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Powerful relativistic jets are one of the ubiquitous features of accreting black holes in all scales1-3. GRS 1915 + 105 is a well-known fast-spinning black-hole X-ray binary4 with a relativistic jet, termed a 'microquasar', as indicated by its superluminal motion of radio emission5,6. It has exhibited persistent X-ray activity over the last 30 years, with quasiperiodic oscillations of approximately 1-10 Hz (refs. 7-9) and 34 and 67 Hz in the X-ray band10. These oscillations probably originate in the inner accretion disk, but other origins have been considered11. Radio observations found variable light curves with quasiperiodic flares or oscillations with periods of approximately 20-50 min (refs. 12-14). Here we report two instances of approximately 5-Hz transient periodic oscillation features from the source detected in the 1.05- to 1.45-GHz radio band that occurred in January 2021 and June 2022. Circular polarization was also observed during the oscillation phase.
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The functional relevance of an organoid is dependent on the differentiation, morphology, cell arrangement and biophysical properties, which collectively define the state of an organoid. For an organoid culture, an individual organoid or the cells that compose it, these state variables can be characterised, most easily by transcriptomics and by high-content image analysis. Their states can be compared to their in vivo counterparts. Current evidence suggests that organoids explore a wider state space than organs in vivo due to the lack of niche signalling and the variability of boundary conditions in vitro. Using data-driven state inference and in silico modelling, phase diagrams can be constructed to systematically sort organoids along biochemical or biophysical axes. These phase diagrams allow us to identify control strategies to modulate organoid state. To do so, the biochemical and biophysical environment, as well as the cells that seed organoids, can be manipulated.
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Organoides , Biología Sintética , Diferenciación Celular , Transducción de SeñalRESUMEN
Phosphate (Pi) limitation represents a primary constraint on crop production. To better cope with Pi deficiency stress, plants have evolved multiple adaptive mechanisms for phosphorus acquisition and utilization, including the alteration of growth and the activation of Pi starvation signaling. However, how these strategies are coordinated remains largely unknown. Here, we found that the alternative splicing (AS) of REGULATOR OF LEAF INCLINATION 1 (RLI1) in rice (Oryza sativa) produces two protein isoforms: RLI1a, containing MYB DNA binding domain and RLI1b, containing both MYB and coiled-coil (CC) domains. The absence of a CC domain in RLI1a enables it to activate broader target genes than RLI1b. RLI1a, but not RLI1b, regulates both brassinolide (BL) biosynthesis and signaling by directly activating BL-biosynthesis and signaling genes. Both RLI1a and RLI1b modulate Pi starvation signaling. RLI1 and PHOSPHATE STARVATION RESPONSE 2 function redundantly to regulate Pi starvation signaling and growth in response to Pi deficiency. Furthermore, the AS of RLI1-related genes to produce two isoforms for growth and Pi signaling is widely present in both dicots and monocots. Together, these findings indicate that the AS of RLI1 is an important and functionally conserved strategy to orchestrate Pi starvation signaling and growth to help plants adapt to Pi-limitation stress.
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Oryza , Fosfatos , Empalme Alternativo , Regulación de la Expresión Génica de las Plantas , Proteínas de PlantasRESUMEN
All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.
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INTRODUCTION: In this study, we investigated the correlation and clinical significance of peripheral blood leukocytes, neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) in patients with acute urticaria. METHODS: Complete blood count with differential, CRP, and PCT tests were conducted on patients with acute urticaria. A total of 614 patients with acute urticaria were divided into three groups: the first group consisted of patients with elevated leukocyte and neutrophil count, the second group consisted of patients with normal leukocyte and neutrophil count, and the third group consisted of patients with abnormal leukocyte and neutrophil count. A correlation analysis was conducted to investigate the levels of leukocytes, neutrophils, CRP, and PCT in the three groups. RESULTS: The results of Kruskal-Wallis' nonparametric test revealed statistically significant variations in leukocytes, neutrophils, CRP, and PCT among the three groups (p < 0.001). However, CRP and PCT showed no statistically significant differences between the second and third groups (p < 0.001, p = 0.0041, p = 0.0032). Additional multiple comparisons in Spearman correlation analysis indicated statistically significant differences (p = 0.55). Across all groups, there was a statistically significant difference in the correlation between CRP-PCT and leukocytes-neutrophils (p = 0.53). CONCLUSION: Leukocytes and neutrophils are sensitive to the impact of medications and stress on the body. Combining CRP and PCT, as well as routine blood test, may be a comprehensive assessment of infection presence and severity in patients, providing guidance for antibiotic treatment.
