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We propose using physical-informed neural network (PINN) for power evolution prediction in bidirectional Raman amplified WDM systems with Rayleigh backscattering (RBS). Unlike models based on data-driven machine learning, PINN can be effectively trained without preparing a large amount of data in advance and can learn the potential rules of power evolution. Compared to previous applications of PINN in power prediction, our model considers bidirectional Raman pumping and RBS, which is more practical. We experimentally demonstrate power evolution prediction of 200â km bidirectional Raman amplified wavelength-division multiplexed (WDM) system with 47 channels and 8 pumps using PINN. The maximum prediction error of PINN compared to experimental results is only 0.38â dB, demonstrating great potential for application in power evolution prediction. The power evolution predicted by PINN shows good agreement with the results simulated by traditional numerical method, but its efficiency is more suitable for establishing models and calculating noise, providing convenience for subsequent power configuration optimization.
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With the increasing trend of global aging, sarcopenia has become a significant public health issue. Goji berry, also known as "Gou qi zi" in China, is a traditional Chinese herb that can enhance the structure and function of muscles and bones. Otherwise, previous excellent publications illustrated that plant-derived exosome-like nanoparticles can exert good bioactive functions in different aging or disease models. Thus, we issued the hypothesis that Gouqi-derived nanovesicles (GqDNVs) may also have the ability to improve skeletal muscle health, though the effect and its mechanism need to be explored. Hence, we have extracted GqDNVs from fresh berries of Lycium barbarum L. (goji) and found that the contents of GqDNVs are rich in saccharides and lipids. Based on the pathway annotations and predictions in non-targeted metabolome analysis, GqDNVs are tightly associated with the pathways in metabolism. In muscle atrophy model mice, intramuscular injection of GqDNVs improves the cross-sectional area of the quadriceps muscle, grip strength and the AMPK/SIRT1/PGC1α pathway expression. After separately inhibiting AMPK or PGC1α in C2C12 cells with dexamethasone administration, we have found that the activated AMPK plays the chief role in improving cell proliferation induced by GqDNVs. Furthermore, the energy-targeted metabolome analysis in the quadriceps muscle demonstrates that the GqDNVs up-regulate the metabolism of amino sugar and nucleotide sugar, autophagy and oxidative phosphorylation process, which indicates the activation of muscle regeneration. Besides, the Spearman rank analysis shows close associations between the quality and function of skeletal muscle, metabolites and expression levels of AMPK and SIRT1. In this study, we provide a new founding that GqDNVs can improve the quality and function of skeletal muscle accompanying the activated AMPK/SIRT1/PGC1α signaling pathway. Therefore, GqDNVs have the effect of anti-aging skeletal muscle as a potential adjuvant or complementary method or idea in future therapy and research.
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Proteínas Quinasas Activadas por AMP , Dexametasona , Atrofia Muscular , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Transducción de Señal , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Dexametasona/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/inducido químicamente , Línea Celular , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Ratones Endogámicos C57BL , Nanopartículas/química , Exosomas/metabolismo , Exosomas/efectos de los fármacosRESUMEN
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.
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Aldo-Ceto Reductasas , Curcumina , Enfermedad del Hígado Graso no Alcohólico , Triglicéridos , Curcumina/farmacología , Curcumina/análogos & derivados , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Humanos , Células Hep G2 , Aldo-Ceto Reductasas/metabolismo , Ratas , Masculino , Triglicéridos/sangre , Triglicéridos/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Aldehído Reductasa/metabolismo , Aldehído Reductasa/antagonistas & inhibidores , Dieta Alta en Grasa/efectos adversos , Simulación del Acoplamiento Molecular , Hígado/efectos de los fármacos , Hígado/metabolismo , Metformina/farmacología , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Rodanina/análogos & derivados , TiazolidinasRESUMEN
Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.
