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JOURNAL/nrgr/04.03/01300535-202501000-00032/figure1/v/2024-05-14T021156Z/r/image-tiff Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies.
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This paper presents a case report of a patient with intestinal obstruction caused by intestinal metastasis of bladder cancer treated with sonodynamic therapy. Sonodynamic therapy is a novel anti-tumor therapy that is safe, effi- cacious, and has minimal side effects. After treatment, the patient's intestinal obstruction was effectively relieved.
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The addition of polar functional groups to porous structures is an effective strategy for increasing the ability of metal-organic frameworks (MOFs) to capture CO2 by enhancing interactions between the dipoles of the polar functional groups and the quadrupoles of CO2. However, the potential of MOFs grafted to polar functional group to activate CO2 has not been investigated in the context of CO2 electrolysis. In this study, we report a mixed-ligand strategy to incorporate various functional groups in the MOFs. We found that substituents with strong polarity led to increased catalytic performance of electrochemical CO2 reduction for these polarized MOFs. Both experimental and theoretical evidence indicates that the presence of polar functional groups induces a charge redistribution in the micropores of MOFs. We have shown that higher electron densities of sp2-carbon atoms in benzimidazolate ligands reduces the energy barrier to generate *COOH, which is simultaneously controlled by the mass transfer of CO2. Our research offers an effective method of disrupting local electron neutrality in the pores of electrocatalysts/supports to activate CO2 under electrochemical conditions.
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We report a systematic molecular design in BF2bdk-based afterglow emitters with photoluminescence quantum yields up to 46.3% and lifetimes around 1 s. Suitable excited-state types, diverse excited state species, relatively small singlet-triplet energy gaps and strong dipole-dipole interactions are critical in determining the afterglow properties.
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The incidence of cervical cancer is increasing. Immunotherapies show better patient outcomes than monotherapies; however, the mainstay treatment for cervical cancer remains surgery and chemotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) acts on multiple tryptophan substrates, exhibiting antitumor, immunomodulatory, and antioxidant activities. Despite the association of elevated IDO1 expression with unfavorable outcomes in various cancers, its precise function in cervical cancer remains ambiguous. Here, we explored the prognostic significance of IDO1 in cervical carcinoma. Gene expression datasets were obtained from The Cancer Genome Atlas. Gene Expression Omnibus datasets were used for differential expression and functional correlation analyses. Using Human Protein Atlas alongside Tumor-Immune System Interaction Database, we assessed the association of IDO1 with survival rates. Given the link between cervical cancer prognosis and immune invasion, CIBERSORT was used to assess the connection between immune cells and IDO1, while the percentage of tumor-penetrating immune cells based on IDO1 expression in cervical cancer patients was analyzed using Tumor-Immune System Interaction Database. Incorporating a clinicopathological characteristic-based risk score model with IDO1 risk score, we devised a nomogram to predict cervical cancer patient survival. The effects of IDO1 in immune regulation and its prognostic significance were validated using data from patients with cervical cancer obtained from The Cancer Imaging Archive database. Compared with that in normal cervical tissues, IDO1 expression was significantly upregulated in cervical cancer tissues and significantly correlated with cervical cancer progression and prognosis. IDO1 expression showed a positive association with monocyte and macrophage abundance, while exhibiting a negative correlation with that of endothelial cells and eosinophils. Cox regression analyses highlighted IDO1 as the core immune gene implicated in cervical cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed an association of IDO1 with the metabolic pathways of tryptophan, phenylalanine, and tyrosine. Univariate and multivariate analyses revealed that elevated IDO1 expression correlates markedly with cervical cancer outcomes, suggesting it as a promising therapeutic target. The Cancer Imaging Archive data analysis revealed that the impact of anti-PD1 and CTLA4 therapy is more pronounced in cervical cancer patients exhibiting elevated IDO1 expression. IDO1 is a potential target for immunotherapy for cervical cancer.
