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Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca2+ transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.
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Calcio , Neuronas , Animales , Calcio/metabolismo , Neuronas/fisiología , Señalización del Calcio/fisiología , Indicadores y Reactivos , Mamíferos/metabolismoRESUMEN
Iron-based sulfate cathodes of alluaudite Na2+2 δ Fe2- δ (SO4 )3 (NFS) in sodium-ion batteries with low cost, steady cycling performance, and high voltage are promising for grid-scale energy storage systems. However, the poor electronic conductivity and the limited understanding of the phase-evolution of precursors hinder obtaining high-rate capacity and the pure phase. Distinctive NFS@C@n%CNTs (n = 1, 2, 5, 10) sphere-shell conductive networks composite cathode materials are constructed creatively, which exhibit superior reversible capacity and rate performance. In detail, the designed NFS@C@2%CNTs cathode delivers an initial discharge capacity of 95.9 mAh g-1 at 0.05 C and up to 60 mAh g-1 at a high rate of 10 C. The full NFS@C@2%CNTs//HC cell delivers a practical operating voltage of 3.5 V and mass-energy density of 140 Wh kg-1 at 0.1 C, and it can also retain 67.37 mAh g-1 with a capacity retention rate of 96.4% after 200 cycles at 2 C. On the other hand, a novel combination reaction mechanism is first revealed for forming NFS from the mixtures of Na2 Fe(SO4 )2 ·nH2 O (n = 2, 4) and FeSO4 ·H2 O during the sintering process. The inspiring results would provide a novel perspective to synthesize high-performance alluaudite sulfate and analogs by aqueous methods.
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BACKGROUND: Diabetic foot ulcer (DFU) is a frequently diagnosed complication of diabetes, and remains a heathcare burden worldwide. However, the pathogenesis of DFU is still largely unclear. The objective of this study is to delineate the function and underlying mechanism of lncRNA antisense non coding RNA in the INK4 locus (ANRIL) in endothelial progenitor cells (EPCs) and DFU mice. METHODS: The DFU mouse model was established, and EPCs were subjected to high glucose (HG) treatment to mimic diabetes. qRT-PCR or western blot was employed to detected the expression of ANRIL, HIF1A, FUS and VEGFA. CCK-8 and Annexin V/PI staining were used to monitor cell proliferation and apoptosis. Wound healing, Transwell invasion and tube formation assays were conducted to assess cell migration, invasion and angiogenesis, respectively. The association between ANRIL and FUS was verified by RNA pull-down and RIP assays. Luciferase and ChIP assays were employed to investigate HIF1A-mediated transcriptional regulation of VEGFA and ANRIL. The histological alterations of DFU wound healing were observed by H&E and Masson staining. RESULTS: ANRIL was downregulated in peripheral blood samples of DFU patients, DFU mice and HG-treated EPCs. Mechanistically, ANRIL regulated HIFA mRNA stability via recruiting FUS. VEGFA and ANRIL were transcriptionally regulated by HIF1A. Functional experiments revealed that HG suppressed EPC proliferation, migration, invasion and tube formation, but promoted apoptosis via ANRIL/HIF1A axis. ANRIL accelerated DFU wound healing via modulating HIF1A expression in vivo. CONCLUSION: ANRIL accelerated wound healing in DFU via modulating HIF1A/VEGFA signaling in a FUS-dependent manner.
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Diabetes Mellitus , Pie Diabético , MicroARNs , ARN Largo no Codificante , Ratones , Animales , Pie Diabético/genética , Pie Diabético/metabolismo , Pie Diabético/terapia , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cicatrización de Heridas/genética , Transducción de Señal , Proliferación Celular/genéticaRESUMEN
Lithium-oxygen batteries (LOBs) are well known for their high energy density. However, their reversibility and rate performance are challenged due to the sluggish oxygen reduction/evolution reactions (ORR/OER) kinetics, serious side reactions and uncontrollable Li dendrite growth. The electrolyte plays a key role in transport of Li+ and reactive oxygen species in LOBs. Here, we tailored a dilute electrolyte by screening suitable crown ether additives to promote lithium salt dissociation and Li+ solvation through electrostatic interaction. The electrolyte containing 100â mM 18-crown-6 ether (100-18C6) exhibits enhanced electrochemical stability and triggers a solution-mediated Li2 O2 growth pathway in LOBs, showing high discharge capacity of 10 828.8â mAh gcarbon -1 . Moreover, optimized electrode/electrolyte interfaces promote ORR/OER kinetics on cathode and achieve dendrite-free Li anode, which enhances the cycle life. This work casts new lights on the design of low-cost dilute electrolytes for high performance LOBs.