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Apoptosis , Carcinoma Hepatocelular , Estrés del Retículo Endoplásmico , Neoplasias Hepáticas , Oligopéptidos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Oligopéptidos/farmacología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ratones , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Movimiento Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones Endogámicos BALB CRESUMEN
The natural extracellular matrix, with its heterogeneous structure, provides a stable and dynamic biophysical framework and biochemical signals to guide cellular behaviors. It is challenging but highly desirable to develop a synthetic matrix that emulates the heterogeneous fibrous structure with macroscopic stability and microscopical dynamics and contains inductive biochemical signals. Herein, we introduce a peptide fiber-reinforced hydrogel in which the stiff ß-sheet fiber functions as a multivalent cross-linker to enhance the hydrogel's macroscopic stability. The dynamic imine cross-link between the peptide fiber and polymer network endows the hydrogel with a microscopically dynamic network. The obtained fibrillar nanocomposite hydrogel, with its cell-adaptable dynamic network, enhances cell-matrix and cell-cell interactions and therefore significantly promotes the mechanotransduction, metabolic energetics, and osteogenesis of encapsulated stem cells. Furthermore, the hydrogel can codeliver a fiber-attached inductive drug to further enhance osteogenesis and bone regeneration. We believe that our work provides valuable guidance for the design of cell-adaptive and bioactive biomaterials for therapeutic applications.
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Hidrogeles , Mecanotransducción Celular , Hidrogeles/química , Biomimética , Regeneración Ósea , Péptidos/química , OsteogénesisRESUMEN
Selective fluorescence imaging of analytes is a challenge for monitoring diseases as homologues interfere with the imaging agents. Leucine aminopeptidase (LAP), a kind of protease, is related to tumor pathogenesis. The known LAP fluorescent probes based on leucine recognition have limited selectivity. Herein, a selective t-butyl-alanine recognition unit for LAP through the ligand regulation strategy is prepared as a new near-infrared (NIR) fluorescent probe (DCM-LAP) having a large Stokes shift of 214 nm and a high sensitivity with a detection limit of 168 mU/L. DCM-LAP has an enhanced response toward LAP with NIR fluorescence at 656 nm based on intramolecular charge transfer. The probe is selective without being interfered with by biological enzymes including the aminopeptidase N (APN). DCM-LAP can image LAP activity in living cells. It can also visualize the cell invasion and migration processes. DCM-LAP is employed in the real-time imaging of LAP in tumor-bearing nude mice and guides in the accurate resection of breast tumors. It also distinguishes tumor tissues from normal with a high tumor-to-normal ratio (9.8). The DCM-LAP probe can thus assist in the investigations of LAP-associated clinical disease.
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Colorantes Fluorescentes , Neoplasias , Animales , Ratones , Leucil Aminopeptidasa , Ratones Desnudos , Neoplasias/diagnóstico por imagen , Imagen ÓpticaRESUMEN
γ-Glutamyltransferase (GGT) has been recognized as an important clinical biomarker that is closely related to many diseases. Visualizing the GGT fluctuation facilitates early disease-related diagnosis and therapy. Herein, an activated probe (NIR-GGT) for the imaging of GGT activity was prepared. The probe consists of a stable NIR fluorophore with the tunable amino group decorated with the γ-glutamate group as a GGT-sensing unit linked by a self-elimination group. NIR-GGT can sensitively recognize GGT and cause a strong turn-on fluorescent and photoacoustic signal. The up-regulation of the GGT expression in acetaminophen-induced acute liver injury was imaged using NIR-GGT. The probe can track changes in the GGT level in the early stages of drug-induced acute liver injury (DIALI) and its remedy process by fluorescent and photoacoustic dual-modality imaging with a high temporal-spatial resolution. NIR-GGT can also be used to differentiate between tumor and para-carcinowa tissues in vivo. The probe may be a potential tool for the diagnosis of early-stage DIALI and accurate tumor resection in the clinical field.
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BACKGROUND: Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women. METHODS: Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA). RESULTS: Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (ß = -79.79 g; 95% CI: -119.09, -40.49) and birth length (ß = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05). CONCLUSIONS: Maternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.
