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The experiment investigated the effects of sea-buckthorn flavonoids (SF) on lipopolysaccharide (LPS)-challenged broilers. A total of 288 one-day-old male broilers were randomly assigned to 4 groups, with 6 replicates of 12 broilers each. The experiment lasted for 20 days. The diet included two levels of SF (0 or 1000 mg/kg) and broilers intraperitoneally injected with 500 µg/kg LPS on 16, 18, and 20 days, or an equal amount of saline. LPS challenge decreased final body weight, average daily gain, and average daily feed intake, increased feed-to-gain ratio, and elevated serum IL-1ß, IL-2, TNF-α, D-LA, and endotoxin levels. Moreover, it resulted in a reduction in the IL-10 level. LPS impaired the intestinal morphology of the duodenum, jejunum, and ileum, down-regulated the mRNA relative expression of Occludin, ZO-1, and MUC-2 in the jejunum mucosa, up-regulated the mRNA relative expression of TLR4, MyD88, NF-κB, and IL-1ß, and increased the relative abundance of Erysipelatoclostridium in broilers (p < 0.05). However, SF supplementation mitigated the decrease in growth performance, reduced serum IL-1ß, IL-2, and D-LA levels, increased IL-10 levels, alleviated intestinal morphological damage, up-regulated mRNA expression of Occludin and ZO-1, down-regulated the mRNA expression of TLR4, NF-κB, and IL-lß in jejunum mucosal (p < 0.05), and SF supplementation presented a tendency to decrease the relative abundance of proteobacteria (0.05 < p < 0.1). Collectively, incorporating SF can enhance the growth performance, alleviate serum inflammation, and improve the intestinal health of broilers, effectively mitigating the damage triggered by LPS-challenges.
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Background: Diaphragmatic dysfunction escalates the susceptibility to postoperative pulmonary complications (PPCs). Currently, no study reports the occurrence of diaphragmatic dysfunction correlated with PPCs following radical resection of esophageal cancer in aged patients. We aimed to diagnose diaphragmatic dysfunction via ultrasonography and analyze diaphragmatic dysfunction's relation with PPCs after radical resection of esophageal cancer surgery in aged patients. Methods: This prospective observational study comprised 86 aged patients undergoing radical resection of esophageal cancer. Patient characteristics data and intraoperative details were collected. Ultrasonography was performed before (preoperative) and after (first, third, and fifth day postoperatively) surgery. Outcome measures included PPCs within seven days postoperative, occurrence of diaphragmatic dysfunction, and short-term prognosis. Results: After excluding 14 patients, we finally analyzed clinical data from 72 patients. The prevalence of PPCs was higher in the patients with diaphragmatic dysfunction than those without (19 of 23, 83% vs. 21 of 49, 43%, P=0.004). Postoperative diaphragmatic dysfunction was positively correlated with PPCs in patients who underwent elective radical esophageal cancer surgery (r=0.37, P=0.001). Persistent diaphragmatic dysfunction, furthermore, was positively correlated with the development of multiple PPCs (r=0.43, P<0.001). The logistic regression analysis revealed that age, total open procedure, and postoperative diaphragmatic dysfunction were identified as significant risk factors for PPCs, while total open procedure was an independent risk factor for diaphragmatic dysfunction. Conclusions: Postoperative diaphragmatic dysfunction positively correlates with developing PPCs. Continuous monitoring of postoperative diaphragmatic function can screen high-risk patients with PPCs, which has specific clinical significance. Age, total open procedure, and diaphragmatic dysfunction are identified as risk factors for developing PPCs, while total open procedure specifically increases the risk for postoperative diaphragmatic dysfunction.