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BACKGROUND: Only 1.5% of the human genome encodes proteins, while large part of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. RESULTS: Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs may have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. CONCLUSIONS: By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis suggests that some newly discovered ncRNA motifs may have biological functions. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.
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Genómica , ARN no Traducido , Animales , Genoma , Humanos , Motivos de Nucleótidos , ARN , ARN no Traducido/genéticaRESUMEN
BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state falling between normal aging and dementia. The relation between alcohol intake and risk of MCI as well as progression to dementia in people with MCI (PDM) remained unclear. OBJECTIVE: To synthesize available evidence and clarify the relation between alcohol intake and risk of MCI as well as PDM. METHOD: We searched electronic databases consisting of PubMed, EMBASE, Cochrane Library, and China Biology Medicine disc (CBM) from inception to October 1, 2019. Prospective studies reporting at least three levels of alcohol exposure were included. Categorical meta-analysis was used for quantitative synthesis of the relation between light, moderate and heavy alcohol intake with risk of MCI and PDM. Restricted cubic spline and fixed-effects dose-response models were used for dose-response analysis. RESULT: Six cohort studies including 4244 individuals were finally included. We observed an unstable linear relation between alcohol intake (drinks/week) and risk of MCI (P linear = 0.0396). It suggested that a one-drink increment per week of alcohol intake was associated with an increased risk of 3.8% for MCI (RR, 1.038; 95% CI 1.002-1.075). Heavy alcohol intake (> 14 drinks/week) was associated with higher risk of PDM (RR = 1.76; 95% CI 1.10-2.82). And we found a nonlinear relation between alcohol intake and risk of PDM. Drinking more than 16 drinks/week (P nonlinear = 0.0038, HR = 1.42; 95% CI 1.00-2.02), or 27.5 g/day (P nonlinear = 0.0047, HR = 1.46; 95% CI 1.00-2.11) would elevate the risk of PDM. CONCLUSION: There was a nonlinear dose-response relation between alcohol intake and risk of PDM. Excessive alcohol intake would elevate the risk of PDM.
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Disfunción Cognitiva , Demencia , Consumo de Bebidas Alcohólicas/efectos adversos , China/epidemiología , Disfunción Cognitiva/etiología , Demencia/epidemiología , Demencia/etiología , Humanos , Estudios ProspectivosRESUMEN
Bradysia difformis is one of the most damaging pests in mushroom production in China. In this study, eight Bacillus thuringiensis strains were analyzed for insecticidal activity in B. difformis. The strain JW-1 showed the highest insecticidal activity against B. difformis larvae, but did not inhibit the mycelial growth of Pleurotus ostreatus and P. geesteranus. The 16S rRNA gene (1397 bp) and cyt2 gene (792 bp) were obtained from strain JW-1. The phylogenetic tree based on 16S rRNA gene and Cyt2 toxin showed that strain JW-1 was a member of B. thuringiensis and Cyt2 toxin belonged to Cyt2Ba toxin cluster. The Cyt2Ba toxin from strain JW-1 was overexpressed in E. coli as a fusion protein and the fusion protein (70 kDa) was purified by Ni-IDA affinity chromatography. The purified Cyt2Ba fusion protein was toxic to B. difformis larvae (LC50 was 2.25 ng/mL). The identification of Cyt2Ba from strain JW-1 and confirmation of the insecticidal activity of Cyt2Ba in B. difformis provided a new means of biological control of the important pest in mushroom production.
