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Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.
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Metabolómica , Embarazo , Animales , Femenino , Humanos , Embarazo/metabolismo , Corticosterona/metabolismo , Metaboloma/fisiología , Placenta/metabolismo , Preeclampsia , Primates/metabolismoRESUMEN
Spartina alterniflora Loisel, a perennial grass, has become an invasive species in China's coastal wetlands (Zhang et al. 2018). In July 2021, brown spot symptoms were observed on S. alterniflora in a coastal wetland (21°45'48â³N, 108°44'00â³E) in Beihai City, Guangxi Province, China. The disease affected approximately 50% of the plants in the surveyed area (0.2 ha) and was also observed in other regions of Beihai. It caused brown lesions with a gray or whitish center on the leaves and stems of S. alterniflora. As the disease developed, it ultimately led to leaf shedding and plant death. To isolate the causal agent, 18 fragments (~ 5 mm) from six symptomatic plants (3 leaf pieces per plant) were surface sterilized with 1% NaOCl solution for 2 min and rinsed three times with sterilized water. Subsequently, the tissues were placed on potato dextrose agar (PDA) medium supplemented with chloramphenicol (0.1 g/liter) and incubated at 28°C for three days. The hyphal tips were transferred onto fresh PDA to obtain pure cultures. A total of 25 isolates were obtained, 20 of which shared similar morphologies, while the remaining five exhibited distinct morphological characteristics and were non-pathogenic to S. alterniflora. Three isolates (MC16.1.3, MC16.6.2, and MC16.8.3) were randomly selected from the 20 for further investigation. The colonies on PDA were flat with dense aerial mycelia. The colony margins were entire, light brown in the centre, white to grey at the margin; reverse dark brown in the centre, gray at the margin. Conidia were straight to slightly curved, light olive-brown to dark olive-brown, septate, measured 33.5 to 79.1 µm × 10.4 to 18.7 µm (average 52.9 × 14.4 µm, n = 100), with a distinctly protruding hilum swelled from the basal cell. For molecular identification, the genomic DNA was extracted from mycelium on PDA using the CTAB method (Guo et al. 2000). The internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and translation elongation factor 1 alpha (TEF1-α) genes were amplified and sequenced with the primer pairs ITS1/ITS4 (White et al. 1990), GPD1/GPD2 (Berbee et al. 1999), and EF1-983/EF1-2218 (Rehner et al. 2005), respectively. A BLAST analysis revealed that the ITS (OR516787-9), GAPDH (OR523686-8), and TEF-α (OR523683-5) had 99.1 to 99.7% identity with those of E. rostratum strains BRIP 11417 (LT837836, LT882553, and LT896656) and CBS 128061 (KT265240, LT715900, and LT896658) (Hernández-Restrepo et al. 2018). Based on the concatenated sequences, a phylogenetic tree generated by PhyloSuite software (Zhang et al., 2020) through Bayesian inference (BI) and Maximum Likelihood (ML) methods placed the isolates within E. rostratum. These morphological characteristics and molecular analyses confirmed the pathogen as E. rostratum (Hernández-Restrepo et al. 2018; Kaboré et al. 2022). To confirm pathogenicity, a conidial water suspension (~ 1 × 106 conidia/ml) of each of the three strains was inoculated on nine healthy S. alterniflora plants that had been grown for six months. Control plants were treated with sterile water. All plants were then enclosed in plastic bags and incubated in a greenhouse at 28°C. Six days after inoculation, the plants exhibited symptoms similar to those observed in nature. The control plants developed no symptoms. These experiments were replicated three times with similar results. To fulfill Koch's postulates, E. rostratum was consistently re-isolated from symptomatic tissue and confirmed by morphology and sequencing, whereas no fungus was isolated from the control plants. In recent years, S. alterniflora has posed a serious threat to the indigenous biodiversity of wetland ecosystems (Zhang et al. 2018). To our knowledge, this is the first report of E. rostratum causing brown spot on S. alterniflora worldwide.