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Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncogenic membrane protein in several malignancies and has been considered an attractive target for the treatment of human cancers. In this study, structure-based virtual screening and structure optimization were conducted to identify novel ROR1 inhibitors. Based on hit compound 2, 45 novel ROR1 inhibitors were designed and synthesized, and the detailed structure-activity relationship was investigated. Representative compound 19h potently binds ROR1 with a KD value of 0.10 µM, exhibiting antitumor activity in lung cancer and breast cancer cell lines (IC50: 0.36-1.37 µM). Additionally, a mechanism investigation demonstrated that compound 19h induces the apoptosis of tumor cells. Importantly, compound 19h significantly suppressed tumor growth in a mouse model without obvious toxicity. Overall, this work identified compound 19h as a new ROR1 inhibitor, providing a novel lead compound for the treatment of lung cancer and breast cancer.
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Antineoplásicos , Receptores Huérfanos Similares al Receptor Tirosina Quinasa , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/antagonistas & inhibidores , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Humanos , Animales , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Ratones , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/uso terapéutico , Apoptosis/efectos de los fármacos , Femenino , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Ratones Desnudos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones Endogámicos BALB C , Estructura Molecular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms. AIM OF THE STUDY: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug. MATERIALS AND METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels. RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (â ¡) and iron (â ¢) ions in equal amounts with high doses of Haematitum. CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.
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Caenorhabditis elegans , Animales , Ratones , Caenorhabditis elegans/efectos de los fármacos , Masculino , Apoptosis/efectos de los fármacos , Femenino , Reproducción/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Materia Medica/toxicidad , Medicina Tradicional China , Metabolómica , Pruebas de ToxicidadRESUMEN
BACKGROUND: Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary syndrome (PCOS). Nevertheless, conventional observational studies may be susceptible to bias. Consequently, we conducted a two-sample Mendelian randomization (MR) investigation to delve deeper into the connection between SHBG levels and the risk of PCOS. METHODS: We employed single-nucleotide polymorphisms (SNPs) linked to serum SHBG levels as instrumental variables (IVs). Genetic associations with PCOS were derived from a meta-analysis of GWAS data. Our primary analytical approach relied on the inverse-variance weighted (IVW) method, complemented by alternative MR techniques, including simple-median, weighted-median, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) testing. Additionally, sensitivity analyses were conducted to assess the robustness of the association. RESULTS: We utilized 289 SNPs associated with serum SHBG levels, achieving genome-wide significance, as instrumental variables (IVs). Our MR analyses revealed that genetically predicted elevated circulating SHBG concentrations were linked to a reduced risk of PCOS (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.39-0.78, P = 8.30 × 10-4) using the IVW method. MR-Egger regression did not detect any directional pleiotropic effects (P intercept = 0.626). Sensitivity analyses, employing alternative MR methods and IV sets, consistently reaffirmed our results, underscoring the robustness of our findings. CONCLUSIONS: Through a genetic epidemiological approach, we have substantiated prior observational literature, indicating a potential causal inverse relationship between serum SHBG concentrations and PCOS risk. Nevertheless, further research is needed to elucidate the underlying mechanism of SHBG in the development of PCOS.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Síndrome del Ovario Poliquístico , Polimorfismo de Nucleótido Simple , Globulina de Unión a Hormona Sexual , Humanos , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/genética , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/sangre , Femenino , Predisposición Genética a la Enfermedad , Factores de RiesgoRESUMEN
BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) in the elderly increase refracture risk post-surgery, leading to higher mortality rates. Genome-wide association studies (GWAS) have identified susceptibility genes for osteoporosis, but the phenotypic variance explained by these genes has been limited, indicating the need to explore additional causal factors. Epigenetic modifications, such as DNA methylation, may influence osteoporosis and refracture risk. However, prospective cohorts for assessing epigenetic alterations in Chinese elderly patients are lacking. Here, we propose to conduct a prospective cohort study to investigate the causal network of DNA polymorphisms, DNA methylation, and environmental factors on the development of osteoporosis and the risk of refracture. METHODS: We will collect vertebral and peripheral blood from 500 elderly OVCF patients undergoing surgery, extract DNA, and generate whole genome genotype data and DNA methylation data. Observation indicators will be collected and combined with one-year follow-up data. A healthy control group will be selected from a natural population cohort. Epigenome-wide association studies (EWAS) of osteoporosis and bone mineral density will be conducted. Differential methylation analysis will compare candidate gene methylation patterns in patients with and without refracture. Multi-omics prediction models using genetic variants and DNA methylation sites will be built to predict OVCF risk. DISCUSSION: This study will be the first large-scale population-based study of osteoporosis and bone mineral density phenotypes based on genome-wide data, multi-time point methylation data, and phenotype data. By analyzing methylation changes related to osteoporosis and bone mineral density in OVCF patients, the study will explore the feasibility of DNA methylation in evaluating postoperative osteoporosis intervention effects. The findings may identify new molecular markers for effective anti-osteoporosis treatment and inform individualized prevention and treatment strategies. TRIAL REGISTRATION: chictr.org.cn ChiCTR2200065316, 02/11/2022.