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Proteína C-Reactiva , Neutrófilos , Polipéptido alfa Relacionado con Calcitonina , Urticaria , Humanos , Proteína C-Reactiva/análisis , Polipéptido alfa Relacionado con Calcitonina/sangre , Urticaria/diagnóstico , Urticaria/sangre , Urticaria/inmunología , Urticaria/etiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedad Aguda , Neutrófilos/inmunología , Recuento de Leucocitos , Biomarcadores/sangre , Adolescente , Anciano , Adulto Joven , Infecciones/diagnóstico , Infecciones/sangre , Infecciones/complicaciones , Infecciones/etiologíaRESUMEN
Safety problems caused by organophosphorus pesticide (OP) residues are constantly occurring, so the development of new methods for the degradation and detection of OPs is of great scientific significance. In the present study, ß-sheet peptides and ß-hairpin peptides for catalyzing the hydrolysis of OPs were designed and synthesized. The peptide sequences with the highest hydrolytic activity (EHSGGVTVDPPLTVEHSAG) were screened by investigating the effect of the location of the active sites of the peptide and the peptide's structure on the degradation of OPs. In addition, the relationship between the peptides' conformation and hydrolytic activity was further analyzed based on density functional theory calculations. The noncovalent interactions of the peptides with the OPs and the electrostatic potential on the molecular surface and molecular docking properties were also investigated. It was found that peptides with approximate active amino acids consisting of the catalytic triad and with the hairpin structure had enhanced hydrolytic activity toward the hydrolysis of OPs. To develop an electrochemical sensor technique to detect OPs, the conductive MXene (Ti3C2) material was first immobilized with a caffeic acid monolayer via enediol-metal complex chemistry and then bound with the ß-hairpin peptide (EHSGGVTVDPPLTVEHSAG) via carboxy-amine condensation chemistry between the -COOH of caffeic acid and the -NH2 of the peptide to prepare a MXene-peptide composite. Then, the prepared composite was modified on the surface of a glassy carbon electrode to construct an electrochemical sensor for the detection of OPs. The developed technique could be used to monitor OPs within 15 min with a two orders of linear working range and with a detection limit of 0.15 µM. Meanwhile, the sensor showed good reliability for the detection of OPs in real vegetables.
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Compuestos Organofosforados , Plaguicidas , Plaguicidas/análisis , Plaguicidas/química , Compuestos Organofosforados/química , Compuestos Organofosforados/análisis , Hidrólisis , Simulación del Acoplamiento Molecular , Péptidos/química , Límite de Detección , Técnicas Electroquímicas/métodos , Secuencia de Aminoácidos , Ácidos CafeicosRESUMEN
BACKGROUND: Acute pancreatitis (AP) is an unpredictable and potentially fatal disorder. A derailed or unbalanced immune response may be the root of the disease's severe course. Disorders of lipid metabolism are highly correlated with the occurrence and severity of AP. We aimed to characterize the contribution and immunological characteristics of lipid metabolism-related genes (LMRGs) in non-mild acute pancreatitis (NMAP) and identify a robust subtype and biomarker for NMAP. METHODS: The expression mode of LMRGs and immune characteristics in NMAP were examined. Then LMRG-derived subtypes were identified using consensus clustering. The weighted gene co-expression network analysis (WGCNA) was utilized to determine hub genes and perform functional enrichment analyses. Multiple machine learning methods were used to build the diagnostic model for NMAP patients. To validate the predictive effectiveness, nomograms, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) were used. Using gene set variation analysis (GSVA) and single-cell analysis to study the biological roles of model genes. RESULTS: Dysregulated LMRGs and immunological responses were identified between NMAP and normal individuals. NMAP individuals were divided into two LMRG-related subtypes with significant differences in biological function. The cluster-specific genes are primarily engaged in the regulation of defense response, T cell activation, and positive regulation of cytokine production. Moreover, we constructed a two-gene prediction model with good performance. The expression of CARD16 and MSGT1 was significantly increased in NMAP samples and positively correlated with neutrophil and mast cell infiltration. GSVA results showed that they are mainly upregulated in the T cell receptor complex, immunoglobulin complex circulating, and some immune-related routes. Single-cell analysis indicated that CARD16 was mainly distributed in mixed immune cells and macrophages, and MGST1 was mainly distributed in exocrine glandular cells. CONCLUSIONS: This study presents a novel approach to categorizing NMAP into different clusters based on LMRGs and developing a reliable two-gene biomarker for NMAP.
