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1.
Cell ; 179(6): 1276-1288.e14, 2019 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-31778654

RESUMEN

Although human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating hepatic very low-density lipoprotein (VLDL) secretion, and subsequently circulating low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels. Remarkably, GPR146 deficiency reduces plasma cholesterol levels substantially in both wild-type and LDL receptor (LDLR)-deficient mice. Finally, aortic atherosclerotic lesions are reduced by 90% and 70%, respectively, in male and female LDLR-deficient mice upon GPR146 depletion. Taken together, these findings outline a regulatory role for the GPR146/ERK axis in systemic cholesterol metabolism and suggest that GPR146 inhibition could be an effective strategy to reduce plasma cholesterol levels and atherosclerosis.


Asunto(s)
Aterosclerosis/metabolismo , Hipercolesterolemia/metabolismo , Receptores Acoplados a Proteínas G/deficiencia , Animales , Aterosclerosis/sangre , Secuencia de Bases , Colesterol/sangre , Dependovirus/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ayuno , Femenino , Hepatocitos/metabolismo , Humanos , Hipercolesterolemia/sangre , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , ARN Interferente Pequeño/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de LDL/metabolismo , Transducción de Señal , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/sangre , Regulación hacia Arriba
2.
Small ; 20(38): e2401258, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38794878

RESUMEN

Manganese oxide-based aqueous zinc-ion batteries (ZIBs) are attractive energy storage devices, owing to their good safety, low cost, and ecofriendly features. However, various critical issues, including poor conductivity, sluggish reaction kinetics, and unstable structure still restrict their further development. Oxygen defect engineering is an effective strategy to improve the electrochemical performance of manganese oxides, but challenging in the accurate regulation of oxygen defects. In this work, an effective and controllable defect engineering strategy-controllable electrochemical lithium-ion intercalation - is proposed to tackle this issue. The incorporation of lithium ions and oxygen defects can promote the conductivity, lattice spacing, and structural stability of Mn2O3 (MO), thus improving its capacity (232.7 mAh g-1), rate performance, and long-term cycling stability (99.0% capacity retention after 3000 cycles). Interestingly, the optimal ratio of intercalated lithium-ion varies at different temperature or mass-loading of MO, which provides the possibility to customize diverse ZIBs to meet different application conditions. In addition, the fabricated ZIBs present good flexibility, superior safety, and admirable adaptability under extreme temperatures (-20-100 °C). This work provides an inspiration on the structural customization of metal oxide nanomaterials for diverse ZIBs, and sheds light on the construction of future portable electronics.

3.
Bioinformatics ; 39(4)2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37018146

RESUMEN

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.


Asunto(s)
Cromatina , ADN Circular , Cromatina/genética , Cromosomas , ADN , Secuencia de Bases
4.
Circ Res ; 131(12): 1004-1017, 2022 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-36321446

RESUMEN

BACKGROUND: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the FES (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. METHODS AND RESULTS: Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed FES were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed FES. There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that Fes knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. CONCLUSIONS: We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Proteínas Proto-Oncogénicas c-fes , Animales , Humanos , Ratones , Arterias/metabolismo , Aterosclerosis/genética , Aterosclerosis/metabolismo , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/metabolismo , Estudio de Asociación del Genoma Completo , Miocitos del Músculo Liso/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Proteínas Proto-Oncogénicas c-fes/genética , Proteínas Proto-Oncogénicas c-fes/metabolismo
5.
Arterioscler Thromb Vasc Biol ; 42(10): 1262-1271, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36047410

RESUMEN

BACKGROUND: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. METHODS: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK Biobank. The Lifelines, The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. RESULTS: In the UK Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. CONCLUSIONS: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans.


Asunto(s)
Aterosclerosis , Hipobetalipoproteinemias , Animales , Apolipoproteínas B/genética , Aterosclerosis/genética , Aterosclerosis/prevención & control , Proteína C-Reactiva , HDL-Colesterol , LDL-Colesterol , Humanos , Hipobetalipoproteinemias/genética , Ratones , Preparaciones Farmacéuticas , Receptores Acoplados a Proteínas G/genética
6.
Macromol Rapid Commun ; 44(13): e2300084, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37002643

