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As an important component of secondary aerosols, sulfate plays a crucial role in regulating atmospheric radiative balance and influencing the secondary formation of ozone (O3). In real atmosphere, atmospheric oxidants NO2 and O3 can promote the oxidation of SO2 to form sulfate (SO42-) through multiphase chemistry that occur at different time scales. Due to the combined impact of meteorology, pollution sources, atmospheric chemistry, etc., time-scale dependence of SO2-SO42- conversion makes the impact of NO2/O3 on it more complex. In this study, based on long-term time series (2013-2020) of air pollution variables from seven stations in Hong Kong, the Multifractal Detrended Cross-Correlation Analysis (MFDCCA) method has been employed to quantify the cross-correlations between SO2 and SO42- in real atmosphere at different time scales, for examining the time-scale dependence of SO2-SO42- conversion efficiency. Furthermore, the Pearson correlation analysis has been used to study the influence of NO2/O3 on SO2-SO42- conversion, and the regional and seasonal differences have been analyzed by considering factors such as meteorology, pollution sources, and regional transport. Changes in the main components of secondary aerosols are closely linked with the co-control of regional PM2.5 and O3. Therefore, the exploration of the impact of co-existing NO2/O3 gases on the secondary formation of sulfates in real atmosphere is significant.
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Contaminantes Atmosféricos , Atmósfera , Monitoreo del Ambiente , Dióxido de Nitrógeno , Ozono , Sulfatos , Ozono/química , Sulfatos/química , Sulfatos/análisis , Atmósfera/química , Contaminantes Atmosféricos/análisis , Dióxido de Nitrógeno/análisis , Hong Kong , Aerosoles/análisis , Contaminación del Aire/estadística & datos numéricos , Dióxido de Azufre/análisis , Dióxido de Azufre/químicaRESUMEN
The gut microbiota plays a vital role in human health, and significant effort has been made to predict human phenotypes, especially diseases, with the microbiota as a promising indicator or predictor with machine learning (ML) methods. However, the accuracy is impacted by a lot of factors when predicting host phenotypes with the metagenomic data, e.g. small sample size, class imbalance, high-dimensional features, etc. To address these challenges, we propose MicroHDF, an interpretable deep learning framework to predict host phenotypes, where a cascade layers of deep forest units is designed for handling sample class imbalance and high dimensional features. The experimental results show that the performance of MicroHDF is competitive with that of existing state-of-the-art methods on 13 publicly available datasets of six different diseases. In particular, it performs best with the area under the receiver operating characteristic curve of 0.9182 ± 0.0098 and 0.9469 ± 0.0076 for inflammatory bowel disease (IBD) and liver cirrhosis, respectively. Our MicroHDF also shows better performance and robustness in cross-study validation. Furthermore, MicroHDF is applied to two high-risk diseases, IBD and autism spectrum disorder, as case studies to identify potential biomarkers. In conclusion, our method provides an effective and reliable prediction of the host phenotype and discovers informative features with biological insights.
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Aprendizaje Profundo , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Metagenómica , Fenotipo , Humanos , Metagenómica/métodos , Microbioma Gastrointestinal/genética , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/genética , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/microbiología , Cirrosis Hepática/genética , Cirrosis Hepática/microbiología , Biología Computacional/métodos , Aprendizaje Automático , Metagenoma , Curva ROCRESUMEN
Plants face constant threats from pathogens, leading to growth retardation and crop failure. Cell-surface leucine-rich repeat receptor-like kinases (LRR-RLKs) are crucial for plant growth and defense, but their specific functions, especially to necrotrophic fungal pathogens, are largely unknown. Here, we identified an LRR-RLK (Solyc06g069650) in tomato (Solanum lycopersicum) induced by the economically important necrotrophic pathogen Botrytis cinerea. Knocking out this LRR-RLK reduced plant growth and increased sensitivity to B. cinerea, while its overexpression led to enhanced growth, yield, and resistance. We named this LRR-RLK as BRAK (B. cinerea resistance-associated kinase). Yeast two-hybrid screen revealed BRAK interacted with phytosulfokine (PSK) receptor PSKR1. PSK-induced growth and defense responses were impaired in pskr1, brak single and double mutants, as well as in PSKR1-overexpressing plants with silenced BRAK. Moreover, BRAK and PSKR1 phosphorylated each other, promoting their interaction as detected by microscale thermophoresis. This reciprocal phosphorylation was crucial for growth and resistance. In summary, we identified BRAK as a novel regulator of seedling growth, fruit yield and defense, offering new possibilities for developing fungal disease-tolerant plants without compromising yield.
