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The interactome networks at the DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We have developed a diffusion-based method, Hi-C to geometry (CTG), to obtain reliable geometric information on the chromatin from Hi-C data. CTG produces a consistent and reproducible framework for the 3D genomic structure and provides a reliable and quantitative understanding of the alterations of genomic structures under different cellular conditions. The genomic structure yielded by CTG serves as an architectural blueprint of the dynamic gene regulatory network, based on which cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as transcription correlation, is revealed. We also find that gene fusion events are significantly enriched between genes of short CTG distances and are thus close in 3D space. These findings indicate that 3D chromatin structure is at least partially correlated with downstream processes such as transcription, gene regulation, and even regulatory networking through affecting protein-protein interactions.
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Cromatina , Redes Reguladoras de Genes , Cromatina/genética , Regulación de la Expresión Génica , Cromosomas , ADNRESUMEN
Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics. Using network embedding in the Poincaré disk, the hierarchy depths of chromatin from CRC and T-ALL patients were found to be significantly shallower compared to their normal controls. A reverse trend of change in chromatin structure was observed during early embryo development. We found tissue-specific conservation of hierarchy order in chromatin contact networks. Our findings reveal the top-down hierarchy of chromatin organization, which is significantly attenuated in cancer.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Genoma , Cromatina , Diferenciación CelularRESUMEN
Solar-blind ultraviolet (SBUV) to near-infrared (NIR) broadband photodetectors (BB-PD) have important applications in environmental monitoring and other applications. However, it is challenging to prepare SBUV-IR photosensitive materials via simple steps and to construct SBUV-IR broadband devices for multiplex detection with high sensitivity at different wavelengths. Here, self-powered and broadband photodetectors using a high-performance mixed dimensional Sb2O3 nanorod 1-dimension (1D)/monodisperse microdiamond-like PdTe2 3-dimension (3D)/Si (3D) heterojunction for multiplex detection of environmental pollutants with high sensitivity at broadband wavelength are developed. The 1D/3D mixed dimensional Sb2O3/PdTe2/Si structure combines the advantages of strong light absorption, high carrier transport efficiency of 1D Sb2O3 nanorods, and expansion of interface barrier caused by 3D microdiamond-like PdTe2 interlayer to improve the photocurrent density and self-powered ability. The efficient photogenerated charge separation enables anon/off ratio of more than 5 × 106. The device exhibits excellent photoelectric properties from 255 to 980 nm with the responsivity from 4.56 × 10-2 to 6.55 × 10-1 AW-1, the detectivity from 2.36 × 1012 to 3.39 × 1013 Jones, and the sensitivity from 3.90 × 107 to 1.10 × 1010 cm2 W-1 without external bias. Finally, the proposed device is applied for the multiplex monitoring of environmental pollution gases NO2 with the detection limit of 200 ppb and PM2.5 particles at mild pollution at broadband wavelength. The proposed BB-PD has great potential for multiplex detection of environmental pollutants and other analytes at broadband wavelength.
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Chiral manganese(I) complexes that contain carbocyclic-fused 8-amino-5,6,7,8-tetrahydroquinolinyl groups that are appended with distinct para-R substituents have proven to be effective catalysts in the asymmetric transfer hydrogenation (ATH) of a wide range of ketones (48 examples). Notably, Mn2 proved to be the most productive catalyst, allowing an outstanding turnover number of 8300 with catalyst loadings as low as 0.01 mol %. Furthermore, this catalytic protocol shows considerable promise for applications in the synthesis of chiral drugs such as Lusutrombopag.
