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BACKGROUND: TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1. The aim of this study was to determine whether MARCH1 regulates the mTOR signaling pathway by targeting TBK1. METHODS: The co-immunoprecipitation (Co-IP) assay was used to verify the interaction between MARCH1 with STING or TBK1. The ubiquitination of STING or TBK1 was analyzed using denatured co-immunoprecipitation. The level of proteins detected in the co-immunoprecipitation or denatured co-immunoprecipitation samples were determined by Western blotting. Stable knocked-down cells were constructed by infecting lentivirus bearing the related shRNA sequences. Scratch wound healing and clonogenic cell survival assays were used to detect the migration and proliferation of breast cancer cells. RESULTS: We showed that MARCH1 played an important role in growth factor-induced the TBK1- mTOR signaling pathway. MARCH1 overexpression attenuated the growth factor-induced activation of mTOR signaling pathway, whereas its deficiency resulted in the opposite effect. Mechanistically, MARCH1 interacted with and promoted the K63-linked ubiquitination of TBK1. This ubiquitination of TBK1 then attenuated its interaction with mTOR, thereby inhibiting the growth factor-induced mTOR signaling pathway. Importantly, faster proliferation induced by MARCH1 deficiency was weakened by mTOR, STING, or TBK1 inhibition. CONCLUSION: MARCH1 suppressed growth factors mediated the mTOR signaling pathway by targeting the STING-TBK1-mTOR axis.
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Proliferación Celular , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Serina-Treonina Quinasas TOR , Ubiquitina-Proteína Ligasas , Ubiquitinación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Línea Celular Tumoral , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Femenino , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Movimiento CelularRESUMEN
Patients with bipolar disorder (BD) and their first-degree relatives exhibit alterations in brain volume and cortical structure, whereas the underlying genetic mechanisms remain unclear. In this study, based on the published genome-wide association studies (GWAS), the extent of polygenic overlap between BD and 15 brain structural phenotypes was investigated using linkage disequilibrium score regression and MiXeR tool, and the shared genomic loci were discovered by conjunctional false discovery rate (conjFDR) and expression quantitative trait loci (eQTL) analyses. MiXeR estimated the overall measure of polygenic overlap between BD and brain structural phenotypes as 4-53% on a 0-100% scale (as quantified by the Dice coefficient). Subsequent conjFDR analyses identified 54 independent loci (71 risk single-nucleotide polymorphisms) jointly associated with BD and brain structural phenotypes with a conjFDR < 0.05, among which 33 were novel that had not been reported in the previous BD GWAS. Follow-up eQTL analyses in respective brain regions both confirmed well-known risk genes (e.g. CACNA1C, NEK4, GNL3, MAPK3) and discovered novel risk genes (e.g. LIMK2 and CAMK2N2). This study indicates a substantial shared genetic basis between BD and brain structural phenotypes, and provides novel insights into the developmental origin of BD and related biological mechanisms.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad/genética , Encéfalo/diagnóstico por imagen , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Sitios Genéticos , Proteínas Nucleares/genética , Proteínas de Unión al GTP/genéticaRESUMEN
BACKGROUND: Bipolar disorder (BD) is a highly heritable psychiatric illness exhibiting substantial correlation with intelligence. METHODS: To investigate the shared genetic signatures between BD and intelligence, we utilized the summary statistics from genome-wide association studies (GWAS) to conduct the bivariate causal mixture model (MiXeR) and conjunctional false discovery rate (conjFDR) analyses. Subsequent expression quantitative trait loci (eQTL) mapping in human brain and enrichment analyses were also performed. RESULTS: Analysis with MiXeR suggested that approximately 10.3K variants could influence intelligence, among which 7.6K variants were correlated with the risk of BD (Dice: 0.80), and 47% of these variants predicted BD risk and intelligence in consistent allelic directions. The conjFDR analysis identified 37 distinct genomic loci that were jointly associated with BD and intelligence with a conjFDR < 0.01, and 16 loci (43%) had the same directions of allelic effects in both phenotypes. Brain eQTL analyses found that genes affected by the "concordant loci" were distinct from those modulated by the "discordant loci". Enrichment analyses suggested that genes related to the "concordant loci" were significantly enriched in pathways/phenotypes related with synapses and sleep quality, whereas genes associated with the "discordant loci" were enriched in pathways related to cell adhesion, calcium ion binding, and abnormal emotional phenotypes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between BD and intelligence and identified multiple genomic loci and risk genes. This study provides hints for the mesoscopic phenotypes of BD and relevant biological mechanisms, promoting the knowledge of the genetic and phenotypic heterogeneity of BD. The essential value of leveraging intelligence in BD investigations is also highlighted.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/genética , Estudio de Asociación del Genoma Completo , Inteligencia/genética , Encéfalo , AlelosRESUMEN