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We used deep neural networks to process the mass spectrometry imaging (MSI) data of mouse muscle (young vs aged) and human cancer (tumor vs normal adjacent) tissues, with the aim of using explainable artificial intelligence (XAI) methods to rapidly identify biomarkers that can distinguish different classes of tissues, from several thousands of metabolite features. We also modified classic neural network architectures to construct a deep convolutional neural network that is more suitable for processing high-dimensional MSI data directly, instead of using dimension reduction techniques, and compared it to seven other machine learning analysis methods' performance in classification accuracy. After ascertaining the superiority of Channel-ResNet10, we used a novel channel selection-based XAI method to identify the key metabolite features that were responsible for its learning accuracy. These key metabolite biomarkers were then processed using MetaboAnalyst for pathway enrichment mapping. We found that Channel-ResNet10 was superior to seven other machine learning methods for MSI analysis, reaching > 98% accuracy in muscle aging and colorectal cancer datasets. We also used a novel channel selection-based XAI method to find that in young and aged muscle tissues, the differentially distributed metabolite biomarkers were especially enriched in the propanoate metabolism pathway, suggesting it as a novel target pathway for anti-aging therapy.
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Inteligencia Artificial , Redes Neurales de la Computación , Animales , Ratones , Humanos , Anciano , Aprendizaje Automático , Diagnóstico por Imagen , Procesamiento de Imagen Asistido por ComputadorRESUMEN
BACKGROUND: Increasing bone mass accumulation in adolescence and obtaining greater peak bone mass is one of the effective methods to prevent osteoporosis in the future. We aimed to examine the association between total bilirubin and bone mineral density (BMD) level in adolescents. METHODS: We used the data from 2005-2010 and 2013-2014 cycles of National Health and Nutrition Examination Survey (NHANES). The BMD levels in the region of lumbar spine and femoral regions, including total femur, femoral neck, trochanter, and intertrochanter were measured. Univariable and multivariable linear regression model were used to assess the relationship between total bilirubin concentration and BMD. RESULTS: A total of 3741 participants aged 12-19 years were ultimately included in the study. There were 1997 (53.38%) males and 1744 (46.62%) females. Univariate analysis results showed that age, sex, race, education, income, body mass index, dietary calcium intake, and diabetes were correlated with BMD levels. Compared with the lowest quartile of total bilirubin concentration, the highest quartile of total bilirubin concentration was positively associated with BMD levels in the regions of total femur (ß = 0.036, 95% CI = 0.021 to 0.050, P < 0.001), femur neck (ß = 0.030, 95% CI = 0.016 to 0.044, P < 0.001), trochanter (ß = 0.033, 95% CI = 0.019 to 0.046, P < 0.001), intertrochanter (ß = 0.040, 95% CI = 0.023 to 0.056, P < 0.001), and lumbar spine (ß = 0.032, 95% CI = 0.018 to 0.045, P < 0.001). We also observe the same trend in sensitivity analysis (P for trend < 0.001). CONCLUSION: Our study demonstrated that total bilirubin concentration was positively associated with BMD levels in adolescents in United States. Total bilirubin concentration might be a protective marker against bone loss in adolescents.
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Densidad Ósea , Osteoporosis , Adolescente , Bilirrubina , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Masculino , Encuestas Nutricionales , Estados UnidosRESUMEN
Dental fluorosis is characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation. Excess fluoride could have effects on the ERK signaling, which is essential for the ameloblasts differentiation and tooth development. MAP kinase phosphatase-1 (MKP-1) plays a critical role in regulating ERK related kinases. However, the role of MKP-1 in ameloblast and the mechanisms of MKP-1/ERK signaling in the pathogenesis of dental fluorosis are incompletely understood. Here, we adopted an in vitro fluorosis cell model using murine ameloblasts-like LS8 cells by employing sodium fluoride (NaF) as inducer. Using this system, we demonstrated that fluoride exposure led to an inhibition of p-MEK and p-ERK1/2 with a subsequent increase in MKP-1 expression in a dose-dependent manner. We further identified, under high dose fluoride, MKP-1 acted as a negative regulator of the fluoride-induced p-ERK1/2 signaling, leading to downregulation of CREB, c-myc, and Elk-1. Our results identify a novel MKP-1/ERK signaling mechanism that regulates dental fluorosis and provide a framework for studying the molecular mechanisms of intervention and fluorosis remodeling under normal and pathological conditions. MKP-1 inhibitors may prove to be a benefit therapeutic strategy for dental fluorosis treatment.