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Pancreatitis , Humanos , Pancreatitis/genética , Enfermedad Aguda , Metabolismo de los Lípidos , BiomarcadoresRESUMEN
Acute myeloid leukemia (AML) is a hematological malignancy with an alarming mortality rate. The development of novel therapeutic targets or drugs for AML is urgently needed. Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation. Recently, ferroptosis has emerged as a novel method for targeting cancer, including AML. Epigenetic dysregulation is a hallmark of AML, and a growing body of evidence suggests that ferroptosis is subject to epigenetic regulation. Here, we identified protein arginine methyltransferase 1 (PRMT1) as a ferroptosis regulator in AML. The type I PRMT inhibitor GSK3368715 promoted ferroptosis sensitivity in vitro and in vivo. Moreover, PRMT1-knockout cells exhibited significantly increased sensitivity to ferroptosis, suggesting that PRMT1 is the primary target of GSK3368715 in AML. Mechanistically, both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of AML cells following GSK3368715 treatment. Additionally, the GSK3368715 treatment reduced the abundance of H4R3me2a, the main histone methylation modification mediated by PRMT1, in both genome-wide and ACSL1 promoter regions. Overall, our results demonstrated a previously unknown role of the PRMT1/ACSL1 axis in ferroptosis and suggested the potential value and applications of the combination of PRMT1 inhibitor and ferroptosis inducers in AML treatment.
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Ferroptosis , Leucemia Mieloide Aguda , Humanos , Ferroptosis/genética , Regulación hacia Arriba , Epigénesis Genética , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Inhibidores Enzimáticos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteínas Represoras/metabolismo , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismoRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now the major contributor to chronic liver disease. Disorders of lipid metabolism are a major element in the emergence of NAFLD. This research intended to explore lipid metabolism-related clusters in NAFLD and establish a prediction biomarker. METHODS: The expression mode of lipid metabolism-related genes (LMRGs) and immune characteristics in NAFLD were examined. The "ConsensusClusterPlus" package was utilized to investigate the lipid metabolism-related subgroup. The WGCNA was utilized to determine hub genes and perform functional enrichment analysis. After that, a model was constructed by machine learning techniques. To validate the predictive effectiveness, receiver operating characteristic curves, nomograms, decision curve analysis (DCA), and test sets were used. Lastly, gene set variation analysis (GSVA) was utilized to investigate the biological role of biomarkers in NAFLD. RESULTS: Dysregulated LMRGs and immunological responses were identified between NAFLD and normal samples. Two LMRG-related clusters were identified in NAFLD. Immune infiltration analysis revealed that C2 had much more immune infiltration. GSVA also showed that these two subtypes have distinctly different biological features. Thirty cluster-specific genes were identified by two WGCNAs. Functional enrichment analysis indicated that cluster-specific genes are primarily engaged in adipogenesis, signalling by interleukins, and the JAK-STAT signalling pathway. Comparing several models, the random forest model exhibited good discrimination performance. Importantly, the final five-gene random forest model showed excellent predictive power in two test sets. In addition, the nomogram and DCA confirmed the precision of the model for NAFLD prediction. GSVA revealed that model genes were down-regulated in several immune and inflammatory-related routes. This suggests that these genes may inhibit the progression of NAFLD by inhibiting these pathways. CONCLUSIONS: This research thoroughly emphasized the complex relationship between LMRGs and NAFLD and established a five-gene biomarker to evaluate the risk of the lipid metabolism phenotype and the pathologic results of NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Metabolismo de los Lípidos/genética , Biomarcadores/metabolismo , FenotipoRESUMEN
