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Identifying the biomarkers from the personalized gene interaction network of individual patients is important for disease diagnosis. However, existing methods not only ignore the prior biomarkers for practical use but also ignore the observability of the entire system. Therefore, this paper proposes a new constrained multi-objective optimization-based temporal network observability model (CMTNO) to identify biomarkers, which not only requires minimizing the number of selected nodes including ordinary nodes and prior nodes (the first optimization objective) but also maximizing the number of selected prior nodes (the second optimization objective) on the premise of ensuring network observability (the constraint condition). Considering the temporal feature of cancer (patients belong to different stages and each patient contains one task), an experience learning-based constrained multi-objective evolutionary algorithm is designed to solve the CMTNO problems. The selected probabilities of ordinary nodes and prior nodes are treated as experience, stored in two separate archives and updated by the optimal solutions on each task. Experience utilization refers to using two archives to generate new initial populations for new patients, in order to improve the optimization efficiency of the algorithm. Besides, a two-step neighbor-based connectivity method is proposed to distinguish different nodes with similar connectivity to further improve the effectiveness of archives. The proposed model and algorithm are evaluated on three kinds of cancer patients' data under two kinds of network models, and results show their effectiveness in identifying effective biomarkers.
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This study presents a comprehensive investigation into the optimization of PID control parameters for marine dual-fuel engines using an improved particle swarm algorithm. Through the development of a Matlab/Simulink simulation model, the thermodynamic behavior of the engine and the functionality of its control system are analyzed. The PID control parameters for air-fuel ratio control and mode switching control systems are fine-tuned utilizing the improved particle swarm algorithm (PSO). Simulation results demonstrate that the proposed improved PID-PSO approach outperforms traditional PID and traditional PSO-PID control methods in terms of reduced overshoot, minimized steady-state error, faster response times, and improved stability across various operating conditions and response modes. In comparison to traditional PID and PSO-PID controllers, the improved PSO-PID controller reduces the response time by 0.47 s and 0.21 s, the maximum overshoot by 98.43% and 96.05%, and decreases the absolute errors by 87.42% and 90.55%, respectively, in air-fuel ratio control using the step response method. The study's findings offer valuable insights into enhancing the performance and efficiency of marine dual-fuel engines through advanced control strategies.
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OBJECTIVE: The primary objective of this study was to develop and validate a Social Cognitive Theory-based instrument to identify psychosocial factors that influence diet and physical activity among Chinese children aged 10-12 years. DESIGN: This is a cross-sectional study, with data collected from questionnaires. SETTING: Two elementary schools in Beijing, China. PARTICIPANTS: Fourth to sixth-grade students (N = 1,486) aged 10-12 years were recruited. VARIABLES MEASURED: Gender, height, weight, nation, and grade were collected. Energy-balanced eating behaviors and their related sociopsychological factors were surveyed. ANALYSIS: Confirmatory factor analysis, Pearson correlations, Cronbach α index, and mediation analysis were used. RESULTS: (1) Confirmatory factor analysis revealed a 6-factor solution (51 items) and all factor loadings > 0.32, indicating that the model fitness was acceptable. (2) All correlation coefficients are statistically significant. All of the Cronbach α indexes were > 0.65, indicating acceptable reliability. (3) The mediating effect of goal intention and outcome expectations between self-efficacy and habit strength was statistically significant (P < 0.01), verifying the theory structure. CONCLUSIONS AND IMPLICATIONS: This questionnaire exhibits good internal consistency, reliability, and structural validity. It can be effectively employed to investigate energy-balanced eating behaviors related to the Social Cognitive Theory in Chinese children.
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Ejercicio Físico , Conducta Alimentaria , Humanos , Niño , Masculino , Femenino , Estudios Transversales , Encuestas y Cuestionarios , Ejercicio Físico/psicología , Reproducibilidad de los Resultados , Conducta Alimentaria/psicología , China , Estudiantes/estadística & datos numéricos , Estudiantes/psicología , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.