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The current study focused on analyzing the effect of different types of bulking agents and other factors on fed-batch composting and the structure of microbial communities. The results indicated that the introduction of bulking agents to fed-batch composting significantly improved composting efficiency as well as compost product quality. In particular, using green waste as a bulking agent, the compost products would achieve good performance in the following indicators: moisture (3.16%), weight loss rate (85.26%), and C/N ratio (13.98). The significant difference in moisture of compost products (p < 0.05) was observed in different sizes of bulking agent (green waste), which was because the voids in green waste significantly affected the capacity of the water to permeate. Meanwhile, controlling the size of green waste at 3-6 mm, the following indicators would show great performance from the compost products: moisture (3.12%), organic matter content (63.93%), and electrical conductivity (EC) (5.37 mS/cm). According to 16S rRNA sequencing, the relative abundance (RA) of thermophilic microbes increased as reactor temperature rose in fed-batch composting, among which Firmicutes, Proteobacteria, Basidiomycota, and Rasamsonia were involved in cellulose and lignocellulose degradation.
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Compostaje , Compostaje/métodos , Microbiología del Suelo , ARN Ribosómico 16S/análisis , Microbiota , Bacterias/clasificación , Bacterias/genética , Suelo/químicaRESUMEN
The COVID-19 lockdown has forced young children to spend more time on media and significantly impacted their mothers' mental health. This study explored how mothers' individual distress influences children's problematic media use during the Shanghai citywide lockdown caused by COVID-19. Data were collected from 1889 Chinese mothers (Mage = 34.69 years, SD = 3.94 years) with preschoolers aged 3-6 years (Mage = 4.38 years, SD = 1.06 years; 49.0% boys) via an online survey. The statistical analyses relied on SPSS Statistics version 26.0 and macro-program PROCESS 3.3. to investigate the associations and mediation analysis among all the study variables. The results indicated a positive association between maternal distress and children's problematic media use, mediated by parenting stress and maladaptive parenting. Specifically, the serial mediation analysis revealed that high levels of maternal distress exacerbate parenting stress, which in turn leads to maladaptive parenting practices. These maladaptive practices subsequently increase problematic media use in preschool children. The findings highlighted that parents need to enhance their ability to manage risk and promote mental health during periods of significant stress and routine disruption to reduce children's problematic media use.
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COVID-19 , Madres , Responsabilidad Parental , Estrés Psicológico , Humanos , Preescolar , Femenino , China/epidemiología , Responsabilidad Parental/psicología , Masculino , COVID-19/epidemiología , COVID-19/psicología , Adulto , Madres/psicología , Madres/estadística & datos numéricos , Niño , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Distrés PsicológicoRESUMEN
Tobacco etch virus protease (TEVp) is wildly exploited for various biotechnological applications. These applications take advantage of TEVp's ability to cleave specific substrate sequences to study protein function and interactions. A major limitation of this enzyme is its relatively slow catalytic rate. In this study, MD simulations were conducted on TEV enzymes and known highly active mutants (eTEV and uTEV3) to explore the relationship between mutation, conformation, and catalytic function. The results suggest that mutations distant from the active site can influence the substrate-binding pocket through interaction networks. MD analysis of eTEV demonstrates that, by stabilizing the orientation of the substrate at the catalytic site, mutations that appropriately enlarge the substrate-binding pocket will be beneficial for Kcat, enhancing the catalytic efficiency of the enzyme. On the contrary, mutations in uTEV3 reduced the flexibility of the active pocket and increased the hydrogen bonding between the substrate and enzyme, resulting in higher affinity. At the same time, the MD simulation demonstrates that mutations outside of the active site residues could affect the dynamic movement of the binding pocket by altering residue networks and communication pathways, thereby having a profound impact on reactivity. These findings not only provide a molecular mechanistic explanation for the excellent mutants, but also serve as a guiding framework for rational computational design.