Magnetic molecularly imprinted nanoparticles (MMINPs) were obtained with a one-step process through miniemulsion self-assembly using an amphiphilic random copolymer as both an emulsifier and MMINP coating, oleic acid-modified magnetite nanoparticles as magnetic cores, and melamine (MEL) as the template molecule. MMINPs were assembled under an external magnetic field to construct photonic crystal (PC) sensor for naked-eye detection of MEL. The MMINPs were characterized by FT-IR, TEM, TGA, and VSM. The analytical performances of the magnetic molecularly imprinted PC sensor for MEL (MEL-MMIPCs) were investigated with respect to sensitivity, response time, selectivity, and stability. As the MEL concentration increases from 1.0 to 1.0 × 106 µg/l, the reflection wavelength of MEL-MMIPCs shifted from 497 to 709 nm, and was linear with the logarithm of MEL concentration in this range. The detection limit was 0.21 µg/l (S/N = 3) and response time was within 30 s. The MEL-MMIPC sensor had an imprinting factor of 5.09, and selectivity factors for the analogs cyanuric acid and atrazine were 8.76 and 5.75, respectively, indicating the high sensitivity and selectivity. After 10 cycles of elution/response, MEL-MMIPCs still had a good ability to recognize MEL.
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Nanopartículas de Magnetita , Impresión Molecular , Fenómenos Magnéticos , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier , TriazinasRESUMEN
With the progress of epidemic containment, the Chinese government has relaxed its regulatory policies on street vending, hoping to help people who have lost their livelihoods and to assist in the restoration of social and economic order. In response, Chinese people poured into the stall economy, especially individual peddlers, with great expectations for street vending. Street vending has become a hot topic on Chinese social network sites (SNSs). Based on the push-pull-mooring framework, SNS information overload theory was introduced and combined with the actual situations of street vending in China, and a structural equation model was established to study factors affecting individual Chinese peddlers' intention to engage in street vending and the effects of SNS information overload on these factors. Results revealed that perceived policy benefits, subjective norms, and switching cost perceptions of individual peddlers were positive factors affecting their intention to engage in street vending. SNS information overload positively affected individual peddlers' dissatisfaction with their original business model, anxieties over their livings, perception of policy benefits, and subjective norms but negatively affected individual peddlers' perception of switching costs.
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There is a continuous need to improve the viral safety of plasma products, and we here report the development and optimization of a manufacturing-scale virus removal nanofiltration step for intravenous immunoglobulin (IVIG) using the recently introduced Planova™ BioEX filter. IVIG throughput was examined for various operating parameters: transmembrane pressure, temperature, protein concentration, and prefiltration methods. The developed procedure was based on filtering undiluted process solution (50.0â¯g/l IVIG) under constant transmembrane pressure filtration at 294â¯kPa and 25⯰C following prefiltration with a 0.1⯵m MILLEX VV filter. The recovery of IgG was approximately 98%, and no substantial changes in biochemical characteristics were observed before and after nanofiltration in scaled-up production. A viral clearance validation study with parvovirus under worst-case conditions performed at the National Institutes for Food and Drug Control of China (NIFDC) showed PPV logarithmic reduction value (LRV)â¯>â¯4. Improved viral safety of IVIG can be assured by implementing a Planova BioEX nanofiltration step to ensure effective parvovirus clearance under conditions providing excellent protein recovery and no detectable impact on product biochemical properties. This plasma-derived IVIG product is the first to be certified for parvovirus safety by the NIFDC in China.