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A series of dye@MOF composites were synthesized through in situ encapsulation of luminous rhodamine B (RhB) molecules into a blue-emissive zirconium-naphthalene-based metal-organic framework (Zr-MOF). The fabricated RhB@Zr-MOF composites exhibit tunable dual-emissive characteristics due to the process of resonant energy transfer from Zr-MOF to RhB. Notably, one of the RhB@Zr-MOF composites (R@D3) exhibited a weak emission at 420â nm and a strong emission at 607â nm, for which the two emissions possess large distinctions in location and intensity and can be referenced with each other in sensing analytes. By using relative fluorescence intensity instead of their absolute fluorescence intensity as the detection signals, R@D3 served as a built-in self-calibrated platform to selectively detect Fe3+ and Cr2 O7 2- ions in water. Compared with the pristine Zr-MOF, the R@D3 composite shows enhanced sensing selectivity to Fe3+ and higher sensibility to Cr2 O7 2- . This study displays the advantages of combining organic dyes with robust Zr-MOFs in tuning fluorescence and sensing performance.
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BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine. METHODS: The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 1:1:1 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group). RESULTS: According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16). CONCLUSIONS: Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines. CLINICAL TRIALS REGISTRATION: NCT03274102.
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Formación de Anticuerpos/inmunología , Vacunas contra Hepatitis B/inmunología , Vacunas Meningococicas/inmunología , Polisacáridos Bacterianos/inmunología , Vacunas Combinadas/inmunología , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/inmunología , Anticuerpos Antivirales/inmunología , Enterovirus/inmunología , Infecciones por Enterovirus/inmunología , Femenino , Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Lactante , Masculino , Infecciones Meningocócicas/inmunología , Neisseria meningitidis/inmunología , Vacunación/efectos adversosRESUMEN
OBJECTIVE: To investigate the possible biological mechanism of dental fluorosis at a molecular level. MATERIAL AND METHODS: Cultured LS8 were incubated with serum-free medium containing selected concentrations of NaF (0 â¼ 2 mM) for either 24 or 48 h. Subcellular microanatomy was characterized using TEM; meanwhile, selected biomolecules were analysed using various biochemistry techniques. Transient transfection was used to modulate a molecular pathway for apoptosis. RESULTS: Apoptosis of LS8 was induced by NaF treatment that showed both time and concentration dependency. The activity of caspase-3, -8, -9 was found to be increased with NaF in a dose-dependent manner. Western blot revealed that the protein expression of p-ERK and p-JNK were decreased, while the expression of p-P38 was increased. Inhibition of the p-ERK and p-JNK pathways resulted in a similar decrease for caspase-3. CONCLUSION: During NaF-induced apoptosis of LS8, p-ERK and p-JNK were closely associated with induction of apoptosis, which might be a mechanism of dental fluorosis.
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Ameloblastos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Cariostáticos/efectos adversos , Fluorosis Dental/etiología , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Fluoruro de Sodio/efectos adversos , Ameloblastos/ultraestructura , Animales , Caspasa 3/efectos de los fármacos , Caspasa 8 , Caspasa 9 , Técnicas de Cultivo de Célula , Línea Celular , Relación Dosis-Respuesta a Droga , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Fluorosis Dental/enzimología , Silenciador del Gen , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , ARN Interferente Pequeño/genética , Transfección , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.
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Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Biomarcadores de Tumor/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
A leaf spot disease affecting Curcuma kwangsiensis (Zingiberaceae) has been observed in Qinzhou City, Guangxi Province. Infected leaves exhibit yellow-brown spots that progressively expand and eventually lead to leaf death. Curvularia isolates were obtained from the diseased leaves with tissue isolation and single spore purification methods. To accurately identify these isolates, we analyzed their morphological characteristics and phylogenetic relationships using combinations of ITS, GAPDH, and EF-1α gene sequences. Phylogenetic analysis showed that the investigated strains formed a distinct clade separate from other recognized Curvularia species. Furthermore, the strains exhibited differences in conidiophore size and conidia shape/size. Based on phylogenetic studies, morphology, and pathogenicity tests, the pathogen was identified as a new species named Curvularia qinzhouensis. Optimal conditions for mycelial growth were observed at 30 °C and pH 8. The sensitivity of the pathogen to various phytochemicals was also examined. Honokiol, thymol, and citral demonstrated effective antifungal effects, with EC50 values of 6.72 ± 1.75, 25.74 ± 4.30, and 54.24 ± 4.69 µg/ml, respectively. The present investigation provides the first report of leaf spot disease on C. kwangsiensis caused by C. qinzhouensis, and valuable insights for the prevention and control of this disease.