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Toxinas de Bacillus thuringiensis , Bacillus thuringiensis , Dípteros , Endotoxinas , Proteínas Hemolisinas , Animales , Bacillus thuringiensis/clasificación , Bacillus thuringiensis/genética , Toxinas de Bacillus thuringiensis/toxicidad , China , Dípteros/efectos de los fármacos , Endotoxinas/toxicidad , Escherichia coli/genética , Proteínas Hemolisinas/toxicidad , Larva , Control Biológico de Vectores , Filogenia , ARN Ribosómico 16S/genética , Proteínas Recombinantes/toxicidadRESUMEN
Age-related changes have been identified in neural and motor level. A prominent change is reduced asymmetry in cortical activation as well as motor performance. Cortical activation models have been established based on cognitive research utilizing neuroimaging techniques to explain age-related effects on neural recruitment and reduced brain asymmetry. Recently, researchers in motor behaviour attempted to apply the models to explain motor pattern changes in aging and proposed compensation as the mechanism of the reduced motor asymmetry in older adults. Age-related alterations in movement patterns and brain activations seem to be correlated. However, based on the literature search result, no direct evidence substantiates the connection between reduced brain asymmetry and motor asymmetry in older adults. Therefore, a theoretical gap was identified. The theoretical gap exists because either neuroimaging studies have not considered motor asymmetry or motor asymmetry studies have not integrated neuroimaging techniques into study designs. Answering the research question can be valuable to both research and clinical practice. With the mechanisms of brain activation patterns during motor tasks in an aging population being better understood, protocols developed upon the new understandings can be applied to current motor interventions and better maintain the longevity of motor function of older adults.
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Encéfalo , Lateralidad Funcional , Envejecimiento/fisiología , Encéfalo/diagnóstico por imagenRESUMEN
During human motor control, the three pathways of motor control coordinate to complete human response and inhibition control, so whether different types of motor skills training will affect the three pathways of motor control is the main question in this study. Magnetic resonance imaging was combined with behavioural evaluation to analyse the effects of different special training sessions on the motor control network of the frontal lobe and basal ganglia and to explore the role of the central nervous system in the regulation of motor behaviour. A Stop-signal paradigm was used to measure reaction and inhibition capacity, functional magnetic resonance imaging was used for whole brain scanning, and resting state data were collected. Compared to the control group, the competitive aerobics athletes had better reflexes while the soccer players had both better reflexes and inhibitory control. Furthermore, we found that training in the two sets of skills resulted in significant differences in different resting state brain function parameters compared with the control group. Additionally, there were significant differences among the three groups in the direct and indirect pathways of motor control in terms of functional connectivity. Open skill training may improve reaction ability while closed skill training improve both reaction and inhibition ability. These results suggest that the strength of the functional connectivity between the right inferior frontal gyrus and the left putamen may be a key to improving the inhibitory, and the left supplementary motor area- bilateral thalamic loop may play an inhibitory role in motor control.
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The mechanism behind exercise-induced fatigue is a significant topic in the field of sports physiology. Therefore, establishing and evaluating an acute exercise-induced fatigue animal model that explores the limits of the motor system may provide greater insight into these mechanisms. Heart rate is an important quantitative parameter that accurately reflects the immediate change in physical function due to exercise load. And there is likely to be an important correlation between heart rate and behavioral performance. In this study, changes in heart rate and behavioral indexes during exercise-induced fatigue were quantitatively analyzed in rats using heart rate telemetry and video methods respectively. The behavioral indexes were used as independent variables and the degree of fatigue was used as the forecast value. Ternary quadratic function curve fitting was used to deduce a formula to calculate a fatigue score: Y = 15.2548+0.4346âxa-0.1154âxb+0.6826âxc+0.0044âxaâxb-0.0021âxbâxc-0.0013âxcâxa-0.0023âxa2-0.0016âxb2 (r2=0.906). It identified a linear relationship between heart rate and exercise intensity, with a plateau in heart rate occurring during difference periods. It will serve as an effective reference for the modeling of exercise-induced fatigue. In addition, it also provides a theoretical method for analyzing the correlation between peripheral and central parameters.
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Prueba de Esfuerzo , Fatiga , Condicionamiento Físico Animal/fisiología , Resistencia Física/fisiología , Animales , Masculino , Modelos Animales , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.