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Inmunoglobulinas Intravenosas/química , Inmunoglobulinas Intravenosas/aislamiento & purificación , Filtros Microporos , Humanos , Parvovirus , Presión , Ultrafiltración/instrumentación , Ultrafiltración/métodos , Inactivación de VirusRESUMEN
PIMT/NCOA6IP, a transcriptional coactivator PRIP/NCOA6 binding protein, enhances nuclear receptor transcriptional activity. Germline disruption of PIMT results in early embryonic lethality due to impairment of development around blastocyst and uterine implantation stages. We now generated mice with Cre-mediated cardiac-specific deletion of PIMT (csPIMT-/-) in adult mice. These mice manifest enlargement of heart, with nearly 100% mortality by 7.5 months of age due to dilated cardiomyopathy. Significant reductions in the expression of genes (i) pertaining to mitochondrial respiratory chain complexes I to IV; (ii) calcium cycling cardiac muscle contraction (Atp2a1, Atp2a2, Ryr2); and (iii) nuclear receptor PPAR- regulated genes involved in glucose and fatty acid energy metabolism were found in csPIMT-/- mouse heart. Elevated levels of Nppa and Nppb mRNAs were noted in csPIMT-/- heart indicative of myocardial damage. These hearts revealed increased reparative fibrosis associated with enhanced expression of Tgfß2 and Ctgf. Furthermore, cardiac-specific deletion of PIMT in adult mice, using tamoxifen-inducible Cre-approach (TmcsPIMT-/-), results in the development of cardiomyopathy. Thus, cumulative evidence suggests that PIMT functions in cardiac energy metabolism by interacting with nuclear receptor coactivators and this property could be useful in the management of heart failure.
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Cardiomiopatías/genética , Cardiomiopatías/metabolismo , Metabolismo Energético , Eliminación de Gen , Coactivadores de Receptor Nuclear/genética , Proteína D-Aspartato-L-Isoaspartato Metiltransferasa/genética , Animales , Cardiomiopatías/patología , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Modelos Animales de Enfermedad , Fibrosis , Expresión Génica , Glucosa/metabolismo , Glucógeno/metabolismo , Ratones , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Contracción Miocárdica/genética , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismoRESUMEN
OBJECTIVE: To determine gene variations and genotype-phenotype correlations in Duchenne/Bayesian muscular mystrophy (DMD/BMD) patients, and the association between dystrophin gene polymorphisms and clinical phenotype. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was adopted to detect dystrophin gene variations in 170 patients. Sanger sequencing was performed in 3 cases with decreased peaks in MLPA results. RESULTS: The MLPA detected 72.94% mutations in dystrophin gene, including 62.35% (106/170) deletions, 8.82% (15/170) duplications, and 1.76% (3/170) point mutations. 64 different types of mutations were found. 75.47% of deletions occurred in the range from exon 44 to 55. Most 5' breakpoints of exonic variations were located in 2 hotspots (major hotspot: intron 43-55; minor hotspot: intron 1-20), which is different from findings of other studies. Genotype-phenotype analysis showed that the severity of DMD/BMD was associated with frame shift mutation (r = 0.640, P < 0.001) but not with deletions or duplications. CONCLUSION: Deletions and duplications of exon compose the main type of dystrophin gene mutations. DMD/BMD is associated with frame shift mutation.