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Ascomicetos , Curcuma , Filogenia , Fitoquímicos , Enfermedades de las Plantas , Hojas de la Planta , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Hojas de la Planta/microbiología , Ascomicetos/genética , Ascomicetos/efectos de los fármacos , Ascomicetos/patogenicidad , Ascomicetos/aislamiento & purificación , Curcuma/microbiología , Fitoquímicos/farmacología , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/crecimiento & desarrollo , Antifúngicos/farmacologíaRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disease. The clinical symptoms of PD are usually related to motor symptoms, including postural instability, rigidity, bradykinesia, and resting tremors. At present, the pathology of PD is not yet clear. Therefore, revealing the underlying pathological mechanism of PD is of great significance. A variety of bioactive molecules are produced during the onset of Parkinson's, and these bioactive molecules may be a key factor in the development of Parkinson's. The emerging fluorescence imaging technology has good sensitivity and high signal-to-noise ratio, making it possible to deeply understand the pathogenesis of PD through these bioactive molecules. Currently, fluorescent probes targeting PD biomarkers are widely developed and applied. This article categorizes and summarizes fluorescent probes based on different PD biomarkers, systematically introduces their applications in the pathological process of PD, and finally briefly elaborates on the challenges and prospects of these probes. We hope that this review will provide in-depth reference insights for designing fluorescent probes, and contribute to study of the pathogenesis and clinical treatment of PD.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Colorantes Fluorescentes , BiomarcadoresRESUMEN
Pigeon coccidiosis caused by Eimeria spp. is an important veterinary disease with a significant economic impact on the pigeon industry. Preventive measures for Eimeria columbarum in pigeons have been hampered by the lack of extensive genetic, morphological, and biological data on the oocysts. In this study, we examined the prevalence and identity of Eimeria spp. in domestic pigeons from seven cities in Guangdong Province, China. Data show that coccidiosis was prevalent in domestic pigeons in Guangdong Province, with an overall Eimeria spp. detection rate of 73.4%. Five Eimeria species were identified, including E. columbarum (73.4%), Eimeria kapotei (25.6%), Eimeria labbeana (19.6%), Eimeria duculai (19.6%), and Eimeria tropicalis (6.7%). We obtained single oocyst-derived lines of the dominant E. columbarum from fecal specimens. E. columbarum oocysts measured 20.06 ± 0.69 µm × 18.63 ± 1.03 µm, and sporocysts measured 10.29 ± 0.82 µm × 85.38 ± 0.46 µm. In infection experiment using obtained E. columbarum isolates, 60-day-old coccidia-free pigeons exhibited a prepatent period of 105 h and patent period of 9-10 days followed by severe diarrhea, depression, anorexia, and emaciation. Endogenous development of the parasite was observed mainly in the cytoplasm of epithelial cells in the duodenum, jejunum, ileum, and rectum. Two generations of meronts developed on days 3 and 4 after infection, respectively, while gamont and gamete developed on day 5 after infection. The morphological, genetic, and biological data are expected to be useful in elucidating the biological characterization of pigeon coccidiosis to develop measures against the treatment and containment of this disease.
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Enfermedades de las Aves , Coccidiosis , Columbidae , Eimeria , Heces , Animales , Columbidae/parasitología , Coccidiosis/veterinaria , Coccidiosis/epidemiología , Coccidiosis/parasitología , Eimeria/aislamiento & purificación , Eimeria/genética , Eimeria/clasificación , China/epidemiología , Enfermedades de las Aves/parasitología , Enfermedades de las Aves/epidemiología , Heces/parasitología , Oocistos/aislamiento & purificación , PrevalenciaRESUMEN
Amino acids are important chiral compounds in the human body, and are important basic components that make up the human body and play an important role in the human body. Among them, different enantiomers of an amino acid may have different roles, and different types of amino acids can be interconverted. However, the content of D-amino acids is much lower than that of L-amino acids, which is difficult to be detected. At present, many of the potential roles of D-amino acids, such as the conversion of D-amino acids to each other, have not yet been fully revealed. Hence, we synthesized fluorescent probe (R)-5 by condensation of 1,1'-Bi-2-naphthol (BINOL) and 2-(Aminomethyl)pyridine with Schiff base, which can recognize both D-arginine and D-glutamic acid at low concentrations. Meanwhile, (R)-5 can be applied to paper-based sensors for the detection of arginine and glutamate in living cells and for food amino acid detection.