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In this study, the effects on silage performance and microbial community of sorghum straw treated with the addition of enzymes (cellulase (CE), xylanase (XE)) and extrusion puffing technology, combined with SEM, XRD, and FTIR techniques, were thoroughly investigated. The results showed that the enzyme preparations, especially xylanase, significantly improved the nutritional value and fermentation efficiency of straw and enhanced the silage effect. Extruding significantly changes the surface structure of the straw, increasing the surface area and porosity, and promoting the attachment of microorganisms. This study not only optimized the sorghum straw silage performance but also provided technical support for the efficient use of straw resources, which is of great significance for the sustainable development of animal husbandry and the resource utilization of agricultural waste.
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Fermentación , Ensilaje , Sorghum , Sorghum/metabolismo , Ensilaje/microbiología , Celulasa/metabolismo , Endo-1,4-beta Xilanasas/metabolismoRESUMEN
Background: Clinical studies have demonstrated that microbes play a crucial role in human health and disease. The identification of microbe-disease interactions can provide insights into the pathogenesis and promote the diagnosis, treatment, and prevention of disease. Although a large number of computational methods are designed to screen novel microbe-disease associations, the accurate and efficient methods are still lacking due to data inconsistence, underutilization of prior information, and model performance. Methods: In this study, we proposed an improved deep learning-based framework, named GIMMDA, to identify latent microbe-disease associations, which is based on graph autoencoder and inductive matrix completion. By co-training the information from microbe and disease space, the new representations of microbes and diseases are used to reconstruct microbe-disease association in the end-to-end framework. In particular, a similarity fusion strategy is conducted to improve prediction performance. Results: The experimental results show that the performance of GIMMDA is competitive with that of existing state-of-the-art methods on 3 datasets (i.e., HMDAD, Disbiome, and multiMDA). In particular, it performs best with the area under the receiver operating characteristic curve (AUC) of 0.9735, 0.9156, 0.9396 on abovementioned 3 datasets, respectively. And the result also confirms that different similarity fusions can improve the prediction performance. Furthermore, case studies on two diseases, i.e., asthma and obesity, validate the effectiveness and reliability of our proposed model. Conclusion: The proposed GIMMDA model show a strong capability in predicting microbe-disease associations. We expect that GPUDMDA will help identify potential microbe-related diseases in the future.
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A palladium-catalyzed annulation reaction of bay-diiodinated arenes with o-chloroaromatic carboxylic acids was established. This approach enables the synthesis of a variety of polycyclic aromatic compounds, especially polyalkoxy-substituted polycyclic aromatic compounds, frequently found in discotic liquid-crystalline materials. The investigations indicate that the product 2,3,8,9,12,13-hexakis(hexyloxy)-5-azadibenzo[fg,op]tetracene demonstrates favorable room-temperature liquid-crystalline properties.
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The identification of fragrant rice varieties using near-infrared reflectance spectroscopy (NIRS) models has attracted extensive attention from regulatory authorities worldwide. In this study, 138 fragrant and 54 nonfragrant rice varieties were planted in the same region and distinguished using sensory evaluation, gas chromatography-mass spectrometry analysis, and betaine aldehyde dehydrogenase 2 (Badh2) genotyping. Then, the 2-acetyl-1-pyrroline (2-AP) content was assessed based on partial least-squares discriminant (PLS-DA) models generated after 2nd individually or combined with SNV/MSC/smoothing preprocessing successfully classified fragrant rice both in the calibration and predictive sets. Moreover, design of experiments (DoE)-based preprocessing selection was employed as an effective strategy to optimize the calibration models compared with the one variable at a time (OVAT) method. Further, Badh2 genotype sample screening assisted with identifying authentic fragrant rice and guaranteed the NIRS model's prediction accuracy in identifying fragrant rice. In conclusion, the high throughput PLS-DA multivariate method coupled with NIRS data was applied to identify fragrant rice varieties in routine monitoring and was effective, accurate, and rapid.
