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The regulation of dopamine (DA) removal from the synaptic cleft is a crucial process in neurotransmission and is facilitated by the sodium- and chloride-coupled dopamine transporter DAT. Psychostimulant drugs, cocaine, and amphetamine, both block the uptake of DA, while amphetamine also triggers the release of DA. As a result, they prolong or even amplify neurotransmitter signaling. Atypical inhibitors of DAT lack cocaine-like rewarding effects and offer a promising strategy for the treatment of drug use disorders. Here, we present the 3.2 Å resolution cryo-electron microscopy structure of the Drosophila melanogaster dopamine transporter (dDAT) in complex with the atypical non-competitive inhibitor AC-4-248. The inhibitor partially binds at the central binding site, extending into the extracellular vestibule, and locks the transporter in an outward open conformation. Our findings propose mechanisms for the non-competitive inhibition of DAT and attenuation of cocaine potency by AC-4-248 and provide a basis for the rational design of more efficacious atypical inhibitors.
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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific alpha subunit and a betac subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface and functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos/química , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/química , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Secuencia de Aminoácidos , Cristalografía , Humanos , Modelos Moleculares , Datos de Secuencia MolecularRESUMEN
BACKGROUND: It has been known that ABO blood groups are linked to the phenotypes of certain diseases; however, and the relationship between ABO blood groups and postoperative pain have not been extensively studied, especially in children. This study was to investigate whether there would be an association between the four major ABO blood groups and postoperative pain, as indicated by the differences in pain scores and rescue fentanyl requirements among blood groups in children after adenotonsillectomy. METHODS: A total of 124 children, aged 3-7 years, ASA I or II, and undergoing elective adenotonsillectomy were enrolled in the study. Postoperative pain was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and the rescue fentanyl requirement in post anesthesia care unit (PACU) was analyzed. Pediatric Anesthesia Emergence Delirium (PAED) score and the duration of PACU were recorded. The postoperative nausea and vomiting (PONV) within 24 h were documented. RESULTS: Among four blood type groups, no significant differences were observed regarding surgery time, and the gaps of fentanyl given at the anesthesia induction and the first rescue fentanyl injection in PACU. However, patients from AB and B blood groups had significantly higher pain score at initial CHEOPS assessment and consequently, higher consumption of rescue fentanyl during PACU stay. A significantly higher percentage of patients had received > 1 µg/kg rescue fentanyl. Higher PAED scores were also observed in AB and B blood groups. CONCLUSION: Paediatric patients with AB and B blood type had higher postoperative CHEOPS pain score and required significantly more fentanyl for pain control than those with A and O blood type after T&A. The initial scores of PAED in patients with AB and B blood type were also higher than that in patients with A and O blood type.
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Delirio del Despertar , Tonsilectomía , Humanos , Sistema del Grupo Sanguíneo ABO , Estudios Prospectivos , Fentanilo , Tonsilectomía/efectos adversos , Dolor Postoperatorio , Método Doble Ciego , Analgésicos Opioides/uso terapéuticoRESUMEN
The immune cell inflammation response is closely related to the occurrence of disease, and much evidence has shown that circular RNAs (circRNAs) play vital roles in the occurrence of disease. However, the biological function and regulatory mechanisms of circRNAs in the immune cell inflammation response remain poorly understood. In this study, we constructed an inflammatory model using lipopolysaccharide (LPS)-stimulated chicken macrophage lines (also known as HD11) to verify the function and mechanism of the novel circDCLRE1C (ID: gga_circ_0001674), which was significantly upregulated in spleen tissues infected by coccidia and the macrophage cells exposed to LPS. The results showed that circDCLRE1C aggravated LPS-induced inflammation and apoptosis in HD11 cells. Systemically, circDCLRE1C acted as a sponge for miR-214b-3p binding sites thereby regulating the expression of STAT3. The overexpression of miR-214b-3p rescued the pro-inflammatory effect of circDCLRE1C in HD11 cells stimulated with LPS, and rescued the high expression of STAT3. In conclusion, our study showed that circDCLRE1C could aggravate LPS-induced inflammation and apoptosis through competitive adsorption of miR-214b-3p, thereby increasing the expression of STAT3.