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Arginina , Colorantes Fluorescentes , Ácido Glutámico , Colorantes Fluorescentes/química , Ácido Glutámico/química , Ácido Glutámico/análisis , Arginina/química , Arginina/análisis , Humanos , Estereoisomerismo , Naftoles/químicaRESUMEN
During pregnancy, placental-fetal nutrient allocation is crucial for fetal and maternal health. However, the regulatory mechanisms for nutrient metabolism and allocation in placental trophoblasts have remained unclear. Here, we used human first-trimester placenta samples and human trophoblast stem cells (hTSCs) to discover that glucose metabolism is highly active in hTSCs and cytotrophoblasts, but during syncytialization, it decreases to basal levels, remaining necessary for fueling acetyl-CoA and differentiation potential. Acetate supplementation could rescue syncytiotrophoblast fusion from glycolysis deficiency by replenishing acetyl-CoA and maintaining histone acetylation, thus rescuing the activation of syncytialization genes. Even brief glycolysis deficiency could permanently inhibit differentiation potential and promote inflammation, which could also be permanently rescued by brief acetate supplementation in vivo. These results suggest that hTSCs retain only basal glycolytic acetyl-CoA metabolism during syncytialization to regulate cell fates via nutrient-responsive histone acetylation, with implications for our understanding of the balance between placental and fetal nutrition.
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Acetilcoenzima A , Histonas , Células Madre , Trofoblastos , Humanos , Trofoblastos/metabolismo , Trofoblastos/citología , Acetilcoenzima A/metabolismo , Femenino , Histonas/metabolismo , Acetilación , Embarazo , Células Madre/metabolismo , Células Madre/citología , Diferenciación Celular , Placenta/metabolismo , Glucólisis , Animales , Glucosa/metabolismoRESUMEN
Skeletal muscle myofibers are heterogeneous in their metabolism. However, metabolomic profiling of single myofibers has remained difficult. Mass spectrometry imaging (MSI) is a powerful tool for imaging molecular distributions. In this work, we optimized the workflow of matrix-assisted laser desorption/ionization (MALDI)-based MSI from cryosectioning to metabolomics data analysis to perform high-spatial resolution metabolomic profiling of slow- and fast-twitch myofibers. Combining the advantages of MSI and liquid chromatography-MS (LC-MS), we produced spatial metabolomics results that were more reliable. After the combination of high-spatial resolution MSI and LC-MS metabolomic analysis, we also discovered a new subtype of superfast type 2B myofibers that were enriched for fatty acid oxidative metabolism. Our technological workflow could serve as an engine for metabolomics discoveries, and our approach has the potential to provide critical insights into the metabolic heterogeneity and pathways that underlie fundamental biological processes and disease states.
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Metabolómica , Músculo Esquelético , Metabolómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
It is well-known that muscle regeneration declines with aging, and aged muscles undergo degenerative atrophy or sarcopenia. While exercise and acute injury are both known to induce muscle regeneration, the molecular signals that help trigger muscle regeneration have remained unclear. Here, mass spectrometry imaging (MSI) is used to show that injured muscles induce a specific subset of prostanoids during regeneration, including PGG1, PGD2, and the prostacyclin PGI2. The spike in prostacyclin promotes skeletal muscle regeneration via myoblasts, and declines with aging. Mechanistically, the prostacyclin spike promotes a spike in PPARγ/PGC1a signaling, which induces a spike in fatty acid oxidation (FAO) to control myogenesis. LC-MS/MS and MSI further confirm that an early FAO spike is associated with normal regeneration, but muscle FAO became dysregulated during aging. Functional experiments demonstrate that the prostacyclin-PPARγ/PGC1a-FAO spike is necessary and sufficient to promote both young and aged muscle regeneration, and that prostacyclin can synergize with PPARγ/PGC1a-FAO signaling to restore aged muscles' regeneration and physical function. Given that the post-injury prostacyclin-PPARγ-FAO spike can be modulated pharmacologically and via post-exercise nutrition, this work has implications for how prostacyclin-PPARγ-FAO might be fine-tuned to promote regeneration and treat muscle diseases of aging.