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Antineoplásicos Fitogénicos/farmacología , Curcumina/farmacología , Metaboloma , Línea Celular Tumoral , Cromatografía de Gases y Espectrometría de Masas , Humanos , Redes y Vías Metabólicas , Metabolómica , Análisis de Componente PrincipalRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) has long-lasting influence on offspring, which is associated with increased risks of insulin resistance, obesity, and type II diabetes mellitus. Calorie restriction (CR) is one of the most common and available nutritional interventions to prevent obesity and diabetes. We are trying to explore the effect of CR on GDM offspring. METHODS: The streptozotocin was used to stimulate C57BL/6J mice to develop GDM, a number of metabolic characteristics and related protein expressions were determined in GDM offspring that were fed ad-libitum or treated with calorie restriction. RESULTS: CR reduced body weight and glucose levels in GDM offspring. CR modulated the lipid metabolism by decreasing triglyceride and cholesterol levels in plasma. We also found that the effect of CR on insulin sensitivity may involve in signaling pathway through the regulations of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and protein kinase B (Akt). CONCLUSION: GDM is a high risk factor for GDM offspring to develop insulin resistance, while CR could ameliorate this adverse outcome. Moreover, the specific decrease in PTEN activation and increase in Akt phosphorylation in livers of GDM offspring with CR improved insulin sensitivity and lipid metabolism.
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Restricción Calórica , Diabetes Gestacional/fisiopatología , Resistencia a la Insulina , Metabolismo de los Lípidos , Efectos Tardíos de la Exposición Prenatal/prevención & control , Animales , Animales Recién Nacidos , Glucemia/análisis , Peso Corporal , Femenino , Regulación del Desarrollo de la Expresión Génica , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fosforilación , Embarazo , Factores de Riesgo , Transducción de SeñalRESUMEN
A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX1 & 2 R) antagonists assays. Compound 14l with potent OXR antagonist activity and suitable pharmacokinetic behavior was chosen to be investigated in an EEG study, which demonstrated effects of sleep promotion comparable to Suvorexant. Furthermore, the di-fluro substituted analogs exhibited reduced hERG inhibition while maintaining moderate potency.
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Antagonistas de los Receptores de Orexina/química , Antagonistas de los Receptores de Orexina/farmacología , Pirroles/química , Pirroles/farmacología , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Animales , Descubrimiento de Drogas , Electroencefalografía , Humanos , Masculino , Antagonistas de los Receptores de Orexina/uso terapéutico , Pirroles/farmacocinética , Pirroles/uso terapéutico , Ratas , Ratas Sprague-Dawley , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Relación Estructura-ActividadRESUMEN
hNav1.7 small molecular inhibitors have attracted lots of attention by its unique analgesic effect. Herein, we report the design and synthesis of a novel series of tetrahydropyridine analogs as hNav1.7 inhibitors for analgesia. Detail structural-activity relationship (SAR) studies were undertaken towards improving hNav1.7 activity, in vitro ADME, and in vivo PK profiles. These efforts resulted in the identification of compound (-)-15h, a highly potent and selective hNav1.7 inhibitor with good ADME and PK profiles.
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Analgésicos/química , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Piridinas/química , Sulfonamidas/química , Bloqueadores del Canal de Sodio Activado por Voltaje/química , Analgésicos/síntesis química , Analgésicos/farmacocinética , Animales , Sitios de Unión , Citocromo P-450 CYP2C9/química , Citocromo P-450 CYP2C9/metabolismo , Diseño de Fármacos , Semivida , Humanos , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Canal de Sodio Activado por Voltaje NAV1.7/química , Estructura Terciaria de Proteína , Piridinas/síntesis química , Piridinas/farmacocinética , Ratas , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/farmacocinética , Bloqueadores del Canal de Sodio Activado por Voltaje/síntesis química , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacocinéticaRESUMEN
hNav1.7 receives a lot of attention owing to its attractive mechanism of action in pain processing pathway. We have previously reported our design of a novel series of tetrahydropyridine analogues towards hNav1.7 selective inhibitors. Herein, we disclose further efforts to the optimization of hit compound (-)-6, which led to the identification of aminocyclohexene analogues (-)-9 and (-)-17 with good potency, high selectivity, and minimal CYP inhibition. Both compounds (-)-9 and (-)-17 demonstrated improved pharmacokinetic profiles in rats, and robust efficacy in rat formalin-induced nociception and spinal nerve ligation (SNL) models.
