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CRISPR-Cas systems with dual functions offer precise sequence-based recognition and efficient catalytic cleavage of nucleic acids, making them highly promising in biosensing and diagnostic technologies. However, current methods encounter challenges of complexity, low turnover efficiency, and the necessity for sophisticated probe design. To better integrate the dual functions of Cas proteins, we proposed a novel approach called CRISPR-Cas Autocatalysis Amplification driven by LNA-modified Split Activators (CALSA) for the highly efficient detection of single-stranded DNA (ssDNA) and genomic DNA. By introducing split ssDNA activators and the site-directed trans-cleavage mediated by LNA modifications, an autocatalysis-driven positive feedback loop of nucleic acids based on the LbCas12a system was constructed. Consequently, CALSA enabled one-pot and real-time detection of genomic DNA and cell-free DNA (cfDNA) from different tumor cell lines. Notably, CALSA achieved high sensitivity, single-base specificity, and remarkably short reaction times. Due to the high programmability of nucleic acid circuits, these results highlighted the immense potential of CALSA as a powerful tool for cascade signal amplification. Moreover, the sensitivity and specificity further emphasized the value of CALSA in biosensing and diagnostics, opening avenues for future clinical applications.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , ADN de Cadena Simple , Oligonucleótidos , Humanos , Oligonucleótidos/química , Oligonucleótidos/genética , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/química , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN/química , ADN/genética , Línea Celular Tumoral , CatálisisRESUMEN
Backgrounds: Glioma stands as one of the most formidable brain tumor types, with patient outcomes remaining bleak even in the face of advancements in treatment modalities. FBXW4, a constituent of the F-box and WD repeat domain-containing protein family, is recognized for its participation in diverse cellular activities, including those related to tumor dynamics. Yet, the therapeutic relevance and specific role of FBXW4 in the context of glioma are not well defined. This study aims to elucidate the functional dynamics and significance of FBXW4 in glioma cases. Methods: This research undertook a comprehensive analysis of FBXW4's expression patterns and clinical relevance in glioma by harnessing data from the TCGA and GTEx databases. Results: The investigation revealed a distinct downregulation of FBXW4 in glioma tissues compared to normal brain counterparts, with a pronounced correlation between FBXW4 levels and disease severity. Intriguingly, FBXW4 expression inversely related to WHO tumor grades, with the most advanced grade IV gliomas exhibiting the lowest FBXW4 levels, whereas grade II tumors demonstrated the highest. Cases presenting with IDH1/2 mutations or 1p/19q codeletions were also associated with elevated FBXW4 levels. Furthermore, diminished FBXW4 expression aligned with an increased risk of mortality. Conclusions: The findings suggest that FBXW4 holds promise as a prognostic marker and a potential therapeutic avenue in glioma management. Nonetheless, future research is imperative to decode the intricate signaling pathways involving FBXW4 and to understand its broader clinical ramifications in glioma treatment paradigms.
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Neoplasias Encefálicas , Proteínas F-Box , Glioma , Humanos , Glioma/genética , Glioma/metabolismo , Glioma/patología , Pronóstico , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Masculino , Femenino , MutaciónRESUMEN
INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.
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Ventrículos Cardíacos , Fallo Renal Crónico , Humanos , Ventrículos Cardíacos/diagnóstico por imagen , Diálisis Renal , Volumen Sistólico , Función Ventricular Izquierda , Estudios Transversales , Fallo Renal Crónico/terapiaRESUMEN
Polyimide aerogels with mechanical robustness, great compressibility, excellent antifatigue properties, and intriguing functionality have captured enormous attention in diverse applications. Here, enlightened by the xylem parenchyma of dicotyledonous stems, a radially architectured polyimide/MXene composite aerogel (RPIMX) with reversible compressibility is developed by combining the interfacial enhancing strategy and radial ice-templating method. The strong interaction between MXene flakes and polymer can glue the MXene to form continuous lamellae, the ice crystals grow preferentially along the radial temperature gradient can effectively constrain the lamellae to create a biomimetic radial lamellar architecture. As a result, the nature-inspired RPIMX composite aerogel with centrosymmetric lamellar structure and oriented channels manifests excellent mechanical strength, electrical conductivity, and water transporting capability along the longitudinal direction, endowing itself with intriguing applications for accurate human motion monitoring and efficient photothermal evaporation. These exciting properties make the biomimetic RPIMX aerogels promising candidates for flexible piezoresistive sensors and photothermal evaporators.
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Hielo , Vapor , Conductividad Eléctrica , Humanos , Luz Solar , XilemaRESUMEN
Stretchable electronics have attracted surging attention for next-generation smart wearables, yet traditional flexible devices fabricated on hermetical elastic substrates cannot satisfy lengthy wearing comfort and signal stability due to their poor moisture and air permeability. Herein, perspiration-wicking and luminescent on-skin electrodes are fabricated on superelastic nonwoven textiles with a Janus configuration. Through the electrospin-assisted face-to-face assembly of all-SEBS microfibers with differentiated diameters and composition, porosity and wettability asymmetry are constructed across the textile, endowing it with antigravity water transport capability for continuous sweat release. Also, the phosphor particles evenly encapsulated in the elastic fibers empower the Janus textile with stable light-emitting capability under extreme stretching in a dark environment. Additionally, the precise printing of highly conductive liquid metal (LM) circuits onto the matrix not only equips the electronic textile with broad detectability for various biophysical and electrophysiological signals but also enables successful implementation of human-machine interface (HMIs) to control a mechanical claw.
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Sudor , Textiles , Acción Capilar , Electrónica , Humanos , AguaRESUMEN
BACKGROUND: There is still a lack of high-level evidence on the effects of problem-based learning (PBL) in general medical and nursing education. AIMS: We aimed to summarize current evidence on the effects of PBL in delivering medical and nursing education from randomized controlled trials (RCTs). METHODS: A systematic search was performed in MEDLINE, EMBASE, Cochrane Central Library, and CINAHL Complete. RCTs that assessed the effects of a PBL module in delivering medical education were eligible. Outcomes included knowledge, performance, and satisfaction. The risk of bias was assessed according to Cochrane handbook guidelines. Standardized mean differences with 95% confidence intervals of each outcome between PBL and control groups were pooled using a random-effects model. RESULTS: In all, 22 RCTs with 1969 participants were included. Both pooled analyses of changes in scores compared with baseline and absolute post-interventional scores favored PBL module in knowledge and performance. The satisfaction degree was also higher in participants receiving PBL methods. Publication bias might exist in satisfaction; however, not in knowledge and performance. Eleven of the 22 studies were assessed as having a high risk of bias. LINKING EVIDENCE TO ACTION: Compared with traditional lecture-based modules, PBL delivered medical education in different medical science specialities more efficiently from both theoretical knowledge and practice skill perspectives. The feedback from participants receiving PBL methods was more positive than that from those receiving traditional methods. However, the high heterogeneity and low quality of the included studies prevented drawing definite conclusions.
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Background: As a part of a healthy lifestyle, exercise has been proven to be beneficial for the treatment of diseases and the prognosis of patients. Based on this, our research focuses on the impact of exercise on human health. Methods: To study and analyze the samples in the GSE18966 gene expression profile, we first performed an analysis on the differential expressed genes (DEGs) through GEO2R, and then the DEGs enrichment in Gene Ontology functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways through the Database for Annotation, Visualization and Integrated Discovery database was conducted. Then, we delved into the gene set enrichment in KEGG through gene set enrichment analysis. After that, we achieved the construction of the protein-protein interaction (PPI) network of DEGs based on the Search Tool for the Retrieval of Interacting Genes online database, and the hub genes were screened and identified. Results: We identified 433 upregulated DEGs and 186 downregulated DEGs from the samples before and after exercise in GSE18966. Through analysis, it was found that these DEGs-enriched pathways, such as the VEGF signaling pathway, the Wnt signaling pathway, and the insulin signaling pathway, were all involved in the regulation of various diseases. Then, GSEA analysis revealed that glycosaminoglycan biosynthesis chondroitin sulfate, type II diabetes mellitus, and basal cell carcinoma were related with exercise samples. The effects of these pathways on various diseases could be improved through exercise. Finally, 3 upregulated hub genes (VEGFA, POMC, and NRAS) and 3 downregulated hub genes (HRAS, NCOR1, and CAV1) were identified through the PPI network. Conclusions: The bioinformatic analysis of samples before and after exercise provides key pathways and genes related to exercise to regulate various diseases, which confirms that exercise has an important influence on the treatment of many diseases.
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Diabetes Mellitus Tipo 2 , Biología Computacional , Diabetes Mellitus Tipo 2/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes/genética , HumanosRESUMEN
Zero-dimensional (0D) all-inorganic cesium lead halide perovskites, particularly Cs4PbBr6, have been attracting wide attention due to their excellent optical properties and stability. The research also focuses on the origin of green emission from Cs4PbBr6, which has a bandgap located in the ultraviolet B (UVB) region. So far, both Cs4PbBr6 without visible emission and with green emission have been successfully prepared; however, the origin of green emission remains controversial. Photocurrent response is one of the effective approaches to explore how the photo-excited carriers influence the photo-physical properties of materials. In our study, Cs4PbBr6 particles without visible emission and with green emission were synthesized and their photocurrent response was investigated. The former showed a positive photocurrent response, while the latter showed a negative photocurrent response. The negative response was believed to be due to a built-in electric field constructed by the charged excitons in green-emissive Cs4PbBr6. From our calculations, numerous vacancies of Br are easier to appear in green-emissive Cs4PbBr6 lattices, which could combine the neutral excitons to form charged excitons. This work may contribute to the explanation of the origin of green emission of Cs4PbBr6 to some extent.
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Chronic kidney disease (CKD) has recently become a serious health and social concern. Vascular calcification, a common complication of CKD, is a risk factor that increases the incidence and mortality of cardiovascular events in patients with CKD. However, there are currently no effective therapeutic targets that can facilitate treatment with fewer side effects for vascular calcification in CKD. To identify potential therapeutic targets, we performed label-free quantification (LFQ) analyses of protein samples from rat aortic vascular smooth muscle cells (RASMCs) after high-phosphorus treatment by nano-UPLC-MS/MS. We determined that ubiquitin-specific protease 47 (USP47) may be associated with CKD vascular calcification by regulating the osteogenic transdifferentiation of the vascular smooth muscle cell (VSMC) phenotype, thus suggesting a novel and potentially effective therapeutic target for CKD vascular calcification. USP47 knockdown significantly reduced the expression of ß-transducin repeat-containing protein (BTRC), serine/threonine-protein kinase akt-1 (AKT1), Klotho, fibroblast growth factor (FGF23), and matrix Gla protein (MGP) in RASMCs after high-phosphorus treatment. Consistent with the results of protein-protein interaction (PPI) analyses, USP47 may be involved in regulating osteogenic transdifferentiation markers, such as runt-related transcription factor 2 (RUNX2), Klotho, FGF23, and MGP through the BTRC/AKT1 pathway upon CKD vascular calcification. These data indicate that USP47 may be associated with vascular calcification in CKD by regulating osteogenic differentiation of VSMCs. USP47 may regulate osteogenic transdifferentiation in VSMCs upon CKD vascular calcification through a process involving the BTRC/AKT1 pathway. This study identified a novel potential therapeutic target for the treatment of vascular calcification in CKD.
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Insuficiencia Renal Crónica , Proteasas Ubiquitina-Específicas , Calcificación Vascular , Animales , Transdiferenciación Celular/genética , Células Cultivadas , Femenino , Humanos , Masculino , Músculo Liso Vascular , Miocitos del Músculo Liso/metabolismo , Osteogénesis/genética , Fósforo/metabolismo , Ratas , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/metabolismo , Espectrometría de Masas en Tándem , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/farmacología , Calcificación Vascular/metabolismoRESUMEN
Vascular calcification is prominent in patients with chronic kidney disease (CKD) and is a strong predictor of cardiovascular mortality in the CKD population. However, the mechanism underlying CKD-associated vascular calcification remains unclear. To identify potential therapeutic targets, a 5/6 nephrectomy rat model was established by feeding of a high-phosphorous diet as the CKD group and compared with sham group rats at 4 and 16 weeks. Sequencing analyses of the rat aorta revealed 643 upregulated and 1023 downregulated genes at 4 weeks, as well as 899 upregulated and 1185 downregulated genes at 16 weeks in the CKD group compared to the sham group. Bioinformatics analyses suggested that SOST (which encodes sclerostin) and Wnt signaling are involved in CKD-associated vascular calcification. Furthermore, protein-protein interactions analysis revealed interactions between SOST, WNT5A, and WNT5B, that involved runt-related transcription factor 2 (RUNX2) and transgelin (TAGLN). SOST was increased in CKD-associated vascular calcification following reduction of the Wnt signaling, including WNT5A and WNT5B, both in vivo and in vitro. TargetScan was used to predict the microRNAs (miRNAs) targeting WNT5A and WNT5B. The expression levels of miR-542-3p, miR-298-3p, miR-376b-5p, and miR-3568 were significantly reduced, whereas that of miR-742-3p was significantly increased in calcified rat aortic vascular smooth muscle cells (VSMCs). In CKD rat aortas, the expression of miR-542-3p, miR-298-3p, miR-376b-5p, miR-3568, miR-742-3p, and miR-22-5p were significantly reduced at both 4 and 16 weeks. Altogether, owing to several assessments, potentially diagnostic and prognostic biomarkers for improving common CKD diagnostic tools were identified in this study. Abbreviations: BUN: blood urea nitrogen; CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral bone disorder; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO: the Gene Ontology; HE: hematoxylin-eosin; HRP: horseradish peroxidase; KEGG: Kyoto Encyclopedia of Genes and Genomes; MiRNAs: microRNAs; PAS: periodic acid-Schiff; RUNX2: runt-related transcription factor 2; SCr: serum creatinine; STRING: the Search Tool for the Retrieval of Interacting Genes/Proteins; TAGLN: transgelin; VSMC: vascular smooth muscle cell.
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MicroARNs , Insuficiencia Renal Crónica , Calcificación Vascular , Animales , Transdiferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Ratas , Insuficiencia Renal Crónica/metabolismo , Calcificación Vascular/genética , Calcificación Vascular/metabolismo , Vía de Señalización WntRESUMEN
In recent years, autonomous driving technology has been changing from "human adapting to vehicle" to "vehicle adapting to human". To improve the adaptability of autonomous driving systems to human drivers, a time-series-based personalized lane change decision (LCD) model is proposed. Firstly, according to the characteristics of the subject vehicle (SV) with respect to speed, acceleration and headway, an unsupervised clustering algorithm, namely, a Gaussian mixture model (GMM), is used to identify its three different driving styles. Secondly, considering the interaction between the SV and the surrounding vehicles, the lane change (LC) gain value is produced by developing a gain function to characterize their interaction. On the basis of the recognition of the driving style, this gain value and LC feature parameters are employed as model inputs to develop a personalized LCD model on the basis of a long short-term memory (LSTM) recurrent neural network model (RNN). The proposed method is tested using the US Open Driving Dataset NGSIM. The results show that the accuracy, F1 score, and macro-average area under the curve (macro-AUC) value of the proposed method for LC behavior prediction are 0.965, 0.951 and 0.983, respectively, and the performance is significantly better than that of other mainstream models. At the same time, the method is able to capture the LCD behavior of different human drivers, enabling personalized driving.
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Accidentes de Tránsito , Conducción de Automóvil , Aceleración , Algoritmos , Humanos , Redes Neurales de la ComputaciónRESUMEN
Background: Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide. Despite the advancements in current diagnosis and treatment strategies of CRC, the incidence and mortality rates of CRC have been rising. To explore novel mechanism of CRC, this study focused on the expression pattern and functional mechanism of murine retrovirus integration site 1 (MRVI1) in CRC.Methods: Tumor tissues and adjacent normal tissues were collected from CRC patients, and the expression levels of MRVI1 were determined by RT-PCR and Western blot. MRVI1 knockdown was achieved by shRNA in HCT116 and HT29 cells, followed by CCK-8 assay to detect the cell proliferation, and caspase-3 activity assay combined with nucleosome ELISA assay to detect cell apoptosis. Transwell assay was used to detect cell invasion and luciferase reporter assay was used to validate the activation of the MRVI1 promoter by p53.Results: MRVI1 was downregulated in CRC tissues and several CRC cell lines. Knockdown of MRVI1 enhanced the proliferation and apoptosis, while promoted invasion and stemness of CRC cells. Mechanism study revealed that MRVI1 was transcriptionally activated by p53 at its upstream. In addition, p53-induced inhibition of CRC prognosis depended on MRVI1.Conclusion: MRVI1 inhibited the prognosis of CRC via a mechanism involving p53 activation. MRVI1 could serve as a potential target for clinical diagnosis and treatment of CRC.
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Neoplasias Colorrectales/metabolismo , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis , Carcinogénesis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Humanos , Proteínas de la Membrana/genética , Fosfoproteínas/genética , Pronóstico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
OBJECTIVE: To further determine the efficacy and safety of direct-acting antiviral (DAA)-based treatments in hepatitis C virus (HCV) infected patients with renal function impairment. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched for relevant studies. All studies assessing the efficacy and safety of DAA-based treatments against HCV infection in patients with renal impairment and HCV infection were eligible for inclusion. Outcomes assessed included efficacy outcomes and safety outcomes. Summary estimates were obtained using an inverse-variance weighted random effect model and Freeman-Tukey double arcsine transformation. RESULTS: Twenty-seven studies (n = 1048 participants) were included. The majority of included studies were of fair quality with Newcastle-Ottawa scale scores between 4 and 6. The pooled virologic response rates at the end of treatment or 4, 12, 24 weeks after treatment (ie, EOTR, SVR4, SVR12 and SVR24 rates) were 97.0% (95% confidence interval [CI], 94.0%-99.0%), 80.9% (95% CI, 49.3%-98.7%), 94.1% (95% CI, 91.6%-96.3%) and 89.6% (95% CI, 75.5%-98.1%), respectively. The pooled relapse rate was 6.4% (95% CI, 3.4%-10.4%). The pooled incidence of adverse events and severe adverse events leading to discontinuation were 47.6% (95% CI, 35.0%-60.4%) and 2.9% (95% CI, 1.4%-5.0%), respectively. High heterogeneity among studies exists for SVR4 and SVR24 rates. Formal statistical testing did not identify the presence of publication bias for all measured outcomes except the relapse rate. CONCLUSION: The results support the efficacy and safety of DAA-based treatments in this population. Future studies with better design, larger sample size and longer follow up will be the next step. SUMMARY AT A GLANCE This systematic review evaluated the efficacy and safety of direct-acting antiviral based therapies in hepatitis C infection in patients with renal impairment. The majority of studies were of fair quality only. These therapies were found to be highly efficacious although there were high rates of adverse events.
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Antivirales/uso terapéutico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Insuficiencia Renal Crónica/virología , Humanos , Insuficiencia Renal Crónica/terapiaRESUMEN
Background: IgG4-related acute tubulointerstitial nephritis is a type of autoimmune-mediated interstitial nephritis. Recently, autoantibodies against modified C-reactive protein (mCRP) were found to play a pathogenic role in renal diseases through the formation of tubulointerstitial lesions. This is the first case report on the presence of mCRP autoantibodies in a patient with IgG4-associated acute tubulointerstitial nephritis. Case presentation: A 70-year-old man was admitted with renal dysfunction and a medical history of bile duct stenosis, an inflammatory pancreatic mass, hypertension, and diabetes. On admission, laboratory tests showed higher than normal levels of serum creatinine and IgG4 and lower than normal levels of complements 3 and 4. In addition, the mCRP autoantibody levels were elevated, and the findings of kidney biopsy revealed interstitial nephritis with rich plasma cells in the renal interstitium. The patient was administered prednisone and cyclophosphamide therapy, which resulted in a rapid improvement in renal function. Conclusion: IgG4-related autoimmune disease should be considered in the diagnosis of patients who have tubulointerstitial nephritis with multisystem involvement. Further, mCRP autoantibodies may be associated with IgG4-related tubulointerstitial nephritis and might be useful as a diagnostic marker of the disease.
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Autoanticuerpos/sangre , Proteína C-Reactiva/inmunología , Riñón/patología , Nefritis Intersticial/inmunología , Anciano , Ciclofosfamida/uso terapéutico , Humanos , Inmunoglobulina G/sangre , Masculino , Nefritis Intersticial/sangre , Nefritis Intersticial/tratamiento farmacológico , Prednisona/uso terapéuticoRESUMEN
In China, sparerib is one of the most valuable parts of the pork carcass. As a result, candidate gene mining for number of ribs has become an interesting study focus. To examine the genetic basis for this major trait, we genotyped 596 individuals from an F2 Large White × Minzhu intercross pig population using the PorcineSNP60 Genotyping BeadChip. The genome-wide association study identified a locus for number of ribs in a 2.38-Mb region on Sus scrofa chromosome 7 (SSC7 of Sus scrofa genome assembly, Sscrofa10.2). We identified the top significant SNP ASGA0035536, which explained 16.51 % of the phenotypic variance. A previously reported candidate causal mutation (g.19034 A>C) in vertebrae development-associated gene VRTN explained 8.79 % of the phenotypic variation on number of ribs and had a much lower effect than ASGA0035536. Haplotype sharing analysis in F1 boars localized the rib number QTL to a 951-kb interval on SSC7. This interval encompassed 17 annotated genes in Sscrofa10.2, including the previously reported VRTN candidate gene. Of the 17 candidate genes, LTBP2, which encodes a latent transforming growth factor beta binding protein, was previously reported to indirectly regulate the activity of growth differentiation factor Gdf11, which has been shown to increase the number of ribs in knock-out mice. Thus, we propose LTBP2 as a good new candidate gene for number of ribs in the pig population. This finding advances our understanding of the genetic architecture of rib number in pigs.
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Cromosomas de los Mamíferos/genética , Proteínas de Unión a TGF-beta Latente/genética , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Sus scrofa/genética , Animales , Mapeo Cromosómico , Cruzamientos Genéticos , Estudio de Asociación del Genoma Completo , Carácter Cuantitativo Heredable , Costillas , PorcinosRESUMEN
AIM: Renal ischaemia-reperfusion (I/R) injury, a primary cause of acute renal failure, can induce high morbidity and mortality. This study aimed to explore the effect of erythropoietin on renal I/R injury and its underlying mechanism. METHODS: Fifty male Sprague-Dawley rats were randomly allocated to three groups (n = 10): the sham group, the renal ischaemia-reperfusion-saline (IRI) group, and the IRI+-Erythropoietin (EPO) group. Erythropoietin (250, 500, 1000 U/kg) was intraperitoneally injected 30 min before inducing I/R. Renal I/R injury were induced by clamping the left renal artery for 30 min followed by reperfusion, along with a contralateral nephrectomy. Renal function and histological damage were determined after 24 h reperfusion. The expression of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 ß (IL-1ß), and tumour necrosis factor-α (TNF-α) in the serum and renal tissue were evaluated by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Further, the effects of erythropoietin on PI3K/Akt signalling, erythropoietin receptor (EPOR) and nuclear factor (NF)-κB activation were measured by Western blotting. RESULTS: Erythropoietin pretreatment can significantly decrease the level of renal dysfunction in a dose-dependent manner, attenuated the renal histological changes, the expression of TNF-α, IL-1ß, and IL-6, the levels of reactive oxygen species (ROS) production and NF-κB p65 phosphorylation in renal tissue upon IRI. Moreover, erythropoietin pretreatment could further activate the PI3K/Akt signalling and induced EPOR activity. CONCLUSIONS: Erythropoietin pretreatment could attenuate renal I/R injury by suppressing inflammation, which was associated with activating PI3K/Akt signalling though EPOR activation. Our findings suggest that erythropoietin may be a novel practical strategy to prevent renal I/R injury.
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Lesión Renal Aguda/prevención & control , Antiinflamatorios/administración & dosificación , Eritropoyetina/administración & dosificación , Riñón/efectos de los fármacos , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Daño por Reperfusión/prevención & control , Transducción de Señal/efectos de los fármacos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/patología , Animales , Biomarcadores/sangre , Citoprotección , Modelos Animales de Enfermedad , Activación Enzimática , Mediadores de Inflamación/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Riñón/enzimología , Riñón/patología , Masculino , Fosforilación , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores de Eritropoyetina/agonistas , Receptores de Eritropoyetina/metabolismo , Daño por Reperfusión/sangre , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length. METHODS: A total of 571 F2 individuals from a Large White and Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for femur length (FL), humerus length (HL), hipbone length (HIPL), scapula length (SL), tibia length (TL), and ulna length (UL). A genome-wide association study was performed by applying the previously reported approach of genome-wide rapid association using mixed model and regression. Statistical significance of the associations was based on Bonferroni-corrected P-values. RESULTS: A total of 39 significant SNPs were mapped to a 11.93 Mb long region on pig chromosome 7 (SSC7). Linkage analysis of these significant SNPs revealed three haplotype blocks of 495 kb, 376 kb and 492 kb, respectively, in the 11.93 Mb region. Annotation based on the pig reference genome identified 15 genes that were located near or contained the significant SNPs in these linkage disequilibrium intervals. Conditioned analysis revealed that four SNPs, one on SSC2 and three on SSC4, showed significant associations with SL and HL, respectively. CONCLUSIONS: Analysis of the 15 annotated genes that were identified in these three haplotype blocks indicated that HMGA1 and PPARD, which are expressed in limbs and influence chondrocyte cell growth and differentiation, could be considered as relevant biological candidates for limb bone length in pig, with potential applications in breeding programs. Our results may also be useful for the study of the mechanisms that underlie human limb length and body height.
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Variación Anatómica/genética , Huesos de la Extremidad Inferior/anatomía & histología , Huesos de la Extremidad Superior/anatomía & histología , Proteínas HMGA/genética , PPAR delta/genética , Sus scrofa/genética , Animales , Cruzamientos Genéticos , Femenino , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple , Sus scrofa/anatomía & histologíaRESUMEN
OBJECTIVE: This study aimed to investigate the effects of dietary supplementation with Agaricus blazei polysaccharide (ABP) at varying concentrations on the performance, egg quality, blood biochemistry, intestinal morphology, and microflora of quail. METHODS: The study involved a total of 2,700 Korean quails, which were randomly divided into three groups. The measured variables encompassed productive performance, egg parameters, carcass parameters, serum metabolites, immune response parameters, antioxidative properties, and gut microbiome. RESULTS: The addition of ABP did not have a significant effect on average daily feed intake. However, it was found to increase the average daily egg weight and egg production rate, reduce the feed-egg ratio. There were no significant impacts on egg quality measures such as egg shape index, egg yolk index and color, egg yolk and protein content. However, ABP supplementation significantly increased the Hough unit (p<0.01) and decreased the rate of unqualified eggs (p<0.01). Regarding serum parameters, the inclusion led to an increase in total protein concentration (p<0.05) and a reduction in low-density lipoprotein cholesterol (p<0.05). There were no significant effects observed on immune indicators such as immunoglobulin A (IgA) and IgM. ABP supplementation increased the levels of serum antioxidant indicators, including glutathione peroxidase, total superoxide dismutase (p<0.05), and total antioxidant capacity colorimeter (p<0.05). Furthermore, ABP supplementation significantly elevated the intramuscular fatty acid content in quail meat. Additionally, ABP supplementation demonstrated a significant improvement in the diversity of gut microbiota and induced alterations in the composition of the gut microbiota. CONCLUSION: The findings of this study indicate that dietary supplementation of ABP enhanced production performance and antioxidant capacity while increasing the levels of polyunsaturated fatty acids in quail muscle.
RESUMEN
This study was performed to investigate the effects of potassium diformate (KDF) on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora of Cherry Valley ducks. In total, 144 female healthy 1-day-old Cherry Valley ducks were divided into 3 groups with 6 replicates per group and 8 ducks per replicate according to the principle of similar body weight. The control group was fed a basic diet. In the 2 experimental groups, 0.8% and 1.2% KDF was added to the basic diet, respectively. The trial period was 6 wk and the pretrial period was 3 wk. The final weight and ADG were significantly higher in the 0.8% KDF group than in the control group (P < 0.05). The feed-to-gain ratio was significantly lower in both KDF groups than in the control group (P < 0.05). The apparent digestibility of CP was significantly higher in both KDF groups than in the control group (P < 0.05). The apparent digestibility of calcium was also significantly higher in the 0.8% KDF group (P < 0.05). The serum levels of alkaline phosphatase, cholesterol, and total protein were significantly lower in the 0.8% KDF group than in the control group (P < 0.05), the IgM content was significantly higher (P < 0.05), the low-density lipoprotein cholesterol, triglyceride, and urea levels were significantly lower (P < 0.01), and the glucose level was significantly higher (P < 0.01). The serum total protein level was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of Firmicutes and Patescibacteria in the gut of ducks was significantly higher in the 0.8% KDF group than in the control group (P < 0.05), the relative abundance of unclassified Erysipelotrichaceae and Lactobacillus was significantly higher (P < 0.01), and the relative abundance of Fusobacteriota was significantly lower (P < 0.05). However, the relative abundance of Firmicutes in the gut of ducks was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of unclassified Erysipelotrichaceae and Clostridium sensu stricto 1 was significantly higher (P < 0.01), as was the relative abundance of Fusobacteriota and Proteobacteria (P < 0.05). These findings indicate that the addition of 0.8% KDF to the diet can improve the growth performance of Cherry Valley ducks, promote the absorption of nutrients, change the structure of the microflora in the cecum, and increase the relative abundance of dominant bacteria. It was also shown that there was a significant difference between the 0.8% and 1.2% KDF levels which suggest that the safety margin for overdosing is quite low.
Asunto(s)
Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta , Suplementos Dietéticos , Digestión , Patos , Microbioma Gastrointestinal , Animales , Patos/crecimiento & desarrollo , Patos/fisiología , Alimentación Animal/análisis , Dieta/veterinaria , Digestión/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Femenino , Suplementos Dietéticos/análisis , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Distribución Aleatoria , Nutrientes/metabolismo , Relación Dosis-Respuesta a Droga , Análisis Químico de la Sangre/veterinariaRESUMEN
This research investigates the dynamic alterations that occur in protein molecular structure during the fermentation process of feed. Fourier transform infrared spectroscopy (FTIR), coupled with deconvolution, second derivative and curve-fitting methodologies, was employed to comparatively analyse the protein molecular structures in fermented feed. At the 48-h fermentation mark, the α-helix and ß-sheet contents reached their peaks, while the random coil and ß-turn contents were at their lowest. Simultaneously, the ß-sheet/α-helix ratio was minimized. FTIR spectroscopy emerged as a comprehensive tool, revealing the nuanced changes in molecular structure throughout the fermentation process of corn-soybean meal feed. When integrated with spectral quantitative analysis, it provides a novel perspective for evaluating the nutritional value of fermented feed.