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Intervertebral Disc Herniation (IVDH) is a common spinal disease in dogs, significantly impacting their health, mobility, and overall well-being. This study initiates an effort to automate the detection and localization of IVDH lesions in veterinary MRI scans, utilizing advanced artificial intelligence (AI) methods. A comprehensive canine IVDH dataset, comprising T2-weighted sagittal MRI images from 213 pet dogs of various breeds, ages, and sizes, was compiled and utilized to train and test the IVDH detection models. The experimental results showed that traditional two-stage detection models reliably outperformed one-stage models, including the recent You Only Look Once X (YOLOX) detector. In terms of methodology, this study introduced a novel spinal localization module, successfully integrated into different object detection models to enhance IVDH detection, achieving an average precision (AP) of up to 75.32%. Additionally, transfer learning was explored to adapt the IVDH detection model for a smaller feline dataset. Overall, this study provides insights into advancing AI for veterinary care, identifying challenges and exploring potential strategies for future development in veterinary radiology.
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Aprendizaje Profundo , Enfermedades de los Perros , Desplazamiento del Disco Intervertebral , Imagen por Resonancia Magnética , Animales , Desplazamiento del Disco Intervertebral/veterinaria , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Perros , Imagen por Resonancia Magnética/métodos , Enfermedades de los Perros/diagnóstico por imagen , Gatos , Inteligencia ArtificialRESUMEN
Decay-accelerating factor (DAF) is an essential member of the complement regulatory protein family that plays an important role in immune response and host homeostasis in mammals. However, the immune function of DAF has not been well characterized in bony fish. In this study, a complement regulatory protein named CiDAF was firstly characterized from Ctenopharyngodon idella and its potential roles were investigated in intestine following bacterial infection. Similar to mammalian DAFs, CiDAF has multiple complement control protein (CCP) functional domains, suggesting the evolutionary conservation of DAFs. CiDAF was broadly expressed in all tested tissues, with a relatively high expression level detected in the spleen and kidney. In vivo immune challenge experiments revealed that CiDAF strongly responded to bacterial pathogens (Aeromonas hydrophila and Aeromonas veronii) and PAMPs (lipopolysaccharide (LPS) or muramyl dipeptide (MDP)) challenges. In vitro RNAi experiments indicated that knockdown of CiDAF could upregulate the expression of complement genes (C4b, C5 and C7) and inflammatory cytokines (TNF-α, IL-1ß and IL-8). Moreover, 2000 ng/mL of CiDAF agonist progesterone effectively alleviated LPS- or MDP-induced intestinal inflammation by regulating expression of complement factors, TLR/PepT1 pathway genes and inflammatory cytokines. Overall, these findings revealed that CiDAF may act as a negative regulator of intestinal complement pathway and immune response to bacterial challenge in grass carp.