RESUMEN

As a common oxidizer, ammonium perchlorate (AP) is an important component in composite solid propellants (CSPs). Ferrocene (Fc)-based compounds are often selected as burning rate catalysts (BRCs) to catalyze AP decomposition owing to their excellent catalytic behavior. However, one of the drawbacks of Fc-based BRCs is migration in CSPs. In this study, five Fc-terminated dendrimers are designed and synthesized to improve the anti-migration properties, and their chemical structures are confirmed systemically by the related spectra characterization techniques. Moreover, the redox performance, catalytic effect on AP decomposition, combustion performance, and mechanical properties in CSPs are also studied. The shapes of the prepared propellant samples are observed via scanning electron microscopy. The obtained Fc-based BRCs have good redox performance, a positive effect on promoting AP decomposition, excellent combustion catalytic performance, and good mechanical properties. Meanwhile, they have a higher anti-migration ability than catocene (Cat) and Fc. This study demonstrates that Fc-terminated dendrimers have great potential to be applied as anti-migration BRCs in CSPs.


Asunto(s)
Dendrímeros , Metalocenos , Catálisis , Indio
7.
Circ Res ; 126(3): 330-346, 2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-31739742

RESUMEN

Rationale: Genome-wide association studies have identified genetic loci associated with insulin resistance (IR) but pinpointing the causal genes of a risk locus has been challenging. Objective: To identify candidate causal genes for IR, we screened regional and biologically plausible genes (16 in total) near the top 10 IR-loci in risk-relevant cell types, namely preadipocytes and adipocytes. Methods and Results: We generated 16 human Simpson-Golabi-Behmel syndrome preadipocyte knockout lines each with a single IR-gene knocked out by lentivirus-mediated CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system. We evaluated each gene knockout by screening IR-relevant phenotypes in the 3 insulin-sensitizing mechanisms, including adipogenesis, lipid metabolism, and insulin signaling. We performed genetic analyses using data on the genotype-tissue expression portal expression quantitative trait loci database and accelerating medicines partnership type 2 diabetes mellitus Knowledge Portal to evaluate whether candidate genes prioritized by our in vitro studies were expression quantitative trait loci genes in human subcutaneous adipose tissue, and whether expression of these genes is associated with risk of IR, type 2 diabetes mellitus, and cardiovascular diseases. We further validated the functions of 3 new adipose IR genes by overexpression-based phenotypic rescue in the Simpson-Golabi-Behmel syndrome preadipocyte knockout lines. Twelve genes, PPARG, IRS-1, FST, PEPD, PDGFC, MAP3K1, GRB14, ARL15, ANKRD55, RSPO3, COBLL1, and LYPLAL1, showed diverse phenotypes in the 3 insulin-sensitizing mechanisms, and the first 7 of these genes could affect all the 3 mechanisms. Five out of 6 expression quantitative trait loci genes are among the top candidate causal genes and the abnormal expression levels of these genes (IRS-1, GRB14, FST, PEPD, and PDGFC) in human subcutaneous adipose tissue could be associated with increased risk of IR, type 2 diabetes mellitus, and cardiovascular disease. Phenotypic rescue by overexpression of the candidate causal genes (FST, PEPD, and PDGFC) in the Simpson-Golabi-Behmel syndrome preadipocyte knockout lines confirmed their function in adipose IR. Conclusions: Twelve genes showed diverse phenotypes indicating differential roles in insulin sensitization, suggesting mechanisms bridging the association of their genomic loci with IR. We prioritized PPARG, IRS-1, GRB14, MAP3K1, FST, PEPD, and PDGFC as top candidate genes. Our work points to novel roles for FST, PEPD, and PDGFC in adipose tissue, with consequences for cardiometabolic diseases.


Asunto(s)
Adipocitos/metabolismo , Resistencia a la Insulina/genética , Sitios de Carácter Cuantitativo , Proteínas Adaptadoras Transductoras de Señales/genética , Línea Celular , Dipeptidasas/genética , Folistatina/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Proteínas Sustrato del Receptor de Insulina/genética , Mutación con Pérdida de Función , Linfocinas/genética , Quinasa 1 de Quinasa de Quinasa MAP/genética , PPAR gamma/genética , Factor de Crecimiento Derivado de Plaquetas/genética
8.
Pol J Pathol ; 73(4): 343-351, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36946271

RESUMEN

Osteosarcoma (OS) is the most common malignant bone tumour; however, the underlying mechanisms are mainly unknown. Enhancer of zeste homologue 2 (EZH2) and NOTCH pathway are important molecular signals related to carcinogenesis and tumour progression, but they are not fully understand in OS. Enhancer of zeste homologue 2, Notch3, HES1, and Nanog were detected on OS samples and statistically analysed. Expressions of these genes were investigate, and stem-like phenotype was verified in OS cells. This study found that higher EZH2 expression, Notch3 pathway, or Nanog were associated with tumour relapse and metastasis and a significantly shorter survival time. Moreover, the Notch3 pathway was activated in osteosarcoma stem cells. Enhancer of zeste homologue 2 overexpression could activate the Notch3 pathway and increase HES1 expression, leading to upregulated stem cell-related gene expression and self-renewal of OS cells. Our study demonstrates that EZH2, Notch3, and Nanog are important prognostic factors. Enhancer of zeste homologue 2 could maintain the self-renewal of OS cells, where the Notch3 pathway activation may be involved.