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BACKGROUND: Prednisolone/prednisone coadministration with abiraterone may explain abiraterone-related increase in cardiovascular risk. We explored this postulation and glucocorticoid's association with cardiovascular risk. METHODS: Patients with prostate cancer on androgen deprivation therapy and enzalutamide, or abiraterone with 5 mg (ABI + P5) or 10 mg (ABI + P10) daily total prednisolone/prednisone were followed up for major adverse cardiovascular events (MACE). RESULTS: We analyzed 933 patients. ABI + P10, but not enzalutamide, had higher risk of MACE than ABI + P5. Cumulative glucocorticoid dose before enzalutamide/abiraterone initiation was associated with MACE. CONCLUSIONS: Prednisolone/prednisone coadministration with abiraterone likely contributed to abiraterone-related increased cardiovascular risk. Prevalent cumulative glucocorticoid dose was associated with cardiovascular risk.
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Carbon Fiber Reinforced Polymer (CFRP) can be used to reinforce steel structures depending on its high strength and lightweight resistance. To analyze and evaluate the load-carrying capacity of CFRP-reinforced steel structures. This study uses the Finite Element Analysis (FEA) and the experimental tests combined to investigate the influence that the reinforcement patterns and the relevant parameters have on the load-carrying capacity. We made specimens with different reinforcement patterns. Take the steel beam specimen with full reinforcement as an example. Compared with the load-carrying capacity of the steel beam reinforced by two-layer CFRP cloth, that respectively increases by 5.16% and 11.1% when the number of the CFRP cloth increases to four and six, respectively. Based on a specimen set consisting of CFRP-reinforced steel structures under different reinforcement patterns, the random forest algorithm is used to develop an evaluation model for the load carrying. The performance test results show that the MAE (Mean Absolute Error) of the evaluation model can reach 0.12 and the RMSE (Root Mean Square Error) is 0.25, presenting a good prediction accuracy, which lays a solid foundation for the research on the CFRP-based reinforcement technology and process.
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Egg-laying is an important trait in chickens, and it is affected by many factors, such as hormones regulated by the hypothalamic-pituitary axis and precursors synthesized by the liver. Recent studies showed that gut microbiota was associated with egg-laying, however, its underlying mechanism remains unclear. We comprehensively analyzed the host transcriptome, gut microbiota, and metabolome in broiler breeder hens during the pre-laying, peak-laying, and late-laying periods. The transcriptome analysis of the tissues related to the hypothalamic-pituitary-liver (HPL) axis revealed dynamic gene expression during egg-laying periods. Differentially expressed genes (DEGs) (i.e., PENK, NPY, AVP, PRL, RLN3, and FST) from the hypothalamus and pituitary gland were involved in female gonadal development, hormone secretion, response to endogenous stimulus, liver development, and amide metabolism. In liver, DEGs (i.e., FABP3, VTG1, LPL, APOA5, APOV1, and RBP5) were enriched in efferocytosis, sphingolipid metabolism, amide, and peptide biosynthesis. Alpha and beta diversity changed significantly in cecum microbiota during different laying periods. The abundance of Firmicutes was decreased and the abundance of Bacteroidota was increased during the peak-laying period. Functional analysis showed that the biosynthesis of secondary metabolites, amino acids, purine, and steroid hormones was altered during laying. The metabolome analysis from cecal contents showed that amino acid metabolism and steroid hormone biosynthesis changed during laying. Integrated analysis of the cecal microbiota and metabolites showed the genus Megasphaera was involved in amino acid metabolism, which included 3-phenyllatic acid, quinic acid, caffeic acid, and folic acid, and the genus Hungatella participated in steroid hormone biosynthesis through its strong correlation with estradiol. These results explored the dynamic changes in tissues related to the HPL axis and cecal microbiota and provided new insights into the interaction between the host and microbiota during egg-laying in chickens.
Egg-laying is a crucial and intricate trait in chickens. To comprehensively explore the egg-laying mechanism in chickens, we analyzed the host transcriptome, gut microbiota, and metabolome during the pre-laying, peak-laying, and late-laying periods. Transcriptome analysis of the tissues related to the hypothalamic-pituitary-liver (HPL) axis revealed the dynamic gene expression of hormone secretion and amino acid metabolism. Metagenome and metabolome analysis of cecal contents suggested that biosynthesis of amino acids and hormones was changed. Integrated analysis showed that the genus Megasphaera was correlated with several amino acids, and the genus Hungatella was associated with hormones. These results explored the dynamic changes in tissues related to the HPL axis and cecal microbiota and provided new insights into the interaction between the host and microbiota during egg-laying in chickens.