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Indolamina-Pirrol 2,3,-Dioxigenasa , Neoplasias del Cuello Uterino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Femenino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , NomogramasRESUMEN
In order to reduce the content of sulfur and ash in coal, improve the desulfurization and deashing rates, a combined experiment method of microwave magnetic separation-flotation was proposed for raw coal. The desulfurization and deashing rates of three experiment methods, namely, single magnetic separation, microwave magnetic separation, and microwave magnetic separation-flotation, were compared. Taking the microwave magnetic separation-flotation experiment method as the main line, the effects of the microwave irradiation time, microwave power, grinding time, magnetic field intensity, plate seam width, foaming agent dosage, collector dosage, and inhibitor dosage on desulfurization and deashing were discussed, and the mechanism of microwave irradiation on magnetic separation and flotation was revealed. The results show that under the conditions of a microwave irradiation time of 60 s, a microwave power of 80% of the rated power (800 W), a grinding time of 8 min, a plate seam width (the plate seam width of a magnetic separator sorting box) of 1 mm, a magnetic field intensity of 2.32 T, a foaming agent dosage of 90 g/t, a collector dosage of 2125 g/t, and an inhibitor dosage of 1500 g/t, the desulfurization and deashing effect is the best. The desulphurization rate is 76.51%, the sulfur removal rate of pyrite is 96.50%, and the deashing rate is 61.91%. Microwaves have the characteristic of selective heating, and the thermal conductivity of organic matter in coal is greater than that of mineral. Microwave irradiation can improve the reactivity of pyrite in coal, pyrolyze pyrite into high-magnetic pyrite, improve the magnetic properties, and improve the magnetic separation effect. Therefore, microwave irradiation plays a role in promoting magnetic separation. Through microwave irradiation, the positive and negative charges in coal molecules constantly vibrate and create friction under the action of an electric field force, and the thermal action generated by this vibration and friction process affects the structural changes in oxygen-containing functional groups in coal. With the increase in the irradiation time and power, the hydrophilic functional groups of -OH and -COOH decrease and the hydrophilicity decreases. Microwave heating evaporates the water in the pores of coal samples and weakens surface hydration. At the same time, microwave irradiation destroys the structure of coal and impurity minerals, produces cracks at the junction, increases the surface area of coal to a certain extent, enhances the hydrophobicity, and then improves the effect of flotation desulfurization and deashing. Therefore, after the microwave irradiation of raw coal, the magnetic separation effect is enhanced, and the flotation desulfurization effect is also enhanced.
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OBJECTIVE: To explore the genetic basis and pathogenesis for a child with type I Hereditary hemorrhagic telangiectasia (HHTâ ) and Splenic sinus shore cell hemangioma (LCA). METHODS: A child with HHT complicated with LCA diagnosed at the First Affiliated Hospital of Dali University in April 2022 was selected as the study subject. Clinical data of the child and her relatives were collected, and pathogenic variants were screened by whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 16-year-old female, had recurrent epitaxis since childhood, which sometimes necessitated hemostasis treatment. She also had splenectomy due to splenic rupture and was diagnosed with LCA. Her father and grandmother also had a history of recurrent epitaxis. Her father had deceased due to cerebral vascular rupture. The child was found to harbor a c.360+1G>A variant in the ENG gene. The same variant was not found in her asymptomatic mother and brother. CONCLUSION: The c.360+1G>A variant of the ENG gene probably underlay the pathogenesis in this child.
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Hemangioma , Telangiectasia Hemorrágica Hereditaria , Humanos , Femenino , Adolescente , Telangiectasia Hemorrágica Hereditaria/genética , Telangiectasia Hemorrágica Hereditaria/complicaciones , Hemangioma/genética , Linaje , Neoplasias del Bazo/genética , Neoplasias del Bazo/complicaciones , Masculino , Pruebas Genéticas , Secuenciación del ExomaRESUMEN
PURPOSE: To investigate the neuroprotective effects of the SOD2 gene in cerebral ischemia reperfusion injury function and the underlying mechanisms in a mice model of middle cerebral artery ischemia reperfusion. METHODS: SOD2 transgenic mice were engineered using transcription activator-like effector nucleases, and the genotype was identified using PCR after every three generations. Transgenic and C57BL/6J wild type mice were simultaneously subjected to the middle cerebral artery occlusion model. RESULTS: SOD2 expression in the brain, heart, kidney, and skeletal muscle of transgenic mice was significantly higher than that in the wild type. Following ischemia reperfusion, the infarct volume of wild type mice decreased after treatment with fenofibrate compared to the CMC group. Infarction volume in SOD2 transgenic mice after CMC and fenofibrate treatment was significantly reduced. The recovery of cerebral blood flow in wild type mice treated with fenofibrate was significantly enhanced compared with that in the CMC group. CONCLUSIONS: The expression of SOD2 in transgenic mice was significantly higher than that in wild type mice, the neuroprotective role of fenofibrate depends on an increase in SOD2 expression.
