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Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1-4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.
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Hipoglucemiantes , Metformina , ATPasas de Translocación de Protón Vacuolares , Proteínas Quinasas Activadas por AMP/metabolismo , Adenosina Trifosfatasas/metabolismo , Secretasas de la Proteína Precursora del Amiloide , Animales , Caenorhabditis elegans/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Glucosa/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/metabolismo , Hipoglucemiantes/farmacología , Lisosomas/metabolismo , Proteínas de la Membrana , Metformina/agonistas , Metformina/metabolismo , Metformina/farmacología , ATPasas de Translocación de Protón Vacuolares/metabolismoRESUMEN
To achieve an autonomously controlled reconfigurable microwave waveform generator, this study proposes and demonstrates a self-adjusting synthesis method based on a photonic delay reservoir computer with ring resonator. The proposed design exploits the ring resonator to configure the reservoir, facilitating a nonlinear transformation and providing delay space. A theoretical analysis is conducted to explain how this configuration addresses the challenges of microwave waveform generation. Considering the generalization performance of waveform generation, the simulations demonstrate the system's capability to produce six distinct representative waveforms, all exhibiting a highly impressive root mean square error (RMSE) of less than 1%. To further optimize the system's flexibility and accuracy, we explore the application of various artificial intelligence algorithms at the reservoir computer's output layer. Furthermore, our investigation delves deeply into the complexities of system performance, specifically exploring the influence of reservoir neurons and micro-ring resonator parameters on calculation performance. We also delve into the scalability of reservoirs, considering both parallel and cascaded arrangements.
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BACKGROUND: Vessels encapsulating tumor cluster (VETC) and microvascular invasion (MVI) have a synergistic effect on prognosis assessment and treatment selection of hepatocellular carcinoma (HCC). Preoperative noninvasive evaluation of VETC and MVI is important. PURPOSE: To explore the diagnosis value of preoperative gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) features for MVI, VETC, and recurrence-free survival (RFS) in HCC. STUDY TYPE: Retrospective. POPULATION: 240 post-surgery patients with 274 pathologically confirmed HCC (allocated to training and validation cohorts with a 7:3 ratio) and available tumor marker data from August 2014 to December 2021. FIELD STRENGTH/SEQUENCE: 3-T, T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT: Three radiologists subjectively reviewed preoperative MRI, evaluated clinical and conventional imaging features associated with MVI+, VETC+, and MVI+/VETC+ HCC. Regression-based nomograms were developed for HCC in the training cohort. Based on the nomograms, the RFS prognostic stratification system was further. Follow-up occurred every 3-6 months. STATISTICAL TESTS: Chi-squared test or Fisher's exact test, Mann-Whitney U-test or t-test, least absolute shrinkage and selection operator-penalized, multivariable logistic regression analyses, receiver operating characteristic analysis, Harrell's concordance index (C-index), Kaplan-Meier plots. Significance level: P < 0.05. RESULTS: In the training group, 44 patients with MVI+ and 74 patients with VETC+ were histologically confirmed. Three nomograms showed good performance in the training (C-indices: MVI+ vs. VETC+ vs. MVI+/VETC+, 0.892 vs. 0.848 vs. 0.910) and validation (C-indices: MVI+ vs. VETC+ vs. MVI+/VETC+, 0.839 vs. 0.810 vs. 0.855) cohorts. The median follow-up duration for the training cohort was 43.6 (95% CI, 35.0-52.2) months and 25.8 (95% CI, 16.1-35.6) months for the validation cohort. Patients with either pathologically confirmed or nomogram-estimated MVI, VETC, and MVI+/VETC+ suffered higher risk of recurrence. DATA CONCLUSION: GA-enhanced MRI and clinical variables might assist in preoperative estimation of MVI, VETC, and MVI+/VETC+ in HCC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Carcinoma Hepatocelular , Medios de Contraste , Gadolinio DTPA , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Nomogramas , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Medición de Riesgo , Anciano , Invasividad Neoplásica , Pronóstico , Microvasos/diagnóstico por imagen , Microvasos/patología , Adulto , Cuidados PreoperatoriosRESUMEN
BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). FIELD STRENGTH/SEQUENCE: 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. ASSESSMENT: LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). DATA CONCLUSION: The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. TECHNICAL EFFICACY: Stage 2.