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Carpas , Enfermedades de los Peces , Proteínas de Peces , Infecciones por Bacterias Gramnegativas , Inmunidad Innata , Intestinos , Animales , Carpas/inmunología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Enfermedades de los Peces/inmunología , Inmunidad Innata/genética , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Intestinos/inmunología , Regulación de la Expresión Génica/inmunología , Filogenia , Perfilación de la Expresión Génica/veterinaria , Aeromonas hydrophila/fisiología , Secuencia de Aminoácidos , Alineación de Secuencia/veterinaria , Proteínas del Sistema Complemento/inmunologíaRESUMEN
Grass carp (Ctenopharyngodon idella) is an intensively cultured and economically important herbivorous fish species in China, but its culture is often impacted by Aeromonas pathogens such as Aeromonas hydrophila and Aeromonas veronii. In this study, healthy grass carp were separately infected with A. hydrophila or A. veronii for 12, 24, 48 or 72 h. The results showed that the mRNA expression levels of intestinal inflammatory factors (tnf-α, il-1ß and il-8), complement factors (c3 and c4), antimicrobial peptides (hepcidin, nk-lysin and ß-defensin-1), immunoglobulins (igm and igt), and immune pathway-related signaling molecules (tlr1, tlr2, tlr4, myd88, irak4, irak1, traf6, nf-κb p65 and ap-1) were differentially upregulated in response to A. hydrophila and A. veronii challenge. Additionally, the expression levels of the intestinal pro-apoptotic genes tnfr1, tnfr2, tradd, caspase-8, caspase-3 and bax were significantly increased, whereas the expression of the inhibitory factor bcl-2 was significantly downregulated, indicating that Aeromonas infection significantly induced apoptosis in the intestine of grass carp. Moreover, the expression of intestinal tight junction proteins (occludin, zo-1, claudin b and claudin c) was significantly decreased after infection with Aeromonas. Histopathological analysis indicated the Aeromonas challenge caused severe damage to the intestinal villi with adhesions and detachment of intestinal villi accompanied by severe inflammatory cell infiltration at 12 h and 72 h. The 16S rRNA sequencing results showed that Aeromonas infection significantly altered the structure of the intestinal microflora of the grass carp at the phylum (Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes) and genus (Proteus, Cetobacterium, Bacteroides, and Aeromonas) levels. Take together, the findings of this study revealed that Aeromonas infection induces an intestinal immune response, triggers cell apoptosis, destroys physical barriers and alters microflora structure in the intestine of juvenile grass carp; the results will help to reveal the pathogenesis of intestinal bacterial diseases in grass carp.
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Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide. Due to the important role of mitochondrial metabolism in cancer progression, a clinical prognostic model based on mitochondrial metabolism and clinical features was constructed in this study to predict the prognosis of ESCC. Firstly, the mitochondrial metabolism scores (MMs) were calculated based on 152 mitochondrial metabolism-related genes (MMRGs) by single sample gene set enrichment analysis (ssGSEA). Subsequently, univariate Cox regression and LASSO algorithm were used to identify prognosis-associated MMRG and risk-stratify patients. Functional enrichment, interaction network and immune-related analyses were performed to explore the features differences in patients at different risks. Finally, a prognostic nomogram incorporating clinical factors was constructed to assess the prognosis of ESCC. Our results found there were differences in clinical features between the MMs-high group and the MMs-low group in the TCGA-ESCC dataset (P<0.05). Afterwards, we identified 6 MMRGs (COX10, ACADVL, IDH3B, AKR1A1, LIAS, and NDUFB8) signature that could accurately distinguish high-risk and low-risk ESCC patients. A predictive nomogram that combined the 6 MMRGs with sex and N stage to predict the prognosis of ESCC was constructed, and the areas under the receiver operating characteristic (ROC) curve at 1, 2 and 3 years were 0.948, 0.927 and 0.848, respectively. Finally, we found that COX10, one of 6 MMRGs, could inhibit the malignant progression of ESCC in vitro. In summary, we constructed a clinical prognosis model based on 6 MMRGs and clinical features which can accurately predict the prognosis of ESCC patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Mitocondrias , Nomogramas , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Pronóstico , Mitocondrias/genética , Mitocondrias/metabolismo , Masculino , Femenino , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Transcriptoma , Perfilación de la Expresión GénicaRESUMEN
A novel multi-longitudinal mode 532 nm photonic Doppler velocimetry (PDV) was proposed to solve the problem of high bandwidth requirements in shock experiments with velocities up to km/s. Compared to the conventional PDV system operating at 1550 nm, the utilization of a shorter wavelength of 532 nm enables nearly three times the velocity resolution. However, it also leads to a threefold increase in the Doppler frequency shift for a given velocity. To mitigate the bandwidth constraints, a multi-longitudinal mode laser is employed to downconvert the signal, effectively reducing the bandwidth requirements. The efficacy of this method is validated through theoretical analysis and experimental investigations on detonation shock scenarios. Furthermore, this approach eliminates the necessity for modulators, frequency shifters, and other devices, facilitating its applicability to non-communication bands.