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Endopeptidasas , Simulación de Dinámica Molecular , Endopeptidasas/metabolismo , Biotecnología , MutaciónRESUMEN
AIM: To investigate the effectiveness of de-escalation of ticagrelor (from ticagrelor 90 mg to clopidogrel 75 mg or ticagrelor 60 mg) on the prognosis of patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) after 3 months of oral dual antiplatelet therapy (DAPT). METHODS: From March 2017 to August 2021, 1056 patients with STEMI in a single centre, through retrospective investigation and analysis, were divided into intensive (ticagrelor 90 mg), standard (clopidogrel 75 mg after PCI) and de-escalation groups (clopidogrel 75 mg or ticagrelor 60 mg after 3 months of treatment with 90 mg ticagrelor) based on the type and dose of P2Y12 inhibitor 3 months after PCI, and the patients had a ≥ 12-month history of oral DAPT. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during the 12-month follow-up period, including composite end points of cardiac death, myocardial infarction, ischaemia-driven revascularization and stroke. The major safety endpoint was bleeding events. RESULTS: The results showed that during the follow-up period, there was no statistically significant difference in the incidence of MACCEs between the intensive and de-escalation groups (P > 0.05). The incidence of MACCEs in the standard treatment group was higher than that in the intensive treatment group (P = 0.014), but the incidence of bleeding events in the de-escalation group was significantly lower than that in the standard group (9.3% vs. 18.4%, χ²=7.191, P = 0.027). The Cox regression analysis showed that increases in haemoglobin (HGB) (HR = 0.986) and estimated glomerular filtration rate (eGFR) (HR = 0.983) could reduce the incidence of MACCEs, while old myocardial infarction (OMI) (P = 0.023) and hypertension (P = 0.013) were independent predictors of MACCEs. CONCLUSION: For STEMI patients undergoing PCI, the de-escalation scheme of ticagrelor to clopidogrel 75 mg or ticagrelor 60 mg at 3 months after PCI was related to the reduction of bleeding events, especially minor bleeding events, without an increase in ischaemic events.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Clopidogrel/efectos adversos , Ticagrelor/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Infarto del Miocardio/terapia , Infarto del Miocardio/tratamiento farmacológico , Hemorragia/epidemiología , Pronóstico , Resultado del TratamientoRESUMEN
Due to the openness of communication network and the complexity of system structures, multi-agent systems are vulnerable to malicious network attacks, which can cause intense instability to these systems. This article provides a survey of state-of-the-art results of network attacks on multi-agent systems. Recent advances on three types of attacks, i.e., those on DoS attacks, spoofing attacks and Byzantine attacks, the three main network attacks, are reviewed. Their attack mechanisms are introduced, and the attack model and the resilient consensus control structure are discussed, respectively, in detail, in terms of the theoretical innovation, the critical limitations and the change of the application. Moreover, some of the existing results along this line are given in a tutorial-like fashion. In the end, some challenges and open issues are indicated to guide future development directions of the resilient consensus of multi-agent system under network attacks.
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Road scene understanding is crucial to the safe driving of autonomous vehicles. Comprehensive road scene understanding requires a visual perception system to deal with a large number of tasks at the same time, which needs a perception model with a small size, fast speed, and high accuracy. As multi-task learning has evident advantages in performance and computational resources, in this paper, a multi-task model YOLO-Object, Drivable Area, and Lane Line Detection (YOLO-ODL) based on hard parameter sharing is proposed to realize joint and efficient detection of traffic objects, drivable areas, and lane lines. In order to balance tasks of YOLO-ODL, a weight balancing strategy is introduced so that the weight parameters of the model can be automatically adjusted during training, and a Mosaic migration optimization scheme is adopted to improve the evaluation indicators of the model. Our YOLO-ODL model performs well on the challenging BDD100K dataset, achieving the state of the art in terms of accuracy and computational efficiency.