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Modelos Animales de Enfermedad , Fenofibrato , Ratones Endogámicos C57BL , Ratones Transgénicos , Daño por Reperfusión , Superóxido Dismutasa , Animales , Daño por Reperfusión/genética , Superóxido Dismutasa/genética , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Isquemia Encefálica/genética , Humanos , Masculino , Ratones , Infarto de la Arteria Cerebral Media/genética , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
Organic room-temperature phosphorescence (RTP) and afterglow materials hold great potential for various applications, but there remain inherent trade-offs between the afterglow efficiency and the lifetime. Here, we propose a dual-mechanism design strategy, leveraging the RTP or thermally activated delayed fluorescence (TADF) mechanism for a high afterglow efficiency and the organic long-persistent luminescence (OLPL) mechanism for a prolonged afterglow duration. The intramolecular charge transfer (ICT)-type difluoroboron ß-diketonate molecules with a large S1 dipole moment are doped as the luminescent component into the organic matrix with a large dipole moment, and a series of TADF-type afterglow materials can be achieved with an afterglow efficiency of up to 88.7% and an afterglow lifetime of 200 ms. To prolong the afterglow duration, an electron donor is introduced as the third component to generate traps and facilitate charge separation. The obtained materials exhibit a dual afterglow mechanism, first exhibiting a TADF/RTP afterglow with an afterglow efficiency of up to 50.9%, followed by an hours-long OLPL afterglow emission with an afterglow efficiency of up to 13.1%. Further investigations reveal that an appropriate heavy-atom effect can facilitate the intersystem crossing process, which can promote the charge separation process and thus improve the OLPL afterglow performance. Additionally, rare-earth upconversion materials are introduced into OLPL materials to enable their near-infrared excitation properties, showcasing their potential applications in bioimaging.
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This study investigates the molecular mechanisms behind ischaemia/reperfusion (I/R) injury in the brain, focusing on neuronal apoptosis. It scrutinizes the role of the Jun proto-oncogene in apoptosis, involvement of SOCS1 in neural precursor cell accumulation in ischaemic regions, and the upregulation of C-EBPß in the hippocampus following I/R. Key to the study is understanding how Jun controls C-EBPß degradation via SOCS1, potentially offering new clinical treatment avenues for I/R. Techniques such as mRNA sequencing, KEGG enrichment analysis and protein-protein interaction (PPI) in mouse models have indicated involvement of Jun (AP-1) in I/R-induced cerebral damage. The study employs middle cerebral artery occlusion in different mouse models and oxygen-glucose deprivation/reoxygenation in cortical neurons to examine the impacts of Jun and SOCS1 manipulation on cerebral I/R injury and neuronal damage. The findings reveal that I/R reduces Jun expression in the brain, but its restoration lessens cerebral I/R injury and neuron death. Jun activates SOCS1 transcriptionally, leading to C-EBPß degradation, thereby diminishing cerebral I/R injury through the SOCS1/C-EBPß pathway. These insights provide a deeper understanding of post-I/R cerebral injury mechanisms and suggest new therapeutic targets for cerebral I/R injury. KEY POINTS: Jun and SOCS1 are poorly expressed, and C-EBPß is highly expressed in ischaemia/reperfusion mouse brain tissues. Jun transcriptionally activates SOCS1. SOCS1 promotes the ubiquitination-dependent C-EBPß protein degradation. Jun blunts oxygen-glucose deprivation/reoxygenation-induced neuron apoptosis and alleviates neuronal injury. This study provides a theoretical basis for the management of post-I/R brain injury.