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Retardo del Crecimiento Fetal , Parto , Femenino , Humanos , Embarazo , Animales , Peso al Nacer , Estudios Prospectivos , China/epidemiologíaRESUMEN
PCV2 has been reported to reduce the protective effects of various vaccines on immunized pigs. Our previous studies showed that the interaction of Cap and host protein gC1qR mediated the PCV2 infection-induced suppression of immune response. Thus, we wondered whether the gC1qR binding site mutant PCV2RmA could be a vaccine strain and whether this mutant PCV2RmA impairs other vaccines. Herein, we showed that PCV2 infection reduced the classic swine fever virus (CSFV) vaccine-induced generation of memory CD4+ T cells through the interaction of Cap with gC1qR. PCV2RmA can effectively induce the production of PCV2-specific antibodies, neutralizing antibodies, and peripheral blood lymphocyte proliferation in piglets at the same levels as the commercial inactivated PCV2 vaccine. The PCV2RmA-induced anti-PCV2 immune responses could eliminate the serum virus and would not lead to pathological lesions like wild-type PCV2. Moreover, compared to the commercial inactivated PCV2 vaccine, PCV2RmA is capable of inducing more durable protective immunity against PCV2 that induced production of PCV2-specific antibodies and neutralizing antibodies for a longer time via stronger induction of memory CD4+ T cells. Importantly, PCV2RmA infection did not impair the CSFV vaccine-induced generation of memory CD4+ T cells. Collectively, our findings showed that PCV2 infection impairs memory CD4+ T-cell generation to affect vaccination and provide evidence for the use of PCV2RmA as an efficient vaccine to prevent PCV2 infection. IMPORTANCE PCV2 is one of the costliest pathogens in pigs worldwide. Usage of PCV2 vaccines can prevent the PCV2 infection-induced clinical syndromes but not the viral spread. Our previous work found that PCV2 infection suppresses the host type I interferon innate immune response and CD4+ T-cell-mediated Th1 immune response through the interaction of Cap with host gC1qR. Here, we showed that the gC1qR binding site mutant PCV2RmA could effectively induce anti-PCV2 immunity and provide more durable protective immunity against wild-type PCV2 infection in pigs. PCV2RmA would not impair the generation of memory CD4+ T cells induced by classic swine fever virus (CSFV) vaccines as wild-type PCV2 did. Therefore, PCV2RmA can serve as a potential vaccine strain to better protect pigs against PCV2 infection.
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Linfocitos T CD4-Positivos , Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Receptores de Complemento , Vacunas Virales , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Sitios de Unión , Linfocitos T CD4-Positivos/inmunología , Proteínas de la Cápside/genética , Peste Porcina Clásica/inmunología , Peste Porcina Clásica/prevención & control , Peste Porcina Clásica/virología , Virus de la Fiebre Porcina Clásica/genética , Memoria Inmunológica , Interferón Tipo I , Receptores de Complemento/metabolismo , Porcinos , Vacunas de Productos Inactivados/genética , Vacunas Virales/genéticaRESUMEN
BACKGROUND AND AIMS: Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis. APPROACH AND RESULTS: In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARS96 phosphorylation is observed in human liver steatotic and HCC tissues and is associated with overall survival and disease-free survival, which has been proven as an independent survival predictor for patients with HCC. CONCLUSIONS: AR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC.