Asunto(s)
Neoplasias Óseas , Proteína Potenciadora del Homólogo Zeste 2 , Osteosarcoma , Receptor Notch3 , Humanos , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular , Proteína Potenciadora del Homólogo Zeste 2/genética , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Receptor Notch3/genética , Células Madre/metabolismo , Células Madre/patología
9.
Int J Paediatr Dent ; 32(6): 785-792, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35315146

RESUMEN

AIM: The purpose of this research was to present an artificial intelligence (AI) model, which can automatically segment and detect ectopic eruption of first permanent molars (EMMs) in early mixed dentition on panoramic radiographs using the no-new-Net (nnU-Net) model. DESIGN: A total of 438 EMMs obtained from 285 panoramic radiographs were included in this study. An AI model based on nnU-Net was trained to segment and detect EMMs. The performance of the model was evaluated by the intersection over union (IoU), precision, F1-score, accuracy and FROC. Furthermore, the detecting performance of nnU-Net was compared with that of three dentists with different years of experience using the McNemar chi-squared test. The reliability of different dentists was evaluated by intraclass correlation coefficients (ICCs). RESULTS: The nnU-Net yielded an IoU of 0.834, a precision of 0.845, an F1-score of 0.902 and an accuracy of 0.990, whereas the dentists yielded a mean IoU of 0.530, a mean precision of 0.539, a mean F1-score of 0.699 and a mean accuracy of 0.811. The ICC of different dentists was 0.776. The statistical analysis of the McNemar chi-squared test showed that the nnU-Net results were statistically significant and superior to those of dentists (p < .05). CONCLUSION: This study validated an AI model based on nnU-Net for automatically segmenting and detecting EMMs more consistently and accurately on panoramic radiography.


Asunto(s)
Inteligencia Artificial , Diente Molar , Dentición Mixta , Humanos , Diente Molar/diagnóstico por imagen , Radiografía Panorámica , Reproducibilidad de los Resultados
10.
Molecules ; 27(11)2022 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-35684525

RESUMEN

This study focused on characterizing the volatile profiles and contributing compounds in pan-fried steaks from different Chinese yellow cattle breeds. The volatile organic compounds (VOCs) of six Chinese yellow cattle breeds (bohai, jiaxian, yiling, wenshan, xinjiang, and pingliang) were analyzed by GC-Q-Orbitrap spectrometry and electronic nose (E-nose). Multivariate statistical analysis was performed to identify the differences in VOCs profiles among breeds. The relationship between odor-active volatiles and sensory evaluation was analyzed by partial least square regression (PLSR) to identify contributing volatiles in pan-fried steaks of Chinese yellow cattle. The results showed that samples were divided into two groups, and 18 VOCs were selected as potential markers for the differentiation of the two groups by GC-Q-Orbitrap combined multivariate statistical analysis. YL and WS were in one group comprising mainly aliphatic compounds, while the rest were in the other group with more cyclic compounds. Steaks from different breeds were better differentiated by GC-Q-Orbitrap in combination with chemometrics than by E-nose. Six highly predictive compounds were selected, including 3-methyl-butanal, benzeneacetaldehyde, 2-ethyl-6-methyl-pyrazine, 2-acetylpyrrole, 2-acetylthiazole, and 2-acetyl-2-thiazoline. Sensory recombination difference and preference testing revealed that the addition of highly predictive compounds induced a perceptible difference to panelists. This study provides valuable data to characterize and discriminate the flavor profiles in pan-fried steaks of Chinese yellow cattle.