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Analgésicos/química , Ciclohexenos/química , Canal de Sodio Activado por Voltaje NAV1.7/química , Bloqueadores del Canal de Sodio Activado por Voltaje/química , Administración Oral , Analgésicos/farmacocinética , Analgésicos/uso terapéutico , Animales , Sitios de Unión , Ciclohexenos/farmacocinética , Ciclohexenos/uso terapéutico , Citocromo P-450 CYP2C9/química , Citocromo P-450 CYP2C9/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Semivida , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Dolor/tratamiento farmacológico , Estructura Terciaria de Proteína , Ratas , Estereoisomerismo , Relación Estructura-Actividad , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacocinética , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéuticoRESUMEN
BACKGROUND: Genome-wide association studies (GWAS) have been extensively used to identify genomic regions associated with a variety of phenotypic traits in pigs. Until now, most GWAS have explored single-trait association models. Here, we conducted both single- and multi-trait GWAS and a meta-analysis for nine fatness and growth traits on 2004 pigs from four diverse populations, including a White Duroc × Erhualian F2 intercross population and Chinese Sutai, Laiwu and Erhualian populations. RESULTS: We identified 44 chromosomal regions that were associated with the nine traits, including four genome-wide significant single nucleotide polymorphisms (SNPs) on SSC2 (SSC for Sus scrofa chromosome), 4, 7 and X. Compared to the single-population GWAS, the meta-analysis was less powerful for the identification of SNPs with population-specific effects but more powerful for the detection of SNPs with population-shared effects. Multiple-trait analysis reduced the power to detect trait-specific SNPs but significantly enhanced the power to identify common SNPs across traits. The SNP on SSC7 had pleiotropic effects on the nine traits in the F2 and Erhualian populations. Another pleiotropic SNP was observed on SSCX for these traits in the F2 and Sutai populations. Both population-specific and shared SNPs were identified in this study, thus reflecting the complex genetic architecture of pig growth and fatness traits. CONCLUSIONS: We demonstrate that the multi-trait method and the meta-analysis on multiple populations can be used to increase the power of GWAS. The two significant SNPs on SSC7 and X had pleiotropic effects in the F2, Erhualian and Sutai populations.
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Adiposidad/genética , Porcinos/genética , Animales , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Masculino , Sitios de Carácter Cuantitativo , Porcinos/crecimiento & desarrolloRESUMEN
Compared with controls, treatment of the cultivation substrate for Volvariella volvacea with 0.02% NaAc at the "spraying water" stage increased the number of fruiting body primordia by 280, the mushroom yield by 16.25%, the number of fruiting bodies by 35.57%, and the biological efficiency by 16.28%. The average single mushroom weight increased by 19.33%, but there was no significant difference between treatments and controls. A correlation analysis revealed a significant (p < 0.05) positive correlation between the total yield and the number of fruiting bodies. Comparisons of the cost and profit values for the sodium acetate-treated and untreated groups revealed that the former generated a higher income for the grower. Our data indicate that sodium acetate treatment is a promising new method for increasing V. volvacea yields. A possible mechanism whereby sodium acetate increased the mushroom yield is discussed.
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Medios de Cultivo/química , Volvariella/crecimiento & desarrollo , Biomasa , Gossypium/metabolismo , Residuos Industriales , Acetato de Sodio/metabolismo , Volvariella/metabolismoRESUMEN
OBJECTIVE: To explore the relationship between intestinal fatty acid binding protein (FABP2) gene G54A polymorphism and simple childhood obesity, the effect of mutant 54A FABP2 gene on serum lipids and glucose metabolism. METHODS: The total of 83 subjects with overweight/obesity and 100 subjects with healthy/normal weight were involved in this study. The G54A FABP2 gene allele and genotype frequencies between control group and overweight/obesity group were detected using polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) technology, and DNA sequences were confirmed by DNA sequencing. The automatic biochemical analyzer was used to detect fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. Plasma insulin (Ins) was detected by radiation immune method, free fatty acids (FFA) was tested by ELISA method, insulin resistance index ( HOMA-IR ) was also calculated. The correlation between FABP2 G54A polymorphism and the development of children' obesity was analyzed. The relation between FABP2 G54A polymorphism and abnormal blood lipid and insulin resistance was assessed. RESULTS: The results of study on FABP2 gene polymorphism revealed as followed. In overweight/obese groups, the frequencies of GG, GA, AA genotypes was 33.7%, 49.4% and 16.9%, respectively. In control group, the frequencies of GG, GA, AA genotypes was 51. 0% , 40. 0% and 9. 0% , respectively. The differences between two groups was statistically significant (Χ2 = 6.27, P < 0.05). In overweight/obesity group, the frequencies of alleles were 58.4% for 54G and 41.6% for 54A. In control group, the frequencies of alleles were 71.0% for 54G and 29.0% for 54A. There was significant differences (Χ2 = 6.32, P < 0.05). The plasma biochemical variables results showed that compared with the normal control group, plasma TG (P < 0.01), Ins (P < 0.05), HOMA-IR (P < 0.05) were elevated in overweight/obesity group, the difference between two groups was statistically significant. At the same time, in overweight/obesity group, the carriers of AA homozygous genotypes had significantly higher plasma TG levels than those with GG wild genotypes (P < 0.05). A increased tendency of plasma Ins, FFA levels and HOMA-IR was found in the carriers with AA homozygous genotypes, but no differences compared with those with GG wild genotypes. Compared with those with GG wild genotypes, related plasma biochemical variables in the carriers with GA heterozygous genotypes had no differences (P > 0.05). CONCLUSION: The FABP2 gene G54A polymorphism is related to simple children obesity and lipid metabolism abnormality. The allele encoding in FABP2 gene may be a potential factor contributing to promoting lipid metabolism abnormality of and insulin resistance.