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Disostosis Mandibulofacial , Infecciones del Sistema Respiratorio , Femenino , Humanos , China , Pérdida Auditiva Conductiva , Disostosis Mandibulofacial/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Estudios RetrospectivosRESUMEN
Previous studies have shown that nuclear binding protein 2 (NUCB2) is expressed in the human placenta and increases with an increase in the syncytialization of trophoblast cells. This study aimed to investigate the role of NUCB2 in the differentiation and fusion of trophectoderm cells. In this study, the expression levels of NUCB2 and E-cadherin in the placentas of rats at different gestation stages were investigated. The results showed that there was an opposite trend between the expression of placental NUCB2 and E-cadherin in rat placentas in different trimesters. When primary human trophoblast (PHT) and BeWo cells were treated with high concentrations of Nesfatin-1, the trophoblast cell syncytialization was significantly inhibited. The effects of NUCB2 knockdown in BeWo cells and Forskolin-induced syncytialization were investigated. These cells showed a significantly decreased cell fusion rate. The mechanism underlying NUCB2-regulated trophoblast cell syncytialization was explored using RNA-Seq and the results indicated that the epidermal growth factor receptor (EGFR)-phospholipase C gamma 1 (PLCG1)-calmodulin-dependent protein kinase IV (CAMK4) pathway might be involved. The results suggested that the placental expression of NUCB2 plays an important role in the fusion of trophoblasts during differentiation via the EGFR-PLCG1-CAMK4 pathway.
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Nucleobindinas , Placenta , Placentación , Trofoblastos , Animales , Femenino , Embarazo , Ratas , Cadherinas/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Proteínas Portadoras/metabolismo , Fusión Celular , Receptores ErbB/metabolismo , Proteínas Nucleares/metabolismo , Fosfolipasa C gamma/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Nucleobindinas/metabolismoRESUMEN
BACKGROUND: The effectiveness of selenium (Se) supplementation on glycemic control is disparate. OBJECTIVE: This study aims to evaluate the effects of different dosages of Se diets on the blood glucose in type 2 diabetes mellitus (T2DM, db/db) and normal (db/m) mice. METHODS: The db/db and db/m mice were fed with different dosages of Se supplemented diets (0, 0.1, 0.3, 0.9, 2.7 mg/kg) for 12 weeks, respectively. Se concentrations of tissues, physical and biochemical characteristics, oxidative stress indexes and gene expression related to glucose, lipid metabolism and Se transporters of liver were detected. RESULTS: The Se concentrations in tissues were related to the dosages of Se supplementation in db/db (blood: slope=11.69, r = 0.924; skeletal muscle: slope=0.36, r = 0.505; liver: slope=22.12, r = 0.828; kidney: slope=11.81, r = 0.736) and db/m mice (blood: slope=19.89, r = 0.876; skeletal muscle: slope=2.80, r = 0.883; liver: slope=44.75, r = 0.717; kidney: slope=60.15, r = 0.960). Compared with Se2.7 group, the fasting blood glucose (FBG) levels of Se0.1 and Se0.3 group were decreased at week3 in db/db mice. Compared with control (Se0) group, the FBG levels of Se2.7 group were increased from week6 to week12 in db/m mice. The oral glucose tolerance test (OGTT) showed that the area under the curve (AUC) of Se0.3 group was lower than that of Se0.9 and Se2.7 group in db/m mice. Furthermore, compared with control group, the malondialdehyde (MDA) level in skeletal muscle of Se0.1 group was decreased, while that of Se2.7 group was increased in db/db mice; the glutathione peroxidase (GPx) activity in skeletal muscle of Se0.3, Se0.9 and Se2.7 group was increased both in db/db and db/m mice. For db/db mice, glucose-6-phosphatase catalytic (G6pc) expression of other groups were lower and fatty acid synthase (Fasn) expression of Se0.9 group were lower compared with Se0.3 group. For db/m mice, compared with Se0.3 group, (peroxisome proliferative activated receptor gamma coactivator 1 alpha) Pgc-1α expression of control and Se0.9 group were higher; (phosphoenolpyruvate carboxykinase 1) Pck1 expression of Se0.1, Se0.9, and Se2.7 group were higher. CONCLUSION: Low dosages (0.1 and 0.3 mg/kg) of Se supplementation exerted beneficial effects on FBG levels and glucose tolerance through regulating hepatic glycolysis and gluconeogenesis and inhibit the oxidative stress while high dosages of Se (0.9 and 2.7 mg/kg) supplementation enhanced FBG levels, impaired glucose tolerance and aggravate oxidative stress.