Asunto(s)
Nariz Electrónica , Compuestos Orgánicos Volátiles , Animales , Bovinos , China , Cromatografía de Gases y Espectrometría de Masas/métodos , Odorantes/análisis , Compuestos Orgánicos Volátiles/análisis
11.
Fish Physiol Biochem ; 47(5): 1489-1505, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34331171

RESUMEN

Grass carp (Ctenopharyngodon idellus) is one of the most essential fishing species in China. The bait for this fish is rapidly developing. However, the study on the attractants in the bait for this fish lacks. This study was designed to systematically investigate the effects of 16 kinds of test substances on the perspective of behaviour and physiology of grass carp by using different kinds of methods, including behavioral tests (maze test and biting-balls test) and electro-olfactogram (EOG). Our experiment's idea is mainly to imitate: in addition to vision, fish in nature also use smell to find food and finally swallow under the action of olfaction, taste, and other sensory systems. Firstly, the behavioral maze test was used to screen the attractive or suppressive effect of 16 test substances on grass carp, and the electronic olfactory recording method was used to further evaluate the olfactory response of grass carp to the eight stimuli selected from the maze test. Then, the best concentrations of these eight stimuli and their combination were investigated by the biting-balls test to compound a formula with the strongest appetite for grass carp. The results of behavioral maze test showed that dimethyl-ß-propiothetin (DMPT), dimethylthetin (DMT), glycine, taurine, L-glutamic, L-alanine, L-proline, and L-arginine have different degrees of usefulness in attracting grass carp. The electro-olfactogram recoding showed that the EOG response of grass carp to the stimuli is a transient biphasic potential change and all of the eight stimuli could induce the EOG response of grass carp. The biting-balls test showed that glycine, L-glutamic, and L-arginine at 10-2 mol/L had significant feeding stimulation and DMT at 10-1 mol/L had significant feeding stimulation than the other groups. Finally, formula 9 composed of DMT, glycine, L-glutamic acid, and L-arginine has the greatest attraction for grass carp. The results of this study verified the attractive effect of some amino acids and other chemicals on grass carp fishing, and would provide support for the production of specific grass carp attractants.


Asunto(s)
Aminoácidos/metabolismo , Carpas , Animales , Arginina , Carpas/fisiología , Glicina , Caza
12.
J Proteome Res ; 19(10): 3968-3980, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-32786677

RESUMEN

Population genetic studies highlight a missense variant (G398S) of A1CF that is strongly associated with higher levels of blood triglycerides (TGs) and total cholesterol (TC). Functional analyses suggest that the mutation accelerates the secretion of very low-density lipoprotein (VLDL) from the liver by an unknown mechanism. Here, we used multiomics approaches to interrogate the functional difference between the WT and mutant A1CF. Using metabolomics analyses, we captured the cellular lipid metabolite changes induced by transient expression of the proteins, confirming that the mutant A1CF is able to relieve the TG accumulation induced by WT A1CF. Using a proteomics approach, we obtained the interactomic data of WT and mutant A1CF. Networking analyses show that WT A1CF interacts with three functional protein groups, RNA/mRNA processing, cytosolic translation, and, surprisingly, mitochondrial translation. The mutation diminishes these interactions, especially with the group of mitochondrial translation. Differential analyses show that the WT A1CF-interacting proteins most significantly different from the mutant are those for mitochondrial translation, whereas the most significant interacting proteins with the mutant are those for cytoskeleton and vesicle-mediated transport. RNA-seq analyses validate that the mutant, but not the WT, A1CF increases the expression of the genes responsible for cellular transport processes. On the contrary, WT A1CF affected the expression of mitochondrial matrix proteins and increased cell oxygen consumption. Thus, our studies confirm the previous hypothesis that A1CF plays broader roles in regulating gene expression. The interactions of the mutant A1CF with the vesicle-mediated transport machinery provide mechanistic insight in understanding the increased VLDL secretion in the A1CF mutation carriers.


Asunto(s)
Metabolismo de los Lípidos , Proteínas de Unión al ARN , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Edición de ARN , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo
13.
Molecules ; 25(19)2020 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-33003556

RESUMEN

For screening excellent lactic acid bacteria (LAB) strains to inhibit enterotoxigenic Escherichia coli (ETEC) K88, inhibitory activities of more than 1100 LAB strains isolated from different materials, and kept in the lab, were evaluated in this study. Nine strains with inhibition zones, at least 22.00 mm (including that of a hole puncher, 10.00 mm), and good physiological and biochemical characteristics identified by 16S DNA gene sequencing and recA gene multiple detection, were assigned to Lactobacillus (L.) plantarum subsp. plantarum (5), L. fermentum (1), L. reuteri (1), Weissella cibaria (1) and Enterococcus faecalis (1), respectively. As investigated for their tolerance abilities and safety, only strain ZA3 possessed high hydrophobicity and auto-aggregation abilities, had high survival rate in low pH, bile salt environment, and gastrointestinal (GI) fluids, was sensitive to ampicillin, and resistant to norfloxacin and amikacin, without hemolytic activity, and did not carry antibiotic resistance genes, but exhibited broad spectrum activity against a wide range of microorganisms. Antibacterial substance may attribute to organic acids, especially lactic acid and acetic acid. The results indicated that the selected strain L. plantarum subsp. plantarum ZA3 could be considered a potential probiotic to inhibit ETEC K88 in weaned piglets for further research.