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Pollos , Microbioma Gastrointestinal , Metaboloma , Animales , Pollos/microbiología , Pollos/metabolismo , Femenino , Transcriptoma , Hígado/metabolismo , Perfilación de la Expresión Génica , Expresión Génica , MultiómicaRESUMEN
INTRODUCTION: Updated guidelines for heart failure with reduced ejection fraction (HFrEF) and acute decompensation have improved outcomes, but ongoing efforts are focused on uncovering new evidence and developing novel therapies. This review examines the limitations of current treatments and the potential impact of emerging therapies. AREAS COVERED: A literature search focused on studies investigating drugs for HFrEF. We review recent clinical trials and emerging therapies to assess evidence strength, explore guideline updates, and identify strategies to optimize patient outcomes. EXPERT OPINION: The HFrEF treatment landscape is rapidly evolving, with advances in therapies like sodium/glucose cotransporter inhibitors and sacubitril-valsartan. Though managing acute decompensated heart failure remains challenging, recent trials suggest improvements in diuretic strategies and anti-inflammatory treatments. Ongoing research is essential for validating these therapies and incorporating them into standard practice.
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Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/efectos de los fármacos , Guías de Práctica Clínica como Asunto , Combinación de Medicamentos , Aminobutiratos/uso terapéutico , Valsartán/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Desarrollo de Medicamentos , Fármacos Cardiovasculares/uso terapéuticoRESUMEN
BACKGROUND: Cardiomyopathy (CDM) in pregnancy is associated with maternal morbidity and mortality. OBJECTIVES: To explore trends and clinical outcomes in CDM subtypes during delivery hospitalizations. METHODS: We used the National Inpatient Sample database to identify delivery hospitalizations between 2005-2020 by CDM subtypes: peripartum (PPCM), dilated (DCM), hypertrophic (HCM), and restrictive (RCM). Maternal and fetal outcomes were identified using International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes. Baseline characteristics and temporal trends of CDM subtypes were analyzed. Maternal cardiovascular, pregnancy, and fetal outcomes were evaluated by CDM subtype using univariate logistic regression. The primary outcome was in-hospital mortality. RESULTS: During 2005-2020, 37,125 out of 61,811,842 delivery hospitalizations were complicated by CDM. Among CDM-related delivery hospitalizations, the most prevalent were DCM (46%), followed by PPCM (45.6%), HCM (4.6%), and RCM (3.9%). The rates of in-hospital mortality (1.7%), adverse cardiovascular events such as acute heart failure (17%), cardiogenic shock (3.4%), and cardiac arrest (3.1%), and adverse pregnancy outcomes such as preeclampsia (14.2%) and preterm labor (11%), were highest among PPCM (all p < 0.0001). The prevalence of PPCM (49.1% to 38.5%) decreased while the prevalence of HCM (2.7% to 8.8%) and DCM (48% to 52.2%) increased over time. CONCLUSIONS: Over a 15-year period, PPCM had higher rates of in-hospital mortality, cardiovascular events, and adverse pregnancy outcomes compared to other CDM subtypes. While the prevalence of PPCM decreased over time, the prevalence of HCM and DCM increased. Hence, further research on cardiomyopathies during pregnancy and prospective studies on this vulnerable patient cohort are urgently needed.
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Cardiac ischaemia/reperfusion (I/R) impairs mitochondrial function, resulting in excessive oxidative stress and cardiomyocyte ferroptosis and death. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of redox homeostasis and has cardioprotective effects against various stresses. Here, we tested whether CBR-470-1, a noncovalent Nrf2 activator, can protect against cardiomyocyte death caused by I/R stress. Compared with vehicle treatment, the administration of CBR-470-1 (2 mg/kg) to mice significantly increased Nrf2 protein levels and ameliorated the infarct size, the I/R-induced decrease in cardiac contractile performance, and the I/R-induced increases in cell apoptosis, ROS levels, and inflammation. Consistently, the beneficial effects of CBR-470-1 on cardiomyocytes were verified in a hypoxia/reoxygenation (H/R) model in vitro, but this cardioprotection was dramatically attenuated by the GPX4 inhibitor RSL3. Mechanistically, CBR-470-1 upregulated Nrf2 expression, which increased the expression levels of antioxidant enzymes (NQO1, SOD1, Prdx1, and Gclc) and antiferroptotic proteins (SLC7A11 and GPX4) and downregulated the protein expression of p53 and Nlrp3, leading to the inhibition of ROS production and inflammation and subsequent cardiomyocyte death (apoptosis, ferroptosis and pyroptosis). In summary, CBR-470-1 prevented I/R-mediated cardiac injury possibly through inhibiting cardiomyocyte apoptosis, ferroptosis and pyroptosis via Nrf2-mediated inhibition of p53 and Nlrp3 and activation of the SLC7A11/GPX4 pathway. Our data also highlight that CBR-470-1 may serve as a valuable agent for treating ischaemic heart disease.