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Diabetes Mellitus Tipo 2 , Selenio , Ratones , Animales , Glucemia/metabolismo , Antioxidantes/metabolismo , Estrés Oxidativo , Ratones Endogámicos , Suplementos Dietéticos , Hígado/metabolismo , Ratones Endogámicos C57BL , Glucosa/metabolismoRESUMEN
Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph+ B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph+ B-ALL patients. IL-17A promotes the progression of Ph+ B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph+ B-ALL cells, resulting in robust cell proliferation and survival. In addition, IL-17A-activated Ph+ B-ALL cells secrete the chemokine CXCL16, which in turn promotes Th17 differentiation, attracts Th17 cells and forms a positive feedback loop supporting leukemia progression. These data demonstrate an involvement of Th17 cells in Ph+ B-ALL progression and suggest potential therapeutic options for Ph+ B-ALL with Th17-enriched niches.
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Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Interleucina-17/genética , Resistencia a Antineoplásicos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Enfermedad AgudaRESUMEN
Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.
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Hidroxicolesteroles , Hipercolesterolemia , Placenta , Embarazo , Femenino , Humanos , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Trofoblastos , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Oat ß-glucan (OG) has been shown to improve intestinal microecology in gestational diabetes mellitus (GDM), but the effect on fetal intestine health is unknown. Herein, we aimed to investigate the effects of OG supplementation during gestation in GDM dams on fetal intestinal immune development. OG was supplemented one week before mating until the end of the experiment. GDM rats were made with a high-fat diet (HFD) with a minimal streptozotocin (STZ) dose. The fetal intestines were sampled at gestation day (GD) 19.5, and the intestinal morphology, chemical barrier molecules, intraepithelial immune cell makers, and levels of inflammatory cytokines were investigated. The results showed that OG supplementation alleviated the decrease of the depth of fetal intestinal villi and crypts, the number of goblet cells (GCs), protein expression of mucin-1 (Muc1) and Muc2, the mRNA levels of Gpr41, Gpr43, and T cell markers, and increased the number of paneth cells (PCs), the mRNA levels of defensin-6 (defa6), and macrophage (Mø) marker and the expression of cytokines induced by GDM. In addition, OG supplementation alleviated the function of immune cell self-proliferation, chemotaxis and assembly capabilities, protein, fat, folic acid, and zinc absorption damaged by GDM. As indicated by these findings, OG supplementation before and during pregnancy improved the fetal intestinal chemical barriers, immune cells, cytokines, and the metabolism of nutrients to protect the fetal intestinal immunity.
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Diabetes Gestacional , Femenino , Embarazo , Humanos , Animales , Ratas , Intestinos , Citocinas , Suplementos DietéticosRESUMEN
Oxygen evolution reaction (OER) is a limiting reaction for highly efficient water electrolysis. Thus, the development of cost-effective and highly efficient OER catalysts is the key to large-scale water electrolysis for hydrogen production. Herein, by using an interfacial engineering strategy, a unique nanoflower-like Fe1-xNix(PO3)2/Ni2P/NF heterostructure with abundant heterogeneous interfaces is successfully fabricated. The catalyst exhibits excellent OER catalytic activity in alkaline fresh water and alkaline natural seawater at high current densities, which only, respectively, requires overpotentials of 318 and 367 mV to drive 1000 mA cm-2 in fresh water and natural seawater both containing 1 M KOH. Furthermore, Fe1-xNix(PO3)2/Ni2P/NF demonstrates excellent durability, which can basically remain stable for 80 h during the electrocatalytic OER processes, respectively, in alkaline fresh water and natural seawater. This work provides a new construction strategy for designing highly efficient electrocatalysts for OER at high current densities both in alkaline fresh water and in natural seawater.
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Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.