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Fenpropathrin (Fen), a volatile pyrethroid insecticide, is used widely for agricultural applications and has been reported to increase the risk of Parkinson's disease (PD). However, the molecular basis, underlying mechanisms, and pathophysiology of Fen-exposed Parkinsonism remain unknown. Recent studies have revealed epigenetic mechanisms underlying PD-related pathway regulation, including DNA methylation. Epigenetic mechanisms are potential targets for therapeutic intervention in neurodegenerative diseases. After whole-genome bisulfite sequencing (WGBS) of midbrain tissues from a Fen-exposed PD-like mouse model, we performed an association analysis of DNA methylation and gene expression. Then we successfully screened for the DNA methylation differential gene Ambra1, which is closely related to PD. The hypermethylation-low expression Ambra1 gene aggravated DA neuron damage in vitro and in vivo through the Ambra1/Parkin/LC3B-mediated mitophagy pathway. We administered 5-aza-2'-deoxycytidine (5-Aza-dC) to upregulate Ambra1 expression, thereby reducing Ambra1-mediated mitophagy and protecting DA neurons against Fen-induced damage. In conclusion, these findings elucidate the potential function of Ambra1 under the regulation of DNA methylation, suggesting that the inhibition of DNA methylation may alleviate Fen-exposed neuron damage.
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Enfermedad de Parkinson , Piretrinas , Ratones , Animales , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Neuronas Dopaminérgicas/metabolismo , Metilación de ADN , Regulación hacia Abajo , Piretrinas/toxicidad , Piretrinas/metabolismo , Modelos Animales de Enfermedad , Decitabina , Proteínas Adaptadoras Transductoras de Señales/genéticaRESUMEN
BACKGROUND: Acquired symmastia is a rare complication after breast augmentation that is difficult to fix. METHODS: The medical records of 18 female patients with symmastia treated by our team were reviewed. Data collected included preoperative medical history, implant size, and breast base width. Surgical techniques were systematically reviewed and analyzed based on postoperative follow-up results. RESULTS: Of the 18 patients, 15 patients had undergone implanted breast augmentation and 3 had injected breast augmentation. All 18 patients underwent comprehensive repair with various surgical techniques. Three patients showed recurrence after operation. Four patients were dissatisfied with postoperative breast size and underwent 2-stage replacement surgery. CONCLUSIONS: Symmastia is an intractable surgical complication. Surgical classification can help assess the difficulty of surgery in advance, and the surgical strategy plan can help the surgeon to control the quality of the repair surgery.
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Implantación de Mama , Implantes de Mama , Mamoplastia , Humanos , Femenino , Implantes de Mama/efectos adversos , Implantación de Mama/efectos adversos , Implantación de Mama/métodos , Reoperación/métodos , Mamoplastia/efectos adversos , Mamoplastia/métodos , Estudios RetrospectivosRESUMEN
Giant reed (Arundo donax) is widely distributed across the globe and is considered an important energy crop. This study presents the first comprehensive analysis of the chloroplast genome of giant reed, revealing detailed characteristics of this species' chloroplast genome. The chloroplast genome has a total length of 137,153 bp, containing 84 protein-coding genes, 38 tRNA genes, and 8 rRNA genes, with a GC content of 39%. Functional analysis indicates that a total of 45 photosynthesis-related genes and 78 self-replication-related genes were identified, which may be closely associated with its adaptability and growth characteristics. Phylogenetic analysis confirmed that Arundo donax cv. Lvzhou No.1 belongs to the Arundionideae clade and occupies a distinct evolutionary position compared to other Arundo species. The findings of this study not only enhance our understanding of the giant reed genome but also provide valuable genetic resources for its application in biotechnology, bioenergy crop development, and ecological restoration.