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Proteína beta Potenciadora de Unión a CCAAT , Ratones Endogámicos C57BL , Daño por Reperfusión , Proteína 1 Supresora de la Señalización de Citocinas , Ubiquitinación , Animales , Masculino , Ratones , Apoptosis , Isquemia Encefálica/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/genética , Neuronas/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Proto-Oncogénicas c-jun/genética , Daño por Reperfusión/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/genéticaRESUMEN
BACKGROUND: Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. METHODS: Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. RESULTS: The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017-5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073-5.396, P = 0.033). CONCLUSIONS: NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS.
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Predisposición Genética a la Enfermedad , Accidente Cerebrovascular Isquémico , NAD(P)H Deshidrogenasa (Quinona) , Polimorfismo de Nucleótido Simple , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , China , Pueblos del Este de Asia/genética , Accidente Cerebrovascular Isquémico/genética , NAD(P)H Deshidrogenasa (Quinona)/genética , Factores de RiesgoRESUMEN
The long-emission-lifetime nature of room-temperature phosphorescence (RTP) materials lays the foundation of their applications in diverse areas. Despite the advantage of mechanical property, processability and solvent dispersity, the emission lifetimes of polymer-based room-temperature phosphorescence materials remain not particularly long because of the labile nature of organic triplet excited states under ambient conditions. Specifically, ambient phosphorescence lifetime (τP) longer than 2â s and even 4â s have rarely been reported in polymer systems. Here, luminescent compounds with small phosphorescence rate on the order of approximately 10-1â s-1 are designed, ethylene-vinyl alcohol copolymer (EVOH) as polymer matrix and antioxidant 1010 to protect organic triplets are employed, and ultralong phosphorescence lifetime up to 4.6â s under ambient conditions by short-term and low-power excitation are achieved. The resultant materials exhibit high afterglow brightness, long afterglow duration, excellent processability into large area thin films, high transparency and thermal stability, which display promising anticounterfeiting and data encryption functions.
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BACKGROUND: Both ischemic stroke (IS) and myocardial infarction (MI) are caused by vascular occlusion that results in ischemia. While there may be similarities in their mechanisms, the potential relationship between these 2 diseases has not been comprehensively analyzed. Therefore, this study explored the commonalities in the pathogenesis of IS and MI. METHODS: Datasets for IS (GSE58294, GSE16561) and MI (GSE60993, GSE61144) were downloaded from the Gene Expression Omnibus database. Transcriptome data from each of the 4 datasets were analyzed using bioinformatics, and the differentially expressed genes (DEGs) shared between IS and MI were identified and subsequently visualized using a Venn diagram. A protein-protein interaction (PPI) network was constructed using the Interacting Gene Retrieval Tool database, and identification of key core genes was performed using CytoHubba. Gene Ontology (GO) term annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the shared DEGs were conducted using prediction and network analysis methods, and the functions of the hub genes were determined using Metascape. RESULTS: The analysis revealed 116 and 1321 DEGs in the IS and MI datasets, respectively. Of the 75 DEGs shared between IS and MI, 56 were upregulated and 19 were downregulated. Furthermore, 15 core genes - S100a12, Hp, Clec4d, Cd163, Mmp9, Ormdl3, Il2rb, Orm1, Irak3, Tlr5, Lrg1, Clec4e, Clec5a, Mcemp1, and Ly96 - were identified. GO enrichment analysis of the DEGs showed that they were mainly involved in the biological functions of neutrophil degranulation, neutrophil activation during immune response, and cytokine secretion. KEGG analysis showed enrichment in pathways pertaining to Salmonella infection, Legionellosis, and inflammatory bowel disease. Finally, the core gene-transcription factor, gene-microRNA, and small-molecule relationships were predicted. CONCLUSION: These core genes may provide a novel theoretical basis for the diagnosis and treatment of IS and MI.