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Distrofina/genética , Estudios de Asociación Genética , Distrofia Muscular de Duchenne/genética , Polimorfismo Genético , China , Análisis Mutacional de ADN , Exones , Humanos , Intrones , Mutación , FenotipoRESUMEN
BACKGROUND: Lipolytic enzymes are commonly used to produce desired flavors in lipolyzed milkfat (LMF) manufacturing processes. However, the choice of enzyme is critical because it determines the final profile of fatty acids released and the consequent flavor of the product. We previously constructed a metagenomic library from marine sediments, to explore the novel enzymes which have unique properties useful in flavor-enhancing LMF. RESULTS: A novel lipase Est_p6 was isolated from a metagenomic library and was expressed highly in E.coli. Bioinformatic analysis indicated that Est_p6 belongs to lipolytic enzyme family IV, the molecular weight of purified Est_p6 was estimated at 36 kDa by SDS-PAGE. The hydrolytic activity of the enzyme was stable under alkaline condition and the optimal temperature was 50°C. It had a high specific activity (2500 U/mg) toward pNP butyrate (pNP-C4), with K(m) and V(max) values of 1.148 mM and 3497 µmolâmin⻹âmg⻹, respectively. The enzyme activity was enhanced by DTT and was not significantly inhibited by PMSF, EDTA or SDS. This enzyme also showed high hydrolysis specificity for myristate (C14) and palmitate (C16). It seems that Est_p6 has safety for commercial LMF flavor production and food manufacturing processes. CONCLUSIONS: The ocean is a vast and largely unexplored resource for enzymes. According the outstanding alkaline-stability of Est_p6 and it produced myristic acid and palmitic acid more efficiently than other free fatty acids in lipolyzed milkfat. This novel lipase may be used to impart a distinctive and desirable flavor and odor in milkfat flavor production.
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Aromatizantes/metabolismo , Lipasa/metabolismo , Secuencia de Aminoácidos , Biología Computacional , Escherichia coli/metabolismo , Aromatizantes/química , Aromatizantes/aislamiento & purificación , Biblioteca de Genes , Sedimentos Geológicos/microbiología , Concentración de Iones de Hidrógeno , Cinética , Lipasa/clasificación , Lipasa/genética , Metagenómica , Datos de Secuencia Molecular , Ácido Mirístico/metabolismo , Ácido Palmítico/metabolismo , Filogenia , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Alineación de Secuencia , Especificidad por Sustrato , TemperaturaRESUMEN
Importance: Hemorrhagic fever with renal syndrome (HFRS), a neglected zoonotic disease, has received only short-term attention in postflood prevention and control initiatives, possibly because of a lack of evidence regarding the long-term association of flooding with HFRS. Objectives: To quantify the association between severe floods and long-term incidence of HFRS in the Yangtze River basin and to examine the modifying role of geographical factors in this association. Design, Setting, and Participants: This cross-sectional study collected data on HFRS cases between July 1, 2013, and June 30, 2019, from 58 cities in 4 provinces (Anhui, Hubei, Hunan, and Jiangxi) in the Yangtze River basin of China, with a breakpoint of flooding in July 2016, generating monthly data. The 3 years after July 2016 were defined as the postflood period, while the 3 years before the breakpoint were defined as the control period. Statistical analysis was performed from October to December 2023. Exposures: City-level monthly flooding, elevation, ruggedness index, and closest distance from each city to the Yangtze River and its tributaries. Main Outcomes and Measures: The primary outcomes were the number of city-level monthly HFRS cases and the number of type 1 (spring or summer) and type 2 (autumn or winter) HFRS cases. Results: A total of 11â¯745 patients with HFRS were reported during the study period: 5216 patients (mean [SD] age, 47.1 [16.2] years; 3737 men [71.6%]) in the control period and 6529 patients (mean [SD] age, 49.8 [15.8] years; 4672 men [71.6%]) in the postflood period. The pooled effects of interrupted time series analysis indicated a long-term association between flooding and HFRS incidence (odds ratio, 1.38; 95% CI, 1.13-1.68), with type 1 cases being at highest risk (odds ratio, 1.71; 95% CI, 1.40-2.09). The metaregression results indicated that elevation and ruggedness index were negatively associated with the risk of HFRS, while the distance to rivers interacted with these associations. Conclusions and Relevance: This cross-sectional study of the long-term association between flooding and HFRS incidence, as well as the modification effects of geographical factors, suggests that severe floods were associated with an increased risk of HFRS within 3 years. This study provides evidence for the development of HFRS prevention and control strategies after floods.