Asunto(s)
Escherichia coli Enterotoxigénica/efectos de los fármacos , Lactobacillus/química , Probióticos/farmacología , Destete , Ácidos/metabolismo , Animales , Ácidos y Sales Biliares/metabolismo , Biomasa , Carbohidratos/química , Línea Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Fermentación/efectos de los fármacos , Tracto Gastrointestinal/microbiología , Hemólisis/efectos de los fármacos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Lactobacillus/genética , Lactobacillus/crecimiento & desarrollo , Lactobacillus/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Filogenia , ARN Ribosómico 16S/genética , Porcinos , Pruebas de Toxicidad , Factores de Virulencia/genética
14.
Trends Biochem Sci ; 39(5): 219-20, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24637041

RESUMEN

Dynamic (-) DNA supercoiling generated in the wake of translocating protein complexes is known to occur during transcription. Recent studies indicate that (-) superhelical tension also builds up specifically in the leading duplex during replication. Here, we argue that this unrecognized supercoiling is causally involved in the regulation of key DNA transactions and deserves further consideration.


Asunto(s)
ADN/química , Replicación del ADN , ADN Bacteriano/química , ADN Polimerasa Dirigida por ADN/metabolismo , Conformación de Ácido Nucleico , Transcripción Genética
15.
Nucleic Acids Res ; 44(22): e162, 2016 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-27587582

RESUMEN

HMGA2 is an important chromatin factor that interacts with DNA via three AT-hook domains, thereby regulating chromatin architecture and transcription during embryonic and fetal development. The protein is absent from differentiated somatic cells, but aberrantly re-expressed in most aggressive human neoplasias where it is causally linked to cell transformation and metastasis. DNA-binding also enables HMGA2 to protect cancer cells from DNA-damaging agents. HMGA2 therefore is considered to be a prime drug target for many aggressive malignancies. Here, we have developed a broadly applicable cell-based reporter system which can identify HMGA2 antagonists targeting functionally important protein domains, as validated with the known AT-hook competitor netropsin. In addition, high-throughput screening can uncover functional links between HMGA2 and cellular factors important for cell transformation. This is demonstrated with the discovery that HMGA2 potentiates the clinically important topoisomerase I inhibitor irinotecan/SN-38 in trapping the enzyme in covalent DNA-complexes, thereby attenuating transcription.


Asunto(s)
Camptotecina/análogos & derivados , ADN-Topoisomerasas de Tipo I/fisiología , Proteína HMGA2/fisiología , Inhibidores de Topoisomerasa I/farmacología , Secuencia de Aminoácidos , Camptotecina/farmacología , Diferenciación Celular/efectos de los fármacos , Estabilidad de Enzimas , Genes Reporteros , Células HEK293 , Células HeLa , Ensayos Analíticos de Alto Rendimiento , Humanos , Irinotecán , Luciferasas de Renilla/biosíntesis , Luciferasas de Renilla/genética , Netropsina/farmacología , Regiones Promotoras Genéticas , Transcripción Genética/efectos de los fármacos , Activación Transcripcional
17.
Beilstein J Org Chem ; 12: 939-49, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27340484

RESUMEN

The topic of stimuli-responsive nanocarriers for loading guest molecules is dynamic. It has been widely studied in applications including drug controlled release, smart sensing, catalysis, and modeling. In this paper, a graft copolymer (hyperbranched polystyrene)-g-poly[2-(dimethylamino)ethyl methacrylate] (HBPS-g-PDMAEMA) was synthesized and characterized by (1)H NMR and GPC. It was observed that the star-like HBPS-g-PDMAEMA formed aggregates in aqueous solution. The influence of polymer concentration, ionic strength and pH value on the aggregates in aqueous solution was investigated by using UV-vis spectroscopy and DLS analysis. The results showed that size of aggregates was affected by a corresponding stimulus. In addition, the loading ability of HBPS-g-PDMAEMA aggregates was investigated by using pyrene or Nile red as the model guest molecules by using UV-vis and fluorescence spectroscopy. The results showed that HBPS-g-PDMAEMA aggregates were capable to encapsulate small hydrophobic molecules. These newly prepared HBPS-g-PDMAEMA nanocarriers might be used in, e.g., medicine or catalysis.