BACKGROUND: Atherosclerosis is now the main cause of cardiac-cerebral vascular diseases around the world. Disturbances in lipid metabolism have an essential role in the development and progression of atherosclerosis. Thus, we aimed to investigate lipid metabolism-related molecular clusters and develop a diagnostic model for atherosclerosis. METHODS: First, we used the GSE100927 and GSE43292 datasets to screen differentially expressed lipid metabolism-related genes (LMRGs). Subsequent enrichment analysis of these key genes was performed using the Metascape database. Using 101 atherosclerosis samples, we investigated the LMRG-based molecular clusters and the corresponding immune cell infiltration. After that, a diagnostic model for atherosclerosis was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a series of bioinformatics techniques, including CIBERSORT, gene set variation analysis, and single-cell data analysis, were used to analyze the potential mechanisms of the model genes in atherosclerosis. RESULTS: A total of 29 LMRGs were found to be differentially expressed between atherosclerosis and normal samples. Functional and DisGeNET enrichment analyses indicated that 29 LMRGs are primarily engaged in cholesterol and lipid metabolism, the PPAR signaling pathway, and regulation of the inflammatory response and are also closely associated with atherosclerotic lesions. Two LMRG-related molecular clusters with significant biological functional differences are defined in atherosclerosis. A three-gene diagnostic model containing ADCY7, SCD, and CD36 was subsequently constructed. Receiver operating characteristic curves, decision curves, and an external validation dataset showed that our model exhibits good predictive performance. In addition, three model genes were found to be closely associated with immune cell infiltration, especially macrophage infiltration. CONCLUSIONS: Our study comprehensively highlighted the intricate association between lipid metabolism and atherosclerosis and created a three-gene model for future clinical diagnosis.
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Aterosclerosis , Metabolismo de los Lípidos , Humanos , Metabolismo de los Lípidos/genética , Aterosclerosis/diagnóstico , Aterosclerosis/genética , Biomarcadores , Antígenos CD36/genética , Biología ComputacionalRESUMEN
BACKGROUND: Abnormalities of the fetal cardiovascular system caused by fetal growth restriction (FGR) may lead to adverse outcomes. The fetal cardiac function assessment is of great significance for treatment selection and prognostic evaluation of fetuses with FGR. OBJECTIVE: This study aimed to explore the value of fetal HQ analysis based on speckle tracking imaging (STI) to evaluate the global and regional cardiac function of fetuses with early-onset or late-onset FGR. METHODS: From June 2020 to November 2022, 30 pregnant women with early-onset FGR (21-38 gestational weeks) and 30 pregnant women with late-onset FGR (21-38 gestational weeks) in the Department of Ultrasound, Shandong Maternal and Child Health Hospital were enrolled. Also, 60 healthy volunteer pregnant women were enrolled as two control groups according to the principle of matching gestational weeks (21-38 gestational weeks). The fetal cardiac functions, including fetal cardiac global spherical index (GSI), left ventricular ejection fraction (LVEF), fractional area change (FAC) of both ventricles, global longitudinal strain (GLS) of both ventricles, 24-segmental fractional shortening (FS), 24-segmental end-diastolic ventricular diameter (EDD), and 24-segmental spherical index (SI), were assessed using fetal HQ. The standard biological values of fetuses and Doppler blood flow parameters of fetuses and mothers were measured. The estimated fetal weight (EFW) measured by the last prenatal ultrasound was calculated, and the weights of newborns were followed up. RESULTS: Among early FGR, late FGR and total control group, significant differences were found in global cardiac indexes of right ventricle (RV), left ventricle (LV) and GSI. For the segmental cardiac indexes, there are significant differences in three groups except parameter of LVSI. Compared with the control group at the same gestational week, the Doppler indexes including MCAPI and CPR in both the early-onset FGR group and the late-onset FGR group were significantly different. The intra- and inter-observer correlation coefficients of RV FAC, LV FAC, RV GLS, and LV GLS were good. Further, the intra- and inter-observer variability in FAC and GLS was small, as analyzed using the Bland-Altman scatter plot. CONCLUSIONS: Fetal HQ software based on STI showed that FGR affected the global and segmental cardiac function of both ventricles. FGR no matter early-onset or late-onset altered Doppler indexes significantly. The FAC and the GLS had satisfactory repeatability in evaluating fetal cardiac function.