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Metilación de ADN , Osteoporosis , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Estudios Prospectivos , Anciano , Femenino , Osteoporosis/genética , Masculino , Fracturas Osteoporóticas/genética , Fracturas de la Columna Vertebral/genética , Estudio de Asociación del Genoma Completo , Densidad Ósea/genética , Fracturas por Compresión/genética , Persona de Mediana Edad , Epigénesis Genética , Recurrencia , Anciano de 80 o más Años , China/epidemiologíaRESUMEN
Ionic liquids (ILs) based on hybrid anions have recently garnered attention as beguiling alternative electrolytes for energy storage devices. This attention stems from the potential of these asymmetric anions to reduce the melting point of ILs and impede the crystallization of ILs. Furthermore, they uphold the advantages associated with their more conventional symmetric counterparts. In this study, we employed dispersion-corrected density functional theory (DFT-D) calculations to scrutinize the interplay between two hybrid anions found in ionic liquids [FTFSA]- and [MCTFSA]- and the [C4mpyr]+ cation, as well as in lithium polysulfides in lithium-sulfur batteries. For comparison, we also examined the corresponding ILs containing symmetric anions, [TFSA]- and [FSA]-. We found that the hybrid anion [MCTFSA]- and its ionic liquid exhibited exceptional stability and interaction strength. Additionally, our investigation unveiled a remarkably consistent interaction between ionic liquids (ILs) and anions with lithium polysulfides (and S8) during the transition from octathiocane (S8) to the liquid long-chain Li2Sn (4 ≤ n ≤ 8). This contrasts with the gradual alignment observed between cations and lithium polysulfides during the intermediate state from Li2S4 to the solid short-chain Li2S2 and Li2S1. We thoroughly analyzed the interaction mechanism of ionic liquids composed of different symmetry anions and their interactions with lithium polysulfides.
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Bacterial RecJ exhibits 5'â3' exonuclease activity that is specific to ssDNA; however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.
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Proteínas Arqueales , Proteínas Arqueales/química , Proteínas Arqueales/metabolismo , Proteínas Arqueales/genética , Cristalografía por Rayos X , Methanocaldococcus/enzimología , Methanocaldococcus/metabolismo , Unión Proteica , Multimerización de Proteína , ADN Helicasas/metabolismo , ADN Helicasas/química , ADN Helicasas/genética , Modelos Moleculares , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/química , Exodesoxirribonucleasas/genéticaRESUMEN
BACKGROUND: Comprehending the patterns of alteration in boar semen quality and identifying effective nutritional interventions are crucial for enhancing the productivity of commercial pig systems. This study aimed to examine the alteration in semen quality in boars, and assess the impact of protocatechuic acid (PCA) on semen quality during the phase of declining semen quality. METHODS: In Exp. 1, a total of 38 Pig Improvement Company (PIC) boars were selected and their semen quality data were recorded from the age of 9 to 37 months. In Exp. 2, 18 PIC boars (28 months old) were randomly assigned into three groups (n = 6) and fed a basal diet, a basal diet containing 500 or 1,000 mg/kg PCA, respectively. The experiment lasted for 12 weeks. RESULTS: The semen volume, concentration, and total number of spermatozoa in boars exhibited an increase from 9 to 19 months old and showed a significant linear decreased trend in 28, 24, and 22 months old. Sperm motility displayed an upward trajectory, reaching its peak at 20 months of age, and showed a significant linear decreased trend at 20 months old. Dietary supplementation of PCA demonstrated an effect to mitigate the decrease in semen volume, concentration of spermatozoa, total number of spermatozoa (P > 0.05), and significantly increased the sperm motility (P < 0.05). Moreover, supplementation of 1,000 mg/kg PCA significantly increased the sperm viability (P < 0.05). Analysis on cellular signaling pathways revealed that PCA restored serum testosterone levels and alleviated oxidative damage by upregulating the expression of HO-1, SOD2, and NQO1 in testicular stromal cells. Notably, PCA can enhance phosphorylation by selectively binding to AMP-activated protein kinase (AMPK) protein, thereby improving sperm mitochondrial function and augmenting sperm motility via PGC-1/Nrf1. CONCLUSIONS: These data elucidated the pattern of semen quality variation in boars within the age range of 9 to 37 months old, and PCA has the potential to be a natural antioxidant to enhance sperm quality through modulation of the AMPK/PGC-1/Nrf1 signaling pathway.