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Carcinoma Hepatocelular , Hígado Graso , Neoplasias Hepáticas , Andrógenos , Animales , Carcinogénesis , Carcinoma Hepatocelular/patología , Transformación Celular Neoplásica , Humanos , Neoplasias Hepáticas/patología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Fosforilación , Receptores Androgénicos/metabolismoRESUMEN
OBJECTIVE: Ferritin levels are well known to be associated with gestational diabetes mellitus (GDM). However, the association of the combination of ferritin and triglyceride (TG) levels in early mid-pregnancy with GDM has not been studied in depth. We investigated the independent and combined relationships of plasma ferritin and TG concentrations with the risk of GDM as well as the mediation effect of TG on ferritin. METHODS: We analysed 2071 pregnant women from the Tongji Maternal and Child Health Cohort who had their plasma ferritin and TG concentrations measured at 11-20 weeks of gestation. Associations between ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Youden's index was calculated to find the cut-off values of ferritin and TG by ROC curve analysis. The mediation effect of the TG concentration on the ferritin level with GDM risk was explored by a mediation analysis. RESULTS: A total of 264 (12.3%) participants developed GDM. The median and IQR of ferritin was 53.9 (30.5-92.7) ng/mL. After adjusting for potential confounders, the relative risks (RRs) and 95% confidence intervals of GDM were 2.19 (1.42, 3.39) for ferritin and 2.02 (1.37, 2.97) for TG. The adjusted RR for combination was 2.40 (1.62, 3.55). Moreover, we found that the TG concentration mediated 15.0% of the total effect of the ferritin concentration on the risk of GDM. CONCLUSIONS: Women with a combination of both high plasma ferritin (Ë55.7 ng/mL) and high TG (Ë1.9 mmoL/L) were at the highest risk of GDM. Additionally, we have revealed for the first time that an elevated maternal TG concentration in early pregnancy mediates the relationship between ferritin concentration and GDM risk. TRIAL REGISTRATION: This trial is registered at https://ClinicalTrials.gov as NCT03099837.
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Diabetes Gestacional , Niño , Embarazo , Femenino , Humanos , Diabetes Gestacional/etiología , Triglicéridos , Estudios Prospectivos , Factores de Riesgo , FerritinasRESUMEN
BACKGROUND: Breastfeeding has numerous effects on maternal and child health. The effect of breastfeeding on infant sleep remains inconclusive. OBJECTIVES: We aimed to examine whether full breastfeeding (FBF) during the first 3 mo is associated with longitudinal infant sleep trajectories in their first 2 y of life. METHODS: The study was embedded in the Tongji Maternal and Child Health Cohort study. Information on infant feeding practices was collected at 3 mo of age, and maternal/child pairs were assigned to the FBF or the non-FBF group (including partially breastfeeding and exclusive formula feeding) on the basis of feeding practices during the first 3 mo of life. Sleep data of infants were obtained at 3, 6, 12, and 24 mo. Total, night, and day sleep trajectories across 3 to 24 mo were estimated with group-based models. Each sleep trajectory was differentiated on the basis of sleep duration at 3 mo (long/moderate/short) and the interval from 6 to 24 mo (moderate/short). Multinomial logistic regression was used to investigate the association of breastfeeding practices with infant sleep trajectories. RESULTS: Among the 4056 infants studied, 2558 (63.1%) received FBF for 3 mo. When compared with FBF infants, non-FBF infants had shorter sleep duration at 3, 6, and 12 mo (P < 0.01). Non-FBF infants were more likely to experience Moderate-Short (OR: 1.31; 95% CI: 1.06, 1.61) and Short-Short (OR: 1.56; 95% CI: 1.12, 2.16) total sleep trajectories and more likely to experience Moderate-Short (OR: 1.84; 95% CI: 1.22, 2.77), and Short-Moderate (OR: 1.40; 95% CI: 1.06, 1.85) night sleep trajectories than FBF infants. CONCLUSIONS: Full breastfeeding for ≥3 mo were positively associated with longer infant sleep duration. Infants fully breastfed were more likely to experience better sleep trajectories characterized by longer duration in their first 2 y of life. Full breastfeeding may benefit infants through healthy sleep.