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Inundaciones , Fiebre Hemorrágica con Síndrome Renal , Humanos , China/epidemiología , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Estudios Transversales , Incidencia , Masculino , Persona de Mediana Edad , Femenino , Adulto , Ríos , Anciano , Adulto Joven , AdolescenteRESUMEN
Crowdsourcing logistics-based O2O (online to offline) has been increasingly implemented to help individuals or merchants tackle down the problem of intra city instant delivery in China. However, since insufficient control is imposed on free couriers, consumers are subjected to certain risks generated by the uneven service quality provided by free couriers, such that the continuous-use intention to adopt crowdsourcing logistics may be affected in an unexpected manner. A sampling survey was carried out in China's first- and second-tier cities, with 292 valid questionnaires collected. On that basis, the corresponding hypotheses were tested using the partial least squares (PLS) method. The findings of this study revealed that trust, perceived value, and satisfaction positively contributed to continuous-use intention, where trust contributed the most. Perceived risk exerted a significant negative effect on continuous use intention. Trust is capable of notably reducing perceived risk. Crowdsourcing logistics service quality is the critical driving variable of perceived value and satisfaction. Perceived risk has a negative moderating effect on satisfaction-continuous-use intention relationship, showing that the higher the perceived risk, the weaker the effect of satisfaction on continuous-use intention. Given perceived risk, a conceptual model was built by integrating e-CSI model (e-Customer Satisfaction Index Model) and PAM-ISC model (Post-acceptance Model of IS Continuance Model). From the integration, the findings of this study are expected to provide decision-making basis for crowdsourcing logistics platforms to help solve the "last mile" delivery problem.
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Introduction: Plague is a significant global infectious disease, its spread is linked to host and flea populations. Meteorological conditions can impact flea populations and host densities, hence influencing plague outbreaks. Investigating the connection between meteorological factors, flea populations, and rodent densities in Inner Mongolia's natural plague foci can aid in predicting and managing plague outbreaks. Methods: Monthly data on flea index, rodent density, meteorological factors, and normalized difference vegetation index (NDVI) were collected for the study area. Generalized additive modeling (GAM) was used to analyze the non-linear and lag effects of meteorological factors on flea index and rodent density. Structural equation modeling (SEM) was employed to investigate the relationships among meteorological factors, NDVI, flea index, and rodent density. Results: GAM analysis revealed that temperature, precipitation, relative humidity, and NDVI had significant linear, non-linear, and time-lagged impacts on the density of Mongolian gerbils and the flea index. SEM analysis indicated that meteorological factors could directly influence the density and flea index of Mongolian gerbils, or indirectly impact NDVI, subsequently influencing gerbil density and the flea index. Conclusions: Meteorological factors primarily influence gerbil density and flea index indirectly by affecting NDVI and the relationship between flea index and gerbil density. This study offers additional support for the significance of meteorological factors and NDVI in influencing the vector-rodent system, offering valuable insights for predicting and managing plague outbreaks.
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Spin crossover (SCO) has long been a hot topic in the field of molecular magnetism owing to its unique bistability character. Rational control of thermal hysteresis and transition temperature (T1/2) is crucial for their practical applications, which rely on precise manipulation of the substituents of SCO coordinating ligands and molecular packing interactions. In this study, we designed two different bridging ligands (2-FDPB: 4,4'-(2-fluoro-1,4-phenylene)dipyridine; 2,3-FDPB: 4,4'-(2,3-difluoro-1,4-phenylene)dipyridine) featuring one and two fluoro substitution on the central benzene ring and applied a Schiff base-like equatorial tetradentate ligand {diethyl(E,E)-2,2'-[4,5-difluoro-1,2-phenyl-bis(iminomethylidyne)]bis(3-oxobutanoate)-(2-)-N,N',O3,O3'} (H2L) to coordinate with the FeII ion. Two FeII-coordination chain polymers [FeII(L)(2,3-FDPB)]·0.25CH2Cl2 (1) and [FeII(L)(2-FDPB)]·0.5CH3OH (2) were obtained. 1 crystallizes in the monoclinic P21/n space group with only one FeII center, while 2 crystallizes in the triclinic P1Ì space group with two independent FeII centers. Unlike the identical 2D layer stacking in 1, 2 exhibited alternating stacking of the extending 2D layers and meshed chains. Magnetic measurements revealed the typical thermally induced spin crossover behavior (SCO): 1 exhibited a 41 K-wide thermal hysteresis with transition temperatures of T1/2↑ = 245 K and T1/2↓ = 204 K, while 2 showed a higher transition temperature (T1/2 = 330 K) with no thermal hysteresis. Magneto-structural correlation studies suggest that the electron-withdrawing effect present in the fluoro substituents does not have a significant impact on the SCO behaviors. Despite the fluoro substituents having a similar atomic radius of hydrogen atoms, variations in the number of these substituents can alter the crystallization behavior of these complexes, which in turn affects the solvents, molecular stacking patterns, and intermolecular interactions, ultimately influencing the SCO behaviors.
