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Objective: To investigate the factors affecting the time taken for B cell reconstitution after rituximab (RTX) treatment in children with steroid-sensitive nephrotic syndrome. Methods: This was a retrospective cohort study. The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology, Rheumatology and Immunology, Children's Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively. The data of demographics, immunosuppressant treatment and laboratory tests such as CD19+B cell count, urinary protein quantification were collected. The patients were divided into 2 groups, the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction. A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction, and the predictive value of these factors was assessed by plotting the receiver operating characteristic (ROC) curve. Results: There were 42 children, with 35 males and 7 females. They were aged 3.5 (2.2, 5.9) years at the onset of PNS and (8.4±3.3) years at their first RTX treatment. The time for B cell reconstitution was (152±53) d. There were 20 children in the early reconstruction group and 22 children in the late reconstruction group. There were no statistically significant differences (all P>0.05) between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion (0.29 (0.16, 0.50) vs. 0.29 (0.19, 0.46) mg/(kg·d)), the percentage of children using tacrolimus before RTX (65%(13/20) vs. 45%(10/22)) and cumulative doses (0.04 (0.03, 0.05) vs. 0.03 (0.03, 0.06) mg/(kg·d)), the steroid doses at the time of RTX infusion (0.73 (0.49, 0.90) vs. 0.71 (0.58, 0.89) mg/(kg·d)), the percentage of children using tacrolimus at the initial RTX infusion (50% (10/20)vs. 41% (9/22)) and the doses (0.03 (0.02, 0.04) vs. 0.02 (0.01, 0.04) mg/(kg·d)), the discontinuation time of tacrolimus post-RTX infusion (71 (42, 91) vs. 64 (42, 91) d). A multivariate analysis revealed a correlation (OR=0.26, 95%CI 0.10-0.68, P=0.006) between B cell count following the second RTX infusion and the time taken for B cell reconstruction. The area under the ROC curve for B cell count after the RTX infusion in predicting the time to B cell reconstruction was 0.89 (95%CI 0.78-0.99, P<0.001) and the cut-off value was 0.925×106/L. Conclusions: The time of B cell reconstruction is not influenced by the previous or concurrent use of tacrolimus, regardless of its duration and the dosage of steroid and tacrolimus prior to the RTX infusion. Insteadly, the peripheral blood B cell count (0.925×106/L) following the second RTX infusion for SSNS is identified as an independent predictor of reconstruction time, allowing for a more precise prediction and early intervention to maintain disease remission.
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Complicated many-body interactions between ions and surrounding particles exist in warm and hot dense plasmas. It will significantly alter the atomic structures and dynamic properties of the embedded ions. Recently, the atomic-state-dependent (ASD) screening model has been proposed and shown to be valid for investigating the screening effect in warm and hot dense plasmas over a wide range of electron densities and temperatures. By employing the ASD model, we investigate the photoionization process for the hydrogenlike carbon ion embedded in warm and hot dense plasmas with corresponding Coulomb coupling parameter ranges of 0.05 ≤ Γ ≤ 1.16, where Γ characterizes the ratio of the average potential to thermal energy. It is found that there are stronger plasma screening effects on the ionization energy and photoionization cross section due to the negative-energy electron distributions considered in the ASD model compared to those considering only free electrons. The present results from the ASD model show reasonable agreement with the classical Debye-Hückel (DH) model in weakly coupled plasmas. However, significant deviations of the ionization energy and cross section between these two models are observed in moderately and strongly coupled plasmas, due to the approximate treatment of the plasma-electron density distribution of the DH model. In the region of low photoelectron energies, the positions of the shape resonance peaks of the cross sections obtained from the ASD model differ significantly from those of the DH model due to the different screening effects.
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Semen is a measure of the reproductive efficiency of roosters, which affects the economic benefits of white-feathered broilers. Over the years, research in this field has mainly focused on hens, while there have been fewer studies on the reproductive traits of roosters. To identify the genes related to the semen traits of roosters, we used a chicken 55 K SNP chip to genetically type the white-feathered population (220) and performed imputation with resequencing data from 97 roosters. In total, 1 048 576 SNPs were obtained and used for genome-wide association analysis of semen volume, from which 197 genome-wide significant markers were identified, all within the interval of 13.82-16.12 Mb on chromosome 7. By combining our results with the biological functions of genes in the interval, four candidate genes were identified that potentially relate to semen volume: FAPP1, OSBPL6, SESTD1 and SSFA2. Our findings may provide a basis for further research on the genetic mechanism and marker-assisted selection of semen volume in white-feathered broilers.