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Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Mapas de Interacción de Proteínas , Humanos , Infarto del Miocardio/genética , Accidente Cerebrovascular Isquémico/genética , Mapas de Interacción de Proteínas/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Redes Reguladoras de Genes , Transcriptoma/genética , Ontología de GenesRESUMEN
Background: Eteplirsen (Exondys 51) is an orphan drug approved for the treatment of Duchenne muscular dystrophy (DMD), having received accelerated approval from the U.S. Food and Drug Administration (FDA) in 2016. The primary aim of this study is to closely monitor adverse events (AEs) associated with eteplirsen and to identify emerging signals to better characterize their safety profile. Methods: AEs due to eteplirsen usage reported from the third quarter (Q3) of 2016 to the fourth quarter (Q4) of 2023 were collected from the FDA Adverse Event Reporting System (FAERS). The role_code of AEs mainly includes primary suspect (PS), secondary suspect (SS), concomitant (C), and interaction (I). This study targeted reports with a role_cod of 'PS.' According to the FDA deduplication rule, the latest FDA_DT is selected when the CASEID is the same, and the higher PRIMARYID is selected when the CASEID and FDA_DT are the same. Disproportionality analyses, encompassing four algorithms for reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian configuration promotion neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were utilized to quantify the signals of AEs associated with eteplirsen. Results: From the FAERS database, a total of 13,205,369 reports were amassed throughout the study duration. Following the eradication of duplicates, the number of reports with eteplirsen designated as the PS amounted to 1480 encompassed 25 organ systems. Among these, "general disorders and administration site conditions," "injury, poisoning, and procedural complications," "respiratory, thoracic, and mediastinal disorders," "infections and infestations," "vascular disorders," and "product issues" met at least one of the four computational criteria. Additionally, 55 Preferred Terms (PTs) aligned with the prescribed algorithms. The median time to AEs in these patients was 903 days with an interquartile range (IQR) of 269-1575 days. Moreover, 70.04 % of AEs manifested one year or more after the initiation of treatment. Conclusion: As an orphan drug granted accelerated approval, our study has confirmed well-known adverse drug reactions and identified potential safety issues associated with eteplirsen treatment. This has contributed to a deeper understanding of the complex interrelations between adverse reactions and the use of eteplirsen. The findings underscore the critical importance of ongoing monitoring and sustained observation to promptly detect and effectively manage AEs, thereby enhancing the overall safety and well-being of patients treated with eteplirsen for DMD.
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DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/virología , COVID-19/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Escherichia coli/genética , MutaciónRESUMEN
Narrowband afterglow materials display interesting functions in high-quality anti-counterfeiting and multiplexed bioimaging. However, there is still a limited exploration of these afterglow materials, especially for those with a full width at half maxima (FWHM) around 30 nm. Here, we report the fabrication of narrowband organic/inorganic hybrid afterglow materials via energy transfer technology. Coronene (Cor) with a long phosphorescence feature and broad phosphorescence band is selected as the donor for energy transfer, and inorganic quantum dots (QDs) of CdSe/ZnS with a narrowband emission are used as acceptors. Upon doping into the organic matrix, the resultant three-component materials exhibit a narrowband afterglow with an afterglow lifetime of approximately 3.4 s and an FWHM of 31 nm. The afterglow wavelength of the afterglow materials can be controlled by the QDs. This work based on organic/inorganic hybrids provides a facile approach for developing multicolor and narrowband afterglow materials, as well as opens a new way for expanding the features of organic afterglow for multifunctional applications. It is expected to rely on narrowband afterglow emitters to solve the "spectrum congestion" problem of high-density information storage in optical anti-counterfeiting and information encryption.
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The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.