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Evolución Molecular , Genoma del Cloroplasto , Filogenia , Poaceae , Poaceae/genética , Poaceae/clasificación , Fotosíntesis/genética , Composición de Base , ARN de Transferencia/genéticaRESUMEN
Pearl millet is a major cereal crop that feeds more than 90 million people worldwide in arid and semi-arid regions. The stalk phenotypes of Poaceous grasses are critical for their productivity and stress tolerance; however, the molecular mechanisms governing stalk development in pearl millet remain to be deciphered. In this study, we spatiotemporally measured 19 transcriptomes for stalk internodes of four different early developmental stages. Data analysis of the transcriptomes defined four developmental zones on the stalks and identified 12 specific gene sets with specific expression patterns across the zones. Using weighted gene co-expression network analysis (WGCNA), we found that two co-expression modules together with candidate genes were involved in stalk elongation and the thickening of pearl millet. Among the elongation-related candidate genes, we established by SELEX that a MYB-family transcription factor PMF7G02448 can bind to the promoters of three cell wall synthases genes (CesAs). In summary, these findings provide insights into stalk development and offer potential targets for future genetic improvement in pearl millet.
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Regulación de la Expresión Génica de las Plantas , Pennisetum , Proteínas de Plantas , Transcriptoma , Pennisetum/genética , Pennisetum/crecimiento & desarrollo , Transcriptoma/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Regiones Promotoras GenéticasRESUMEN
We report the ionization reduction of atoms in two-color femtosecond laser fields in this joint theoretical-experimental study. For the multiphoton ionization of atoms using a 400 nm laser pulse, the ionization probability is reduced if another relatively weak 800 nm laser pulse is overlapped. Such ionization reduction consistently occurs regardless of the relative phase between the two pulses. The time-dependent Schrödinger equation simulation results indicate that with the assisted 800 nm photons the electron can be launched to Rydberg states with large angular quantum numbers, which stand off the nuclei and thus are hard to be freed in the multiphoton regime. This mechanism works for hydrogen, helium, and probably some other atoms if two-color laser fields are properly tuned.
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OBJECTIVE: To investigate the diagnostic value of liver imaging reporting and data system (LI-RADS) v2018 and other imaging features in dual-phenotype hepatocellular carcinoma (DPHCC), establish a prediagnostic model based on gadoxetic acid-enhanced MRI, and explore the prognostic significance after surgery of the DPHCC. MATERIALS AND METHODS: Preoperative enhanced MRI findings and the clinical and pathological data of patients with surgically confirmed HCC were analysed retrospectively. Image analysis was based on LI-RADS v2018 and other image features. Univariate analysis was used to screen for predictive factors of DPHCC, and multivariate logistic regression analysis was used to determine the predictive factors. A regression diagnostic model was established. Receiver operating characteristic (ROC) curve analysis was used to determine the critical value, area under curve (AUC), and the corresponding 95% confidence interval (95% CI). The diagnostic performance was verified by fivefold cross-validation. Cox regression analysis was used to determine the prognostic factors associated with early recurrence after surgical resection. RESULTS: In total, 158 patients were included, of whom 79 had DPHCC and 79 had non-DPHCC. Multivariate analysis showed that rim arterial phase hyperenhancement (Rim APHE) and targetoid restriction were independent risk factors for DPHCC (P < 0.05). The AUC (95% CI) of the model was 0.862 (0.807-0.918), sensitivity was 81.01%, and specificity was 89.874%. Cox regression analysis showed that DPHCC, microvascular invasion, tumour diameter, and an increase of alpha-fetoprotein were independent factors for recurrence. CONCLUSION: Rim APHE and targetoid restriction were sensitive imaging features of DPHCC before surgery, and the identification of DPHCC has important prognostic significance for early recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Medios de Contraste , Gadolinio DTPA , Imagen por Resonancia Magnética/métodos , Fenotipo , Sensibilidad y EspecificidadRESUMEN
The surface-enhanced Raman scattering (SERS) technique has displayed a broad application prospect in disease diagnosis owing to its high sensitivity, fast responsiveness, and high specificity. In this study, we developed a SERS-based immunoassay for the detection of cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM), which is an important biomarker of cryptococcosis. The coupled localized surface plasmon resonance effect between magnetic SERS substrates and SERS tags gave rise to an enhanced Raman signal upon the formation of sandwich complexes, which contributes to the sensitive and specific detection of GXM. As a result, the developed method provided a lower limit of detection (1.25 ng/mL) than conventional methods, such as latex agglutination, lateral flow assay, and enzyme-linked immunosorbent assay. Additionally, a recovery experiment was performed to detect GXM in human serum, which also validated the potential advantages of a SERS-based immunoassay in the clinical diagnosis of cryptococcosis.