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Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1ß (IL-1ß) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Obesidad Infantil , Prevotella , Humanos , Niño , Animales , Ratones , Insulina , Ácidos y Sales Biliares/farmacología , Glucemia , Ratones Obesos , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
Fat synthesis and lipolysis are natural processes in growth and have a close association with health. Fat provides energy, maintains physiological function, and so on, and thus plays a significant role in the body. However, excessive/abnormal fat accumulation leads to obesity and lipid metabolism disorder, which can have a detrimental impact on growth and even harm one's health. Aside from genetic effects, there are a range of factors related to obesity, such as excessive nutrient intake, inflammation, glycometabolism disease, and so on. These factors could serve as potential targets for anti-obesity therapy. Quercetin is a flavonol that has received a lot of attention recently because of its role in anti-obesity. It was thought to have the ability to regulate lipid metabolism and have a positive effect on anti-obesity, but the processes are still unknown. Recent studies have shown the role of quercetin in lipid metabolism might be related to its effects on inflammatory responses and glycometabolism. The references were chosen for this review with no date restrictions applied based on the topics they addressed, and the databases PubMed and Web of Sicence was used to conduct the references research, using the following search terms: "quercetin", "obesity", "inflammation", "glycometabolism", "insulin sensitivity", etc. This review summarizes the potential mechanisms of quercetin in alleviating lipid metabolism through anti-inflammatory and hypoglycemic signaling pathways, and describes the possible signaling pathways in the interaction of inflammation and glycometabolism, with the goal of providing references for future research and application of quercetin in the regulation of lipid metabolism.
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Inflamación , Metabolismo de los Lípidos , Obesidad , Quercetina , Transducción de Señal , Quercetina/farmacología , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Inflamación/metabolismo , Transducción de Señal/efectos de los fármacos , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Animales , Resistencia a la Insulina , Antiinflamatorios/farmacología , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacosRESUMEN
This study evaluates the effects of dietary Chinese herb ultrafine powder (CHUP) supplementation in late-phase laying hens on the quality and nutritional values of eggs. A total of 576 Xinyang black-feather laying hens (300-day-old) were randomly allocated into eight groups for a 120-day feeding trial. Each group contained eight replicates with nine hens per replicate. The experimental groups included the control (basal diet) and different levels of CHUP groups (details in 'Materials and methods'). The results showed that the eggshell strength was increased (p < 0.05) in the L, LF, L-LF, L-T, and LF-T groups on day 60 of the trial. In addition, the plasma estradiol level in the L-LF, LF-T, and L-LF-T groups and unsaturated fatty acids concentrations in egg yolk of the CHUP groups (except LF-T group) were increased, whereas total cholesterol (T, L-LF, L-T, and L-LF-T groups) in egg yolk and the atherogenicity (T, L-T, and L-LF-T groups) and thrombogenicity (T, L-LF, L-T, and L-LF-T groups) indexes were decreased (p < 0.05) on day 60 of the trial compared with the control group. Moreover, bitter amino acids in egg albumen were decreased (p < 0.05) in the L-LF group on day 60 and the L-LF-T group on day 120 of the trial. Collectively, these findings indicate that dietary CHUP supplementation could improve eggshell quality and increase plasma reproductive hormone, fatty acid and amino acid composition, and nutritional values of eggs, especially L-LF and L-LF-T.
