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T loops and telomeric G-quadruplex (G4) DNA structures pose a potential threat to genome stability and must be dismantled to permit efficient telomere replication. Here we implicate the helicase RTEL1 in the removal of telomeric DNA secondary structures, which is essential for preventing telomere fragility and loss. In the absence of RTEL1, T loops are inappropriately resolved by the SLX4 nuclease complex, resulting in loss of the telomere as a circle. Depleting SLX4 or blocking DNA replication abolished telomere circles (TCs) and rescued telomere loss in RTEL1(-/-) cells but failed to suppress telomere fragility. Conversely, stabilization of telomeric G4-DNA or loss of BLM dramatically enhanced telomere fragility in RTEL1-deficient cells but had no impact on TC formation or telomere loss. We propose that RTEL1 performs two distinct functions at telomeres: it disassembles T loops and also counteracts telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.
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ADN Helicasas/metabolismo , G-Cuádruplex , Telómero/metabolismo , Animales , Replicación del ADN , Fibroblastos/metabolismo , Ratones , Conformación de Ácido Nucleico , Recombinasas/metabolismoRESUMEN
BACKGROUND: Developing a prognostic model for lung adenocarcinoma (LUAD) that utilizes m6A/m5C/m1A genes holds immense importance in providing precise prognosis predictions for individuals. METHODS: This study mined m6A/m5C/m1A-related differential genes in LUAD based on public databases, identified LUAD tumor subtypes based on these genes, and further built a risk prognostic model grounded in differential genes between subtypes. The immune status between high- and low-risk groups was investigated, and the distribution of feature genes in tumor immune cells was analyzed using single-cell analysis. Based on the expression levels of feature genes, a projection of chemotherapeutic and targeted drugs was made for individuals identified as high-risk. Ultimately, cell experiments were further verified. RESULTS: The 6-gene risk prognosis model based on differential genes between tumor subtypes had good predictive performance. Individuals classified as low-risk exhibited a higher (P < 0.05) abundance of infiltrating immune cells. Feature genes were mainly distributed in tumor immune cells like CD4+T cells, CD8+T cells, and regulatory T cells. Four drugs with relatively low IC50 values were found in the high-risk group: Elesclomol, Pyrimethamine, Saracatinib, and Temsirolimus. In addition, four drugs with significant positive correlation (P < 0.001) between IC50 values and feature gene expression were found, including Alectinib, Estramustine, Brigatinib, and Elesclomol. The low expression of key gene NTSR1 reduced the IC50 value of irinotecan. CONCLUSION: Based on the m6A/m5C/m1A-related genes in LUAD, LUAD patients were divided into 2 subtypes, and a m6A/m5C/m1A-related LUAD prognostic model was constructed to provide a reference for the prognosis prediction of LUAD.
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Adenina/análogos & derivados , Adenocarcinoma del Pulmón , Hidrazinas , Neoplasias Pulmonares , Humanos , Pronóstico , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Microambiente TumoralRESUMEN
Phages can specifically recognize and kill bacteria, which lead to important application value of bacteriophage in bacterial identification and typing, livestock aquaculture and treatment of human bacterial infection. Considering the variety of human-infected bacteria and the continuous discovery of numerous pathogenic bacteria, screening suitable therapeutic phages that are capable of infecting pathogens from massive phage databases has been a principal step in phage therapy design. Experimental methods to identify phage-host interaction (PHI) are time-consuming and expensive; high-throughput computational method to predict PHI is therefore a potential substitute. Here, we systemically review bioinformatic methods for predicting PHI, introduce reference databases and in silico models applied in these methods and highlight the strengths and challenges of current tools. Finally, we discuss the application scope and future research direction of computational prediction methods, which contribute to the performance improvement of prediction models and the development of personalized phage therapy.
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Bacteriófagos , Biología Computacional , Simulación por Computador , Terapia de Fagos , Terapia de Fagos/métodos , Bacteriófagos/genética , Humanos , Biología Computacional/métodos , Animales , Infecciones Bacterianas/terapia , Infecciones Bacterianas/microbiología , Bacterias/virología , Bacterias/genética , Interacciones Huésped-PatógenoRESUMEN
Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage-bacteria relationships. In this paper, we present, PB-LKS, to predict the phage-bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design.