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A novel polysaccharide (GSPA-0.3) was isolated and purified from the root of cultivated Panax ginseng C. A. Meyer, and its structure, adjuvant activities, and mechanisms for inducing the maturation of mouse dendritic 2.4 cells (DC2.4) were extensively studied. Fraction GSPA-0.3, mainly composed by the galacturonic acid, galactose, arabinose, glucose, rhamnose, mannose, and xylose, had a molecular weight of 62,722 Da. The main chain of GSPA-0.3 was composed of â3)-α-L-Rhap-(1â, â4)-α-D-GalpA-(1â, and â3, 4)-α-D-GalpA-(1â. Branched chains comprised α-L-Araf-(1â3, 5)-α-L-Araf-(1â5)-α-L-Araf-(1â, α-D-Glcp-(1â6)-α-D-Glcp-(1â6)-α-D-Glcp-(1â, ß-D-Galp-(1â4)-ß-D-Galp-(1â4)-ß-D-Galp-(1â, and α-D-GalpA-(1â units connected to the C3 position of â3, 4)-α-D-GalpA-(1â. In vivo, GSPA-0.3 was found to stimulate the production of IgG, IgG1, and IgG2a; increase the splenocyte proliferation index; and promote the expression of GATA-3, T-bet, IFN-γ, and IL-4 in H1N1 vaccine-immunized mice. Moreover, GSPA-0.3 significantly increased the levels of neutralizing antibodies in the mice, and its adjuvant activity was found to be superior to aluminum adjuvant (Alum adjuvant). Mechanistic investigations showed that GSPA-0.3 activated the TLR4-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and NF-κB proteins and gens. The results presented herein suggested that GSPA-0.3 could significantly promote the efficacy of the H1N1 vaccine by modulating Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway.
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Subtipo H1N1 del Virus de la Influenza A , Panax , Vacunas , Ratones , Animales , Panax/química , Factor 88 de Diferenciación Mieloide , FN-kappa B , Receptor Toll-Like 4 , Polisacáridos/química , Adyuvantes Inmunológicos/farmacologíaRESUMEN
Otago Exercise Program (OEP) is a rehabilitation program for older adults to improve frailty, sarcopenia, and balance. Accurate monitoring of patient involvement in OEP is challenging, as self-reports (diaries) are often unreliable. The development of wearable sensors and their use in Human Activity Recognition (HAR) systems has lead to a revolution in healthcare. However, the use of such HAR systems for OEP still shows limited performance. The objective of this study is to build an unobtrusive and accurate system to monitor OEP for older adults. Data was collected from 18 older adults wearing a single waist-mounted Inertial Measurement Unit (IMU). Two datasets were recorded, one in a laboratory setting, and one at the homes of the patients. A hierarchical system is proposed with two stages: 1) using a deep learning model to recognize whether the patients are performing OEP or activities of daily life (ADLs) using a 10-minute sliding window; 2) based on stage 1, using a 6-second sliding window to recognize the OEP sub-classes. Results showed that in stage 1, OEP could be recognized with window-wise f1-scores over 0.95 and Intersection-over-Union (IoU) f1-scores over 0.85 for both datasets. In stage 2, for the home scenario, four activities could be recognized with f1-scores over 0.8: ankle plantarflexors, abdominal muscles, knee bends, and sit-to-stand. These results showed the potential of monitoring the compliance of OEP using a single IMU in daily life. Also, some OEP sub-classes are possible to be recognized for further analysis.