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Pollos , Estudio de Asociación del Genoma Completo , Animales , Masculino , Femenino , Estudio de Asociación del Genoma Completo/veterinaria , Pollos/genética , Semen , Análisis de Semen , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) binding properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal complexes were investigated by UV-Vis spectrophotometry and viscosity titration. The toxicological properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tridentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)2], [Ni(HL1)2], [Cu(HL1)2], [Co(L2)2], [Cu(L2)2], [Zn(L2)2], [ScL2(NO3)2(H2O)2], [Pr(L2)2(NO3)] and [Dy(L2)2(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 104~105 L mol-1 compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 × 104 L mol-1]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)2] and [Cu(HL1)2] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 µmol L-1 and 2.2 µmol L-1, respectively. CONCLUSIONS: These compounds, especially [Ni(HL1)2] and [Cu(HL1)2], will be promising for anti-tumor drugs, which should be further studied.
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Complejos de Coordinación , Humanos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Tiofenos , Supervivencia Celular , Células HeLa , Ligandos , Espectroscopía Infrarroja por Transformada de Fourier , ADN/metabolismoRESUMEN
Objectives: To establish a geographic information application system for analyzing the spatial and temporal distribution of major infectious diseases in various regions of the world and to assess the risk of importation of those diseases, to China. Methods: We collected and integrated the following information on: 1) outbreaks and areas of epidemics of major infectious diseases in the world from 2000 to 2017, 2) cases of infectious diseases in arriving travelers through active surveillance at international entry-exit ports in mainland China from 2014 to 2016, 3) numbers of annual global international flights and travelers in the country. With the above information, a global space-time distribution database on major infectious diseases was then established, using the technology related to the system. Models regarding technologies on time-space analysis, probabilistic risk assessment and geographic information visualization, were applied to establish a geographic information system on risk assessment of infectious diseases that imported to China. Results: Through integration of information on outbreaks and epidemic areas of 60 major infectious diseases in 220 countries and regions around the world, as well as 42 kinds of infectious diseases identified among the international arrivals in mainland China, a system was then developed. Information on the distribution of major infectious diseases and their potential risks in the worldwide various regions, characteristics of spectrum and disease burden of infectious diseases imported to each province of mainland China were displayed. Thus, risks on importing infectious diseases in each province via air way were able to be evaluated and simulated by the probabilistic risk assessment model, under the information on specific kind of infectious disease, outside China. Conclusion: Geographic Information System on Risk Assessment Regarding Infectious Diseases Imported to China provides basic data for epidemiological reconnaissance and assessment on risks of importing infectious diseases outside China, thus would be helpful for the improvement of strategies on surveillance, prevention and control regarding the importing infectious diseases, in China.
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Enfermedades Transmisibles Importadas/epidemiología , Brotes de Enfermedades/prevención & control , Monitoreo Epidemiológico , Sistemas de Información Geográfica , China , Humanos , Medición de RiesgoRESUMEN
The blue-eggshell and dwarf traits have an important economic value in poultry production. Using a genetic aggregation-based strategy, the molecular marker-assisted selection technology was jointly used to provide a rapid breeding method for pure strain chickens simultaneously with hens exhibiting the blue-eggshell and dwarf traits. Overall, 80 male dwarf chickens and 1,000 hybrid blue-eggshell hens (F0) were used for the hybridization experiment. Subsequently, the crossing of F1 or F2 chicks was performed in succession. The F1 and F2 chicks were respectively detected by the joint molecular markers of the solute carrier organic anion transporter family, namely, 1B3 (SLCO1B3) and the growth hormone receptor (GHR) genes, which relate to blue-eggshell and dwarf traits. Meanwhile, the selection of blue-eggshell and dwarf phenotypes was used to validate the data obtained by the molecular markers. The results showed that F1 chicks included the heterozygous and wild-type of SLCO1B3, as well as the homozygous (hens) and heterozygous (roosters) of GHR. However, F2 chicks included 3 different genotypes of both SLCO1B3 and GHR. Ultimately, 196 F1 roosters (concurrently with heterozygous genotype of SLCO1B3 and GHR) and 1,073 F1 hens (concurrently with heterozygous genotype of SLCO1B3 and homozygous genotype of GHR) were obtained from the initial 10,040 F1 chicks. Further, 27 F2 roosters and 345 F2 hens, which simultaneously carried the homozygous genotype of SLCO1B3 and GHR, were screened from the initial 6,000 F2 chicks. Data obtained on the blue-eggshell and dwarf phenotypes were consistent with the results by molecular markers. Similarly, the purity verification of the strain obtained through 2 crossing experiments (F0â × F2â and F2â × F2â) revealed that all chickens had the blue-eggshell and dwarf traits, supporting that the obtained F2 strain was pure. In summary, for the first time, we successfully bred a pure strain chicken with blue-eggshell and dwarf traits by jointly using the molecular markers of the SLCO1B3 and GHR genes. Our study provides a new method for the rapid cultivation of new chicken strains.