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Infecciones Bacterianas , Bacteriófagos , Humanos , Bacteriófagos/genética , Bacterias/genéticaRESUMEN
Quorum sensing (QS) is one of the most studied cell-cell communication mechanisms in fungi. Research in the last 20 years has explored various fungal QS systems that are involved in a wide range of biological processes, especially eukaryote- or fungus-specific behaviors, mirroring the significant contribution of QS regulation to fungal biology and evolution. Based on recent progress, we summarize in this review fungal QS regulation, with an emphasis on its functional role in behaviors unique to fungi or eukaryotes. We suggest that using fungi as genetically amenable eukaryotic model systems to address why and how QS regulation is integrated into eukaryotic reproductive strategies and molecular or cellular processes could be an important direction for QS research.
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Regulación Bacteriana de la Expresión Génica , Percepción de Quorum , Células Eucariotas , Hongos/genética , Percepción de Quorum/fisiologíaRESUMEN
How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Folistatina/genética , Folistatina/metabolismo , Tipificación del Cuerpo/genética , Factor de Crecimiento Transformador beta/metabolismo , Regulación del Desarrollo de la Expresión GénicaRESUMEN
Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome's pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the mycn mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in mycn mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of mycn mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.
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Microcefalia , Pez Cebra , Animales , Proteína Proto-Oncogénica N-Myc , Pez Cebra/metabolismo , Microcefalia/genética , Serina-Treonina Quinasas TOR/metabolismo , LeucinaRESUMEN
Symmetry and topology are central to understanding quantum Hall ferromagnets (QHFMs), two-dimensional electronic phases with spontaneously broken spin or pseudospin symmetry whose wavefunctions also have topological properties1,2. Domain walls between distinct broken-symmetry QHFM phases are predicted to host gapless one-dimensional modes-that is, quantum channels that emerge because of a topological change in the underlying electronic wavefunctions at such interfaces. Although various QHFMs have been identified in different materials3-8, interacting electronic modes at these domain walls have not been probed. Here we use a scanning tunnelling microscope to directly visualize the spontaneous formation of boundary modes at domain walls between QHFM phases with different valley polarization (that is, the occupation of equal-energy but quantum mechanically distinct valleys in the electronic structure) on the surface of bismuth. Spectroscopy shows that these modes occur within a topological energy gap, which closes and reopens as the valley polarization switches across the domain wall. By changing the valley flavour and the number of modes at the domain wall, we can realize different regimes in which the valley-polarized channels are either metallic or develop a spectroscopic gap. This behaviour is a consequence of Coulomb interactions constrained by the valley flavour, which determines whether electrons in the topological modes can backscatter, making these channels a unique class of interacting one-dimensional quantum wires. QHFM domain walls can be realized in different classes of two-dimensional materials, providing the opportunity to explore a rich phase space of interactions in these quantum wires.
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Inspired by the intriguing adaptivity of natural life, such as squids and flowers, we propose a series of dynamic and responsive multifunctional devices based on multiscale structural design, which contain metal nanocoating layers overlaid with other micro-/nanoscale soft or rigid layers. Since the optical/photothermal properties of a metal nanocoating are thickness dependent, metal nanocoatings with different thicknesses were chosen to integrate with other structural design elements to achieve dynamic multistimuli responses. The resultant devices demonstrate 1) strain-regulated cracked and/or wrinkled topography with tunable light-scattering properties, 2) moisture/photothermal-responsive structural color coupled with wrinkled surface, and 3) mechanically controllable light-shielding properties attributed to the strain-dependent crack width of the nanocoating. These devices can adapt external stimuli, such as mechanical strain, moisture, light, and/or heat, into corresponding changes of optical signals, such as transparency, reflectance, and/or coloration. Therefore, these devices can be applied as multistimuli-responsive encryption devices, smart windows, moisture/photothermal-responsive dynamic optics, and smartphone app-assisted pressure-mapping sensors. All the devices exhibit high reversibility and rapid responsiveness. Thus, this hybrid system containing ultrathin metal nanocoatings holds a unique design flexibility and adaptivity and is promising for developing next-generation multifunctional devices with widespread application.