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Lactancia Materna , Conducta Alimentaria , Niño , Femenino , Lactante , Humanos , Estudios de Cohortes , Estudios Prospectivos , SueñoRESUMEN
Cardiovascular disease events are the result of functional and structural abnormalities in the arteries and heart. Atherosclerosis is the main cause and pathological basis of cardiovascular diseases. Atherosclerosis is a multifactorial disease associated with dyslipidemia, inflammation, and oxidative stress, among which dyslipidemia and chronic inflammation occur in all processes. Under the influence of lipoproteins, the arterial intima causes inflammation, necrosis, fibrosis, and calcification, leading to plaque formation in specific parts of the artery, which further develops into plaque rupture and secondary thrombosis. Foam cell formation from macrophages is an early event in the development of atherosclerosis. Lipid uptake causes a vascular inflammatory response, and persistent inflammatory infiltration in the lesion area further promotes the development of the disease. Inhibition of macrophage differentiation into foam cell and reduction of the level of proinflammatory factors in macrophages can effectively alleviate the occurrence and development of atherosclerosis. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor that plays an important antiatherosclerotic role by regulating triglyceride metabolism, lipid uptake, cholesterol efflux, macrophage polarity, and inhibiting inflammatory signaling pathways. In addition, PPARγ shifts its binding to ligands and co-activators or co-repressors of transcription of target genes through posttranslational modification, thereby affecting the regulation of its downstream target genes. Many ligand agonists have also been developed targeting PPARγ. In this review, we summarized the role of PPARγ in lipid metabolism and inflammation in development of atherosclerosis, the posttranslational regulatory mechanism of PPARγ, and further discusses the value of PPARγ as an antiatherosclerosis target.
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Aterosclerosis , Enfermedades Cardiovasculares , PPAR gamma , Humanos , Aterosclerosis/metabolismo , Inflamación/metabolismo , Ligandos , Metabolismo de los Lípidos , PPAR gamma/metabolismoRESUMEN
PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.
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Infecciones del Sistema Respiratorio , Recién Nacido , Lactante , Humanos , Estudios de Casos y Controles , Estudios Prospectivos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , Suplementos Dietéticos , Vitamina DRESUMEN
OBJECTIVE: To evaluate the association between patterns of gestational weight gain (GWG) and allergic diseases in offspring. DESIGN: Prospective cohort study. SETTING: Prenatal clinics in Wuhan, China. POPULATION: A cohort of 2546 mother and offspring pairs were enrolled before 16 weeks of gestation and followed up to 24 months postpartum. METHODS: Maternal body weights were measured regularly during pregnancy, and their GWG patterns were estimated using the growth mixture model. Robust Poisson models were used to evaluate relative risk (RR) and 95% CI after multivariable adjustment. MAIN OUTCOME MEASURES: Offspring atopic allergy and allergic contact dermatitis were defined according to a physician's diagnosis reported by the mother, and food allergy was reported by the mother. RESULTS: Three GWG patterns were identified: 18.1% (461) of the women were described as pattern 1, characterised by rapid GWG earlier in pregnancy; 56.6% (1442) of the women were described as pattern 2, with steady GWG throughout pregnancy; and 25.3% (643) of the women was described as pattern 3, with rapid GWG later in pregnancy. By the age of 24 months, 360 (14.1%), 109 (4.3%) and 757 (29.7%) offspring had atopic allergy, allergic contact dermatitis or food allergy, respectively. Compared with women in GWG pattern 2, the RRs (95% CIs) among women in pattern 1 were 0.74 (0.55-0.99) for atopic allergy, 0.64 (0.36-1.15) for allergic contact dermatitis and 0.95 (0.81-1.12) for food allergy. CONCLUSIONS: Maternal GWG pattern characterised by rapid GWG earlier in pregnancy was associated with a lower risk of atopic allergy in offspring.
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Dermatitis Alérgica por Contacto , Ganancia de Peso Gestacional , Embarazo , Humanos , Femenino , Preescolar , Estudios Prospectivos , Índice de Masa Corporal , RiesgoRESUMEN
Due to the asymmetrical structure in the vertical direction, Janus two-dimensional (2D) monolayer (ML) materials possess some unique physical properties, holding great promise for nanoscale devices. In this paper, based on the newly discovered MoA2Z4 (A = Si, Ge; Z = N, P, As) ML, we propose a class of 2D Janus MoAZ3H ML materials with good stability and excellent mechanical properties using first-principles calculations. We demonstrate that the novel Janus MoAZ3H ML materials are all semiconductors with bandgaps ranging from 0.69 to 2.44 eV, giving rise to good absorption in the visible light region. Especially, both MoSiN3H and MoGeN3H MLs can be used as catalysts for producing hydrogen through water splitting. This catalytic property is much more efficient than that of the MoA2Z4 ML, attributed to the intrinsic electric field induced by the vertical asymmetry effectively separating electrons and holes. More importantly, the carrier mobility of the MoAZ3H ML is up to 103-104 cm2 V-1 s-1 due to the large elastic modulus or small effective mass. Additionally, the electronic properties of the MoAZ3H ML can be easily tuned by strain. Our results suggest a new strategy for designing novel 2D Janus materials, which not only expands the members in the 2D MA2Z4-based Janus family, but also provide candidates with excellent performances in photovoltaic and catalytic fields.