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Vehículos Autónomos , Aprendizaje , Registros , Programas InformáticosRESUMEN
The use of magnetic biosorbents for the remediation of heavy metals has attracted increasing attention due to their ease of separation and reusability. We developed a method for preparing superparamagnetic biosorbent materials using water-based magnetic fluids. Water-based magnetic fluid-spores (WMFSs) were obtained by combining water-based magnetic fluid (WMF) with Aspergillus niger spores at ratios of 0.6:1 (WMFS1), 0.8:1 (WMFS2), 1:1 (WMFS3), 1.2:1 (WMFS4), and 1.4:1 (WMFS5). A magnetic composite material was prepared from magnetic nanoparticles and spores in a ratio of 1:1 as a control. The adsorption efficiency and separation effect of WMFS3 were significantly better than those of the magnetic composite material. The morphology and structure of WMFS3 were characterized by performing transmission electron microscopy. The results showed that Fe3O4 magnetic particles were uniformly coated on the spore surface. The superparamagnetism of WMFS3 was tested using a vibrating sample magnetometer. At pH 2.0, the maximum adsorption capacity of WMFS3 for Cr(VI) was 105 mg/g; in the pH range of 2.0-3.0, the adsorption equilibrium time of WMFS3 was 60 min. Thus, the adsorption process conformed to the pseudo-second-order kinetic model and Freundlich isotherm. Thermodynamic studies showed that the process was spontaneous and endothermic. The adsorption mechanisms of WMF3 for Cr(VI) included electrostatic, reduction, and complexation adsorption. This biosorbent material showed excellent adsorption performance for Cr(VI) and is promising for wastewater resource applications.
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Contaminantes Químicos del Agua , Agua , Adsorción , Aspergillus niger , Cromo/análisis , Concentración de Iones de Hidrógeno , Cinética , Fenómenos Magnéticos , Esporas Fúngicas/química , Contaminantes Químicos del Agua/análisisRESUMEN
COVID-19 threatens human life because of the super destructiveness produced from its coronal morphology and strong transmembrane infection based on spike glycoprotein. Inspired by the coronal morphology of COVID-19 and its means of infecting, we designed an "artificial virus" with coronal morphology based on the concept of "defeating superbacteria with superviruses" by self-assembling a transacting activator of transduction peptide with triple-shell porous graphitic carbon nitride (g-C3N4) embedded with cobalt nanoparticles to forcefully infect methicillin-resistant Staphylococcus aureus (MRSA). The results confirmed that this "artificial virus" had unique properties of crossing the bacterial cell membrane barrier, heating the internal bacterial microenvironment and triggering ROS outbreak, based on its coronal morphology, membrane penetration, temperature-rising and heat insulation, oxidase-like activity and excellent visible-light harvesting properties. It had a high sterilization efficiency of 99.99% at 20 min, which was 18.6 times that of g-C3N4, and the efficiency remained at 99.99% after 3 rounds of recycling and reuse. Additionally, it can rapidly inactivate bacteria in river water and accelerate wound healing.
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Streptococcus pneumoniae coinfection is a major cause of mortality in influenza pandemics. Growing evidence shows that uncontrolled immune response results in severe tissue damage and thereby promotes death in coinfection. Progranulin (PGRN) is widely expressed in immune and epithelial cells and exerts anti-inflammatory role in many diseases. We found that PGRN levels were significantly elevated in clinical influenza/S. pneumoniae-coinfected patients. C57BL/6 wild-type (WT) and PGRN-deficient (PGRN-/-) mice were infected with influenza virus PR8 and then superchallenged with S. pneumoniae serotype 19F. Coinfected PGRN-/- mice showed increased mortality and weight loss compared with WT mice. PGRN deficiency led to increased bacterial loads in lungs without altering influenza virus replication, suggesting a role of PGRN in decreasing postinfluenza susceptibility to S. pneumoniae coinfection. Administration of recombinant PGRN improved survival of WT and PGRN-/- mice in lethal coinfection. Additionally, loss of PGRN resulted in aggravated lung damage along with massive proinflammatory cytokine production and immune cell infiltration during coinfection. Endoplasmic reticulum stress (ERS) during influenza, and coinfection was strongly induced in PGRN-/- mice that subsequently activated apoptosis signaling pathways. Treatment of recombinant PGRN or inhibition of ERS by 4-phenylbutyrate decreased apoptosis and bacterial loads in lungs of coinfected mice. These results suggest that PGRN decreases postinfluenza susceptibility to S. pneumoniae coinfection via suppressing ERS-mediated apoptosis. Impaired bacterial clearance and increased lung inflammation are associated with the lethal outcome of coinfected PGRN-/- mice. Our study provides therapeutic implication of PGRN to reduce morbidity and mortality in influenza/S. pneumoniae coinfection.