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Lipopolisacáridos , MicroARNs , Apoptosis/genética , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Lipopolisacáridos/toxicidad , Macrófagos , MicroARNs/genética , ARN Circular/genética , Factor de Transcripción STAT3/genética , Transducción de SeñalRESUMEN
BACKGROUND: Biomedical named entity recognition is one of the most essential tasks in biomedical information extraction. Previous studies suffer from inadequate annotated datasets, especially the limited knowledge contained in them. METHODS: To remedy the above issue, we propose a novel Biomedical Named Entity Recognition (BioNER) framework with label re-correction and knowledge distillation strategies, which could not only create large and high-quality datasets but also obtain a high-performance recognition model. Our framework is inspired by two points: (1) named entity recognition should be considered from the perspective of both coverage and accuracy; (2) trustable annotations should be yielded by iterative correction. Firstly, for coverage, we annotate chemical and disease entities in a large-scale unlabeled dataset by PubTator to generate a weakly labeled dataset. For accuracy, we then filter it by utilizing multiple knowledge bases to generate another weakly labeled dataset. Next, the two datasets are revised by a label re-correction strategy to construct two high-quality datasets, which are used to train two recognition models, respectively. Finally, we compress the knowledge in the two models into a single recognition model with knowledge distillation. RESULTS: Experiments on the BioCreative V chemical-disease relation corpus and NCBI Disease corpus show that knowledge from large-scale datasets significantly improves the performance of BioNER, especially the recall of it, leading to new state-of-the-art results. CONCLUSIONS: We propose a framework with label re-correction and knowledge distillation strategies. Comparison results show that the two perspectives of knowledge in the two re-corrected datasets respectively are complementary and both effective for BioNER.
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Bases del Conocimiento , Almacenamiento y Recuperación de la InformaciónRESUMEN
BACKGROUND: Eligibility criteria are the primary strategy for screening the target participants of a clinical trial. Automated classification of clinical trial eligibility criteria text by using machine learning methods improves recruitment efficiency to reduce the cost of clinical research. However, existing methods suffer from poor classification performance due to the complexity and imbalance of eligibility criteria text data. METHODS: An ensemble learning-based model with metric learning is proposed for eligibility criteria classification. The model integrates a set of pre-trained models including Bidirectional Encoder Representations from Transformers (BERT), A Robustly Optimized BERT Pretraining Approach (RoBERTa), XLNet, Pre-training Text Encoders as Discriminators Rather Than Generators (ELECTRA), and Enhanced Representation through Knowledge Integration (ERNIE). Focal Loss is used as a loss function to address the data imbalance problem. Metric learning is employed to train the embedding of each base model for feature distinguish. Soft Voting is applied to achieve final classification of the ensemble model. The dataset is from the standard evaluation task 3 of 5th China Health Information Processing Conference containing 38,341 eligibility criteria text in 44 categories. RESULTS: Our ensemble method had an accuracy of 0.8497, a precision of 0.8229, and a recall of 0.8216 on the dataset. The macro F1-score was 0.8169, outperforming state-of-the-art baseline methods by 0.84% improvement on average. In addition, the performance improvement had a p-value of 2.152e-07 with a standard t-test, indicating that our model achieved a significant improvement. CONCLUSIONS: A model for classifying eligibility criteria text of clinical trials based on multi-model ensemble learning and metric learning was proposed. The experiments demonstrated that the classification performance was improved by our ensemble model significantly. In addition, metric learning was able to improve word embedding representation and the focal loss reduced the impact of data imbalance to model performance.