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Criptococosis , Nanopartículas del Metal , Biomarcadores , Criptococosis/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Oro/química , Humanos , Inmunoensayo/métodos , Nanopartículas del Metal/química , Espectrometría Raman/métodosRESUMEN
OBJECTIVE: This study aimed to conduct proteomic analysis of the sphincter in a neurogenic bladder caused by T10 spinal cord injury. The differentially expressed proteins (DEPs) of the sphincters (internal urethral sphincter) in the neurogenic bladders (NBs) of rats after complete transection of the T10 spinal cord segment were screened using tandem mass tag (TMT)-based quantitative labeling, and their biological information was analyzed. METHODS: Twelve adult Sprague Dawley rats out of 40 were randomly assigned to the blank group (n = 12), while the remaining 28 were placed in the T10 spinal cord injury model via modified Hassan Shaker spinal cord transection; 12 of these rats were then randomly selected as the model group. The rats in both groups underwent urodynamics detection and hematoxylin and eosin (H&E) staining. The proteins expressed in the bladder sphincter were detected using TMT-based quantitative proteomics. DEPs were defined as proteins with fold change >1.5 or <1/1.5, p < 0.05, and unique peptide ≥2. The DEPs were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using KOBAS 3.0., and gene ontology functional annotation analysis was performed using the Cytoscape 3.7.1. BiNGO plug-in. The protein-protein interaction network was then constructed using the interactive gene-retrieval tool STRING and Cytoscape software. RESULTS: The leak-point pressure and maximum cystometric volume in the model group were significantly higher than those in the blank group (p < 0.01), and H&E staining showed continuous interruption of the bladder sphincter fibers in the model group. A total of 250 DEPs were screened in the bladder sphincter, 83 of which were up-regulated and 167 of which were down-regulated. KEGG analysis of the DEPs was used to screen 15 pathways, including metabolic pathways, extracellular matrix (ECM)-receptor interaction, adhesion spots, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, the cytochalasin signaling pathway, and the advanced glycation end-products (AGE)/receptor for AGEs (RAGE) signaling pathway in diabetic complications and vascular smooth muscle contraction. CONCLUSIONS: It is of great significance to explore the pathological mechanism of non-inhibitory contraction of the bladder sphincter caused by spinal cord injury above the T10 segment from the perspective of ECM-receptor interaction, focal adhesion-activated PI3K/Akt signaling pathway, and cell relaxation signaling pathways. Synaptic vesicle glycoprotein (Sv2A) involved in the release of neurotransmitters from synaptic vesicles, arrestin ß2 inhibitory proteins involved in α-adrenergic receptors and G-protein-coupled receptor internalization, and calmodulin and calmodulin binding protein involved in calcium-sensitive signaling pathways may be potential targets for developing new ways to treat bladder sphincter overactivity caused by T10 spinal cord injury.
