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Ascaris is highly adaptable, allowing its offspring to thrive in various conditions and posing significant health risks widely among animal populations. Most studies regarding the efficacy of disinfectants against Ascaris eggs in animal houses have been limited and lack a systematic and comprehensive evaluation. Currently, Ascaris suum is one of the most extensively studied helminths in the context of parasitology. Here, 8 disinfectants, UV radiation and quicklime were used to treat A. suum eggs, which were subsequently incubated at a room temperature of 22-25ºC for 15 days. The inactivation rate of A. suum eggs (expressed as a percentage) was measured to assess the efficacy of disinfectants, UV radiation, and quicklime in inactivating A. suum eggs. The results indicated that 1â¯%-10â¯% povidone iodine, 5â¯%-25â¯% ammonia solution, 0.5-2â¯% chlorine dioxide, 75â¯% ethanol and formalin in long-term (15 days), as well as the 5â¯% and 10â¯% povidone iodine, 25â¯% ammonia solution and UV irradiation in short-term (30-120â¯min) completely inhibited the normal development of A. suum eggs up to L2 stage. In conclusion, 75â¯% ethanol, povidone iodine, chlorine dioxide, ammonia solution, formalin, and UV irradiation are effective in inactivating A. suum eggs for dual disinfection of parasites and microorganisms. Among them, povidone iodine and UV irradiation are relatively efficient and environmentally friendly disinfection methods, and chlorine dioxide, a relatively harmless and broad-spectrum disinfectant, is an alternative choice for A. suum eggs elimination.
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OBJECTIVES: To analyze the lung structure of small airway dysfunction (SAD) defined by spirometry and parametric response mapping (PRM) using high-resolution computed tomography (HRCT), and to analyze the predictive factors for SAD. METHODS: A prospective study was conducted with 388 participants undergoing pulmonary function test (PFT) and inspiratory-expiratory chest CT scans. The clinical data and HRCT assessments of SAD patients defined by both methods were compared. A prediction model for SAD was constructed based on logistic regression. RESULTS: SAD was defined in 122 individuals by spirometry and 158 by PRM. In HRCT visual assessment, emphysema, tree-in-bud sign, and bronchial wall thickening have higher incidence in SAD defined by each method. (p < 0.001). Quantitative CT showed that spirometry-SAD had thicker airway walls (p < 0.001), smaller lumens (p = 0.011), fewer bronchi (p < 0.001), while PRM-SAD had slender blood vessels. Predictive factors for spirometry-SAD were age, male gender, the volume percentage of emphysema in PRM (PRMEmph), tree-in-bud sign, bronchial wall thickening, bronchial count; for PRM-SAD were age, male gender, BMI, tree-in-bud sign, emphysema, the percentage of blood vessel volume with a cross-sectional area less than 1 mm2 (BV1/TBV). The area under curve (AUC) values for the fitted predictive models were 0.855 and 0.808 respectively. CONCLUSIONS: Compared with PRM, SAD defined by spirometry is more closely related to airway morphology, while PRM is sensitive to early pulmonary dysfunction but may be interfered by pulmonary vessels. Models combining patient information and HRCT assessment have good predictive value for SAD. CRITICAL RELEVANCE STATEMENT: HRCT reveals lung structural differences in small airway dysfunction defined by spirometry and parametric response mapping. This insight aids in understanding methodological differences and developing radiological tools for small airways that align with pathophysiology. KEY POINTS: Spirometry-SAD shows thickened airway walls, narrowed lumen, and reduced branch count, which are closely related to airway morphology. PRM shows good sensitivity to early pulmonary dysfunction, although its assessment of SAD based on gas trapping may be affected by the density of pulmonary vessels and other lung structures. Combining patient information and HRCT features, the fitted model has good predictive performance for SAD defined by both spirometry and PRM (AUC values are 0.855 and 0.808, respectively).
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Intramuscular adipogenesis plays an important role in muscle development, which determines the quality of goat meat. However, its underlying cellular and molecular mechanisms remain poorly understood. In this study, we provided detailed cellular atlases of goat longissimus dorsi during muscle development at single-nucleus resolution, and identified the subpopulations of fibroblasts/fibro-adipogenic progenitors (FAPs) and muscle satellite cell (MuSC), as well as the differentiation trajectory of FAPs subpopulations. Cellular ligand-receptor interaction analysis revealed enriched BMP and IGF pathways implicated in within-tissue crosstalk centered around FAPs. Through single-nucleus gene regulatory network analysis and in vitro interference verification, we found that TCF7L2 was a critical transcriptional factor (TF) in early adipogenesis in skeletal muscle. Overall, our work reveals the cellular intricacies and diversity of goat longissimus dorsi during muscle development, implementing insights into the critical roles of BMP, IGF pathways and TCF7L2 TF in intramuscular adipogenesis.
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INTRODUCTION: Postoperative gastroparesis occurs after surgeries which affect the upper digestive tract. Gastric peroral endoscopic myotomy (G-POEM) is a treatment for postoperative gastroparesis. The present study boasts the long-term efficacy and safety of G-POEM in a large cohort of patients. PATIENTS AND METHODS: Gastroparesis Cardinal Symptom Index (GCSI) and Gastroesophageal Reflux Disease Questionnaire (GERDQ) were utilized for the assessment of postsurgical gastroparesis symptoms. Gastroscope was used to observe the anastomotic site. Three-dimensional ultrasound was used to measure the morphological structure of the gastric antrum and pylorus tube. Gastric emptying time was calculated by analyzing the volume change of gastric antrum. RESULTS: Significant clinical effectiveness of G-POEM was observed. The GCSI score, including each subscale score, showed significant decrease after G-POEM. Before G-POEM, there was a negative correlation between GCSI score and the inner diameter of pylorus, as well as a positive correlation with the length of pyloric tube. The similar results were found in the scores of nausea/vomiting and postprandial fullness/early satiety subscales. No correlation was observed between GCSI score and the emptying time, nor between the emptying time and the parameters of antrum morphology. After G-POEM, no correlation was found between GCSI (including subscales) score, the emptying time, and the parameters of antrum morphology. Patients who exhibited as clinical non-responders often accompanied with GERD symptoms. After G-POEM, the score of GERDQ decreased significantly. Either before or after G-POEM, no correlation was noticed between GERDQ scores, the emptying time and the parameters of antrum morphology. CONCLUSION: The technique of G-POEM was demonstrated as a minimally invasive approach with the long-term efficacy and safety in therapying postoperative gastroparesis.
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Rivers are hotspots for methane (CH4) emissions, and aerobic methane oxidation is a crucial process in controlling emissions. The spatio-temporal heterogeneity of river environment can greatly affect the methane oxidation process. However, currently, few studies have focused on the spatio-temporal changes in activity of methane oxidation and the associated microbiome in riverine ecosystems, which hinders a comprehensive understanding the role of this process in reducing emissions of CH4. Here, we investigated the variations in methane oxidation activity and community of methanotrophs in sediment of a mountain river across different reaches and seasons. The potential methane oxidation rate ranged from 24.11 to 493.03 nmol CH4 g-1 (sediment) d-1, which was significantly greater in sediment obtained during the winter than in that obtained during the summer. Moreover, the rate in middle reaches was significantly greater than that in upper and lower reaches in summer. The abundance of pmoA gene of methanotrophs ranged from 2.45×106 to 2.98×107 copies g-1 (sediment), which was also significantly greater in winter than in summer and showed significant variations among reaches. Additionally, methanotrophic diversity and community composition exhibited significant variations across both reaches and seasons, and the relative abundance of Methylococcus and Methylocystis was closely associated with methane oxidation activity. Sediment NH4+ content, pH and temperature were potentially crucial factors affecting the activity or methanotrophic community. In conclusion, it is necessary to consider both temporal and spatial scales to improve our understanding of the significance and driving mechanisms of methane oxidation in controlling CH4 emissions from rivers.
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AIM: This study aimed to evaluate the preclinical safety of Shenfu injection for the treatment of sepsis. Tests were designed and conducted to determine the acute and long-term toxicity of Shenfu injection in rats, based on the recommended indications and dosage for human use. MATERIALS AND METHODS: Rats were administered 22.5 g of raw drug/kg/day via tail vein injection. Toxicity symptoms were monitored for 14 days following the intravenous injection of Shenfu injection, and target organs affected by toxicity were analyzed. To assess long-term toxicity, rats were given 12, 9, or 6 g of raw drug/kg/day by intraperitoneal injection, equivalent to 12, 9, and 6 times the daily clinical dose for adult sepsis patients (3.3 mL of stock solution per 1 g of raw drug/kg/day), for 30 consecutive days. This was followed by a 28-day recovery period after withdrawal of the drug. During the administration and recovery periods, signs of toxicity were observed and compared with those in the control (stromal fluid) group. The aim was to predict potential clinical adverse reactions, including the nature and severity of these reactions, dose-response and time-response relationships, and the reversibility of the effects. Additionally, the study sought to identify the target organs or tissues potentially affected by repeated administration and suggest clinical indicators that should be monitored during the product's use. Furthermore, the safety of co-administration with commonly used chemical medications for the treatment of sepsis was investigated. RESULTS: In the acute toxicity test, administration of the maximum dose of Shenfu injection (75 mL of stock solution/22.5 g of raw drug/kg/day) via tail vein injection resulted in transient symptoms, including piloerection (vertical hair response), weight loss, and reduced food intake. In the long-term toxicity experiments, rats received intraperitoneal injections of 0.3 g/mL (stock solution), 0.225 g/mL, and 0.15 g/mL Shenfu injection per day, which corresponded to 12, 9, and 6 times the daily clinical dose for adults with sepsis. The injections were administered twice daily for 30 days, followed by a 28-day drug withdrawal period for recovery. After 28 days, no significant toxicological changes were observed, apart from a hemodilution effect caused by the excessive volume of the drug and a slight increase in alkaline phosphatase and total bilirubin levels. The effects were reversible upon drug discontinuation. CONCLUSIONS: A single intravenous injection of 22.5 g of raw drug/kg/day and long-term intraperitoneal administration of up to 12 g of raw drug/kg/day are considered safe doses for rats.
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Pyropia spp. seaweeds are delicious and nutritious red algae widely consumed for a long history. However, due to the non-digestibility of cell wall components by the human intestinal tract, the bioaccessibility of the intracellular bioactive compounds is low. The current industrial processing of Pyropia spp. food by drying and roasting cannot break down the cell wall; however, studies indicate that fermentation of Pyropia spp. by food-derived microorganisms is an efficient processing method to solve this problem. This paper reviews research on the fermentation of Pyropia spp., including the manufacturing process, alterations in chemical composition, flavor properties, bioactivities, and mechanisms. Furthermore, the limitations and opportunities for developing Pyropia spp. fermentation food are explored. Studies demonstrated that key metabolites of fermented Pyropia spp. were degraded polysaccharides, released phenolic compounds and flavonoids, and formed amino acids, which possessed bioactivities such as antioxidant, anti-glycation, anti-diabetic, lipid metabolism regulation beneficial to human health. The increased bioactivities implied the promoted bioaccessibility of intracellular components. Notably, fermentation positively contributed to the safety of Pyropia spp. food. In conclusion, benefits in nutrition, flavor, bioactivity, and safety suggest that fermentation technology has a promising future for application in Pyropia spp. food industry.
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Meat quality in goats is partly determined by the intramuscular fat (IMF) content, which is associated with the proliferation and differentiation of intramuscular preadipocytes. Emerging studies have suggested that miRNA plays a crucial role in adipocyte proliferation and differentiation. In our recent study, we observed the expression variations in miR-196a in the longissimus dorsi muscle of Jianzhou goats at different ages. However, the specific function and underlying mechanism of miR-196a in IMF deposition are still unclear. This study demonstrated that miR-196a significantly enhanced adipogenesis and apoptosis and reduced the proliferation of preadipocytes. Subsequently, RNA-seq was employed to determine genes regulated by miR-196a, and 677 differentially expressed genes were detected after miR-196a overexpression. The PI3K-Akt pathway was identified as activated in miR-196a regulating intramuscular adipogenesis via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and further verified via Western blot and rescue assays. Lastly, using RT-qPCR, Western blot, dual-luciferase, and rescue assays, we found that miR-196a promoted adipogenesis and suppressed the proliferation of intramuscular preadipocytes by the downregulation of MAP3K1. In summary, these results suggest that miR-196a regulates IMF deposition by targeting MAP3K1 and activating the PI3K-Akt pathway and provide a theoretical foundation for improving goat meat quality through molecular breeding.
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Adipocitos , Cabras , MicroARNs , Transducción de Señal , Animales , Adipocitos/metabolismo , Adipocitos/citología , Adipogénesis , Apoptosis , Diferenciación Celular , Proliferación Celular , Cabras/genética , Cabras/metabolismo , Metabolismo de los Lípidos/genética , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
BACKGROUND: Accurately redirecting reconstructed Positron emission tomography (PET) images into short-axis (SA) images shows great significance for subsequent clinical diagnosis. We developed a system for automatic redirection and quantitative analysis of myocardial PET images. METHODS: A total of 128 patients were enrolled for 18 F-FDG PET/CT myocardial metabolic images (MMIs), including 3 image classifications: without defects, with defects, and excess uptake. The automatic reorientation system includes five modules: regional division, myocardial segmentation, ellipsoid fitting, image rotation and quantitative analysis. First, the left ventricular geometry-based canny edge detection (LVG-CED) was developed and compared with the other 5 common region segmentation algorithms, the optimized partitioning was determined based on partition success rate. Then, 9 myocardial segmentation methods and 4 ellipsoid fitting methods were combined to derive 36 cross combinations for diagnostic performance in terms of Pearson correlation coefficient (PCC), Kendall correlation coefficient (KCC), Spearman correlation coefficient (SCC), and determination coefficient. Finally, the deflection angles were computed by ellipsoid fitting and the SA images were derived by affine transformation. Furthermore, the polar maps were used for quantitative analysis of SA images, and the redirection effects of 3 different image classifications were analyzed using correlation coefficients. RESULTS: On the dataset, LVG-CED outperformed other methods in the regional division module with a 100% success rate. In 36 cross combinations, PSO-FCM and LLS-SVD performed the best in terms of correlation coefficient. The linear results indicate that our algorithm (LVG-CED, PSO-FCM, and LLS-SVD) has good consistency with the reference manual method. In quantitative analysis, the similarities between our method and the reference manual method were higher than 96% at 17 segments. Moreover, our method demonstrated excellent performance in all 3 image classifications. CONCLUSION: Our algorithm system could realize accurate automatic reorientation and quantitative analysis of PET MMIs, which is also effective for images suffering from interference.
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Iron is an abundant element in the environment and acts as a thermodynamically favorable electron acceptor driving the anaerobic oxidation of methane (AOM). Presently, the role and environmental regulation of iron-driven AOM in rivers, an important source of methane emission, are nearly unknown. Here, we provided direct evidence for iron-driven AOM activity in sediment of a mountainous river (Wuxijiang River, China) through 13C-labeled isotopic experiment. The potential rate of iron-driven AOM ranged between 0.40 and 1.84 nmol 13CO2 g (sediment) d-1, which contributed 36% on average to total AOM activity when combined the potential nitrate- and nitrite-driven AOM rates measured previously. There were significant variations in iron-driven AOM rates among different reaches (upper, middle, and lower) and between seasons (summer and winter). Sediment temperature, pH, and nitrate content were closely associated with the dynamic of AOM activity. Our results indicate that iron-driven AOM has great potential for reducing methane emissions from riverine ecosystems, and suggest the necessity of taking both spatial and temporal scales into account to evaluate the quantitative role of this AOM process.
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Preeclampsia is the main cause of maternal and infant mortality and morbidity during pregnancy. Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) and human leukocyte antigen G (HLA-G) play crucial roles in immune tolerance at the maternal-fetal interface. In this caseâcontrol study, 154 maternal-fetal pairs were recruited, including 74 pairs with preeclampsia (56 of 74 pairs from family triads) and 80 pairs with a normal pregnancy (78 of 80 pairs from family triads). SNaPshot technology was used to detect genetic polymorphisms for 7 TagSNPs in the KIR2DL4 and HLA-G genes. Among the fetal HLA-G gene polymorphisms, rs9380142 (A vs. G: OR = 2.802, 95% CI = 1.761-4.458) and rs1063320 (G vs. C: OR = 1.807, 95% CI = 1.144-2.852) differed between the preeclampsia group and the control group. The transmission disequilibrium test (TDT) suggested that the differences in the rs9380142G/A polymorphism in foetuses between preeclampsia triads and control triads were due to differences in transmission from the parents (P = 0.001). There was no significant difference in the distribution of maternal KIR2DL4 alleles or genotype frequency between the preeclampsia group and the control group. Geneâgene interaction analysis revealed that the combined genotypes of maternal rs649216-CC and fetal rs9380142-GG, maternal rs1051456-CG/GG and fetal rs9380142-GG, maternal rs34785252-CC and fetal rs9380142-AA/GA, and maternal rs34785252-CC/AA and fetal rs9380142-GG were associated with a significantly lower risk of preeclampsia. Therefore, this study suggested that the combination of maternal KIR2DL4 and fetal HLA-G polymorphisms was associated with preeclampsia in a Han Chinese population.
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Protein arginine methyltransferases (PRMTs) in mammals play a role in various signaling pathways, such as virus infection, inflammasome responses, and cancer growth. While some PRMTs have been found to regulate interferon production in mammals, the mechanism in chickens remains to be fully understood. This study focused on investigating the function of chicken PRMTs. Our findings indicate that chicken PRMTs act as inhibitors of interferon production in response to dsRNA or MDA5 stimulation. Each PRMT is involved in different stages of interferon induction through the MDA5-MAVS-TBK1 pathway. Furthermore, we observed the colocalization of multiple PRMTs with the viral protein VP3 of infectious bursal disease virus (IBDV). Among the chicken PRMTs studied, PRMT3 was found to be widely expressed in various organs and its expression was upregulated during IBDV infection. Notably, PRMT3 supported IBDV replication, as demonstrated by ectopic expression and inhibition studies using SGC-707. Silencing of PRMT3 led to enhanced interferon production and inhibition of IBDV replication. This study provides novel insights into the role of chicken PRMTs, particularly PRMT3, in promoting IBDV replication by suppressing interferon signaling.
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Proteínas Aviares , Pollos , Virus de la Enfermedad Infecciosa de la Bolsa , Enfermedades de las Aves de Corral , Proteína-Arginina N-Metiltransferasas , Replicación Viral , Animales , Virus de la Enfermedad Infecciosa de la Bolsa/fisiología , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Aviares/genética , Proteínas Aviares/metabolismo , Enfermedades de las Aves de Corral/virología , Infecciones por Birnaviridae/veterinaria , Infecciones por Birnaviridae/virologíaRESUMEN
Iron-dependent anaerobic oxidation of methane (iron-AOM) has recently been reported to occur in paddy soils, but its actual role and regulation remain unclear. Here, we confirmed the occurrence of iron-AOM at different layers of paddy soils (0-10 cm, 10-20 cm, and 30-40 cm) across tillering, elongation, flowering, and ripening periods under three long-term fertilizer management schemes (CK-unamended, CF-chemical fertilizer, and CFS-chemical fertilizer with straw). The iron-AOM activity contributed 41 % to total AOM, which was greater than that of nitrite- (32 %) and nitrate-AOM (27 %). The iron-AOM activity varied significantly with soil layers, growth periods and fertilizer types, with layer being the most important variable. Soil moisture content and organic carbon content were most significant influencing factors on the AOM activity, and a Candidatus Methanoperedens ferrireducens-like lineage potentially catalyzed iron-AOM. Our results suggest that iron-AOM has an important potential for mitigating methane emissions from rice paddies.
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Agricultura , Fertilizantes , Hierro , Metano , Oryza , Oryza/crecimiento & desarrollo , Metano/análisis , Agricultura/métodos , Suelo/química , Oxidación-Reducción , Microbiología del SueloRESUMEN
The family of cell cycle-dependent kinases (CDKs) serves as catalytic subunits within protein kinase complexes, playing a crucial role in cell cycle progression. While the function of CDK proteins in regulating mammalian innate immune responses and virus replication is well-documented, their role in chickens remains unclear. To address this, we cloned several chicken CDKs, specifically CDK6 through CDK10. We observed that CDK6 is widely expressed across various chicken tissues, with localization in the cytoplasm, nucleus, or both in DF-1 cells. In addition, we also found that multiple chicken CDKs negatively regulate IFN-ß signaling induced by chicken MAVS or chicken STING by targeting different steps. Moreover, during infection with infectious bursal disease virus (IBDV), various chicken CDKs, except CDK10, were recruited and co-localized with viral protein VP1. Interestingly, overexpression of CDK6 in chickens significantly enhanced IBDV replication. Conversely, knocking down CDK6 led to a marked increase in IFN-ß production, triggered by chMDA5. Furthermore, targeting endogenous CDK6 with RNA interference substantially reduced IBDV replication. These findings collectively suggest that chicken CDKs, particularly CDK6, act as suppressors of IFN-ß production and play a facilitative role in IBDV replication.
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Proteínas Aviares , Pollos , Quinasas Ciclina-Dependientes , Replicación Viral , Animales , Pollos/genética , Proteínas Aviares/metabolismo , Proteínas Aviares/genética , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/genética , Virus de la Enfermedad Infecciosa de la Bolsa/fisiología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/metabolismo , Enfermedades de las Aves de Corral/genética , Infecciones por Birnaviridae/veterinaria , Infecciones por Birnaviridae/virología , Inmunidad InnataRESUMEN
Straw incorporation holds significant promise for enhancing soil fertility and mitigating air pollution stemming from straw burning. However, this practice concurrently elevates the production and emission of methane (CH4) from paddy ecosystems. Despite its environmental impact, the precise mechanisms behind the heightened CH4 production resulting from long-term straw incorporation remain elusive. In a 32-year field experiment featuring three fertilization treatments (CFS-chemical fertilizer with wheat straw, CF-chemical fertilizer, and CK-unamended), we investigated the impact of abiotic (soil physicochemical properties) and biotic (methanogenic abundance, diversity, and community composition) factors on CH4 production in paddy fields. Results revealed a significantly higher CH4 production potential under CFS treatment compared to CF and CK treatments. The partial least squares path model revealed that soil physicochemical properties (path coefficient = 0.61), methanogenic diversity (path coefficient = -0.43), and methanogenic abundance (path coefficient = 0.29) collectively determined CH4 production potential, explaining 77% of the variance. Enhanced soil organic carbon content and water content, resulting from straw incorporation, emerged as pivotal factors positively correlated with CH4 production potential. Under CFS treatment, lower Shannon index of methanogens, compared to CF and CK treatments, was attributed to increased Methanosarcina. Notably, the Shannon index and relative abundance of Methanosarcina exhibited negative and positive correlations with CH4 production potential, respectively. Methanogenic abundance, bolstered by straw incorporation, significantly amplified overall potential. This comprehensive analysis underscores the joint influence of abiotic and biotic factors in regulating CH4 production potential during multi-decadal straw incorporation.
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Metano , Microbiología del Suelo , Suelo , Metano/biosíntesis , Metano/metabolismo , Suelo/química , Oryza , Agricultura/métodos , Fertilizantes/análisisRESUMEN
Lenvatinib is a commonly used first-line drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to the drug resistance. EVA1A was a newly identified tumor suppressor, nevertheless, the impact of EVA1A on resistance to lenvatinib treatment in HCC and the potential molecular mechanisms remain unknown. In this study, the expression of EVA1A in HCC lenvatinib-resistant cells is decreased and its low expression was associated with a poor prognosis of HCC. Overexpression of EVA1A reversed lenvatinib resistance in vitro and in vivo, as demonstrated by its ability to promote cell apoptosis and inhibit cell proliferation, invasion, migration, EMT, and tumor growth. Silencing EVA1A in lenvatinib-sensitive parental HCC cells exerted the opposite effect and induced resistance to lenvatinib. Mechanistically, upregulated EVA1A inhibited the PI3K/AKT/MDM2 signaling pathway, resulting in a reduced interaction between MDM2 and p53, thereby stabilizing p53 and enhancing its antitumor activity. In addition, upregulated EVA1A suppressed the PI3K/AKT/mTOR signaling pathway and promoted autophagy, leading to the degradation of mutant p53 and attenuating its oncogenic impact. On the contrary, loss of EVA1A activated the PI3K/AKT/MDM2 signaling pathway and inhibited autophagy, promoting p53 proteasomal degradation and mutant p53 accumulation respectively. These findings establish a crucial role of EVA1A loss in driving lenvatinib resistance involving a mechanism of modulating PI3K/AKT/p53 signaling axis and suggest that upregulating EVA1A is a promising therapeutic strategy for alleviating resistance to lenvatinib, thereby improving the efficacy of HCC treatment.
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Carcinoma Hepatocelular , Resistencia a Antineoplásicos , Neoplasias Hepáticas , Compuestos de Fenilurea , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Quinolinas , Transducción de Señal , Proteína p53 Supresora de Tumor , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Quinolinas/farmacología , Quinolinas/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Animales , Línea Celular Tumoral , Ratones , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , FemeninoRESUMEN
Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.
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BACKGROUND AND AIMS: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. METHODS: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short-Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo-oxygenase regression analysis and Kaplan-Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. RESULTS: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16-fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21-fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan-Meier curves demonstrated early separation among groups, persisting throughout the follow-up period (all p < .0001). CONCLUSIONS: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid-suppressive treatment for patients with ischemic insular damage.
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Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Anciano , Persona de Mediana Edad , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Imagen por Resonancia Magnética , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/epidemiología , Úlcera/patologíaRESUMEN
Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating. This exosome-encapsulated hyaluronic acid macroporous hydrogel HD-DP7/Exo can achieve long-term storage and transport by lyophilization and can be rapidly redissolved for treatment. After comprehensively comparing the therapeutic effects of HucMSC-Exos and HucMSC-loaded hydrogels, we found that HucMSC-Exos could also effectively regulate fibroblasts, vascular endothelial cells, and macrophages and inhibit myofibroblast-mediated fibrosis, thus promoting tissue regeneration and inhibiting scar formation in a mouse model of deep second-degree burn infection healing. These properties of lyophilized storage and whole-process-repair make HD-DP7/Exo have potential application value and application prospects.
Asunto(s)
Péptidos Antimicrobianos , Exosomas , Hidrogeles , MicroARNs , Cicatrización de Heridas , Animales , Exosomas/metabolismo , Hidrogeles/química , Cicatrización de Heridas/efectos de los fármacos , Ratones , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Vendajes , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Quemaduras/terapia , Ácido Hialurónico/química , Masculino , Cicatriz , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Dietary selenium (Se) deficiency, stemming from low Se concentrations in agricultural products, threatens human health. While Se-containing fertilizers can enhance the Se content in crops, the key factors governing Se biofortification with Se fertilization remain unclear. RESULTS: This study constructed a global meta-analysis dataset based on field experiments comprising 364 entries on Se content in agricultural products and 271 entries on their yield. Random forest models and mixed effects meta-analyses revealed that plant types (i.e., cereals, vegetables, legumes, and forages) primarily influenced Se biofortification, with Se fertilization rates being the next significant factor. The random forest model, which included variables like plant types, Se fertilization rates, methods and types of Se application, initial soil conditions (including Se content, organic carbon content, and pH), soil types, mean annual precipitation, and temperature, explained 82.14% of the variation in Se content and 48.42% of the yield variation in agricultural products. For the same agricultural products, the increase in Se content decreased with higher rates of Se fertilization. The increase in Se content in their edible parts will be negligible for cereals, forages, legumes, and vegetable crops, when Se fertilization rates were 164, 103, 144, and 147 g Se ha-1, respectively. Conversely, while low Se fertilization rates enhanced yields, high rates led to a yield reduction, particularly in cereals. CONCLUSION: Our findings highlight the need for balanced and precise Se fertilization strategies to optimize Se biofortification benefits and minimize the risk of yield reduction. © 2024 Society of Chemical Industry.