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Proteínas de Unión a Ácidos Grasos/genética , Resistencia a la Insulina/genética , Metabolismo de los Lípidos/genética , Sobrepeso/sangre , Sobrepeso/genética , Obesidad Infantil/sangre , Obesidad Infantil/genética , Alelos , Biomarcadores/sangre , Niño , HDL-Colesterol , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Glucosa , Humanos , Lípidos , Lipoproteínas LDL , Sobrepeso/diagnóstico , Sobrepeso/epidemiología , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , TriglicéridosRESUMEN
BACKGROUND: Limb bone length is an economically important trait in pigs, because it is negatively correlated with backfat thickness, and is also a determinant to the yield of hip and loin. Moreover, abnormal growth of the limb bone leads to leg structural weakness. Until now, the genetic architecture of the pig lime bone length remains poorly understood. The object of this study was to map genomic loci for limb bone length by genome-wide association study (GWAS) on 4 pig populations. RESULTS: We measured the lengths of five limb bones including scapula, humerus, ulna, femur and tibia that were dissected from the right-side carcass of 925, 331, 314 and 434 animals from White Duroc × Erhualian F2 intercross, Erhualian, Laiwu and Sutai populations, respectively. We genotyped the 2004 pigs for 62,163 single nucleotide polymorphisms (SNPs) on the Porcine SNP60 BeadChip, and performed GWAS and a GWAS meta analysis in the 4 populations. In total, we identified 12 and 4 loci associated with the limb bone lengths at suggestive and genome-wide significant levels respectively, of which 4 loci were reported for the first time. The most prominent locus was identified in a 924-kb (kilo base pairs) linkage disequilibrium block on Sus Scrofa chromosome (SSC) 7, and High Mobility Group AT-hook 1 (HMGA1) appears to be a strong candidate gene in this region. Another promising locus is located in the middle of SSC4, and Pleiomorphic Adenoma Gene 1 (PLAG1) is a functionally plausible candidate gene underlying the locus. Because the lengths of the 5 limb bones are highly correlated to each other, most of significant loci were associated with all of the 5 traits; however, several loci showed specific effect on the length of one limb bone, such as the locus at the proximal end of SSC2 associated with only the scapula length. CONCLUSION: To our knowledge, this study was the first GWAS meta analysis for limb bone lengths in pigs. As expected, the meta analysis is more powerful to identify genomic loci. A total of 16 loci were identified in this study, including four novel loci. HMGA1 and PLAG1 are two appearing candidate genes for pig limb bone lengths, which warrant further investigations.
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Huesos/anatomía & histología , Extremidades/anatomía & histología , Estudio de Asociación del Genoma Completo , Porcinos/anatomía & histología , Porcinos/genética , Animales , Mapeo Cromosómico , Genética de Población , Desequilibrio de Ligamiento , Modelos Estadísticos , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Carácter Cuantitativo HeredableRESUMEN
Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clinical application as an anticancer agent. Moreover, the 6-OH forms an intramolecular hydrogen bond with 8-CO, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-molecular hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a methyl group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.