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Aprendizaje Automático , China , HumanosRESUMEN
We present a computational approach for identifying the important descriptors of the ionic conductivities of lithium solid electrolytes. Our approach discriminates the factors of both bulk and grain boundary conductivities, which have been rarely reported. The effects of the interrelated structural (e.g. grain size, phase), material (e.g. Li ratio), chemical (e.g. electronegativity, polarizability) and experimental (e.g. sintering temperature, synthesis method) properties on the bulk and grain boundary conductivities are investigated via machine learning. The data are trained using the bulk and grain boundary conductivities of Li solid conductors at room temperature. The important descriptors are elucidated by their feature importance and predictive performances, as determined by a nonlinear XGBoost algorithm: (i) the experimental descriptors of sintering conditions are significant for both bulk and grain boundary, (ii) the material descriptors of Li site occupancy and Li ratio are the prior descriptors for bulk, (iii) the density and unit cell volume are the prior structural descriptors while the polarizability and electronegativity are the prior chemical descriptors for grain boundary, (iv) the grain size provides physical insights such as the thermodynamic condition and should be considered for determining grain boundary conductance in solid polycrystalline ionic conductors.
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Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.
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Sistemas de Liberación de Medicamentos , Compuestos Férricos/química , Nanopartículas de Magnetita/química , Fotoquimioterapia/métodos , Células A549 , Antineoplásicos/farmacología , Aptámeros de Nucleótidos/química , Movimiento Celular , Daunorrubicina/química , G-Cuádruplex , Humanos , Hibridación de Ácido Nucleico , Oligonucleótidos/química , Fármacos Fotosensibilizantes/farmacología , Porfirinas/químicaRESUMEN
We demonstrate bandwidth broadening in cascaded MgO-doped periodically poled lithium niobate (MgO:PPLN) crystals (Λ=10.3 µm) using the temperature-gradient technique. Up to 2.8 nm bandwidth at 600 nm spectral region is achieved using two 50 mm long cascaded MgO:PPLN crystals via sum frequency generation. This technique combines the merits of high conversion efficiency attributed to cascaded nonlinearity and the reconfigurability of temperature-gradient-induced chirp for broadening of the input wavelength acceptance range.
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For harvesting energy from waste heat, the power generation densities and fabrication costs of thermoelectric generators (TEGs) are considered more important than their conversion efficiency because waste heat energy is essentially obtained free of charge. In this study, we propose a miniaturized planar Si-nanowire micro-thermoelectric generator (SiNW-µTEG) architecture, which could be simply fabricated using the complementary metal-oxide-semiconductor-compatible process. Compared with the conventional nanowire µTEGs, this SiNW-µTEG features the use of an exuded thermal field for power generation. Thus, there is no need to etch away the substrate to form suspended SiNWs, which leads to a low fabrication cost and well-protected SiNWs. We experimentally demonstrate that the power generation density of the SiNW-µTEGs was enhanced by four orders of magnitude when the SiNWs were shortened from 280 to 8 µm. Furthermore, we reduced the parasitic thermal resistance, which becomes significant in the shortened SiNW-µTEGs, by optimizing the fabrication process of AlN films as a thermally conductive layer. As a result, the power generation density of the SiNW-µTEGs was enhanced by an order of magnitude for reactive sputtering as compared to non-reactive sputtering process. A power density of 27.9 nW/cm2 has been achieved. By measuring the thermal conductivities of the two AlN films, we found that the reduction in the parasitic thermal resistance was caused by an increase in the thermal conductivity of the AlN film and a decrease in the thermal boundary resistance.
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Here we first identified a novel pyridazinone derivative, compound 3711, as a nonnucleosidic hepatitis B virus (HBV) inhibitor in a cell model system. 3711 decreased extracellular HBV DNA levels by 50% (50% inhibitory concentration [IC50]) at 1.5 ± 0.2 µM and intracellular DNA levels at 1.9 ± 0.1 µM, which demonstrated antiviral activity at levels far below those associated with toxicity. Both the 3TC/ETV dually resistant L180M/M204I mutant and the adefovir (ADV)-resistant A181T/N236T mutant were as susceptible to 3711 as wild-type HBV. 3711 treatment induced the formation of genome-free capsids, a portion of which migrated faster on 1.8% native agarose gel. The induced genome-free capsids sedimented more slowly in isopycnic CsCl gradient centrifugation without significant morphological changes. 3711 treatment decreased levels of HBV DNA contained in both secreted enveloped virion and naked virus particles in supernatant. 3711 could interfere with capsid formation of the core protein (Cp) assembly domain. A Cp V124W mutant, which strengthens capsid interdimer interactions, recapitulated the effect of 3711 on capsid assembly. Pyridazinone derivative 3711, a novel chemical entity and HBV inhibitor, may provide a new opportunity to combat chronic HBV infection.