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Pollos/genética , Enanismo/genética , Cáscara de Huevo , Hibridación Genética , Animales , Cruzamiento/métodos , Color , Femenino , Masculino , Receptores de Somatotropina/genética , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/genéticaRESUMEN
Magnetic skyrmions are topologically protected domain structures related to the Dzyaloshinskii-Moriya interaction (DMI). To understand how magnetic skyrmions occur under different circumstances, we propose a model for skyrmion formation in a bilayer system of ferromagnetic/antiferromagnetic (FM/AFM) films, in which the bulk DMI is only present in the AFM film. Micromagnetic simulations reveal that skyrmions are formed in this system due to the competition between the DMI and demagnetization energies. A critical interfacial exchange energy (Ai = 6.5 mJ/m2) is determined, above which the competition occurs at its full extent. More skyrmions are formed with increasing external magnetic field till a critical value above which the external field is too large and thus leading to the annihilation of skyrmions. The spacing between two skyrmions can be as small as 45 nm. Our results may give technological implications for future skyrmion applications.
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Intramuscular fat is important in improving meat quality; however, the lack of high-purity intramuscular preadipocyte (IMP) in vitro has severely limited the in-depth research on the mutual regulation of myocytes and adipocytes in chicken. In this study, we establish a new method by combining the mature adipocyte ceiling method and the transwell co-culture system. Mature intramuscular adipocyte (MIA) and muscle satellite cell (MSC) were obtained from digested pectoralis major, and MIAs were transformed into IMPs by dedifferentiation with ceiling culture. MSCs were then purified by differential adhesion for 2 h. The results by inverted-microscope observation, MTT assay, Oil Red O staining, and q-PCR revealed that the de-differentiated cells from MIA were identified as the IMPs, and had the same the cellular morphology, the capacity on differentiation, proliferation and passage with the abdominal fat preadipocytes (P > 0.05). The applicability of the obtained IMPs in co-cultured experiment with the MSC revealed that it could meet the requirements of the experimental study. Finally, a co-culture system of IMPs and MSCs was established using a transwell chamber. The co-cultured results indicated that MSCs in the proliferative stage tend to accelerate the differentiation of IMPs to induce more fat content in co-cultured IMPs than in single-culture IMPs (P < 0.05), in the non-proliferative stage, the results tend to show the opposite (P < 0.05). The mRNA levels of related genes significantly changed in accordance with the fat content in cells. The results strongly supported the view that the established co-culture system was effective and feasible. In summary, we successfully found a new method to explore the interaction between myocytes and adipocytes of chicken. Our findings can deepen research on the regulation of chicken myocytes and adipocytes.
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Adipocitos/citología , Técnicas de Cultivo de Célula/veterinaria , Pollos , Técnicas de Cocultivo/veterinaria , Músculos Pectorales/fisiología , Células Satélite del Músculo Esquelético/citología , Animales , Técnicas de Cultivo de Célula/métodos , Técnicas de Cocultivo/métodos , Células Musculares/citologíaRESUMEN
Calpain 9 (CAPN9) is expressed in the stomach and small intestine. CAPN9 has regulatory roles in hypertension, heart disease, gastric mucosal defense, and kidney disease. The involvement of CAPN9 has not been reported in the development of chickens. CAPN9 mRNA was found in adipose and muscle tissue in this study. Two linkage single nucleotide polymorphisms (SNP; G7518A and C7542G) in intron 4 were screened from 160 birds of the D2 chicken line. The 2 mutation sites were associated with carcass weight, evisceration weight, abdominal fat weight (AFW), abdominal fat percentage (AFP), and breast muscle percentage (all P < 0.05). Intramuscular fat (IMF) content was not significantly different in the 3 genotypes. But, the AA(7518)/GG(7542) genotype had the highest IMF content, highest breast muscle weight, and lower AFW and AFP. Moreover, the mRNA level of CAPN9 in abdominal fat tissue was significantly different (P < 0.05 or P < 0.01) between any 2 genotypes, consistent with AFW and AFP. In summary, the expression of CAPN9 in adipose and breast muscle tissue is reported for the first time. CAPN9 affected production performance of chickens. As a marker, the linkage G7518A and C7542G polymorphisms in intron 4 of CAPN9 could affect the production traits by regulating mRNA expression. The findings concerning the marker enrich the theoretical foundation for molecular breeding of high-quality broilers.
