predictive efficiency, with AUCs of 0.829 and 0.846 in the training and test cohorts, respectively. The clinical model had AUCs of 0.760 and 0.777 in the corresponding cohorts. The combined model had AUCs of 0.847 and 0.857 in the corresponding cohorts. Furthermore, compared to the radiomic model, the combined model significantly improved performance in both the training (DeLong test P = 0.045, NRI 0.206, IDI 0.024) and test cohorts (P = 0.029, NRI 0.125, IDI 0.032), as well as compared to the clinical model in both the training (P = 0.01, NRI 0.310, IDI 0.09) and test cohorts (P = 0.047, NRI 0.382, IDI 0.085). Conclusion: the combined model exhibited excellent performance in distinguishing between IMA and INMA in SPNs ≤3 cm.
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Despite the great potential of sulfur-based autotrophic denitrification, an improvement in nitrate removal rate is still needed. This study used the desulfurized products of Mn ore to develop the MnS-S0-limestone autotrophic denitrification system (MSLAD). The feasibility of MSLAD for denitrification was explored and the possible mechanism was proposed. The nitrate (100 mg/L) was almost removed within 24 h in batch experiment in MSLAD. Also, an average TN removal of 98 % (472.0 mg/L/d) at hydraulic retention time of 1.5 h in column experiment (30 mg/L) was achieved. MnS and S0 could act as coupled electron donors and show synergistic effects for nitrate removal. γ-MnS with smaller particle size and lower crystallinity was more readily utilized by the bacterium and had higher nitrate removal efficiency than that of α-MnS. Thiobacillus and Sulfurimonas were the core functional bacterium in denitrification. Therefore, MnS-S0-limestone bio-denitrification provides an efficient alternative method for nitrate removal in wastewater.
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Procesos Autotróficos , Carbonato de Calcio , Desnitrificación , Nitratos , Azufre , Nitratos/metabolismo , Carbonato de Calcio/química , Azufre/metabolismo , Sulfuros/química , Sulfuros/metabolismo , Estudios de Factibilidad , Thiobacillus/metabolismo , Compuestos de Manganeso/química , Purificación del Agua/métodos , ManganesoRESUMEN
Pancreatic ß cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.
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Encéfalo , Proteínas de Drosophila , Drosophila melanogaster , Secreción de Insulina , Insulina , Animales , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Encéfalo/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Eje Cerebro-Intestino/fisiología , Lipasa/metabolismo , Lipasa/genética , Grasas de la Dieta/metabolismo , Glucosa/metabolismo , Cuerpo Adiposo/metabolismo , Lipoproteína Lipasa/metabolismo , Lipoproteína Lipasa/genética , MasculinoRESUMEN
As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.
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Glicerol , Ratas Sprague-Dawley , Animales , Masculino , Glicerol/toxicidad , Femenino , Ratas , Pruebas de Toxicidad Subcrónica , Pruebas de Mutagenicidad , Conservantes de Alimentos/toxicidad , Exposición Dietética , Peso Corporal/efectos de los fármacos , ChinaRESUMEN
PURPOSE: Genetic mutations stand as pivotal factors leading to the occurrence of embryonal tumor with multilayered rosettes (ETMR). This study aims to identify improved treatment approaches by unraveling the genetic drivers and immune infiltration in ETMR. METHODS: Two siblings with ETMR, treated at the General Hospital of Ningxia Medical University, were enrolled. Diagnosis involved MRI, Hematoxylin and Eosin (HE), and immunohistochemical (IHC) staining. Differentially expressed genes (DEGs) in ETMR were identified using GSE122077 and GSE14296 datasets. GO and KEGG analyses were used to determine ETMR-related pathways. Whole exome sequencing (WES) was utilized to annotate genetic variations in ETMR. Core genes, identified by protein-protein interaction (PPI), formed a diagnostic model evaluated by Logistic Regression. Single-sample Gene Set Enrichment Analysis (ssGSEA) assessed immune infiltration in ETMR, examining correlations between immune cells and core genes. RESULTS: Two siblings were diagnosed with ETMR. In ETMR, 135 DEGs were identified, of which 25 genes were annotated with 28 mutation sites. Moreover, ETMR-related pathways included cell cycle, synaptic functions, and neurodegeneration. Three ETMR-related core genes (ALB, PSMD1, and PAK2) were screened by protein-protein interaction (PPI). The diagnostic model constructed using these genes demonstrated an AUC value of 0.901 (95% CI: 0.811-0.991) in the training set, indicating accurate predictions in ETMR. Enhanced ssGSEA scores for 16 immune cells in ETMR tissues suggested a strong immune response. CONCLUSION: This study identifies diagnostic models associated with three core variant genes (ALB, PSMD1, PAK2) and enhanced immune cell activity in ETMR. It reveals crucial genetic features and significant immune responses in ETMR.
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Mutación , Neoplasias de Células Germinales y Embrionarias , Humanos , Mutación/genética , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/inmunología , Masculino , Femenino , Niño , Secuenciación del Exoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , HermanosRESUMEN
Kaempferol is a natural flavonoid with reported bioactivities found in many fruits, vegetables, and medicinal herbs. However, its effects on exercise performance and muscle metabolism remain inconclusive. The present study investigated kaempferol's effects on improving exercise performance and potential mechanisms in vivo and in vitro. The grip strength, exhaustive running time, and distance of mice were increased in the high-dose kaempferol group (p < 0.01). Also, kaempferol reduced fatigue-related biochemical markers and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) related to antioxidant capacity. Kaempferol also increased the glycogen and adenosine triphosphate (ATP) content in the liver and skeletal muscle, as well as glucose in the blood. In vitro, kaempferol promoted glucose uptake, protein synthesis, and mitochondrial function and decreased oxidative stress in both 2D and 3D C2C12 myotube cultures. Moreover, kaempferol activated the PI3K/AKT and MAPK signaling pathways in the C2C12 cells. It also upregulated the key targets of glucose uptake, mitochondrial function, and protein synthesis. These findings suggest that kaempferol improves exercise performance and alleviates physical fatigue by increasing glucose uptake, mitochondrial biogenesis, and protein synthesis and by decreasing ROS. Kaempferol's molecular mechanism may be related to the regulation of the PI3K/AKT and MAPK signaling pathways.