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Antivirales/farmacología , Cápside/metabolismo , Virus de la Hepatitis B/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Proteínas de la Cápside/metabolismo , ADN Viral/genética , Farmacorresistencia ViralRESUMEN
Mint adaptor proteins bind to the amyloid precursor protein (APP) and regulate APP processing associated with Alzheimer's disease; however, the molecular mechanisms underlying Mint regulation in APP binding and processing remain unclear. Biochemical, biophysical, and cellular experiments now show that the Mint1 phosphotyrosine binding (PTB) domain that binds to APP is intramolecularly inhibited by the adjacent C-terminal linker region. The crystal structure of a C-terminally extended Mint1 PTB fragment reveals that the linker region forms a short α-helix that folds back onto the PTB domain and sterically hinders APP binding. This intramolecular interaction is disrupted by mutation of Tyr633 within the Mint1 autoinhibitory helix leading to enhanced APP binding and ß-amyloid production. Our findings suggest that an autoinhibitory mechanism in Mint1 is important for regulating APP processing and may provide novel therapies for Alzheimer's disease.
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Proteínas Adaptadoras Transductoras de Señales/química , Precursor de Proteína beta-Amiloide/química , Proteínas del Tejido Nervioso/química , Enfermedad de Alzheimer/metabolismo , Bioquímica/métodos , Biofisica/métodos , Cristalografía por Rayos X/métodos , Análisis Mutacional de ADN , Células HEK293 , Humanos , Cinética , Espectroscopía de Resonancia Magnética/métodos , Conformación Molecular , Neuronas/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Tirosina/químicaRESUMEN
Gene deletion studies in mice have revealed critical roles for IL (interleukin)-4 and -13 in asthma development, with the latter controlling lung airways resistance and mucus secretion. We have now developed human neutralizing monoclonal antibodies against human IL-13Rα1 (IL-13 receptor α1) subunit that prevent activation of the receptor complex by both IL-4 and IL-13. We describe the crystal structures of the Fab fragment of antibody 10G5H6 alone and in complex with D3 (ectodomain 3) of IL-13Rα1. Although the structure showed significant domain swapping within a D3 dimer, we showed that Arg(230), Phe(233), Tyr(250), Gln(252) and Leu(293) in each D3 monomer and Ser(32), Asn(102) and Trp(103) in 10G5H6 Fab are the key interacting residues at the interface of the 10G5H6 Fab-D3 complex. One of the most striking contacts is the insertion of the ligand-contacting residue Leu(293) of D3 into a deep pocket on the surface of 10G5H6 Fab, and this appears to be a central determinant of the high binding affinity and neutralizing activity of the antibody.