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Traumatismos de la Médula Espinal , Vejiga Urinaria Neurogénica , Animales , Arrestinas , Calcio , Calmodulina , Proteínas de Unión a Calmodulina , Citocalasinas , Eosina Amarillenta-(YS) , Hematoxilina , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas , Proteómica , Proteínas Proto-Oncogénicas c-akt , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa , Receptores Acoplados a Proteínas G , Médula Espinal , Traumatismos de la Médula Espinal/complicaciones , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/terapiaRESUMEN
Triterpenes, with high diversity and a wide range of sources, can be found in many medicinal plants. They have been found free or as glycosides/esters by combining with sugars. Most of them act as signaling molecules and function in stress response. They are also the material basis for the therapeutic effect of various medicinal plants. Modern pharmacological research has shown that they have the anti-inflammatory, antibacterial, antiviral, anti-tumor, fertility-regulating, and immunomodulatory effects. They top plant natural products in both quantity and diversity, and among them, tetrachyclic triterpenes and pentachyclic triterpenes are most abundant. The first step of the structural diversification is the cyclization 2,3-oxidosqualene, which is catalyzed by oxidosqualene cyclases(OSCs). Numerous OSCs exist, each with a specific cyclization mechanism, and thus over 100 different cyclic triterpene skeletons have been found in nature. This study reviewed the research on the biosynthetic pathways of triterpenes in medicinal plants, regulatory mechanisms of the pathways, and the key enzymes, and analyzed the expression regulation and structural characteristics of key enzyme genes involved in the synthetic pathways. This study is expected to serve as a reference for further research on triterpenes, such as the directional regulation of metabolic flow and heterologous biosynthesis and lay a basis for the regulation of triterpene synthesis and the selection of high-quality germplasm. This study also provides basic materials for further research and development of triterpenes from medicinal plants.
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Vías Biosintéticas , Plantas Medicinales , Triterpenos , Plantas Medicinales/química , Plantas Medicinales/genética , Triterpenos/químicaRESUMEN
BACKGROUND: Capsular contracture (CC) is a complication of breast augmentation that frequently requires revision surgery. The axillary approach reduces the visibility of the postoperative scar. It is unclear whether the previous incision can be used to repair the deformity caused by CC. METHODS: This study analyzed 21 patients (42 breasts) with grade III-IV CC during 2012-2017. The mean age of the patients was 32 years (range 23-48). Previous axillary scars were used to expose, and CCs were taken out completely or partially. Breast implants were removed. The dissection was performed with endoscopic assistance, using electrocautery under direct visualization. RESULTS: The mean follow-up period was 13 months (range 6-24 months). The dissection plane was changed to dual plane. Thirty-five CCs were taken out completely. Thirty-eight breast implants taken out remained intact. None of the patients required additional surgery. CONCLUSION: Endoscopic-assisted treatment may be an effective technique for treating CC and avoiding the additional scar. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Implantación de Mama , Implantes de Mama , Contractura , Mamoplastia , Adulto , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Contractura/etiología , Contractura/cirugía , Humanos , Mamoplastia/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Hydrophilic and hydrophobic deep eutectic solvents (DESs) as "green" solvents were applied in this study for the microextraction of environmental samples. A series of DESs (five hydrophilic and three hydrophobic) were synthesized and characterized by Fourier transform infrared spectroscopy. Physicochemical property parameters of eight DESs including water solubility, density, conductivity, and freezing point were assessed. Compared with the performance of five hydrophilic DESs in water phase, the three hydrophobic DESs were more suitable for application in dispersive liquid-liquid microextraction for the determination of sulfonamides in water sample. In dispersive liquid-liquid microextraction process, analytical parameters including type and volume of extraction solvent, extraction time, and pH of water sample were investigated. Under optimum conditions, 60 µL of hydrophobic DESs was used for extraction for 2 min in pH = 7.0 sample. The linear ranges were 0.05-5.0 µg/mL for the four sulfonamides with the correlation coefficients in the range of 0.9991-0.9999. The limits of detection were in the range of 0.0005-0.0009 µg/mL and the limits of quantification were in the range of 0.0019-0.0033 µg/mL. The recoveries of the analytes of the proposed method for the spiked samples were 80.17-93.5%, with the relative standard deviation less than 6.31%. The results indicated that three hydrophobic DESs showed commendable performance for extraction of sulfonamides, and hydrophobic DES-based microextraction method was successfully applied for monitoring sulfonamides in water samples. Graphical abstract.