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The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Encéfalo/fisiología , Adulto Joven , Ontologías Biológicas , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Red Nerviosa/anatomía & histología , Persona de Mediana Edad , Conectoma/métodos , Reproducibilidad de los Resultados , AncianoRESUMEN
Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.
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The high potassization/depotassization energy barriers and lack of efficient ion diffusion pathways are two serious obstacles for carbon-based materials to achieve satisfactory potassium ion storage performance. Herein, a facile and controllable one-step exfoliation-doping-etching strategy is proposed to construct heteroatoms (N, O, and S)-doped mesoporous few-layer carbon nanosheets (NOS-C). The mixed molten salts of KCl/K2SO4 are innovatively used as the exfoliators, dopants, and etching agents, which enable NOS-C with expanded interlayer spacing and uniformly distributed mesopores with the adjusted electronic structure of surrounding carbon atoms, contributing efficient dual (vertical and horizontal) K-ion diffusion pathways, low potassization/depotassization energy barriers and abundant active sites. Thus, the NOS anodes achieve a high reversible capacity of 516.8 mAh g-1 at 0.05 A g-1, superior rate capability of 202.8 mAh g-1 at 5 A g-1 and excellent long-term cyclic stability, and their practical application potential is demonstrated by the assembled potassium-ion full batteries. Moreover, a surface-interlayer synergetic K+ storage mechanism is revealed by a combined theoretical and experimental approach including in situ EIS, in situ Raman, ex situ XPS, and SEM analysis. The proposed K+ storage mechanism and unique structural engineering provide a new pathway for potassium-ion storage devices and even beyond.
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Li-rich manganese-based cathode (LRMC) has attracted intense attention to developing advanced lithium-ion batteries with high energy density. However, LRMC is still plagued by poor cyclic stability, undesired rate capacity, and irreversible oxygen release. To address these issues, herein, a feasible polyvinylidene fluoride (PVDF)-assisted interface modification strategy is proposed for modulating the surface architecture and electronic conductivity of LRMC by intruding the F-doped carbon coating, spinel structure, and oxygen vacancy on the LRMC, which can greatly enhance the cyclic stability and rate capacity, and restrain the oxygen release for LRMC. As a result, the modified material delivers satisfactory cyclic performance with a capacity retention of 90.22% after 200 cycles at 1 C, an enhanced rate capacity of 153.58 mAh g-1 at 5 C and 126.32 mAh g-1 at 10 C, and an elevated initial Coulombic efficiency of 85.63%. Moreover, the thermal stability, electronic conductivity, and structure stability of LRMC are also significantly improved by the PVDF-assisted interface modification strategy. Therefore, the strategy of simultaneously modulating the surface architecture and the electronic conductivity of LRMC provides a valuable idea to improve the comprehensive electrochemical performance of LRMC, which offers a promising reference for designing LRMC with high electrochemical performance.
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BACKGROUND: Circadian rhythm (CR) disturbance is intricately associated with Parkinson's disease (PD). However, the involvement of CR-related mechanisms in the pathogenesis and progression of PD remains elusive. METHODS: A total of 141 PD patients and 113 healthy participants completed CR-related clinical examinations in this study. To further investigate the CR-related mechanisms in PD, we obtained datasets (GSE7621, GSE20141, GSE20292) from the Gene Expression Omnibus database to identify differentially expressed genes between PD patients and healthy controls and further selected CR-related genes (CRRGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) followed by logistic algorithms were employed to identify the hub genes and construct a diagnostic model. The predictive performance was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses in the training set and external validation sets. Finally, RTâqPCR and Western blotting were conducted to verify the expression of these hub genes in blood samples. In addition, Pearson correlation analysis was utilized to validate the association between expression of hub genes and circadian rhythm function. RESULTS: Our clinical observational study revealed that even early-stage PD patients exhibited a higher likelihood of experiencing sleep disturbances, nocturnal hypertension, reverse-dipper blood pressure, and reduced heart rate variability compared to healthy controls. Furthermore, 4 CR-related hub genes (AGTR1, CALR, BRM14, and XPA) were identified and subsequently incorporated as candidate biomarkers to construct a diagnostic model. The model showed satisfactory diagnostic performance in the training set (AUC = 0.941), an external validation set GSE20295 (AUC = 0.842), and our clinical centre set (AUC = 0.805). Additionally, the up-regulation of CALR, BRM14 and the down-regulation of AGTR1, XPA were associated with circadian rhythm disruption. CONCLUSION: CR disturbance seems to occur in the early stage of PD. The diagnostic model based on CR-related genes demonstrated robust diagnostic efficacy, offering novel insights for future clinical diagnosis of PD and providing a foundation for further exploration into the role of CR-related mechanisms in the progression of PD.