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Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic-pituitary-gonadal axis in mammals to trigger the juvenile-adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.
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Proteínas de Drosophila , Drosophila melanogaster , Hormonas de Insectos , Neuronas , Receptores de Esteroides , Conducta Sexual Animal , Animales , Drosophila melanogaster/fisiología , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Conducta Sexual Animal/fisiología , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Neuronas/fisiología , Neuronas/metabolismo , Hormonas de Insectos/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Ecdisona/metabolismo , Metamorfosis Biológica/fisiología , Masculino , Larva/crecimiento & desarrollo , Larva/fisiología , Proteínas de InsectosRESUMEN
Clinically, conventional sutures for repair of short-distance nerve injuries (< 5 mm) may contribute to uncontrolled inflammation and scar formation, thus negatively impacting nerve regeneration. To repair transected peripheral nerves with short distances, a rapid-forming, robust adhesive chitosan hydrogel is prepared by synthesizing maleic and dopamine bi-functionalized fungal-sourced chitosan (DM) and subsequently photopolymerizing DM precursor solution. The hydrogel rapidly polymerized under UV light irradiation (≈2 s) and possessed a strong adhesive strength (273.33 ± 55.07 kPa), facilitating a fast bonding of nerve stump. Especially, its tailored degradation profile over 28 days supported both early gap bridging and subsequent nerve regeneration. Furthermore, deferoxamine (DFO), a pro-angiogenic drug, is loaded into the hydrogel to reach sustainable release, accelerating axonal growth synergistically. A 3 mm long sciatic nerve defects model in rats is used to investigate the efficacy of DM@DFO hydrogel for repairing peripheral nerve defects. After 60 days, the DM@DFO hydrogel significantly outperformed conventional sutures and fibrin glue, improving motor and sensory recovery by reducing inflammation, inhibiting scar formation, and accelerating vascular regeneration within 14 days post-repair. This work highlights the DM@DFO hydrogel as a promising tissue adhesive for effective short-distance peripheral nerve repair.
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ELONGATED HYPOCOTOYL5 (HY5) and PHYTOCHROME INTERACTING FACTORs (PIFs) are two types of important light-related regulators of plant growth, however, their interplay remains elusive. Here, we report that the activated tomato (Solanum lycopersicum) HY5 (SlHY5) triggers the transcription of a Calcium-dependent Protein Kinase SlCPK27. SlCPK27 interacts with and phosphorylates SlPIF4 at Ser-252 and Ser-308 phosphosites to promote its degradation. SlPIF4 promotes hypocotyl elongation mainly by activating the transcription of SlDWF, a key gene in brassinosteroid (BR) biosynthesis. Such a SlHY5-SlCPK27-SlPIF4-BR cascade not only plays a crucial role in photomorphogenesis but also regulates thermomorphogenesis. Our results uncover a previously unidentified mechanism that integrates Ca2+ signaling with the light signaling pathways to regulate plant growth by modulating BR biosynthesis in response to changes in ambient light and temperature.
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Brasinoesteroides , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Proteínas Quinasas , Solanum lycopersicum , Solanum lycopersicum/metabolismo , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/genética , Brasinoesteroides/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Luz , Fosforilación , Hipocótilo/metabolismo , Hipocótilo/crecimiento & desarrollo , Temperatura , MorfogénesisRESUMEN
Tibial dyschondroplasia (TD) is a severe bone disease that affects fast-growing broiler chickens and causes economic loss. Despite previous studies, the regulatory mechanism of TD remains unclear and is thought to be primarily based on thiram induction, which may differ from that of naturally occurring diseases. To better understand TD, a digital X-ray machine was used in the present study to determine its incidence in four hundred yellow-feathered broiler chickens. The results showed that the incidence of TD was 22% after 6 weeks and gradually decreased after 8 and 10 weeks. The body weight of broilers with TD decreased significantly compared to that of NTD broilers. In addition, the length and density of the tibia were reduced after eight and 10 weeks, and the density of the tibia was reduced after 6 weeks compared with the NTD chickens. This study also examined tibial quality parameters from TD (n = 12) and NTD broilers (n = 12) and found that bone mineral content, bone mineral density, bone ash content, calcium content, and phosphorus content were significantly reduced in TD broilers. Transcriptome analysis revealed 849 differentially expressed genes (DEGs) in the growth plate between TD (n = 6) and NTD groups (n = 6). These genes were enriched in ECM-receptor interaction, cytokine-cytokine receptor interaction, calcium signaling pathway, and TGF-ß signaling. Genes encoding the alpha chain of type XII collagen, that is, COL1A1, COL5A1, and COL8A1) were identified as critical in the regulatory network of TD. Gene set enrichment analysis (GSEA) revealed that the pathways of cartilage development, circulatory system development, and nervous system development were changed in the growth plates of TD birds. In the blood transcriptome, 12 DEGs were found in TD (n = 4) and NTD chickens (n = 4), and GSEA revealed that the pathways from TD broilers' blood related to the phagosome, linoleic acid metabolism, monoatomic ion homeostasis, and calcium ion transport were downregulated. This study provides a comprehensive understanding of TD, including its effects on tibial quality, tibial changes, and the circulatory system, along with identifying important genes that may lead to the development of TD.