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Proteínas Aviares/genética , Calpaína/genética , Pollos/genética , Regulación de la Expresión Génica , Polimorfismo de Nucleótido Simple , Grasa Abdominal/metabolismo , Animales , Proteínas Aviares/metabolismo , Secuencia de Bases , Peso Corporal/genética , Calpaína/metabolismo , Pollos/metabolismo , Músculos Pectorales/crecimiento & desarrollo , Músculos Pectorales/metabolismoRESUMEN
1. Lipid metabolism is an indispensable process in an organism, though little is known about the regulatory mechanisms of fat deposition in different types of adipose tissues. 2. The differentially expressed genes related to triglyceride (TG) metabolism between abdominal and intramuscular fat (IMF) of Beijing-You chickens were investigated in this study. 3. TG content in abdominal fat (AF) (349.7 mg/g) was significantly higher (P < 0.01) than in the breast and thigh (12.3 mg/g and 24.8 mg/g, respectively). 4. Using Agilent chicken gene-expression profiling in adipose tissues between AF and muscle (breast and thigh), certain representative genes related to fatty acid metabolism, lipoprotein catabolism and esterification reactions were significantly upregulated (P < 0.05 or P < 0.01). 5. Genes involved in fatty acid oxidation or carbohydrate utilisation were significantly up- or downregulated (P < 0.05 or P < 0.01), including those involved with highly enriched pathways of lipid metabolism (PPAR, Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion and regulation of actin cytoskeleton) and muscle contraction. 6. Overall, higher TG levels were observed in AF tissue than in adipose tissues of breast and thigh, which could be regulated through gene expression of pathways related to lipid metabolism (PPAR, Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion and regulation of actin cytoskeleton) and muscle contraction. These results provide clues to understanding the molecular mechanisms of TG metabolism between abdominal and IMF.
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Grasa Abdominal/metabolismo , Tejido Adiposo/metabolismo , Pollos/metabolismo , Perfilación de la Expresión Génica , Metabolismo de los Lípidos/genética , Triglicéridos/metabolismo , Animales , Pollos/genética , Regulación de la Expresión Génica , Redes y Vías Metabólicas/genética , Músculo Esquelético/metabolismo , Muslo/fisiologíaRESUMEN
Magnetic skyrmions are promising building blocks for next generation data storage due to their stability, small size and extremely low currents to drive them, which can be used instead of traditional magnetic domain walls to store information as data bits in metalic racetrack memories. However, skyrmions can drift from the direction of electron flow due to the Magnus force and thus may annihilate at the racetrack edges, resulting in the loss of information. Here we propose a new skyrmion-based racetrack structure by adding high-K materials (materials with high magnetic crystalline anisotropy) at the edges, which confines the skyrmions in the center region of the metalic racetrack efficiently. This design can overcome both the clogging and annihilation of skyrmions according to our micromagnetic simulation, which occur normally for skyrmions moving on a racetrack under small and large driving currents, respectively. Phase diagrams for skyrmion motion on the proposed racetrack with various values of current density and racetrack edge width have been calculated and given, showing that skyrmions can be driven at a high speed (about 300 m/s) in the racetrack under relatively smaller driving currents. This design offers the possiblity of building an ultrafast and energy-efficient skyrmion transport device.