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The impact of global greenhouse gas emissions is increasingly serious, and the development of green low-carbon circular economy has become an inevitable trend for the development of all countries in the world. To achieve emission peak and carbon neutrality is the primary goal of energy conservation and emission reduction. As the core province in central China, Hubei Province is under prominent pressure of carbon emission reduction. In this paper, the future development trend of carbon emissions is analyzed, and the emission peak value and carbon peak time in Hubei Province is predicted. Firstly, the generalized Divisia index method (GDIM) model is proposed to determine the main influencing factors of carbon emissions in Hubei Province. Secondly, based on the main influencing factors identified, a novel STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) extended model with ridge regression is established to predict carbon emissions. Thirdly, the scenario analysis method is used to set the variables of the STIRPAT extended model and to predict the emission peak value and carbon peak time in Hubei Province. The results show that Hubei Province's carbon emissions peaked first in 2025, with a peak value of 361.81 million tons. Finally, according to the prediction results, the corresponding suggestions on carbon emission reduction are provided in three aspects of industrial structure, energy structure, and urbanization, so as to help government establish a green, low-carbon, and circular development economic system and achieve the industry's cleaner production and sustainable development of society.
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Desarrollo Económico , Gases de Efecto Invernadero , Carbono/análisis , Dióxido de Carbono/análisis , Industrias , Gases de Efecto Invernadero/análisis , ChinaRESUMEN
Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.
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Alcaloides , Berberina , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Ratas , Animales , Xenobióticos , Alcaloides/química , Medicamentos Herbarios Chinos/químicaRESUMEN
Extensive phytochemical investigation on the methanol extract of the inflorescences, twigs, and leaves of Brucea javanica led to the isolation and identification of 27 triterpenoids, including 21 previously undescribed ones, named brujavanoids A-U (1-21). Their structures were determined based on comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Of these compounds, brujavanoid A (1) represents the first apotirucallane-type triterpenoid with a novel 19(10 â 9)abeo motif, and brujavanoids B and C (2-3) are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment. All the isolates were evaluated for their anti-inflammatory effect in an LPS-activated RAW264.7 cells model. Furthermore, the most active one, brujavanoid E (5), can suppress the transcriptional expression of typical pro-inflammatory mediators and inhibit the nuclear translocation of NF-κB p65 in the LPS- activated RAW264.7 cells.
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Brucea , Triterpenos , Antiinflamatorios/farmacología , Brucea/química , Brucea javanica , Lipopolisacáridos/farmacología , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
Finding personalized biomarkers for disease prediction of patients with cancer remains a massive challenge in precision medicine. Most methods focus on one subnetwork or module as a network biomarker; however, this ignores the early warning capabilities of other modules with different configurations of biomarkers (i.e. multi-modal personalized biomarkers). Identifying such modules would not only predict disease but also provide effective therapeutic drug target information for individual patients. To solve this problem, we developed a novel model (denoted multi-modal personalized dynamic network biomarkers (MMPDNB)) based on a multi-modal optimization mechanism and personalized dynamic network biomarker (PDNB) theory, which can provide multiple modules of personalized biomarkers and unveil their multi-modal properties. Using the genomics data of patients with breast or lung cancer from The Cancer Genome Atlas database, we validated the effectiveness of the MMPDNB model. The experimental results showed that compared with other advanced methods, MMPDNB can more effectively predict the critical state with the highest early warning signal score during cancer development. Furthermore, MMPDNB more significantly identified PDNBs containing driver and biomarker genes specific to cancer tissues. More importantly, we validated the biological significance of multi-modal PDNBs, which could provide effective drug targets of individual patients as well as markers for predicting early warning signals of the critical disease state. In conclusion, multi-modal optimization is an effective method to identify PDNBs and offers a new perspective for understanding tumor heterogeneity in cancer precision medicine.
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Genómica , Neoplasias Pulmonares , Biomarcadores , Genómica/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Medicina de Precisión/métodosRESUMEN
In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.
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Placenta , Preeclampsia , Animales , Femenino , Flavonas , Humanos , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Isquemia/tratamiento farmacológico , Isquemia/metabolismo , Placenta/metabolismo , Preeclampsia/prevención & control , Embarazo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Due to rapid development of high-throughput sequencing and biotechnology, it has brought new opportunities and challenges in developing efficient computational methods for exploring personalized genomics data of cancer patients. Because of the high-dimension and small sample size characteristics of these personalized genomics data, it is difficult for excavating effective information by using traditional statistical methods. In the past few years, network control methods have been proposed to solve networked system with high-dimension and small sample size. Researchers have made progress in the design and optimization of network control principles. However, there are few studies comprehensively surveying network control methods to analyze the biomolecular network data of individual patients. To address this problem, here we comprehensively surveyed complex network control methods on personalized omics data for understanding tumor heterogeneity in precision medicine of individual patients with cancer.