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1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in the isolate Pseudomonas sp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a five gene-cluster encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. A glutamine synthetase-like (GS-like) enzyme (NpaA1) initiates 1NA glutamylation, and this enzyme exhibits a broad substrate selectivity toward a variety of anilines and naphthylamine derivatives. Structural analysis revealed that the aromatic residues in the 1NA entry tunnel and the V201 site in the large substrate-binding pocket significantly influence NpaA1's substrate preferences. The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites.
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1-Naftilamina , Pseudomonas , Pseudomonas/enzimología , Pseudomonas/genética , Pseudomonas/metabolismo , Especificidad por Sustrato , 1-Naftilamina/análogos & derivados , 1-Naftilamina/metabolismo , Biodegradación Ambiental , Dioxigenasas/metabolismo , Dioxigenasas/genética , Dioxigenasas/química , Redes y Vías Metabólicas , Familia de Multigenes , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/químicaRESUMEN
The present study examined whether a high-level construal mindset promotes categorizing information according to thematic relations. In three experiments, the construal-level priming task was used to initiate a high-level versus low-level construal mindset, and then all participants were asked to complete the triad task, which is a task measuring the preference to classify. The results of Experiments 1 and 2 have shown that regardless of whether it was a set of artificially produced objects (Experiment 1) or a set of natural objects (Experiment 2), the high-level construal mindset group exhibited a higher proportion of thematic responses in the triad task. Experiment 3 transformed the stimulus set of the triad task into a set that consisted of many, larger, published, and controlled/optimized stimuli. The results of the experiment still showed that the high-level construal mindset group exhibited a higher proportion of thematic responses in the triad task. The findings suggest that a high-level construal mindset promotes categorizing information based on thematic relations.
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BACKGROUND: Numerous studies have assessed surgical resection as a standard treatment option for patients with colorectal cancer (CRC) and resectable pulmonary metastases (PM). However, the role of perioperative chemotherapy after complete resection of isolated PM from patients with CRC patients remains controversial. We hypothesize that perioperative chemotherapy does not provide significant survival benefits for patients undergoing resection of PM from CRC. AIM: To determine whether perioperative chemotherapy affects survival after radical resection of isolated PM from CRC. METHODS: We retrospectively collected demographic, clinical, and pathologic data on patients who underwent radical surgery for isolated PM from CRC. Cancer-specific survival (CSS) and disease-free survival were calculated using Kaplan-Meier analysis. Inter-group differences were compared using the log-rank test. For multivariate analysis, Cox regression was utilized when indicated. RESULTS: This study included 120 patients with a median age of 61.6 years. The 5-year CSS rate was 78.2%, with 36.7% experiencing recurrence. Surgical resection for isolated PM resulted in a 5-year CSS rate of 50.0% for second metastases. Perioperative chemotherapy (P = 0.079) did not enhance survival post-resection. Factors associated with improved survival included fewer metastatic lesions [hazard ratio (HR): 2.51, P = 0.045], longer disease-free intervals (HR: 0.35, P = 0.016), and wedge lung resections (HR: 0.42, P = 0.035). Multiple PM predicted higher recurrence risk (HR: 2.22, P = 0.022). The log-rank test showed no significant difference in CSS between single and repeated metastasectomy (P = 0.92). CONCLUSION: Perioperative chemotherapy shows no survival benefit post-PM resection in CRC. Disease-free intervals and fewer metastatic lesions predict better survival. Repeated metastasectomy is warranted for eligible patients.