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Intramuscular fat (IMF) content contributes to meat flavor and improves meat quality. Excessive abdominal fat, however, leads to a waste of feed resources. Here, an independent up-selection for IMF was used as a control (Line C), and a balanced selection program, with up-selection for IMF and down-selection AFP (Line B), was studied in JingXing yellow chickens. The mean of IMF and AFP within a family was the phenotypic value upon which selection was based. The selective pressures of IMF in line B and line C were the same in each generation. At G5, the IMF was significantly higher (P < 0.05) than that at G0 in both lines. For AFP, Line C was significantly higher at G5 (P < 0.05) than at G0, but the difference in Line B was not significant (P > 0.05). IMF increased by 11.4% and AFP decreased by 1.5% in Line B compared with the G0 generation. In contrast, the IMF increased by 17.6%, but was accompanied by an 18.7% increase in AFP, in control Line C. Of 10 other traits measured, body weight at 56 d age (BW56) and the percentages of eviscerated weight (EWP) showed a significant difference between the 2 lines (P < 0.05). The heritabilities for IMF and AFP, estimated by the DMU package, were 0.16 and 0.32, respectively. A moderate positive correlation existed between IMF and AFP (0.35). A balanced selection program for increasing IMF while controlling AFP (Line B) is shown here to be effective in practical chicken breeding.
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Grasa Abdominal/metabolismo , Tejido Adiposo/metabolismo , Pollos/genética , Herencia , Selección Genética , Animales , Pollos/metabolismo , Femenino , Masculino , Músculo Esquelético/metabolismoAsunto(s)
Pollos/genética , Resistencia a la Enfermedad/genética , Salmonelosis Animal/genética , Receptor Toll-Like 4/genética , Alelos , Animales , Carga Bacteriana , Cruzamiento , Ciego/microbiología , Análisis Mutacional de ADN , Genotipo , Interleucina-1/sangre , Interleucina-6/sangre , Factor 88 de Diferenciación Mieloide/metabolismo , Polimorfismo de Nucleótido Simple , Salmonella enteritidis , Análisis de Secuencia de ADN , Receptor Toll-Like 4/metabolismoRESUMEN
Hard/soft permanent magnets have aroused many interests in the past two decades because of their potential in achieving giant energy products as well as their rich variety of magnetic behaviors. Nevertheless, the experimental energy products are much smaller than the theoretical ones due to the much smaller coercivity measured in the experiments. In this paper, the deterioration of the coercivity due to the interface atomic diffusion is demonstrated based on a three dimensional (3D) micromagnetic software (OOMMF) and a formula derived for the pinning field in a hard/soft multilayer, which can be applied to both permanent magnets and exchange-coupled-composite (ECC) media. It is found that the formation of the interface layer can decrease the coercivity by roughly 50%, which is responsible for the observed smaller coercivity in both composite and single-phased permanent magnets. A method to enhance the coercivity in these systems is proposed based on the discussions, consistent with recent experiments where excellent magnetic properties are achieved.
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Excessive fat accretion is a crucial problem during broiler production. Abdominal fat weight (AbFW) and abdominal fat percentage (AbFP) are major phenotypic indices of fat traits. The present study used F2 females derived from a cross between Beijing-You and Cobb-Vantress chickens. Cohorts with extreme AbFP and AbFW phenotypes were chosen to construct high- and low-abdominal fat libraries (HAbF and LAbF, respectively) to investigate the expression profiles by RNA-sequencing and microRNA (miRNA)-sequencing. Compared with the LAbF library, 62 differentially expressed miRNAs (DEMs) and 303 differentially expressed genes (DEGs) were identified in the HAbF birds. Integrated analysis of DEMs and DEGs showed that a total of 106 DEGs were identified as target genes for the 62 DEMs. These genes were designated as intersection genes, and 11 of these genes are involved in lipid metabolism pathways. The miRNA gga-miR-19b-3p accelerated the proliferation of preadipocytes, as well as adipocyte differentiation, by down- regulating ACSL1. These findings suggest that some strong candidate miRNAs and genes, important in relation to abdominal adipose deposition, were identified by the integrated analysis of DEMs and DEGs. These findings add to our current understanding of the molecular genetic controls underlying abdominal adipose accumulation in chickens.
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Grasa Abdominal/metabolismo , Pollos/genética , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Regiones no Traducidas 3' , Grasa Abdominal/citología , Animales , Secuencia de Bases , Aves/genética , Aves/metabolismo , Diferenciación Celular , Proliferación Celular , Pollos/metabolismo , Coenzima A Ligasas/antagonistas & inhibidores , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Biblioteca de Genes , Redes Reguladoras de Genes , Metabolismo de los Lípidos/genética , MicroARNs/química , Fenotipo , ARN Mensajero/química , Alineación de Secuencia , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway.