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CONTEXT: The joint associations of maternal and fetal single nucleotide polymorphisms (SNPs) of lipid metabolic genes with the risk of maternal supraphysiological hypercholesterolemia (MSPH) are unclear. OBJECTIVE: This study aims to investigate the associations of maternal/fetal SNPs of APOE, LPL, LDLR, PCSK9, and SCARB1 with the risk of MSPH and explore whether the maternal-fetal pairing pattern of the risk alleles can affect MSPH risk. METHODS: A nested case-control study was conducted that included 182 pregnant women with MSPH and 182 with maternal physiological hypercholesterolemia. Maternal venous and umbilical venous blood were collected to detect the SNPs of genes. The primary outcome was MSPH. Logistic regression model was used to determine the associations of SNPs with risk of MSPH. RESULTS: The C-allele in maternal APOE rs429358 Tâ >â C (adjusted odds ratio [OR]â =â 1.72, Pâ =â 0.033), G-allele in fetal APOE rs440446 Câ >â G (adjusted ORâ =â 1.62, Pâ =â 0.012) and T-allele in fetal LPL rs263 Câ >â T (adjusted ORâ =â 1.53, Pâ =â 0.011) increased the risk of MSPH. The A-allele in maternal LDLR rs7258950 Gâ >â A decreased the risk of MSPH (adjusted ORâ =â 0.67, Pâ =â 0.028). For maternal-fetal pairing analysis, the variant concordance of PCSK9 rs2149041, rs7523141, rs7523242, rs7525649, and LDLR rs7258950 were associated with the decreased risk of MSPH under the dominant model. The variant concordance of other SNPs of PCSK9, APOE, LDLR, LPL, and SCARB1 were associated with the increased risk of MSPH. CONCLUSION: This study supports the hypothesis that maternal and fetal genetic polymorphisms of lipid metabolic genes are associated with the risk of MSPH. The maternal-fetal variant concordance is also associated with this risk.
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Hipercolesterolemia , Apolipoproteínas E/genética , Estudios de Casos y Controles , Femenino , Humanos , Hipercolesterolemia/epidemiología , Hipercolesterolemia/genética , Lípidos , Polimorfismo de Nucleótido Simple , Embarazo , Proproteína Convertasa 9/genéticaRESUMEN
Chemical investigation of bioactive components from the whole plant of Euphorbia helioscopia resulted in the isolation and identification of 17 new jatrophane diterpenoids, namely, heliojatrone D (1) and helioscopids A-P (2-17), along with 11 known analogues (18-28). The structural elucidation of the new diterpenoids was achieved by the comprehensive analysis of HRESIMS, NMR, and X-ray crystallographic data, as well as using electronic circular dichroism. Structurally, heliojatone D (1) is the fourth natural diterpenoid with a rare bicyclo[8.3.0]tridecane skeleton. The inhibitory effect of the isolated diterpenoids against Kv1.3 ion channels was evaluated in a human embryonic kidney 293 cell model transfected with plasmid encoding Kv1.3, resulting in the identification of a series of potent Kv1.3 ion channel inhibitors, with the most active ones (2 and 15) showing IC50 values of 0.9 µM.
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Diterpenos , Euphorbia , Cristalografía por Rayos X , Diterpenos/química , Diterpenos/farmacología , Euphorbia/química , Humanos , Estructura MolecularRESUMEN
The phytochemical investigation of the methanol extract of Ixeris sonchifolia led to the isolation and identification of nine analogs, including one new guaiane-type sesquiterpenoid, named ixerinoid A (1). The structure of 1 was determined by extensive analysis of the 1 D and 2 D nuclear magnetic resonance spectroscopic data, as well as quantum chemical calculations. Additionally, all the isolates were tested for their neuroprotective activity using the oxygen-glucose deprivation/reperfusion-induced SH-SY5Y cell injury model. Compounds 3, 5, 6, 8, and 9 displayed remarkable protective effects at concentrations of 1, 5, and 10 µM, respectively.