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Proteínas de la Ataxia Telangiectasia Mutada , Daño del ADN , N-Metiltransferasa de Histona-Lisina , Leucemia Mieloide Aguda , Proteína de la Leucemia Mieloide-Linfoide , Transducción de Señal , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Daño del ADN/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Transducción de Señal/genética , Animales , Ratones , Línea Celular Tumoral , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteína de Unión a CREB/metabolismo , Proteína de Unión a CREB/genética , Reordenamiento Génico , Histonas/metabolismo , Histonas/genética , Fosforilación , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , AcetilaciónRESUMEN
Bauxite is an important strategic resource, and it is facing with the problem of balance between high demand of bauxite ore and low resource of bauxite reserves in China. This research takes the Fuxin coal gangue as the object and extracts Al2O3 by medium-temperature calcination and acid pressure leaching process. The results show that at a calcination temperature of 650 °C, calcination time of 2 h, acid pressure leaching temperature of 160 °C and acid pressure leaching time of 6 h, the extraction ratio of Al2O3 reaches 80.19%. Furthermore, the research finding that the complete activation temperatures of kaolinite and muscovite are 650 °C and 850 °C, respectively, and the decomposition reactions of active Si, active Al, and metakaolinite occur above 800 °C, which leads to a low extraction ratio of Al2O3. The acid pressure leaching process can directly destroy the muscovite structure at a calcination temperature of 650 °C. The acid pressure leaching kinetic equations are studied by three kinetic models, and the apparent activation energies of the reactions are calculated by the Arrhenius formula. The results show that acid pressure leaching is subject to solid residue in-layer diffusion control, and the kinetic equation is "". The apparent activation energy is 13.48 kJ mol-1.
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Coal-series diatomite (CSD) is widely distributed in China and has poor functional and structural properties and exhibits limited utilization of high value-added materials, resulting in a serious waste of resources and tremendous pressure on the environment. Moreover, due to differences in the mineralogical characteristics of CSD, different particle size scales (PSSs) have different functional structures and exhibit different self-similarities. In this study, we took CSD as the research object and PSS as the entry point and carried out a self-similarity study based on gas adsorption and an image processing method to illustrate the microstructures and self-similarities of different PSSs. The results showed that the pore structure of the CSD was dominated by mesopores and macropores and basically lacked micropores. The fractal dimensions were calculated with the Frenkel-Haisey-Hill (FHH) model and Menger model, and the DF1 values for - 0.025 mm and - 2 mm were 2.51 and 2.48, respectively, and the DM1 values were 3.75 and 3.79, respectively, indicating that the mesopore structure of the fine PSS was complex, whereas macropores were present in the coarse PSS. MATLAB was programmed to obtain grayscale thresholds, binarized images, grayscale histograms, three-dimensional (3D) reconstruction images and box dimensions, which enabled us to observe the microstructures and self-similarities of the CSD. Self-similarity studies based on particle sizes are very important for functional application of CSD.Please note that article title mismatch between MS and JS we have followed MS, kindly check and cofirm.Yes, I have checked and confirmed.Kindly check and confirm corresponding author mail id are correctly identified.Yes, I have checked and confirmed.
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In response to the problem of excessive power consumption during the furrowing operation of orchard furrowing fertilizer machines, an optimization experiment of furrowing operation parameters for orchard furrowing fertilizer machine was conducted based on discrete element simulations. This research focused on the impact of furrowing device operation parameters on furrowing power consumption under full machine operating conditions. Firstly, a kinematics analysis of the soil granules during cutting was done. The mathematical model of soil granules through three movement processes of rising, detachment, and falling was established to determine the main factors affecting the power consumption of furrowing. Secondly, in assessing the furrowing power consumption, the stability coefficient of the furrowing depth, and the percentage of soil cover, alongside the key parameters of furrowing depth, forward propulsion velocity, and furrowing blade rotation speed, a comprehensive quadratic orthogonal rotation regression experiment was meticulously conducted. It was established that test metrics and test parameters regress. Finally, the test parameters were comprehensively optimized after analyzing each factor's impact on the test metrics. The orchard furrowing fertilizer machine's optimal operating parameters were determined, and the verification test was performed. According to the field test findings, the forward propulsion velocity was 785 m/h, and the furrowing blade rotation speed was 190 r/min when the furrowing depth was 275 mm. At this point, the furrowing power consumption was 2.39 kW, the soil cover percentage was 69.06%, and the furrowing depth stability coefficient was 95.08%. These results were in line with the requirements of orchard furrowing operation. The findings of the study can be utilized as a guide for structural changes to orchard furrowing equipment and the management of furrowing operation parameters.