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Anticuerpos Monoclonales/química , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/inmunología , Epítopos , Subunidad alfa1 del Receptor de Interleucina-13/química , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/metabolismo , Anticuerpos Neutralizantes/metabolismo , Sitios de Unión/inmunología , Cristalografía por Rayos X , Dimerización , Humanos , Fragmentos Fab de Inmunoglobulinas/química , Interleucina-13/inmunología , Interleucina-13/metabolismo , Subunidad alfa1 del Receptor de Interleucina-13/metabolismo , Interleucina-4/inmunología , Interleucina-4/metabolismo , Leucina/metabolismo , Ratones , Ratones Transgénicos , Estructura Terciaria de ProteínaRESUMEN
Research on complete mitochondrial genomes can help in understanding the molecular evolution and phylogenetic relationships of various species. In this study, the complete mitogenome of Huaaristarchorum was characterized to supplement the limited mitogenomic information on the genus Hua. Three distinct assembly methods, GetOrganelle, NovoPlasty and SPAdes, were used to ensure reliable assembly. The 15,691 bp mitogenome contains 37 genes and an AT-rich region. Notably, the cytochrome c oxidase subunit I (COX1) gene, commonly used for species identification, appears to be slow-evolving and less variable, which may suggest the inclusion of rapidly evolving genes (NADH dehydrogenase subunit 6 [ND6] or NADH dehydrogenase subunit 2 [ND2]) as markers in diagnostic, detection, and population genetic studies of Cerithioidea. Moreover, we identified the unreliability of annotations (e.g., the absence of annotations for NADH dehydrogenase subunit 4L [ND4L] in NC_037771) and potential misidentifications (NC_023364) in public databases, which indicate that data from public databases should be manually curated in future research. Phylogenetic analyses of Cerithioidea based on different datasets generated identical trees using maximum likelihood and Bayesian inference methods. The results confirm that Semisulcospiridae is closely related to Pleuroceridae. The sequences of Semisulcospiridae clustered into three clades, of which H.aristarchorum is one; H.aristarchorum is sister to the other two clades. The findings of this study will contribute to a better understanding of the characteristics of the H.aristarchorum mitogenome and the phylogenetic relationships of Semisulcospiridae. The inclusion of further mitochondrial genome sequences will improve knowledge of the phylogeny and origin of Cerithioidea.
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The continuous expansion of intestinal stem cells (ISCs) is crucial for maintaining the renewal of the intestinal epithelium, particularly in inflammatory conditions. It remains largely unknown how the internal microbiota repair damage to the internal mucosal barrier. Hence, investigating potential anti-inflammatory probiotics from the intestinal symbolic microbes of broilers and analyzing their mechanism of action to support the intestinal mucosal barrier function can offer novel regulatory tools to alleviate broiler enteritis. In this research, we utilized in vivo broilers plus ex vivo organoids model to thoroughly examine the effectiveness of Lactobacillus reuteri (LR) in protecting the integrity of the intestinal mucosa during lipopolysaccharide-induced (LPS-induced) enteritis in broilers. The findings indicated that LR feeding maintained intestinal morphological and structural integrity, enhanced proliferation of intestinal epithelial cells, and inhibited cell apoptosis and inflammatory response against the deleterious effects triggered by LPS. Simultaneously, LR enhanced ISCs activity and stimulated intestinal epithelial regeneration to protect the intestinal barrier during LPS-induced injury conditions. The coculture system of LR and ileum organoids revealed that LR increased the growth of organoids and attenuated LPS-stimulated damage to organoids. Furthermore, the LPS-induced decrease in ISC activity was rescued by reactivation of Wnt/ß-catenin signaling by LR ex vivo and in vivo. This research revealed that LR promoted the expansion of ISCs and intestinal epithelial cell renewal by regulating the Wnt/ß-catenin signaling pathway, thereby maintaining the integrity of the intestinal mucosal barrier. This finding provided theoretical support for lactobacillus as a probiotic additive in livestock feed to improve intestinal inflammation and treat intestinal diseases.
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Understanding the spatial distribution of crop roots is crucial for effectively managing crop water and fertilizer. We investigate the effects of water-nitrogen coupling on the water-salt environment and root distribution in the root zone of S. salsa. Three irrigation levels were established, calculated according to 0.35 (W1), 0.50 (W2), and 0.65 (W3) of local ET0. The three nitrogen levels were 150 (N1), 250 (N2), and 350 (N3) kg·hm-2 in a complete combination design. With the augmentation of irrigation water and nitrogen application, the total root weight density of the root system of Suaeda salsa increased from 17.18×10-3 g·cm-3 to 27.91×10-3 g·cm-3. The distribution of soil water suction significantly influences the root distribution of Suaeda salsa in saline soil, causing a transition from a narrow deep type to a wide shallow type. Under the W2 irrigation level, soil water suction ranges from 1485.60 to 1726.59 KPa, which can provide water for S. salsa.it becomes feasible to attain the necessary water and salt environment for the growth and development of S. salsa, resulting in the attainment of maximum biomass, ash content, and salt uptake. No significant differences in the biomass, ash content, and salt uptake of S. salsa was noted between N2 and N3 nitrogen application levels (p > 0.05).The optimal irrigation volume and nitrogen application level were 0.50 ET0 and 250 kg·hm-2, respectively. The results of this study provide a scientific basis for the large-scale planting of S. salsa in extreme arid areas to improve and utilize saline wastelands.