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BACKGROUND AIMS: Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics. METHODS: We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism. RESULTS: After 7 days of culture, compared with those cultured with cytokines alone (3.25 ± 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 ± 0.61 (P = 0.003) and 4.06 ± 0.43 (P = 0.025)-fold, respectively. Direct cell-to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38- cells than stroma-free culture (156.17 ± 21.32 versus 79.12 ± 19.77-fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% ± 11.0% versus 16.0% ± 14.3%; P = 0.750). EPCs highly expressed interleukin 6 (IL6) and angiopoietin 1 (ANGPT1), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo. DISCUSSION: These data demonstrated that EPCs improve the CD34+ population but do not compromise the repopulating efficacy of the amplified HSPCs, possibly via cytokine secretion and Wnt signaling pathway activation.
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Técnicas de Cultivo de Célula/métodos , Proliferación Celular , Células Progenitoras Endoteliales/citología , Células Progenitoras Endoteliales/fisiología , Sangre Fetal/citología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Animales , Antígenos CD34/metabolismo , Células Cultivadas , Técnicas de Cocultivo/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Recién Nacido , Ratones , Ratones Endogámicos NOD , Ratones SCID , EmbarazoRESUMEN
OBJECTIVE: To assess the beneficial effects of silver foam dressing on the healing of wounds with ulcers and infection control of burn patients. METHODS: Eighty-four second-degree burn patients were selected and divided into a study group and a control group (n=42). After disinfection and cleaning, wound beds of the study group were covered with silver-containing soft-silicone foam dressing, and wound surfaces of the control group were wiped with 1% silver sulfadiazine cream (60 g/100 cm(2)). The two groups were checked weekly to observe wound healing progress and adverse reactions of the skin around wounds. Wound secretions were collected and subjected to bacterial culture. Related indices were recorded and quantified. RESULTS: Thirty seven cases of the study group (88.1%) and 36 cases of the control group (85.7%) recovered to normal, and 3 (7.1%) and 2 cases (4.8%) in the two groups failed to recover. The recovery rates of the two groups were similar (P>0.05), but unrecovered patients in the study group had significantly higher proportions of repaired wounds (P<0.05). Wounds of the study group were healed significantly more rapidly than those of the control group (22.3±3.1 vs. 25.1±4.4, P<0.05). The study group had significantly higher proportions of repaired wounds from Day 7 to Day 21 (P<0.05), but the difference became less obvious with extended time to Day 28. The bacterial culture-positive (exceeding 10(5) organisms per gram of tissue) rates of both groups significantly reduced after treatment (Day 7 for the study group and Day 14 for the control group), and the rate of the study group was significantly lower at last (P<0.05). The study and control groups were observed 134 and 149 person-times respectively, with the normal wound-surrounding skin rates of 96.3% (129/134) and 88.6% (132/149) (P>0.05 except for on Day 14). Except for on Day 28, the study group had significantly lower pain scores than those of the control group (P<0.05), especially on Day 7 and Day 14 (P<0.01). From Day 7 to Day 28, the study group was significantly less prone to burning sensation than the control group (P<0.05), but both groups felt anxious during dressing change (P>0.05). Dressing of the study group was changed significantly more easily (P<0.05), but the fixing outcomes were similar (P>0.05). CONCLUSION: Silver foam dressing rapidly, easily and safely resisted wound bacteria, promoted wound healing and shortened recovery time, effectively relieving the pain of patients.