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Retardo del Crecimiento Fetal , Corazón Fetal , Niño , Recién Nacido , Embarazo , Femenino , Humanos , Retardo del Crecimiento Fetal/diagnóstico por imagen , Volumen Sistólico , Corazón Fetal/diagnóstico por imagen , Función Ventricular Izquierda , Atención Prenatal , Ultrasonografía Prenatal/métodosRESUMEN
It is generally believed that the majority of head and neck cancers develop in the mucosal epithelial cells of the mouth, pharynx, and larynx, which is collectively known as head and neck squamous cell carcinoma (HNSC). As a complex pathological process, HNSC develops through a variety of cellular and molecular events. Cancerous cells and immune cells infiltrating tumors are the main components of the tumor microenvironment. However, infiltration of HNSCs by the immune system has not been determined to date. In this work, we proposed computational algorithms to identify different immune subtypes. An analysis of the Cancer Genome Atlas (TCGA) database revealed gene expression profiles and corresponding clinical information. In HNSC patients, two immune-related genes (ZAP70 and IGKV2D-40) may be targets for immunotherapy, and these genes appear to be closely related to the prognosis. Several immunological subtypes were associated with immune function, immune checkpoints, and prognostic factors in HNSCs. Furthermore, ZAP70 is closely related to the overall survival (OS), progress-free interval (PFI), and disease-specific survival (DSS) of HNSC patients. The potential pathways that are associated with ZAP70 were found to have included adaptive immune response, response to oxidative stress, DNA replication, and lipid binding. This study provides a theoretical foundation for developing immunotherapy drugs for HNSC patients. By evaluating larger cohorts, we can gain a deeper understanding of immunotherapy and provide direction for current research on immunotherapy strategies in HNSCs.
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Células Epiteliales , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Pronóstico , Algoritmos , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Microambiente Tumoral/genética , Biomarcadores de TumorRESUMEN
Control of heterogeneous ice nucleation (HIN) is critical for applications that range from iceophobic surfaces to ice-templated materials. HIN on 2D materials is a particular interesting topic that still lacks extensive experimental investigations. Here, we focus on the HIN on single-layer graphene (SLG) transferred onto different substrates, including silicon, silica, and thermal oxide on silicon. Complemented by other samples without SLG, we obtain a large range of wetting contact angles (WCAs) from 2° to 95°. All pristine SLG samples exhibit a large contact angle of â¼95°, which is close to the theoretical value of 96° for free-standing SLG, irrespective of the substrate and even in the presence of nanoscale wrinkles on SLG, which are due to the transfer process, indicating that the topographical features have little impact on the wetting behavior. Interestingly, SLG displays changes in hydrophobicity upon repeated water droplet freezing-melting-drying cycles due to a shift in Fermi level and/or enhanced water-substrate polar molecular interactions, likely induced by residual adsorption of H2O molecules. We found that a 0.04 eV decrease in SLG Fermi level reduces the SLG/water interface energy by â¼6 mJ/m2, thereby making SLG less hydrophobic. Counterintuitively, the reduction in SLG/water interface energy and the enhanced hydrophilicity after repeated freezing-melting-evaporation cycles actually decreases the freezing temperature by â¼3-4 °C, thereby slightly retarding rather than enhancing HIN. We also found that the water droplet freezing temperature differed by only â¼1 °C on different substrates with WCAs from 2° to 95°, an intriguing and yet reasonable result that confirms that wettability alone is not a good indicator of HIN capability. The HIN rate is rather determined by the difference between substrate/water and substrate/ice interface energies, which was found to stay almost constant for substrates weakly interacting with water/ice via van der Waals or hydrogen bonds, irrespective of hydrophilicity.