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Músculo Esquelético , PPAR gamma , Epoprostenol , Cromatografía Liquida , Espectrometría de Masas en Tándem , Prostaglandinas I , Regeneración/fisiologíaRESUMEN
Parkinson's disease (PD) is a common irreversible neurodegenerative disease associated with cognitive impairment. To investigate the serum level of phosphatidylinositol-3-kinase (PI3K) and the distribution of the genotypes and alleles of 3 PI3K single-nucleotide polymorphisms (RS37,30,087, RS37,30,088, and RS37,30,089) in PD patients with different clinical characteristics. A total of 54 PD patients and 50 healthy individuals were recruited. The serum PI3K level was measured using the enzyme-linked immunosorbent assay. The severity of PD was assessed using the modified Hoehn-Yahr scale. The cognitive function of PD patients was evaluated using the Mini-Mental State Examination scale and the Montreal Cognitive Assessment. The distribution of the alleles and genotypes of PI3K single-nucleotide polymorphisms (SNPs) was calculated using the Hardy-Weinberg equilibrium. PD patients showed a significantly higher serum level of PI3K compared to healthy individuals. Increased serum PI3K level was observed in PD patients with more severe disease, longer disease duration, and impaired cognitive function. Additionally, no significant differences were observed in the distributions of the genotypes and alleles of 3 PI3K SNPs between PD patients with normal cognitive function and those with cognitive impairment. PD patients with different levels of disease severity, disease duration, and cognitive function had significantly different serum levels of PI3K. However, the PI3K SNPs in patients with normal cognitive function were not significantly different from those in patients with cognitive impairment. These findings contribute to a better understanding of the roles of PI3K and SNPs of the PI3K gene in PD.
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Disfunción Cognitiva , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Fosfatidilinositol 3-Quinasas/genética , Enfermedad de Parkinson/complicaciones , Fosfatidilinositol 3-Quinasa , Enfermedades Neurodegenerativas/complicaciones , Disfunción Cognitiva/genética , Disfunción Cognitiva/complicaciones , Polimorfismo de Nucleótido SimpleRESUMEN
In recent years, effective methods for cyanobacterial blooms treatment have been an important issue. In this study, we demonstrated a rapid catalytic microwave method to deal with Microcystis aeruginosa with FeCl(3)-loaded active carbon. Microcystis aeruginosa damage process was monitored by measuring optical density, chlorophyll-a content, superoxide dismutase activity, l-glutathione content, and turbidity of the treated Microcystis aeruginosa suspension. It was found that this method could quickly and efficiently induce the degradation of Microcystis aeruginosa. On the basis of control experiments and characterization results, we attributed the excellent catalytic performance to the synergy effect between hole-doping of the catalyst and hot spot of microwave irradiation. This work provides a fast and green treatment method for cyanobacterial blooms.
Asunto(s)
Carbón Orgánico/química , Cloruros/química , Compuestos Férricos/química , Microcystis/efectos de la radiación , Microondas , Adhesión Bacteriana , Catálisis , Clorofilidas/metabolismo , Eutrofización/efectos de los fármacos , Glutatión/metabolismo , Microcystis/metabolismo , Superóxido Dismutasa/metabolismo , Propiedades de Superficie , Eliminación de Residuos Líquidos/métodos , Microbiología del Agua , Purificación del Agua/métodosRESUMEN
BACKGROUND: The quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was approved for use in Chinese women aged 20-45 years in 2017. This Phase 3, open-label study (NCT03493542) aimed to assess immunogenicity and safety of the qHPV vaccine in Chinese girls aged 9-19 years versus Chinese young women aged 20-26 years; we report results from Day 1 through Month 7. The study will continue through Month 60 to assess antibody persistence in Chinese girls aged 9-19 years. METHODS: Participants aged 9-26 years received three doses of the qHPV vaccine (Day 1, Month 2, Month 6). Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18 antibodies were determined by competitive Luminex immunoassay (cLIA) in serum samples obtained on Day 1 and at Month 7. Injection-site adverse events (AEs) and systemic AEs within 30 days post-vaccination, and serious AEs (SAEs) occurring at any time during the study, were recorded. RESULTS: In total, 766 participants (383 aged 9-19 years; 383 aged 20-26 years) were enrolled and received ≥1 vaccine dose. All participants in the per-protocol immunogenicity population of both age groups seroconverted to each of the vaccine HPV types at Month 7. Anti-HPV6/11/16/18 antibody GMTs at Month 7 in participants aged 9-19 years were non-inferior to those in participants aged 20-26 years. Injection-site AEs and systemic AEs were reported by 36.6% and 49.3% of 9-19-year-olds, and 40.7% and 54.8% of 20-26-year-olds, respectively. There were no vaccine-related SAEs. No participants discontinued the vaccine due to an AE and no deaths were reported. CONCLUSION: Antibody responses induced by the 3-dose qHPV vaccination regimen in Chinese girls aged 9-19 years were non-inferior to those in Chinese young women aged 20-26 years. The vaccine was generally well tolerated in the study population. ClinicalTrials.gov Identifier: NCT03493542.