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Bird's nest fungi involve six different genera, but only one of these genera (i.e. Cyathus) have available mitochondrial genomes (mitogenomes) to date. In this study, we report the first mitogenome in the genus Nidula with Nidula shingbaensis K. Das & R.L. Zhao 2013 as a representative. The mitogenome is a circular molecule of 65,793 bp with a GC content of 26.2%. There are a total of 43 genes, including 14 typical protein-coding genes, 26 tRNA genes, two rRNA genes, and one free-standing intergenic open reading frame (ORF). Three introns (two in cox1 and one in cob) are present in the mitogenome, with each containing an ORF encoding for a LAGLIDADG endonuclease. Phylogenetic analysis based on mitochondrial amino acid sequences confirms the phylogenetic placement of N. shingbaensis in Nidulariaceae in Agaricales. This study serves as a springboard for future investigation on fungal evolution in Nidulariaceae.
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BACKGROUND: In recent years, as societal awareness of the risks associated with primary osteoporosis (POP) has deepened, numerous studies have explored the relationship between POP and Traditional Chinese Medicine (TCM) constitution types. To further clarify the TCM constitution types closely associated with POP and provide evidence-based medical support for the prevention and treatment of osteoporosis from a TCM perspective, we have employed evidence-based methods to investigate the relationship between POP and TCM constitution types. METHODS: We conducted a comprehensive search of observational studies on the relationship between POP and TCM constitutional types in databases, including PubMed, Embase, MEDLINE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journal Database (VIP), up to October 2023. RESULTS: After literature selection, data extraction, and bias assessment, 29 studies were included in the meta-analysis, comprising 20 cross-sectional studies and 9 case-control studies. Using R software (version 4.2.3), we analyzed the distribution of TCM constitutional types in POP patients and compared the TCM constitutional types between POP patients and healthy individuals. The meta-analysis results revealed that in POP patients, Yang-deficiency constitution accounted for 22.7% (95% CI: 19.8-25.8%), Yin-deficiency constitution accounted for 15.8% (95% CI: 13.0-18.6%), and Qi-deficiency constitution accounted for 14.1% (95% CI: 12.2-16.0%). The proportions of the three mentioned TCM constitutions all exceed that of the Balanced constitution, with the balanced constitution accounting for 12.3% (95% CI: 7.4-18.1%). The proportions of Yang-deficiency, Yin-deficiency, and Qi-deficiency constitutions were higher in POP patients compared to healthy individuals, with odds ratios (OR) of 2.36 (95% CI: 1.43-3.89), 1.69 (95% CI: 1.36-2.04), and 1.80 (95% CI: 1.23-2.64), respectively, while the Balanced type was lower in POP patients with an OR of 0.16 (95% CI: 0.11-0.23) compared to healthy individuals. CONCLUSION: The evidence suggests that the Yang-deficiency constitution, Yin-deficiency constitution, and Qi-deficiency constitution are the predominant TCM constitutional types in POP patients. Furthermore, Yang-deficiency constitution, Yin-deficiency constitution, and Qi-deficiency constitution may serve as potential risk factors for POP, while the Balanced constitution may act as a protective factor.
Asunto(s)
Medicina Tradicional China , Osteoporosis , Humanos , Constitución Corporal/fisiología , Medicina Tradicional China/métodos , Osteoporosis/epidemiología , Osteoporosis/fisiopatología , Deficiencia Yang/epidemiología , Deficiencia Yang/fisiopatología , Deficiencia Yin/epidemiología , Deficiencia Yin/fisiopatologíaRESUMEN
Introduction: The association of air pollution with bone mineral density (BMD) has attracted increasing attention. However, establishing a causal relationship remains uncertain. Methods: We conducted a Mendelian randomization (MR) study employing PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides as exposures and BMD as the outcome to explore the causality between air pollution and the occurrence of decreased BMD. Results: By employing the IVW method, we identified a negative causality between air pollution (PM2.5, PM10, and nitrogen oxides) and BMD. Conclusions: Our findings demonstrate that PM2.5, PM10 and nitrogen oxides exposure may contribute to decreased BMD.