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Ritmo Circadiano , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Ritmo Circadiano/genética , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Curva ROC , Regulación de la Expresión Génica , Perfilación de la Expresión Génica , Modelos Biológicos , Bases de Datos GenéticasRESUMEN
Candida albicans is the most frequent pathogen of fungal sepsis associated with substantial mortality in critically ill patients and those who are immunocompromised. Identification of novel immune-based therapeutic targets from a better understanding of its molecular pathogenesis is required. Here, we reported that the production of progranulin (PGRN) levels was significantly increased in mice after invasive C.albicans infection. Mice that lacked PGRN exhibited attenuated kidney injury and increased survival upon a lethal systemic infection with C. albicans. In mice, PGRN deficiency protected against systemic candidiasis by decreasing aberrant inflammatory reactions that led to renal immune cell apoptosis and kidney injury, and by enhancing antifungal capacity of macrophages and neutrophils that limited fungal burden in the kidneys. PGRN in hematopoietic cell compartment was important for this effect. Moreover, anti-PGRN antibody treatment limited renal inflammation and fungal burden and prolonged survival after invasive C. albicans infection. In vitro, PGRN loss increased phagocytosis, phagosome formation, reactive oxygen species production, neutrophil extracellular traps release, and killing activity in macrophages or neutrophils. Mechanistic studies demonstrated that PGRN loss up-regulated Dectin-2 expression, and enhanced spleen tyrosine kinase phosphorylation and extracellular signal-regulated kinase activation in macrophages and neutrophils. In summary, we identified PGRN as a critical factor that contributes to the immunopathology of invasive C.albicans infection, suggesting that targeting PGRN might serve as a novel treatment for fungal infection.
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Candida albicans , Sepsis , Animales , Antifúngicos , Quinasas MAP Reguladas por Señal Extracelular , Ratones , Neutrófilos , Progranulinas , Especies Reactivas de Oxígeno/metabolismo , Sepsis/patología , Quinasa SykRESUMEN
Optical scattering measurement is one of the most commonly used methods for non-contact online measurement of film properties in industrial film manufacturing. Terahertz photons have low energy and are non-ionizing when measuring objects, so combining these two methods can enable online nondestructive testing of thin films. In the visible light band, some materials are transparent, and their thickness and material properties cannot be measured. Therefore, a method based on physical consistency modeling and machine learning is proposed in this paper, which realizes the method of obtaining high-precision thin film parameters through single-frequency terahertz wave measurement, and shows good performance. Through the experimental measurement of organic material thin films, it is proved that the proposed method is an effective terahertz online detection technology with high precision and high throughput.