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Heterocyclic amines (HCA) are the main mutagenic factors in cooked meat products and are considered to be hazardous chemicals in the field of food safety. In this study, inspired by the "host-guest" interaction mechanism, a new technique for detecting 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) was developed, taking advantage of the molecular cavities of cucurbit[7]uril (CB[7]) and the powerful guest recognition properties between CB[7] and PhIP. Based on this recognition mechanism, three steps were included in the detection procedure: firstly, regenerated cellulose (RC) membrane was oxidized by NaIO4 to generate aldehyde groups; secondly, the PhIP molecules to be detected were trapped by the aldehyde groups via amine-aldehyde conjugation chemistry; thirdly, the RC membrane with trapped PhIP was immersed into solutions of dansyl chloride-labelled CB[7] to allow the host-guest interaction to occur, so that PhIP could be quantified by fluorescence of the dansyl chloride dye. The limit of detection, linear range and recovery of this method were about 0.224 µg kg-1, 10-1000 nM and 89.0-96.4%, respectively. So far, most reported techniques for HCA detection are based on HPLC coupled with mass spectroscopy, and the method reported here might be the first quick measurement technique for HCA and may find wide application in food safety detection.
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Carcinógenos , Carne , Aldehídos , Aminas , Carcinógenos/análisis , Compuestos Heterocíclicos con 2 Anillos , Imidazoles , Imidazolidinas , Compuestos Macrocíclicos , Carne/análisisRESUMEN
Majucin-type Illicium sesquiterpenes with potent neurotrophic activity are considered to be promising candidates for the treatment of various neurodegenerative disease. Owing to the low-abundance metabolites in Illicium genus, there are few studies on their structural modifications, structure-activity relationships, and pharmacophoric motif. Herein, structural modifications were conducted on the hydroxyl groups at C-3 and C-6 positions of two majucin-type compounds neomajucin (1) and majucin (2), and 39 neomajucin/majucin based esters were synthesized and evaluated for their neurite outgrowth-promoting activities. Among all the target derivatives, compounds 1a, 1j, 1r, 2b, 2d, 3a, 3b, 3d and 3h displayed more potent neurite outgrowth-promoting activity than their precursors. Some interesting structure-activity relationships (SARs) were also observed. Moreover, compound 1a showed good neuroprotective effect on MPP+-induced PC12 cell damage. Finally, compounds 1a and 3a exhibited relatively no cytotoxicity to normal human H9C2 cardiac cells. This work will shed light on the development of neomajucin/majucin derivatives as potential neurotrophic agents.
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Factores de Crecimiento Nervioso/farmacología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Proyección Neuronal/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Illicium/química , Estructura Molecular , Factores de Crecimiento Nervioso/síntesis química , Factores de Crecimiento Nervioso/química , Enfermedades Neurodegenerativas/metabolismo , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Células PC12 , Ratas , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-ActividadRESUMEN
Magnolol and honokiol, derived from a Magnolia officinalis Rehd. et Wils, are a class of natural biphenolic lignans. Currently, the discovery of new α-glucosidase inhibitors from natural analogues is of interest. Here, four series of thirty new Mannich base analogues of magnolol/honokiol were prepared and evaluated for their α-glucosidase inhibitory activities. Among these Mannich base analogues of magnolol/honokiol, 3k and 3l exhibited more potent inhibitory effects on α-glucosidase than the reference drug acarbose, and their IC50 values were 14.94 ± 0.17 µM and 13.78 ± 1.42 µM, respectively. Some interesting structure-activity relationships (SARs) were also analyzed. The enzyme inhibition kinetics indicated that 3k and 3l were noncompetitive inhibitors. This result was in agreement with molecular docking studies, where the binding sites of 3k and 3l to α-glucosidase were different from that of the competitive inhibitor acarbose to α-glucosidase. Moverover, compounds 3k and 3l exhibited low toxicity to normal cells (LO2). Thus, analogues 3k and 3l could be deeply developed for the discovery of natural products based antidiabetic candidates.
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A flaring X-ray source was found near the galaxy NGC 4697 (ref. 1). Two brief flares were seen, separated by four years. During each flare, the flux increased by a factor of 90 on a timescale of about one minute. There is no associated optical source at the position of the flares, but if the source was at the distance of NGC 4697, then the luminosities of the flares were greater than 1039 erg per second. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar flares. We found two ultraluminous flaring sources in globular clusters or ultracompact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 × 1040 erg per second; the other flared five times to 1040 erg per second. The rise times of all of the flares were less than one minute, and the flares then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron-star or black-hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft γ repeaters that have repetitive flares of similar luminosities.