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Alimentación Animal , Pollos , Animales , Femenino , Polvos/análisis , Polvos/farmacología , Alimentación Animal/análisis , Óvulo , Yema de Huevo/química , Dieta/veterinaria , Aminoácidos , Suplementos DietéticosRESUMEN
In power electronics systems, system design and operation often involve multiple time and space scales, ranging from nanosecond switching dynamics to hour-level system operation behavior. Due to the complexity of these systems and the rise of wide-gap semiconductor technology, a series of multi-scale phenomena have emerged that are difficult to ignore. The high frequency of switching operations makes multi-scale effects particularly significant, including the fast dynamic response of the power loop, EMI, and heat conduction problems. They are key factors that must be considered in the design to ensure the efficient and reliable operation of power electronic devices. This study proposes the construction and simulation of a joint scale model for power electronic converters based on wavelet decomposition and reconstruction algorithms to address the multi-scale phenomenon and limitations of single-scale power electronic converters. Firstly, a joint scale model for power electronic converters at both macro and micro-scales was established, targeting both single-scale models and simple combinations of multiple scale models for power electronic converters. The traditional single-scale model is sufficient to describe the average behavior of the converter, but it has serious limitations in capturing fast transient processes and high-frequency switching behavior in power electronic systems. These limitations often manifest themselves when there is a need to capture fine timescales of detail. By transforming between the time domain and the frequency domain, wavelet decomposition enables the model to capture both macroscopic average characteristics and microscopic transient dynamics. The wavelet reconstruction algorithm can simulate all kinds of fast changes in the actual working process more accurately and compress irrelevant information while retaining key signal features, so as to optimize the simulation performance of the model. Secondly, this algorithm is used to analyze BC in short time scale. Finally, the short time scale characteristics of power electronic converters are analyzed. Experimental results show that the fusion of wavelet decomposition and reconstruction algorithm enhances the accuracy of the power electronic converter model and improves the performance of the system. The model achieves an error reduction of nearly 3% in the calculation step size of 10-7s, which has a significant impact on the high precision requirements of high-frequency operations. In addition, the optimal calculation step size of 8×10-8s achieves an error reduction of more than 14%, making an important contribution to the transient analysis and fine structure simulation. The wavelet algorithm can improve the accuracy of multi-scale modeling in power electronic system and reduce the simulation time. The reduction of error not only shows the improvement of the accuracy of the model, but also shows its practical significance in the design and test of the actual power electronic system. The reduction in error reveals the ability to more accurately predict and mitigate potential performance problems in matching tests with actual hardware, as well as its ability to adapt to emerging wide bandgap semiconductor materials and structures.
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Algoritmos , Electrónica , Simulación por Computador , Frecuencia CardíacaRESUMEN
This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.
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Dieta Alta en Grasa , Mitocondrias , Resultado del Embarazo , Resveratrol , Útero , Animales , Resveratrol/farmacología , Femenino , Embarazo , Ratones , Dieta Alta en Grasa/efectos adversos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Útero/metabolismo , Útero/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Ratones Endogámicos C57BL , Obesidad/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismoRESUMEN
In the service industry, highway toll collectors serve as a distinctive frontline workforce who frequently encounter mistreatment from customers. Unfortunately, these behaviors have not received the attention and resolution they deserve, resulting in significant physical and psychological stress for toll collectors and exacerbating turnover rates. The study highlights how customer mistreatment affects toll collectors' turnover intentions by performing the sequential mediating roles of stress symptoms and affective commitment and assumes that neuroticism exacerbates the stress symptoms resulting from customer mistreatment based on affective events theory. The model was tested using data collected from 230 highway toll collectors in Zhuhai, China. All hypotheses received support. This study holds both theoretical and practical implications for future research.