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Antiinflamatorios no Esteroideos/farmacología , Coinfección/prevención & control , Infecciones por Orthomyxoviridae/complicaciones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones Neumocócicas/complicaciones , Infecciones Neumocócicas/prevención & control , Progranulinas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Animales , Coinfección/mortalidad , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/inmunología , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/inmunologíaRESUMEN
BACKGROUND: The effect of ambient temperature on allergic rhinitis (AR) remains unclear. Accordingly, this study aimed to explore the relationship between ambient temperature and the risk of AR outpatients in Xinxiang, China. METHOD: Daily data of outpatients for AR, meteorological conditions, and ambient air pollution in Xinxiang, China were collected from 2015 to 2018. The lag-exposure-response relationship between daily mean temperature and the number of hospital outpatient visits for AR was analyzed by distributed lag non-linear model (DLNM). Humidity, long-time trends, day of the week, public holidays, and air pollutants including sulfur dioxide (SO2), and nitrogen dioxide (NO2) were controlled as covariates simultaneously. RESULTS: A total of 14,965 AR outpatient records were collected. The relationship between ambient temperature and AR outpatients was generally M-shaped. There was a higher risk of AR outpatient when the temperature was 1.6-9.3 °C, at a lag of 0-7 days. Additionally, the positive association became significant when the temperature rose to 23.5-28.5 °C, at lag 0-3 days. The effects were strongest at the 25th (7 °C) percentile, at lag of 0-7 days (RR: 1.32, 95% confidence intervals (CI): 1.05-1.67), and at the 75th (25 °C) percentile at a lag of 0-3 days (RR: 1.15, 95% CI: 1.02-1.29), respectively. Furthermore, men were more sensitive to temperature changes than women, and the younger groups appeared to be more influenced. CONCLUSIONS: Both mild cold and mild hot temperatures may significantly increase the risk of AR outpatients in Xinxiang, China. These findings could have important public health implications for the occurrence and prevention of AR.
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Contaminantes Atmosféricos , Contaminación del Aire , Rinitis Alérgica , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China/epidemiología , Femenino , Hospitales , Humanos , Masculino , Pacientes Ambulatorios , Material Particulado/análisis , Rinitis Alérgica/epidemiología , TemperaturaRESUMEN
The diagnosis of renal cell carcinoma (RCC) is often made late since there is no early symptom, which thus results in dismal patient prognosis. As a result, new biomarkers are urgently needed and efforts should be made to identify their functions in predicting RCC prognosis. microRNAs (miRNAs) are a class of small noncoding RNAs that are about 20-22 nucleotides in length, and they have been demonstrated to function as prognostic markers in numerous tumors. This study aimed to assess the role of miR-30b-5p in predicting the prognosis of RCC postoperatively. In this study, RNA was extracted from 284 formalin-fixed and paraffin-embedded kidney cancer tissue samples. After cDNA synthesis, real-time quantitative PCR (RT-qPCR) was adopted for detecting the relative miR-30b-5p level. Then, the Kaplan-Meier method, Cox regression analysis, and the receiver operating characteristic curve analysis were applied in analyzing the miR-30b-5p effect on the prognosis for patients. Our findings indicated that, following adjustment for age, gender, tumor stage, and tumor size, patients with low miR-30b-5p expression had remarkably longer overall survival. Thus, the miR-30b-5p level might be related to RCC prognosis.