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Adipocitos/metabolismo , Proteínas Aviares/metabolismo , Metabolismo de los Lípidos , Péptido Natriurético Encefálico/metabolismo , Receptores del Factor Natriurético Atrial/metabolismo , Adipocitos/citología , Animales , Proteínas Aviares/genética , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Pollos , Glucolípidos/metabolismo , Metabolismo de los Lípidos/genética , Lipólisis , Redes y Vías Metabólicas , Péptido Natriurético Encefálico/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores del Factor Natriurético Atrial/genética , Regulación hacia ArribaRESUMEN
Human DCTPP1 (dCTP pyrophosphatase 1), also known as XTP3-transactivated protein A, belongs to MazG-like nucleoside triphosphate pyrophosphatase (NTP-PPase) superfamily. Being a newly identified pyrophosphatase, its relevance to tumorigenesis and the mechanisms are not well investigated. In the present study, we have confirmed our previous study that DCTPP1 was significantly hyperexpressed in breast cancer and further demonstrated its strong association with tumor progression and poor prognosis in breast cancer. Knockdown of DCTPP1 in breast cancer cell line MCF-7 cells remarkably retarded proliferation and colony formation in vitro. The capacity of mammosphere formation of MCF-7 was suppressed with the silence of DCTPP1, which was consistent with the enhanced mammosphere-forming ability in DCTPP1-overexpressed MDA-MB-231 cells. To further dissect the mechanisms of DCTPP1 in promoting tumor cell growth and stemness maintenance, its biochemical properties and biological functions were investigated. DCTPP1 displayed bioactive form with tetrameric structure similar to other MazG domain-containing pyrophosphatases based on structure simulation. A substrate preference for dCTP and its methylated or halogen-modified derivatives over the other canonical (deoxy-) NTPs was demonstrated from enzymatic assay. This substrate preference was also proved in breast cancer cells that the intracellular 5-methyl-dCTP level increased in DCTPP1-deficient MCF-7 cells but decreased in DCTPP1-overexpressed MDA-MB-231 cells. Moreover, global methylation level was elevated in DCTPP1-knockdown MCF-7 cells or mammosphere-forming MCF-7 cells but decreased significantly in DCTPP1-overexpressed MDA-MB-231 cells and its mammospheres. Our results thus indicated that human DCTPP1 was capable of modulating the concentration of intracellular 5-methyl-dCTP. This in turn affected global methylation, contributing to a known phenomenon of hypomethylation related to the cancer cell growth and stemness maintenance. Our current investigations point to the pathological functions of DCTPP1 overexpression in breast cancer cells with aberrant dCTP metabolism and epigenetic modification.
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Magnetic skyrmions are localized and topologically protected spin configurations, which are of both fundamental and applied interests for future electronics. In this work, we propose a voltage-gated skyrmion transistor within the well-established framework of micromagnetics. Its operating conditions and processes have been theoretically investigated and demonstrated, in which the gate voltage can be used to switch on/off a circuit. Our results provide the first time guidelines for practical realization of hybrid skyrmionic-electronic devices.
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Magnetic skyrmions are topologically protected nanoscale objects, which are promising building blocks for novel magnetic and spintronic devices. Here, we investigate the dynamics of a skyrmion driven by a spin wave in a magnetic nanowire. It is found that (i) the skyrmion is first accelerated and then decelerated exponentially; (ii) it can turn L-corners with both right and left turns; and (iii) it always turns left (right) when the skyrmion number is positive (negative) in the T- and Y-junctions. Our results will be the basis of skyrmionic devices driven by a spin wave.
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Magnetic skyrmions are promising for building next-generation magnetic memories and spintronic devices due to their stability, small size and the extremely low currents needed to move them. In particular, skyrmion-based racetrack memory is attractive for information technology, where skyrmions are used to store information as data bits instead of traditional domain walls. Here we numerically demonstrate the impacts of skyrmion-skyrmion and skyrmion-edge repulsions on the feasibility of skyrmion-based racetrack memory. The reliable and practicable spacing between consecutive skyrmionic bits on the racetrack as well as the ability to adjust it are investigated. Clogging of skyrmionic bits is found at the end of the racetrack, leading to the reduction of skyrmion size. Further, we demonstrate an effective and simple method to avoid the clogging of skyrmionic bits, which ensures the elimination of skyrmionic bits beyond the reading element. Our results give guidance for the design and development of future skyrmion-based racetrack memory.