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Terapia por Ejercicio , Ejercicio Físico , Humanos , Anciano , Terapia por Ejercicio/métodos , Reconocimiento en Psicología , Extremidad Inferior , Aprendizaje AutomáticoRESUMEN
The mammalian target of rapamycin complex1 (mTORC1) can response to amino acid to regulate metabolism and cell growth. GATOR2 act as important role in amino acid mediated mTORC1 signaling pathway by repressing GTPase activity (GAP) of GATOR1. However, it is still unclear how GATOR2 regulates mTORC1 signaling pathway. Here, we found that K63-ubiquitination of Sce13, one component of GATOR2, suppresses the mTORC1 activity by lessening the inter-interaction of GATOR2. Mechanistically, the ubiquitination of Sec13 was mediated by SPOP. Subsequently, the ubiquitination of Sec13 attenuated its interaction with the other component of GATOR2, thus suppressing the activity of mTORC1. Importantly, the deficiency of SPOP promoted the faster proliferation and migration of breast cancer cells, which was attenuated by knocking down of Sec13. Therefore, SPOP can act as a tumor suppressor gene by negatively regulating mTORC1 signaling pathway.
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Aminoácidos , Serina-Treonina Quinasas TOR , Ciclo Celular , Proliferación Celular , Diana Mecanicista del Complejo 1 de la RapamicinaRESUMEN
Silica sol was prepared by acid catalyzed sol-gel process using tetraethylorthosilicate (TEOS) as precursor and dimethyldietoxysilane (DDS) as pore-forming agent. A novel kind of monolayer microporous silica anti-reflective (AR) coating was obtained on K9 glass substrate by dip-coating technique and then heat treated at 500 degrees C. The effects of different DDS/TEOS molar ratios on refractive index, transmittance and hardness were investigated. A positive correlation was found between the transmittance and the DDS/TEOS molar ratio due to the increasing porosity. The maximum transmittance can reach 99.7% with the molar ratio of DDS/TEOS rising to 1 : 1. Meanwhile, the refractive index was found quite close to the ideal value 1.22. Nevertheless, higher molar ratio will lead to a bad film-forming property. On the other hand, the hardness of the coatings decreased with the DDS increasing but still remained more than 2 h when the transmittance reached highest. Besides, these coatings exhibit a well abrasion-resistance and excellent adhesivity. The maximum transmittance was only dropped by 0.071% and 0.112% after abrasion for 500 and 1 000 times respectively. Accelerated corrosion tests indicated that the transmittance of traditional coatings rapidly fell down to the substrate level (-92%) after immersion for 5 min, while the transmittance of our novel coating almost linearly decreased and was kept 93.2% after 56 min. In other words, the environment-resistance of our novel silica AR coating is ten times higher than that of traditional ones. The promotions of the coating performances benefit from its micropore structure (-0. 4 nm) with which water molecule can be effectively prevented. With its high transmittance, good mechanical properties and high environment-resistance, this kind of novel coating has a potential application in the field of solar glass modification to improve its anti-reflective properties.
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In this study, the entropy method and the Super-SBM model with unexpected output are used at first to calculate the digital economy development index and the level of green transformation in manufacturing. Then, a range of multi-dimensional empirical methods, including fixed effects models, threshold models, and mediation models, are applied to analyze the characteristics shown by the impact of digital economy development on the green transformation of manufacturing. The research results are obtained as follows. Firstly, the digital economy contributes significantly to promoting the green transformation of manufacturing after excluding the macro-system environmental effects, conducting such robustness tests as stepwise regression and introducing instrumental variables. Secondly, there is a nonlinear relationship between the development of the digital economy and the green transformation of manufacturing with an increasing marginal effect. Lastly, it is revealed through mechanism analysis that the digital economy promotes the green transformation of manufacturing by enhancing the capabilities of green technological innovation and rationalizing industrial upgrading, with the partial mediation effects reaching 21.2% and 21.8%, respectively. Despite the contribution of digital economy to the advanced upgrading of industries, there is no mediation effect exhibited. In addition to confirming the path of achieving the green transformation of manufacturing through the digital economy, these results also guide the government on how policies can be formulated and improved to grow the digital economy and promote the green transformation of manufacturing.