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Stacking and/or substitutional doping are effective strategies to tune two-dimensional materials with desired properties, greatly extending the applications of the pristine materials. Here, by employing first-principles calculations, we propose that a pristine MoTe2/ZrS2 heterostructure is a distinguished lithium-ion battery anode material with a low Li diffusion barrier (â¼0.26 eV), and it has a high maximum Li storage capacity (476.36 mA h g-1) and a relatively low open-circuit voltage (0.16 V) at Li4/MoTe2/Li/ZrS2/Li4. The other heterostructures with different types can be achieved by substitutional doping and their potential applications in sustainable energy related areas are further unraveled. For instance, a type-II TeMoSe/ZrS2 heterostructure could be a potential direct Z-scheme photocatalyst for water splitting with a high solar-to-hydrogen conversion efficiency of 17.62%. The TeMoSe/SZrO heterostructure is predicted to be a potential candidate for application in highly efficient solar cells. Its maximum power conversion efficiency can be as high as 19.21%, which is quite promising for commercial applications. The present results will shed light on the sustainable energy applications of pristine or doped MoTe2/ZrS2 heterostructures in the future.
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Circularly polarized luminescence (CPL) has been widely demonstrated that the circular polarization in excited state can be significantly amplified through the triplet-triplet annihilation-based upconversion (TTA-UC) luminescence process in various chiral nano-assemblies. However, constructing such an upconverted circularly polarized luminescence (UC-CPL) system in the aqueous phase remains a challenge. In this work, a kind of amphiphilic chiral cationic gemini surfactant is utilized to construct chiral spherical micelle in the aqueous phase, whose internal chiral cavity can provide a hydrophobic and deoxygenated environment for air-sensitive TTA-UC system. In addition, due to the co-assembly process between the emitters and chiral micelles, achiral emitters of upconversion pairs exhibit induced chiroptical properties. More importantly, the luminescence dissymmetry factor (glum ) can be amplified by one order of magnitude through TTA-UC process. This work provides an effective and useful strategy for realizing UC-CPL in aqueous phase.
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Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a "notable marker" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.
Asunto(s)
Vesículas Extracelulares , Leche Humana , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt , Proteínas Quinasas S6 Ribosómicas 70-kDa , Músculos , Serina-Treonina Quinasas TOR , Rendimiento Físico Funcional , Aminoácidos , Transducción de SeñalRESUMEN
We used two a priori diet scores [Mediterranean diet (aMed) and Diet Balance Index (DBI)] and two a posteriori approaches [principal components analysis (PCA) and reduced-rank regression (RRR)] to examine the association of maternal dietary patterns with risk of gestational diabetes mellitus (GDM) and blood glucose among 2202 pregnant women in the Tongji Birth Cohort. Compared to the highest quartile of the aMed and legumes-vegetables-fruits (derived by PCA) scores, the fasting blood glucose (FBG) levels were higher in the lower quartiles (p-trend < 0.05). Lower scores of the meats-eggs-dairy (derived by PCA) and eggs-fish patterns (derived by RRR; characterised by higher intakes of freshwater fish, eggs, and lower intakes of leafy and cruciferous vegetables and fruits) were associated with decreased FBG levels (p-trend < 0.05). Similarities were found across approaches that some dietary patterns were associated with FBG, but not with postprandial glucose and GDM risk.