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Building a novel and efficient photothermal antibacterial nanoplatform is a promising strategy for precise bacterial elimination. Herein, a nanocomposite NiO NPs@AuNPs@Van (NAV) for selective MRSA removal was constructed by electrostatic self-assembly of highly photothermal magnetic NiO NPs and vancomycin (Van)-modified gold nanoparticles (AuNPs). In the presence of MRSA and under NIR irradiation, Van-mediated AuNPs can self-aggregate on MRSA surface, generating photothermal effect in situ and killing 99.6% MRSA in conjunction with magnetic NiO NPs. Additionally, the photothermal efficiency can be improved by magnetic enrichment due to the excellent magnetism of NAV, thereby enhancing the bactericidal effect at a lower experimental dose. In vitro antibacterial experiments and full-thickness skin wound healing test demonstrated that this combination therapy could effectively accelerate wound healing in MRSA-infected mice, increase collagen coverage, reduce IL-6 and TNF-α content, and upregulate VEGF expression. Biological safety experiments confirmed that NAV has good biocompatibility in vivo and in vitro. Overall, this work reveals a new type of nanocomposite with enhanced photothermal antibacterial activity as a potential nano-antibacterial agent for treating bacteria-infected wounds.
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Nanopartículas del Metal , Infecciones Estafilocócicas , Animales , Antibacterianos/uso terapéutico , Oro/uso terapéutico , Fenómenos Magnéticos , Nanopartículas del Metal/uso terapéutico , Ratones , Níquel , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND: The anterolateral thigh (ALT) flap is a popular choice for head and neck reconstruction surgery, but its ungainly thickness makes it of limited value in some intracavitary reconstructions. The ALT adipofascial flap is an improved flap without skin or muscle. Here, we seek to further illustrate the ALT adipofascial flap as an alternate method of hypopharyngeal and oropharyngeal reconstruction in head and neck. METHODS: A retrospective review of 9 patients (7 men, 2 women) ranging from 28 to 67 years (mean age, 53.1 years) who underwent reconstruction with the ALT adipofascial flap after hypopharyngeal carcinoma (4 patients) or oropharyngeal carcinoma (5 patients) resections from August 2018 to December 2019 was performed. Surgical outcomes and functional resoration were assessed. RESULTS: The size of the flaps ranged from 6 × 4 cm2 to 6 × 12 cm2 . The average flap thickness was 0.14 cm (range, 0.1-0.2 cm) and the average pedicle length was 9.8 cm (range, 7-12 cm). The postoperative course was uneventful in eight patients. Reconstruction was successful in all cases during 7-23 months of follow-up (mean time, 14.3 months). All patients resumed oral feeding for 2-8 weeks (mean time, 4.9 weeks) and the tracheal cannula was successfully removed 0.5-4 months postsurgery (mean time, 2.4 months). CONCLUSION: The ALT adipofascial flap is a viable choice for hypopharyngeal and oropharyngeal reconstructions and is thinner than the ALT flap. It could be harvested as a single-pedicled double-island flap for complex defect reconstruction.
Asunto(s)
Carcinoma , Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Carcinoma/cirugía , Femenino , Colgajos Tisulares Libres/cirugía , Humanos , Hipofaringe/cirugía , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Muslo/cirugíaRESUMEN
Two undescribed ether derivatives of sesquiterpenes, 1-ethoxycaryolane-1, 9ß-diol (1) and 2-ethoxyclovane-2ß, 9α-diol (3), and one new monoterpene glycoside, p-menthane-1α,2α,8-triol-4-O-ß-D-glucoside (5), were obtained, together with eight known compounds from the stems and leaves of I. simonsii. Their structures were elucidated by spectroscopic methods. Compounds 1-11 were evaluated for their potency against Staphylococcus aureus and clinical methicillin-resistant S. aureus (MRSA). Among them, compound 3 was weakly active against S. aureus (MIC = 128 µg/mL), and compounds 6 and 7 exhibited good antibacterial activity against S. aureus and MRSA (MICs = 2-8 µg/mL). A primary mechanism study revealed that compounds 6 and 7 could kill bacteria by destroying bacterial cell membranes. Moreover, compounds 6 and 7 were not susceptible to drug resistance development.