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Sexual dimorphism in poultry, especially in Muscovy ducks, is a proven phenomenon characterized by significant differences in body weight, growth patterns, and gene expression between male and female individuals. However, there is a dearth of research on the candidate genes and mechanisms underlying these weight differences. We selected 301 Muscovy ducks and recorded their weekly body weights from birth. We utilized 3 non-linear growth models (Logistic, Bertalanffy, and Gompertz) to fit the growth curve of Muscovy ducks, it was found that the logistic model was the most suitable model for describing the growth curve of Muscovy ducks. The results from the logistic model showed that the inflection point of male Muscovy ducks occurred at a later age, and they had a heavier mature body weight than female Muscovy ducks. At 10 wk of age, we collected Muscovy duck breast muscle tissues for transcriptome sequencing (RNA-seq). To exclude the impact of weight difference, 185 differentially expressed genes (DEGs), such as PPAR, FABP3, PLIN1, and FOXO1, were screened. These DEGs were predominantly enriched in terms related to mitochondria, lipids, and nucleic acids. In addition, the gut microbiota has the ability to influence host physiology through the regulation of multiple processes, including playing a crucial role in host muscle growth and development. We randomly selected male and female Muscovy ducks for 16S rRNA sequencing analysis of their cecal microbiota. The results showed that there were significant differences in the composition of cecal microbiota between male and female Muscovy ducks. At the genus level, the relative abundance of Enterenecus and CAG_269 were lower in males compared to females, while Lawsonibacter, Parabacteroides_B, Streptococcus, UBA2658, Caccousia, and Butyricimonas were higher in males than in females. In summary, this study provides a scientific theoretical basis for revealing the different growth patterns of male and female Muscovy ducks, and offers explanations from both the molecular level and microbiological perspectives.
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Peso Corporal , Patos , Caracteres Sexuales , Animales , Patos/genética , Patos/crecimiento & desarrollo , Patos/fisiología , Masculino , Femenino , Transcriptoma , Factores Sexuales , Microbioma Gastrointestinal , MultiómicaRESUMEN
To efficiently harness resources from Pinus koraiensis seed scales, a type of forestry waste, rigorous studies on the extraction, purification, stability, and free radical scavenging capacity of the proanthocyanidins derived from these seed scales were conducted. Kinetic models showed that under ultrasonic conditions, the proanthocyanidins content reached 2.66 mg/g within 0.5 h. The optimal storage parameters include darkness, 4 °C, and pH 4. The degrees of polymerization of the mixture and the high- and low-polymer components were 4.89, 7.42 and 3.07, respectively, with the low-polymer component exhibiting the highest radical scavenging activity. Through HPLC-QE-MS/MS, 1H NMR, and FT-IR analyses, we identified proanthocyanidin B1, proanthocyanidin B2, (-)-epicatechin, and polymeric trimer esters. The Pinus koraiensis proanthocyanidins exhibited a high molecular weight, a complex internal molecular structure, and commendable stability, with crystallization requiring elevated temperatures. Therefore, the proanthocyanidins from Pinus koraiensis seed scales have emerged as highly promising novel natural antioxidants.