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This study evaluated the effects of flavonoids from mulberry leaves (FML) on plasma biochemical indices, serum activities of lipid metabolism-related enzymes, fat morphology, fatty acid composition, and lipid metabolism in different adipose tissues of finishing pigs. We used 120 Chinese hybrid barrows of Berkshire and Bama mini-pigs with an average initial body weight of 45.11 ± 4.23 kg. The pigs were randomly assigned to five treatment groups and fed a control diet based on corn, soybean meal, and wheat bran or a control diet supplemented with 0.02%, 0.04%, 0.08%, or 0.16% FML. Each experimental group had six replicates (pens), with four pigs per pen. After a 7-d adaptation period, the feeding trial was conducted for 58 d. Blood and adipose tissue samples were collected from 30 pigs (one pig per pen) at the end of the test. The results showed that FML supplementation significantly decreased the feed intake to body gain ratio, the plasma concentrations of total cholesterol and free fatty acids, and the serum activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (linear or quadratic effects, P < 0.05), and decreased the plasma triglyceride concentration (quadratic, P = 0.07). Increasing FML supplementation increased the average daily gain and serum activities of lipoprotein lipase (linear and quadratic effects, P < 0.05) and adipose triglyceride lipase (linear, P < 0.05). Dietary FML supplementation decreased the adipocyte area in the dorsal subcutaneous adipose (DSA) tissue of finishing pigs (linear, P = 0.05) and increased the adipocyte area in the visceral adipose tissue (quadratic, P < 0.01). Increasing FML supplementation decreased the C20:1 content in DSA, abdominal subcutaneous adipose, and visceral adipose tissues of finishing pigs (P < 0.05) and increased the C18:3n3 and n-3 PUFA contents (P < 0.05). The lipid metabolism genes were regulated by the PPARγ-LXRα-ABCA1 signaling pathway, and their expressions differed in different adipose tissues. These findings suggest that FML improved growth performance, regulated lipid metabolism, inhibited fat production, and improved fatty acid distribution in the adipose tissue of finishing pigs, thereby improving pig fat's nutritional quality and health value.
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We investigate the detectability of gravitational waves that have been lensed by a spinless stellar-mass black hole, with respect to the advanced LIGO. By solving the full relativistic linear wave equations in the spacetime of a Schwarzschild black hole, we find that the strong gravity can create unique signals in the lensed waveform, particularly during the merger and ring-down stages. The differences in terms of fitting factor between the lensed waveform and best-fitted unlensed general relativity template with spin precession and higher-order multipoles are greater than 5% for the lens black hole mass within 70M_{â}
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BACKGROUND: The primary purpose of this study was to investigate the predictive value of alterations in cervical artery hemodynamic parameters induced by a simulated end-inspiratory occlusion test (sEIOT) measured by ultrasound for predicting postinduction hypotension (PIH) during general anesthesia. METHODS: Patients undergoing gastrointestinal tumor resection under general anesthesia were selected for this study. Ultrasound has been utilized to assess hemodynamic parameters in carotid artery blood flow before induction, specifically focusing on variations in corrected flow time (ΔFTc) and peak blood flow velocity (ΔCDPV), both before and after sEIOT. Anesthesia was induced by midazolam, sufentanil, propofol, and rocuronium, and blood pressure (BP) and heart rate (HR) were recorded within the first 10 min following endotracheal intubation. PIH was defined as fall in systolic blood pressure (SBP) or mean arterial pressure (MAP) by > 30% of baseline or MAP to < 60 mm Hg. RESULTS: The area under the receiver operating characteristic curves (AUC) for carotid artery ΔFTc was 0.88 (95%CI, 0.81 to 0.96; P < 0.001), and the optimal cutoff value was -16.57%, with a sensitivity of 91.4% and specificity of 77.60%. The gray zone for carotid artery ΔFTc was -16.34% to -15.36% and included 14% of the patients. The AUC for ΔCDPV was 0.54, with an optimal cutoff value of -1.47%. The sensitivity and specificity were calculated as 55.20% and 57.10%, respectively. CONCLUSION: The corrected blood flow time changes in the carotid artery induced by sEIOT can predict hypotension following general anesthesia-induced hypotension, wherein ΔFTc less than 16.57% is the threshold. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ; 20/06/2023; ChiCTR2300072632).