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Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , MicroARNs/genética , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Regulación hacia ArribaRESUMEN
Arctigenin (ARG), a natural lignans compound isolated from Arctium lappa L. In this study, the anti-tumor effect of ARG on prostate cancer cell PC-3M and the mechanism of apoptosis and autophagy induced by phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were discussed, and further confirmed by the joint treatment of ARG and PI3K inhibitor LY294002. Here, the effect of ARG on cell viability was evaluated in PC-3M cells by Cell Counting Kit-8 reagent (CCK-8) assay. After the treatment of ARG, colony formation assay was used to detect the anti-proliferation effect. Annexin V-fluoresceine isothiocyanate/propidium iodide (FITC/PI) kit and 4',6-diamidino-2-phenylindole (DAPI) staining were used to detect the apoptosis level, and cell cycle changes were analyzed by flow cytometry. The expression of autophagy was detected by acridine orange staining. In addition, the expression levels of apoptosis and autophagy-related proteins were analyzed by Western blot. The result showed that different concentrations of ARG inhibited the proliferation of PC-3M cells. DAPI staining and flow cytometry showed that ARG induced PC-3M cell apoptosis and arrested cell in G0/G1 phase. Acridine orange staining showed that ARG induced autophagy in PC-3M cells. Western blot experiments showed that ARG inhibited the expression of Bcl-2, promoted the expression of Bax and cleaved caspase-3. At the same time, the expression of autophagy-related proteins LC3B-II and Beclin-1 increased after ARG treatment, but P62 decreased. In addition, further studies have shown that treatment with LY294002 enhanced the effects of ARG on the expression of proteins associated with apoptosis and autophagy, indicating that ARG may induce apoptosis and autophagy through PI3K/Akt/mTOR pathway.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Furanos/farmacología , Lignanos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Arctium/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Furanos/química , Furanos/aislamiento & purificación , Humanos , Lignanos/química , Lignanos/aislamiento & purificación , Conformación Molecular , Fosfatidilinositol 3-Quinasa/metabolismo , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/aislamiento & purificación , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Células Tumorales CultivadasRESUMEN
Proteolysis targeting chimeras (PROTACs) are hetero-bifunctional molecules that could simultaneously bind to the target protein and the E3 ubiquitin ligase, thereby leading to selective degradation of the target protein. Polo-like kinase 1 (PLK1) and bromodomain 4 (BRD4) are both attractive therapeutic targets in acute myeloid leukemia (AML). Here, we developed a small-molecule BRD4 and PLK1 degrader HBL-4 based on PROTAC technology, which leads to fast, efficient, and prolonged degradation of BRD4 and PLK1 in MV4-11â¯cells tested in vitro and vivo, and potent anti-proliferation and BRD4 and PLK1 degradation ability in human acute leukemia MOLM-13 and KG1 cells. Meanwhile, HBL-4 more effectively suppresses c-Myc levels than inhibitor BI2536, resulting in more effective inducing apoptosis activity in MV4-11â¯cells. At the same time, HBL-4 induced dramatically improved efficacy in the MV4-11 tumor xenograft model as compared with BI2536. This study is, to our knowledge, the first reports about dual PLK1 and BRD4 degraders, which potentially represents an important therapeutic advance in the treatment of cancer.
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Antineoplásicos/farmacología , Proteínas de Ciclo Celular/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Factores de Transcripción/metabolismo , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Genes myc , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones SCID , Terapia Molecular Dirigida , Proteolisis/efectos de los fármacos , Pteridinas/química , Bibliotecas de Moléculas Pequeñas/química , Ensayos Antitumor por Modelo de Xenoinjerto , Quinasa Tipo Polo 1RESUMEN
OBJECTIVE: Previous research has shown that the miR-130 family is closely related to the occurrence and development of bladder cancer. We hope to use the miR-130 family members as new, non-invasive, and easily detectable biomarkers for bladder cancer. METHODS: We analyzed 428 cases in The Cancer Genome Atlas-Bladder Urothelial Carcinoma database and verified that the miR-130 family members were significantly overexpressed in bladder cancer. A total of 74 bladder cancer patients and 90 controls were enrolled. The relative expression of the miR-130 family in serum was detected using quantitative reverse transcription-polymerase chain reaction. The diagnostic efficacy of the miR-130 family members was determined using the receiver operating characteristic method (ROC), and a diagnostic panel was built using logistic regression. The results of the study were further confirmed in an external validation set of 492 samples from the Gene Expression Omnibus database. RESULTS: The expression of the miR-130 family members (except for miR-301b-3p) in the serum of bladder cancer patients was higher than that in the controls. The diagnostic capabilities for bladder cancer were 0.847 (miR-130a-3p), 0.762 (miR-130b-3p), and 0.892 (miR-301a-3p). We established a three-miRNA panel with an area under the ROC curve as high as 0.961, indicating that it is a promising clinical diagnostic biomarker of bladder cancer with high sensitivity and specificity. CONCLUSION: The expression levels of miR-130 family members in serum can effectively distinguish the bladder cancer patients from healthy controls. This finding will facilitate the clinical diagnosis of bladder cancer.
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Biomarcadores de Tumor/sangre , MicroARNs/sangre , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
Many studies have reported that exposure to ambient air pollution has adverse effects on health. However, there are little researches to explore the relationship between ambient air pollution and chronic sinusitis (CS). From January 1 2015 to December 31 2018, a time-series study were carried out to investigate the acute adverse roles of six criteria ambient air pollutants (fine particulate matter [PM2.5], inhalable particulate matter [PM10], nitrogen dioxide [NO2], sulfur dioxide [SO2], ozone [O3], and carbon monoxide [CO]) in hospital outpatients with CS in Xinxiang, China. Then, an over-dispersed Poisson generalized additive model was utilized to analyzed the relationships. In total, 183,943 hospital outpatient cases of CS were identified during the study period. We found that a 10 µg/m3 increase in PM2.5, PM10, SO2, NO2, and CO corresponded to 0.48% (95% confidence interval: 0.22-0.74%), 0.33% (0.16-0.50%), 0.88% (0.13-1.62%), 1.98% (1.31-2.64%), and 0.05% (0.03-0.07%) increments, respectively, in CS outpatients on the current day. The young group (<15 years of age) was more susceptible than the adult or elderly groups. These results suggested that outdoor air pollutants might increase CS outpatient, especially among youth in Xinxiang. Precautions and protective measures should be strengthened to reduce the air pollution level in the future.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/estadística & datos numéricos , Exposición por Inhalación/estadística & datos numéricos , Sinusitis/epidemiología , Adolescente , Adulto , Anciano , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Monóxido de Carbono/análisis , China/epidemiología , Enfermedad Crónica , Femenino , Humanos , Masculino , Dióxido de Nitrógeno/análisis , Pacientes Ambulatorios , Ozono/análisis , Material Particulado/análisis , Sinusitis/inducido químicamente , Dióxido de Azufre/análisis , Adulto JovenRESUMEN
Cardiac hypertrophy is a result of cardiac response to excessive heart burden. The sustention of hypertrophic stress indicates a higher risk of cardiac failure or even sudden death. Despite the increasing research works on cardiac hypertrophy, there remains a considerable space left for further mechanism exploration. Long noncoding RNAs (lncRNAs) are a cluster of transcripts lacking in protein coding potential. Past decades have witnessed the increasing identification of their significant roles in cardiac hypertrophy. Small nucleolar RNA host gene 7 (SNHG7) has been identified as an oncogene in human cancers, but its function in cardiac hypertrophy remains unknown. SDA1 domain containing 1 (SDAD1) is newly discovered to exert procancer function in several cancers, whose role in cardiac hypertrophy remains elusive. Present study sought to investigate the biological function of SNHG7 in cardiac hypertrophy. First, the expressions of SNHG7 and SDAD1 were found to be upregulated in Ang II-induced cardiac hypertrophy model in the neonatal rat cardiomyocytes (NRCMs). Functionally, loss-of-function assays verified that silencing SNHG7 and SDAD1 attenuated the inductive effect of Ang II on cardiac hypertrophy. Mechanistically, we proved that SNHG7 interacted with Hu Antigen R so as to stabilize SDAD1 messenger RNA (mRNA). In conclusion, this study proved that SNHG7 facilitates cardiac hypertrophy via the stabilization of SDAD1 mRNA, indicating SNHG7 as a novel regulator for cardiac hypertrophy.