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BACKGROUND: Re-emergent tremor is characterized as a continuation of resting tremor and is often highly therapy refractory. This study examines variations in brain activity and oscillatory responses between resting and re-emergent tremors in Parkinson's disease. METHODS: Forty patients with Parkinson's disease (25 males, mean age, 66.78 ± 5.03 years) and 40 age- and sex-matched healthy controls were included in the study. Electroencephalogram and electromyography signals were simultaneously recorded during resting and re-emergent tremors in levodopa on and off states for patients and mimicked by healthy controls. Brain activity was localized using the beamforming technique, and information flow between sources was estimated using effective connectivity. Cross-frequency coupling was used to assess neuronal oscillations between tremor frequency and canonical frequency oscillations. RESULTS: During levodopa on, differences in brain activity were observed in the premotor cortex and cerebellum in both the patient and control groups. However, Parkinson's disease patients also exhibited additional activity in the primary sensorimotor cortex. On withdrawal of levodopa, different source patterns were observed in the supplementary motor area and basal ganglia area. Additionally, levodopa was found to suppress the strength of connectivity (P < 0.001) between the identified sources and influence the tremor frequency-related coupling, leading to a decrease in ß (P < 0.001) and an increase in γ frequency coupling (P < 0.001). CONCLUSIONS: Distinct variations in cortical-subcortical brain activity are evident in tremor phenotypes. The primary sensorimotor cortex plays a crucial role in the generation of re-emergent tremor. Moreover, oscillatory neuronal responses in pathological ß and prokinetic γ activity are specific to tremor phenotypes. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Electromiografía , Levodopa , Enfermedad de Parkinson , Temblor , Humanos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Masculino , Femenino , Temblor/fisiopatología , Temblor/etiología , Persona de Mediana Edad , Anciano , Levodopa/uso terapéutico , Levodopa/farmacología , Ritmo Gamma/fisiología , Ritmo Gamma/efectos de los fármacos , Ritmo beta/fisiología , Ritmo beta/efectos de los fármacos , Electroencefalografía/métodos , Antiparkinsonianos/uso terapéuticoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are involved in the neuroblastoma (NB) development. Objectie: The study aimed to determine the biological behaviors of circ_0001361 and explore its underlying mechanism in NB. METHODS: The circ_0001361, miR-490-5p, and IGF2 levels were measured using quantitative real-time polymerase chain reaction. Cellular processes were analyzed using MTT assay or fluorescence-activated cell sorting (FACS). Phosphorylated (p)-PI3K, p-AKT, Bax, and caspase-3 were tested by western blot. Dual-luciferase reporter analysis together with RNA pull-down analysis were utilized to evaluate the correlation of miR-490-5p and circ_0001361 or IGF2. RESULTS: The results in this study illustrated that an elevation of circ_0001361 levels was observed in NB. Depletion of circ_0001361 suppressed the viability but facilitated apoptosis of NB cells. Circ_0001361 sponged miR-490-5p, which targeted to regulate IGF2. Inhibition of miR-490-5p rescued the effect induced by circ_0001361 knockdown, while deletion of IGF2 rescued the effect induced by the miR-490-5p inhibitor. CONCLUSIONS: In summary, a loss of circ_0001361 inhibited NB progression via targeting the miR-490-5p/IGF2 axis, suggesting that circ_0001361 may be a novel therapeutical target of NB.
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Silicon quantum dots (QDs) with stable positively charged intermediates are prepared using chemical etching to generate strong anodic electrochemiluminescence (ECL) under a positive potential. Their surfaces could be passivated in the presence of strong oxidants, leading to enhanced ECL and offering the ability to carry out analysis for hydrogen peroxide.
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OBJECTIVE: The role of ipsilateral descending motor pathways in voluntary movement of humans is still a matter of debate, with partly contradictory results. The aim of our study therefore was to examine the excitability of ipsilateral motor evoked potentials (iMEPs) regarding site and the specificity for unilateral and bilateral elbow flexion extension tasks. METHODS: MR-navigated transcranial magnetic stimulation mapping of the dominant hemisphere was performed in twenty healthy participants during tonic unilateral (iBB), bilateral homologous (bBB) or bilateral antagonistic elbow flexion-extension (iBB-cAE), the map center of gravity (CoG) and iMEP area from BB were obtained. RESULTS: The map CoG of the ipsilateral BB was located more anterior-laterally than the hotspot of the contralateral BB within the primary motor cortex, with a significant difference in CoG in iBB and iBB-cAE, but not bBB compared to the hotspot for the contralateral BB (each p < 0.05). However, different tasks had no effect on the size of the iMEPs. CONCLUSION: Our data demonstrated that excitability of ipsilateral and contralateral MEP differ spatially in a task-specific manner suggesting the involvement of different motor networks within the motor cortex.