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Hipotensión , Humanos , Hipotensión/diagnóstico por imagen , Hipotensión/etiología , Hemodinámica , Presión Sanguínea/fisiología , Anestesia General/efectos adversos , Arterias CarótidasRESUMEN
Weaning is one of the major factors that cause stress and intestinal infection in infants and in young animals due to an immature intestine and not fully developed immune functions. Pectin (PEC), a prebiotic polysaccharide, has attracted considerable attention in intestinal epithelial signaling and function via modulation of the microbial community. A total of 16 weaned piglets (21-d-old) were randomly assigned into two groups: control group and PEC group. Supplementation of 5% pectin improved intestinal mucosal barrier function by modulating the composition of the bile acid pool in piglets. Specifically, piglets in PEC group had less serum D-lactate content and alkaline phosphatase activity. In the ileum, dietary pectin increased the number of crypt PAS/AB-positive goblet cells and the mRNA expressions of MUC2, ZO-1, and Occludin. Piglets in PEC group displayed a decreased abundance of Enterococcus (2.71 vs. 65.92%), but the abundances of Lactobacillus (30.80 vs. 7.93%), Streptococcus (21.41 vs. 14.81%), and Clostridium_sensu_stricto_1 (28.34 vs. 0.01%) were increased. Elevated concentrations of bile acids especially hyocholic acid species (HCAs) including HCA, HDCA, and THDCA were also observed. Besides, correlation analysis revealed that dietary pectin supplementation may have beneficial effects through stimulation of the crosstalk between gut microbes and bile acid synthesis within the enterohepatic circulation. Thus, dietary pectin supplementation exhibited a further positive effect on the healthy growth and development of weaned piglets. These findings suggest pectin supplementation as the prebiotic is beneficial for gut health and improvement of weaned stress via regulating microbiota and bile acid metabolism.
Asunto(s)
Suplementos Dietéticos , Funcion de la Barrera Intestinal , Humanos , Animales , Porcinos , Suplementos Dietéticos/análisis , Pectinas/farmacología , Dieta , Ácidos y Sales Biliares , DesteteRESUMEN
To investigate the regulatory effects of Chito-oligosaccharide (COS) on the anti-oxidative, anti-inflammatory, and MAPK signaling pathways. A total of 40 28-day-old weaned piglets were randomly allotted to 4 equal groups [including the control group, lipopolysaccharide (LPS) group, COS group, and COS*LPS group]. On the morning of d 14 and 21, piglets were injected with saline or LPS. At 2 h post-injection, whole blood samples were collected on d 14 and 21, and small intestine and liver samples were collected and analyzed on d 21. The results showed that COS inhibited the LPS-induced increase of malondialdehyde (MDA) concentration and hepatic TNF-α cytokines. COS significantly increased the serum total antioxidant capability (T-AOC) value on d 14, and total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) activities in both serum and liver on d 21. Furthermore, it increased hepatic catalase (CAT) activity. COS also increased the LPS-induced decrease in serum IgG concentrations. Immunohistochemical analysis results showed that COS significantly increased the jejunal and ileal Caspase 3, and ileal CD4+ values challenged by LPS. Dietary COS decreased the LPS-induced jejunal and ileal BAX and CCL2 mRNA levels, markedly decreased ileal COX2 and SOD1 mRNA levels, while increasing ileal iNOS. Furthermore, COS significantly increased the LPS-induced jejunal and ileal p-P38 and MyD88, as well as jejunal P38, while it effectively suppressed jejunal JNK1, and jejunal and ileal JNK2, p-JNK1, and p-JNK2 protein expressions. These results demonstrated that COS could be beneficial by attenuating LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathways.