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Elucidating the mechanisms underlying Baijiu production is a shared aspiration among academic groups specializing in the field of Baijiu research. This study comprehensively examined the mechanisms underlying the yellowish coloration of Baijiu through a synergistic application of chromatographic, spectroscopic, and physical methodologies. Aging of Baijiu in earthenware pots involves the infiltration of mineral ions such as iron, aluminum, and calcium; however, these ions are detected at extremely low concentrations and are therefore not linked to the development of Baijiu's yellowish color. Instead, the yellowish coloration is attributed to the diverse colorants generated during the high-temperature fermentation of small-molecule sugars derived from the saccharification of grain materials. Although these colorants exist in minimal quantities and exhibit spectral absorption peaks ranging from 300 to 450 nm, their overlapping spectra collectively contribute to the light-absorbing properties of Baijiu across a broad wavelength range, ultimately accounting for its characteristic yellowish color.
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BACKGROUND: The exclusive breastfeeding condition in China is not optimism now. Maternal breastfeeding self-efficacy stands as a pivotal factor influencing exclusive breastfeeding. Interestingly, studies have suggested that father support breastfeeding self-efficacy is a pivotal mediator in infant breastfeeding. Thus, the current research aimed to investigate the association between father support breastfeeding self-efficacy and exclusive breastfeeding at six weeks postpartum, and the influencing factors of father support breastfeeding self-efficacy. METHODS: This research was structured as a multi-centre cross-sectional study, involving 328 fathers, whose partners were six weeks postpartum, and recruited from two public hospitals in Southeast China. Self-designed demographic questionnaires, namely, Father Support Breastfeeding Self-Efficacy Scale-Short Form, Breastfeeding Knowledge Questionnaire, Positive Affect Scale and the 14-item Fatigue Scale, were applied. Descriptive statistics, Chi-square test, logistic regression univariate analysis and multiple linear regression were used to analyse data. RESULTS: Results indicate a significant difference between the infant feeding methods at six weeks postpartum and fathers with different levels of support breastfeeding self-efficacy (p < 0.05). Particularly, father support breastfeeding self-efficacy positively affected exclusive breastfeeding at six weeks postpartum after adjusting all the demographic characteristics of fathers (OR: 2.407; 95% CI: 1.017-4.121). Moreover, results show that the significant influencing factors of father support breastfeeding self-efficacy include breastfeeding knowledge, fatigue, positive affect, successfully experienced helping mothers to breastfeed, spousal relationships and companionship time. CONCLUSIONS: High-level father support breastfeeding self-efficacy effectively increased exclusive breastfeeding rate at six weeks postpartum. To enhance the exclusive breastfeeding rate, nurses or midwives can endeavour to design educational programmes or take supportive interventions customised for fathers, such as enhancing their breastfeeding knowledge education, reducing fatigue and mobilising positive emotions, thereby bolstering paternal self-efficacy in breastfeeding.
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Lactancia Materna , Padre , Periodo Posparto , Autoeficacia , Humanos , Estudios Transversales , Lactancia Materna/psicología , Lactancia Materna/estadística & datos numéricos , China , Adulto , Masculino , Padre/psicología , Padre/estadística & datos numéricos , Femenino , Periodo Posparto/psicología , Encuestas y Cuestionarios , Apoyo Social , Adulto JovenRESUMEN
We examine the effects of nitrogen fertilizer application on air pollution in China. Distinct from the existing literature that tends to utilize field sampling method, we construct a comprehensive panel dataset and discover that 1 g nitrogen increase in fertilizer correlates with a rise of 0.55 µg/m³ in PM2.5 concentrations. Additionally, heterogenous results across the crops indicate that rice and corn crops exacerbate air pollution, whereas the impact of nitrogen fertilizer on wheat remains ambiguous, and these effects predominantly emerge during the initial growth stages. Our findings also suggest that while the nitrogen fertilizer contributes to heightened levels of PM2.5 and SO2, it conversely leads to a reduction in ozone concentrations, which is not provided by existing studies.
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Extracellular vesicles (EVs) are heterogeneous membrane-like vesicles secreted by living cells that are involved in many physiological and pathological processes and act as intermediaries of intercellular communication and molecular transfer. Recent studies have shown that EVs from specific sources regulate tissue repair and regeneration by delivering proteins, lipids, and nucleic acids to target cells as signaling molecules. Nanotechnology breakthroughs have facilitated the development and exploration of engineered EVs for tissue repair. Enhancements through gene editing, surface modification, and content modification have further improved their therapeutic efficacy. This review summarizes the potential of EVs in tissue repair and regeneration, their mechanisms of action, and their research progress in regenerative medicine. This review highlights their design logic through typical examples and explores the development prospects of EVs in tissue repair. The aim of this review is to provide new insights into the design of EVs for tissue repair and regeneration applications, thereby expanding their use in regenerative medicine.
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BACKGROUND: Disulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear. METHODS: Firstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot. RESULTS: Although SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients. CONCLUSION: This study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.
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Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Pronóstico , Microambiente Tumoral , Línea Celular Tumoral , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
The reusable and separable surface frustrated Lewis pairs (SFLPs) open up a novel approach to efficient small-molecule activation and conversion in heterogeneous catalysis. However, SFLPs have only been reported on limited systems due to the difficulty in the design and synthesis process. The inherent Lewis pairs on various solid materials offer promising opportunities for finding natural SFLPs, providing a straightforward and efficient strategy to overcome the current limitations. In this concept, we retrospect the concept of natural SFLPs proposed on wurtzite crystal surfaces and identify other natural SFLPs that probably exist on solid materials, including reduced oxide surfaces, corrugated graphene, and perovskite quantum dots. Having focused on the reactivity of natural SFLPs in small-molecule activation, we discuss the current challenges, propose possible research directions, and highlight potential applications of natural SFLPs in heterogeneous catalysis.
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In this study, we applied thermal dissipation probe technology to examine sap flow in various directions (east, south, west, and north) and at different depths (0-2, 2-4, 4-6 cm) within the stem of natural Picea mongolica trees in the eastern of Otindag Sandy Land to provide a scientific basis for accurately quantifying water consumption of P. mongolica forests through transpiration and to enhance the understanding of water relations. The results showed that the diurnal variation of sap flow in different directions displayed a unimodal curve, with the sap flow sequence being south>east>west>north. The sap flow at different sapwood depths exhibited an obvious unimodal curve, with a significant decrease as sapwood depth increased. Compared with that calculated from the mean sap flux density in four directions (23.57 kg·d-1), water consumption calculated using the mean value in south-east, east-west, south-west, north-east, north-south, and north-west was overestimated by 10.2%, 5.5%, 14.5%, and underestimated by 12.3%, 8.2%, 9.8%, respectively. The water consumption calculated using the values from the east, south, and west was overestimated by 6.1%, 14.4%, and 15.4%, respectively, and underestimated by 30.7% in the north. In addition, compared with the water consumption calculated from the mean value in three sapwood depths (48.51 kg·d-1), that calculated using sap flux density at sapwood depths of 0-2, 2-4, and 4-6 cm were overestimated by 18.8%, underestimated by 1.7%, and underestimated by 62.9%, respectively. These results indicated that sap flow of P. mongolica had significant azimuthal and radial variations, which considerably influence the estimation of tree water consumption. Installing probes at 0-2 cm simultaneously in both the north and east of the trunk could effectively reduce the estimation error of whole-tree water consumption by 4.2%. This approach enabled the accurate quantification of water consumption of individual P. mongolica trees in sandy areas, thereby improving the precision of transpiration water consumption estimates scaling up from individual level to stand level.
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Picea , Tallos de la Planta , Transpiración de Plantas , Agua , Picea/fisiología , Agua/metabolismo , China , Tallos de la Planta/metabolismoRESUMEN
OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.
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Sluggish interfacial water dissociation and the O2 evolution reaction (OER) kinetics are the main obstacles that limit the photocatalytic overall water-splitting performance. A molten salt modulation of potassium-nitrogen-carbon is herein demonstrated as the formation of highly crystalline potassium-doped poly(triazine imide) (KPTI). The in situ X-ray diffraction patterns and theoretical calculation show that the KCl melt can significantly reduce the free energy for the polycondensation of triazine building blocks owing to the formation of a kinetically stable KPTI. Benefiting from the presence of potassium-carbon-nitrogen moiety, the catalyst not only weakens the excitonic confinement to improve the separation efficiency of photogenerated charge carriers but also enhances the stability of carbon sites by suppressing the undesired CâO formation. Moreover, KPTI accelerates water dissociation by forming interfacial K·H2O clusters with an ordered structure, which supplies sufficient protons for the H2 evolution reaction and lowers the energy barrier to enhance the kinetics of OER. Therefore, a stable photocatalytic overall water-splitting performance can be achieved over KPTI with a stoichiometric generation of products (H2 and O2). Life cycle assessment shows that a carbon-neutral scenario can be achieved on KPTI production in the near term with an increase in green power in the electricity grid.
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Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups had statistically significant HbA1c reductions from baseline of -1.81%, -1.90%, and -2.39%, respectively, compared to -0.55% for placebo (P < 0.0001). At end of treatment, 71.9% of the 1.2 mg group had HbA1c ≤ 6.5% versus 9.1% on placebo, and 33.3% had body weight reductions ≥5% versus 3.0% for placebo. Ecnoglutide was generally safe and well tolerated. China Drug Trials Registry CTR20211014.
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Diabetes Mellitus Tipo 2 , Péptido 1 Similar al Glucagón , Hemoglobina Glucada , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Persona de Mediana Edad , Masculino , Femenino , Método Doble Ciego , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/administración & dosificación , Anciano , Resultado del Tratamiento , Peso Corporal/efectos de los fármacosRESUMEN
Staphylococcus aureus expresses three high-affinity neutrophil serine protease (NSP) inhibitors known as the extracellular adherence protein domain (EAPs) proteins. Whereas EapH1 and EapH2 are comprised of a single EAP domain, the modular extracellular adherence protein (Eap) from S. aureus strain Mu50 consists of four EAP domains. We recently reported that EapH2 can simultaneously bind and inhibit cathepsin-G (CG) and neutrophil elastase (NE), which are the two most abundant NSPs. This unusual property of EapH2 arises from independent CG and NE-binding sites that lie on opposing faces of its EAP domain. Here we used X-ray crystallography and enzyme assays to show that all four individual domains of Eap (i.e. Eap1, Eap2, Eap3, and Eap4) exhibit an EapH2-like ability to form ternary complexes with CG and NE that inhibit both enzymes simultaneously. We found that Eap1, Eap2, and Eap3 have similar functional profiles insofar as NSP inhibition is concerned but that Eap4 displays an unexpected ability to inhibit two NE enzymes simultaneously. Using X-ray crystallography, we determined that this second NE-binding site in Eap4 arises through the same region of its EAP domain that also comprises its CG-binding site. Interestingly, small angle X-ray scattering data showed that stable tail-to-tail dimers of the NE/Eap4/NE ternary complex exist in solution. This arrangement is compatible with NSP-binding at all available sites in a two-domain fragment of Eap. Together, our work implies that Eap is a polyvalent inhibitor of NSPs. It also raises the possibility that higher-order structures of NSP-bound Eap may have unique functional properties.
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Proteínas Bacterianas , Elastasa de Leucocito , Inhibidores de Serina Proteinasa , Staphylococcus aureus , Humanos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Sitios de Unión , Catepsina G/metabolismo , Catepsina G/química , Catepsina G/antagonistas & inhibidores , Cristalografía por Rayos X , Elastasa de Leucocito/metabolismo , Elastasa de Leucocito/antagonistas & inhibidores , Elastasa de Leucocito/química , Neutrófilos/metabolismo , Neutrófilos/enzimología , Unión Proteica , Dominios Proteicos , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/metabolismo , Staphylococcus aureus/enzimologíaRESUMEN
The currently available immune checkpoint therapy shows a disappointing therapeutic efficacy for glioblastoma multiforme (GBM), and it is of great importance to discover better immune checkpoints and develop innovative targeting strategies. The discovered metabolic immune checkpoint ecto-5-nucleotidase (CD73) in a tumor contributes to its immune evasion due to the dysregulation of extracellular adenosine (ADO), which significantly inhibits the function of antitumor T cells and increases the activity of immunosuppressive cells. Herein, we drastically inhibit the expression of CD73 to reduce the production of ADO by using versatile Au@Cu2-xSe nanoparticles (ACS NPs). ACS NPs can decrease the expression of CD73 by alleviating the tumor hypoxia through their Fenton-like reaction to weaken the ADO-driven immunosuppression for enhancing antitumor T cell infiltration and activity of GBM. The copper ions (Cu2+) released from ACS NPs can chelate with disulfide, leading to the formation of cytotoxic bis(N,N-diethyldithiocarbamate)-copper complex (CuET), which can be combined with radiotherapy to recruit more antitumor T cells to infiltrate into the tumor site. Based on the inhibition of CD73 to promote the infiltration and activity of antitumor T cells, a cascade of enhancing GBM immunotherapy effects can be achieved. The significant increase in CD8+ T and CD4+ T cells within the tumor and the memory T cells in the spleen effectively reduces tumor size by 92%, which demonstrates the excellent efficacy of immunotherapy achieved by a combination of metabolic immune checkpoint CD73 inhibition with chemoradiotherapy. This work demonstrates that modulation of CD73-mediated tumor immunosuppression is an important strategy of improving the outcome of GBM immunotherapy.
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5'-Nucleotidasa , Glioblastoma , Inmunoterapia , Glioblastoma/terapia , Glioblastoma/inmunología , Glioblastoma/patología , Glioblastoma/tratamiento farmacológico , 5'-Nucleotidasa/metabolismo , 5'-Nucleotidasa/antagonistas & inhibidores , Animales , Humanos , Ratones , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Cobre/química , Cobre/farmacología , Oro/química , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Nanopartículas del Metal/química , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/antagonistas & inhibidores , Adenosina/química , Adenosina/farmacologíaRESUMEN
Background: Outside of pregnancy, intuitive eating (IE) is associated with lower body weight, blood glucose, and higher positive mood. However, little was known about the relationship between IE and anxiety-depression in the GDM population. Thus, this study aimed to investigate the association of IE with anxiety and depression, pregnancy weight and pregnancy blood glucose in the first and second GDM visit. Methods: Data from 310 pregnant women with GDM from the Fujian Maternal and Child Health Hospital Trial (Approval Number: 2020Y9133) were analyzed. IE was assessed using the Intuitive Eating Scale-2 subscales of Eating for Physiological Reasons rather than Emotional Reasons (EPR), Relying on Hunger and Satiety Cues (RHSC) and Body-Food Choice Consistency (B-FCC). Observations included weight, body mass index (BMI), fasting plasma glucose (FPG) and 2-h postprandial blood glucose; the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in pregnant women with GDM. Linear regression analysis was used to assess the correlation between IE and anxiety, depression, pregnancy blood glucose and weight. Results: The cross-sectional analysis showed that the EPR eating behavior was negatively correlated with anxiety and depression, and the B-FCC eating behavior was negatively correlated with depression at both the first and second GDM visit; in addition, the B-FCC eating behavior was associated with lower BMI in the third trimester (all p < 0.05). In longitudinal analyses, the EPR eating behavior in the first visit for GDM predicted lower levels of anxiety and depression in the second GDM visit, whereas the RHSC eating behavior in the first visit for GDM was associated with lower FPG in the second GDM visit (all p < 0.01). Conclusion: These results suggest that practicing intuitive eating may be beneficial and that higher intuitive eating adherence can lead to lower levels of anxiety and depression and more ideal gestational weight and blood glucose values.
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Dihydrogen complexes, which retain the H-H bond, have been extensively studied in molecular science and found to be prevalent in homogeneous and enzymatic catalysis. However, their counterparts in heterogeneous catalysis, specifically nondissociative chemisorbed dihydrogen binding on the catalyst surface, are rarely reported experimentally. This scarcity is due to the complexity of typical material surfaces and the lack of effective characterization techniques to prove and distinguish various dihydrogen binding modes. Herein, using high-pressure operando solid-state NMR technology, we report the first unambiguous experimental observation of activated dihydrogen binding on a reduced ceria catalyst through interactions with surface oxygen vacancies. By employing versatile NMR structural and dynamical analysis methods, we establish a proportional relationship between the degree of ceria surface reduction and dihydrogen binding, as evidenced by NMR observations of H-D through-bond coupling (JHD), T1 relaxation, and proton isotropic chemical shifts. In situ NMR analysis further reveals the participation of bound dihydrogen species in a room-temperature ethylene hydrogenation reaction. The remarkable similarities between surface-activated dihydrogen in heterogeneous catalysis and dihydrogen model molecular complexes can provide valuable insights into the hydrogenation mechanism for many other solid catalysts, potentially enhancing hydrogen utilization.
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To effectively solve the problem of significant loss of transplanted cells caused by thrombosis during cell transplantation, this study simulates the human fibrinolytic system and combines metabolic oligosaccharide engineering with strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry to construct a cell surface with fibrinolytic activity. First, a copolymer (POL) of oligoethylene glycol methacrylate (OEGMA) and 6-amino-2-(2-methylamido)hexanoic acid (Lys) was synthesized by reversible addition-fragmentation chain transfer (RAFT) copolymerization, and the dibenzocyclooctyne (DBCO) functional group was introduced into the side chain of the copolymer through an active ester reaction, resulting in a functionalized copolymer DBCO-PEG4-POL with ε-lysine ligands. Then, azide functional groups were introduced onto the surface of HeLa model cells through metabolic oligosaccharide engineering, and DBCO-PEG4-POL was further specifically modified onto the surface of HeLa cells via the SPAAC "click" reaction. In vitro investigations revealed that compared with unmodified HeLa cells, modified cells not only resist the adsorption of nonspecific proteins such as fibrinogen and human serum albumin but also selectively bind to plasminogen in plasma while maintaining good cell viability and proliferative activity. More importantly, upon the activation of adsorbed plasminogen into plasmin, the modified cells exhibited remarkable fibrinolytic activity and were capable of promptly dissolving the primary thrombus formed on their surfaces. This research not only provides a novel approach for constructing transplantable cells with fibrinolytic activity but also offers a new perspective for effectively addressing the significant loss of transplanted cells caused by thrombosis.
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Química Clic , Reacción de Cicloadición , Fibrinólisis , Oligosacáridos , Humanos , Células HeLa , Oligosacáridos/química , Fibrinólisis/efectos de los fármacos , Ingeniería Metabólica , Azidas/química , Polietilenglicoles/química , Metacrilatos/química , Alquinos/química , Animales , Supervivencia Celular/efectos de los fármacos , Plasminógeno/química , Plasminógeno/metabolismo , Propiedades de SuperficieRESUMEN
OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.
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Autofagia , Aprendizaje Automático , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/patología , Humanos , Pronóstico , Animales , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Medicina de Precisión , Inmunoterapia/métodos , Regulación Neoplásica de la Expresión Génica , Ratones , Medición de RiesgoRESUMEN
This study targeted to explore circUQCRC2's role and mechanism in childhood asthma. A mouse model of ovalbumin-induced asthma was established to evaluate the effects of circUQCRC2 on childhood asthma in terms of oxidative stress, inflammation, and collagen deposition. The effects of circUQCRC2 on platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cells (SMCs) were evaluated, the downstream mRNA of miRNA and its associated pathways were predicted and validated, and their effects on asthmatic mice were evaluated. circUQCRC2 levels were upregulated in bronchoalveolar lavage fluid of asthmatic mice and PDGF-BB-treated SMCs. Depleting circUQCRC2 alleviated tissue damage in asthmatic mice, improved inflammatory levels and oxidative stress in asthmatic mice and PDGF-BB-treated SMC, inhibited malignant proliferation and migration of SMCs, and improved airway remodeling. Mechanistically, circUQCRC2 regulated VEGFA expression through miR-381-3p and activated the NF-κB cascade. circUQCRC2 knockdown inactivated the NF-κB cascade by modulating the miR-381-3p/VEGFA axis. Promoting circUQCRC2 stimulates asthma development by activating the miR-381-3p/VEGFA/NF-κB cascade. Therefore, knocking down circUQCRC2 or overexpressing miR-381-3p offers a new approach to treating childhood asthma.
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Asma , MicroARNs , FN-kappa B , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Asma/genética , Asma/metabolismo , Asma/patología , MicroARNs/genética , MicroARNs/metabolismo , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , FN-kappa B/metabolismo , Ratones , Humanos , Niño , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Becaplermina/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , ARN Circular/genética , ARN Circular/metabolismo , Femenino , Masculino , Ratones Endogámicos BALB C , Proliferación Celular , Estrés Oxidativo , Remodelación de las Vías Aéreas (Respiratorias)/genéticaRESUMEN
OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.
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Contaminantes Ambientales , Simulación del Acoplamiento Molecular , Bifenilos Policlorados , Neoplasias de la Próstata , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/genética , Humanos , Masculino , Bifenilos Policlorados/toxicidad , Contaminantes Ambientales/toxicidad , Progresión de la Enfermedad , Exposición a Riesgos AmbientalesRESUMEN
Objective: To observe the effect of the lung-protective ventilation strategy, static lung expansion, during cardiopulmonary bypass (CPB) on pulmonary function and tracheal intubation time following cardiac surgery in children. Methods: A total of 48 child patients (aged 1-3) with ventricular septal defect (VSD) were enrolled, and all underwent CPB cardiac surgery for the first time. The patients were divided into two groups using the random number table method: the experimental group (Group A, n = 30) and the control group (Group B, n = 18). After terminating the mechanical ventilation during CPB, the adjustable pressure limiting valve of the anesthesia machine was adjusted in the experimental group to maintain the pressure of the breathing circuit at 5 cmH2O, such that both lungs remained in a static expansion state. In the control group, routine mechanical ventilation was terminated as usual. Results: When static lung expansion with a continuous positive airway pressure of 5 cmH2O was employed in the VSD children during CPB, compared with termination of mechanical ventilation, the partial pressure of oxygen in the arterial blood increased, while the respiratory index decreased and the oxygenation index increased following the surgery. Conclusion: In child patients undergoing VSD reparation under CPB, lung injury occurs following the procedure, and the pulmonary oxygenation function and pulmonary oxygen diffusion function decrease. When static lung expansion of 5 cmH2O is performed during CPB, the improvement in lung function is better than that of apnea without lung expansion pressure.