18.
Soft Matter ; 11(7): 1242-52, 2015 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-25614350

RESUMEN

Self-healing polymers, which can spontaneously recover themselves after being ruptured, result in enhanced lifetimes for materials and open up a fascinating direction in material science. Macrocycle-based host-guest interactions, one of the most crucial non-covalent interactions, play a key role in self-healing material fabrication. This review aims to highlight the very recent and important progress made in the area of self-healing polymer materials by focusing on cyclodextrins (CDs), crown ethers, cucurbit[n]urils (CBs), calix[n]arenes and pillar[n]arenes with special guest groups and tailored structures. In addition, we also propose future research directions and hope that this review can in a way reflect the current situation and future trends in this developing area.

19.
J Dent ; : 105399, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39424256

RESUMEN

OBJECTIVES: To construct a diagnostic model for mixed dentition using a multistage deep-learning network to predict potential ectopic eruption in permanent teeth by integrating dentition segmentation into the process of automatic classification of dental development stages. METHODS: A database was established by reviewing 1576 anonymous panoramic radiographs of children aged 6-12 years, collected at the Stomatology Hospital, xxxxxx. These radiographs were categorised as normal or ectopic eruption, with expert diagnoses serving as a benchmark for training and evaluating artificial intelligence (AI) models. Furthermore, tooth boundaries and dental development stages were manually annotated by three pediatric dentistry experts. The dataset was split into training, validation, and test sets at an 8:1:1 ratio. RESULTS: The diagnostic performance of the deep-learning model was rigorously evaluated. The model demonstrated accuracy in tooth segmentation, with Intersection over Union, precision, sensitivity, and F1 scores of 0.959, 0.993, 0.966, and 0.979, respectively. Furthermore, its ability to identify tooth ectopic eruptions on panoramic radiographs, when compared to evaluations by three dentists. Based on McNemar's test, the model's specificity and accuracy in identifying ectopic tooth eruptions on the test dataset surpassed that of Dentist 1 (P < 0.05), while no significant difference was observed compared to the other two dentists. Besides, the deep learning model also showed its potential in classifying dental development stages, as tested against three different standards. CONCLUSIONS: The adaptability of the AI-enabled model in this study was demonstrated across multiple scenarios, with clinical validation highlighting its efficacy in diagnosing ectopic eruptions using a multistage deep-learning approach. CLINICAL SIGNIFICANCE: Our findings provide new insights and technical support for the prevention and treatment of abnormal tooth eruption, laying the groundwork for predictive models for other prevalent pediatric dentistry conditions.

20.
PLoS One ; 19(6): e0304284, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38843129

RESUMEN

Agricultural pests and diseases pose major losses to agricultural productivity, leading to significant economic losses and food safety risks. However, accurately identifying and controlling these pests is still very challenging due to the scarcity of labeling data for agricultural pests and the wide variety of pest species with different morphologies. To this end, we propose a two-stage target detection method that combines Cascade RCNN and Swin Transformer models. To address the scarcity of labeled data, we employ random cut-and-paste and traditional online enhancement techniques to expand the pest dataset and use Swin Transformer for basic feature extraction. Subsequently, we designed the SCF-FPN module to enhance the basic features to extract richer pest features. Specifically, the SCF component provides a self-attentive mechanism with a flexible sliding window to enable adaptive feature extraction based on different pest features. Meanwhile, the feature pyramid network (FPN) enriches multiple levels of features and enhances the discriminative ability of the whole network. Finally, to further improve our detection results, we incorporated non-maximum suppression (Soft NMS) and Cascade R-CNN's cascade structure into the optimization process to ensure more accurate and reliable prediction results. In a detection task involving 28 pest species, our algorithm achieves 92.5%, 91.8%, and 93.7% precision in terms of accuracy, recall, and mean average precision (mAP), respectively, which is an improvement of 12.1%, 5.4%, and 7.6% compared to the original baseline model. The results demonstrate that our method can accurately identify and localize farmland pests, which can help improve farmland's ecological environment.


Asunto(s)
Algoritmos , Animales , Agricultura/métodos , Control de Plagas/métodos , Redes Neurales de la Computación , Granjas , Productos Agrícolas/parasitología
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