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Depuradores de Radicales Libres , Pinus , Polimerizacion , Proantocianidinas , Semillas , Proantocianidinas/química , Proantocianidinas/aislamiento & purificación , Pinus/química , Semillas/química , Cinética , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Peso Molecular , Estructura Molecular , Espectrometría de Masas en TándemRESUMEN
This study aimed to investigate the effects of different levels of xylanase supplementation in a wheat-based diet on growth performance, short-chain fatty acids, intestinal health, microbial composition, and serum metabolism. A total of 1200 male chicks were randomly assigned to four wheat-based diet treatments: Group C (adding 0 mg/kg of xylanase), Group L (adding 50 mg/kg of xylanase), Group M (adding 100 mg/kg of xylanase), and Group H (adding 150 mg/kg of xylanase). The experiment lasted for 56 days. The results indicated that Group H broilers experienced a decreased feed-to-gain ratio throughout the study period. Additionally, dietary supplementation with xylanase led to an increase in the physical barrier, as indicated by increased VH and VH/CD in the gut (p < 0.05). Furthermore, levels of D-lactic acid and endotoxin were reduced. Xylanase supplementation also increased the abundance of Muc-2, ZO-1, and Occludin (p < 0.05). Moreover, xylanase supplementation enhanced the activity of sucrase and maltase in the duodenum (p < 0.05), which may be attributable to the upregulation of the abundance of SI and MGA (p < 0.05). Furthermore, xylanase addition promoted propionic acid produced by specific bacteria, such as Phascolarctobacterium, and influenced the microbial composition to some extent, promoting intestinal health. Additionally, 150 mg/kg of xylanase supplementation increased the amino acid, peptide, and carbohydrate content and upregulated the metabolism of amino acids related to histidine, cysteine, methionine, and other pathways (p < 0.05). These findings suggest adequate xylanase supplementation can enhance nutritional digestibility and absorption, improve growth performance, stimulate endogenous enzyme activity, optimize intestinal morphology and barrier function, and positively influence acid-producing bacteria and amino acid metabolic pathways.
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Coccidiosis, a protozoan disease that substantially impacts poultry production, is characterized by an intracellular parasite. The study utilized 48 one-day-old Horro chickens, randomly divided into the infected (I) and control (C) groups. The challenge group of chickens were administered Eimeria maxima oocysts via oral gavage at 21-days-old, and each chicken received 2 mL containing 7×104 sporulated oocysts. The total RNAs of chicken jejunum and cecum tissues were isolated from three samples, each from I and C groups. Our study aimed to understand the host immune-parasite interactions and compare immune response mRNA profiles in chicken jejunum and cecum tissues at 4 and 7 days postinfection with Eimeria maxima. The results showed that 823 up- and 737 down-regulated differentially expressed mRNAs (DEmRNAs) in jejunum at 4 d infection and control (J4I vs. J4C), and 710 up- and 368 down-regulated DEmRNAs in jejunum at 7 days infection and control (J7I vs. J7C) were identified. In addition, DEmRNAs in cecum tissue, 1424 up- and 1930 down-regulated genes in cecum at 4 days infection and control (C4I vs. C4C), and 77 up- and 191 down-regulated genes in cecum at 7 days infection and control (C7I vs. C7C) were detected. The crucial DEmRNAs, including SLC7A5, IL1R2, GLDC, ITGB6, ADAMTS4, IL1RAP, TNFRSF11B, IMPG2, WNT9A, and FOXF1, played pivotal roles in the immune response during Eimeria maxima infection of chicken jejunum. In addition, the potential detection of FSTL3, RBP7, CCL20, DPP4, PRKG2, TFPI2, and CDKN1A in the cecum during the host immune response against Eimeria maxima infection is particularly noteworthy. Furthermore, our functional enrichment analysis revealed the primary involvement of DEmRNAs in small molecule metabolic process, immune response function, inflammatory response, and toll-like receptor 10 signaling pathway in the jejunum at 4 and 7 days postinfection. Similarly, in the cecum, DEmRNAs at 4 and 7 days postinfection were enriched in processes related to oxidative stress response and immune responses. Our findings provide new insights and contribute significantly to the field of poultry production and parasitology.