Asunto(s)
Comercio , Industrias , Desarrollo Económico , China , ClimaRESUMEN
Phycocyanin and allophycocyanin are important active substances in Arthrospira platensis, because of their fluorescent characteristic and antioxidant capacity. In order to solve the problem of insufficient production and inconvenient modification of natural protein, recombinant expression was performed and the fluorescence activity and antioxidant activity was analyzed to meet the demand for phycocyanin and allophycocyanin. A total of seven recombinant strains were constructed in this study, including individual phycocyanin or allophycocyanin, co-expression of phycocyanin-allophycocyanin, and their co-expression with chromophore, and the expression strain for individual chromophore. Different molecular weights of phycocyanin and allophycocyanin were detected in the recombinant strains, which indicated the different polymers expressed. Through mass spectrometry identification, phycocyanin and allophycocyanin may form a dimer of 66 kDa and a polymer of 300 kDa. The results of fluorescence detection showed that phycocyanin and allophycocyanin combined with phycocyanobilin to show fluorescence activity. The fluorescence peak of recombinant phycocyanin was mainly concentrated at 640 nm, which was similar to natural phycocyanin, the fluorescence peak of purified recombinant allophycocyanin was at about 642 nm. The fluorescence peak of the co-expressed recombinant phycocyanin-allophycocyanin is located at 640 nm, and the fluorescence intensity is between the recombinant phycocyanin and the recombinant allophycocyanin. After purification, the fluorescence peak of the recombinant phycocyanin is more concentrated and the fluorescence intensity is higher, which is about 1.3 times of recombinant phycocyanin-allophycocyanin, 2.8 times of recombinant allophycocyanin, indicating that phycocyanin may be more suitable to be used as fluorescence probe in medicine. The antioxidant capacity was measured by using total antioxidant capacity (T-AOC) and DPPH (2,2'-diphenyl-1-triphenylhydrazino) free radical scavenging method, and the recombinant phycobiliprotein showed antioxidant activity. Phycocyanobilin also has certain antioxidant activity and could enhance the antioxidant activity of phycobiliprotein to a certain extent. Recombinant phycocyanin-allophycocyanin polymer has stronger T-AOC, which is about 1.17-2.25 times that of the other five recombinant proteins. And recombinant phycocyanin has stronger DPPH antioxidant activity, which is about 1.2-2.5 times that of the other five recombinant proteins. This study laid the foundation for the application of recombinant phycocyanin and allophycocyanin in medical detection and drug development.
RESUMEN
Plasminogen activator inhibitor-1 (PAI-1) is a specific and rapid-acting inhibitor of endogenous plasminogen activators (uPA and tPA). The global PAI-1 knockout mice (PAI-1KO) develop age-dependent cardiac-selective fibrosis, and young global PAI-1KO mice exhibit augmented susceptibility to developing cardiac fibrosis in response to hypertension. Here, we tested the hypothesis that cardiomyocyte PAI-1 is necessary to provide cardioprotective effects in a left ventricular pressure overload-induced murine model of cardiac hypertrophy and fibrosis using cardiomyocyte-specific PAI-1 knockout (cmPAI-1KO) mice. The results revealed that cmPAI-1KO mice display significantly worse cardiac fibrosis than controls. To investigate the molecular mechanisms responsible for these effects, genome-wide cardiac transcriptome analysis was performed. Loss of cardiomyocyte PAI-1 led to differential expression of 978 genes compared to controls in response to left ventricular pressure overload. Pathway enrichment analysis identified the inflammatory response, cell substrate adhesion, regulation of cytokine production, leukocyte migration, extracellular matrix organization, and cytokine-mediated signaling pathways as being significantly upregulated in cmPAI-1KO hearts. Conversely, specific epigenetic repressors, cation transmembrane transport, muscle system processes, and nitric oxide signaling were significantly downregulated in cmPAI-1KO hearts compared to control hearts in response to left ventricular pressure overload. Collectively, the present study provides strong evidence of the impact of cardiomyocyte PAI-1 in regulation of the transcriptome network involved in the cardiac stress response. In response to stress, the deregulatory impact of cardiomyocyte PAI-1 loss on the cardiac transcriptome may be the underlying cause of cardiac-selective accelerated fibrogenesis in global PAI-1-deficient mice.