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Epoxiconazole (EPX) is a world widely used chiral triazole fungicide in the agriculture field. The excessive application of this triazole may cause damage to lizards. However, limited information is known about the toxicokinetics of EPX on lizards. Our study aimed to investigate the enantioselective absorption, distribution, metabolism, and elimination (ADME) of EPX in lizards following low and high dose exposure (10 and 100 mg kg-1 bodyweitht (bw)). The results demonstrated that (+)-EPX was easier absorbed than (-)-EPX in lizard plasma. Both (+)-EPX and (-)-EPX were detected in the liver, gonad, kidney, skin, brain, and intestine, with (+)-EPX preferentially distributed in these tissues. The elimination of (-)-EPX was faster than that of (+)-EPX in lizard liver and kidney in the high dose groups. Chiral conversion was found between EPX enantiomers in lizard skin. Simultaneously, five metabolites including M2, M4, M10, M18 and M19 were detected in lizard liver and kidney after EPX enantiomers exposure. The relative concentrations of M2, M4, and M10 were higher in the liver and kidney of (-)-EPX groups than those produced from (+)-EPX groups. The metabolic enzymes CYP3A4 and SULT1A1 primarily mediated enantioselective metabolism of EPX. The conclusions drawn from this study significantly enhance our understanding of the enantioselective behaviors of chiral triazole fungicides in reptiles, offering essential guidance for assessing the risks associated with different enantiomers of triazole fungicides.
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Compuestos Epoxi , Fungicidas Industriales , Lagartos , Triazoles , Animales , Triazoles/química , Triazoles/toxicidad , Triazoles/metabolismo , Lagartos/metabolismo , Fungicidas Industriales/química , Fungicidas Industriales/metabolismo , Compuestos Epoxi/metabolismo , Compuestos Epoxi/química , Estereoisomerismo , Hígado/metabolismo , Riñón/metabolismo , Masculino , Distribución TisularRESUMEN
Hepatopulmonary syndrome (HPS) is a serious pulmonary complication in the advanced stage of liver disease. The occurrence of pulmonary edema in HPS patients is life-threatening. Increased pulmonary vascular permeability is an important mechanism leading to pulmonary edema, and endothelial glycocalyx (EG) is a barrier that maintains stable vascular permeability. However, in HPS, whether the pulmonary vascular EG changes and its regulatory mechanism are still unclear. Spleen derived monocytes are involved in the pathogenesis of HPS. However, whether they regulate the pulmonary vascular permeability in HPS patients or rats and what is the mechanism is still unclear. Healthy volunteers and HPS patients with splenectomy or not were enrolled in this study. We found that the respiration of HPS patients was significantly improved in response to splenectomy, while the EG degradation and pulmonary edema were aggravated. In addition, HPS patients expressed higher levels of oncostatin M (OSM) and fibroblast growth factor (FGF). Subsequently, the co-culture system of monocytes and human umbilical vein endothelial cells (HUVECs) was constructed. It was found that monocytes secreted OSM and activated the FGF/FGFR1 signaling pathway in HUVECs. Then, an HPS rat model was constructed by common bile duct ligation (CBDL) for in vivo verification. HPS rats were intravenously injected with OSM recombinant protein and/or TNF-α into the rats via tail vein 30 min before CBDL. The results showed that the respiration of HPS rats was improved after splenectomy, while the degradation of EG in pulmonary vessels and vascular permeability were increased, and pulmonary edema was aggravated. Moreover, the expression of OSM and FGF was upregulated in HPS rats, while both were downregulated after splenectomy. Intravenous injection of exogenous OSM eliminated the effect of splenectomy on FGF and improved EG degradation. It can be seen that during HPS, spleen-derived monocytes secrete OSM to promote pulmonary vascular EG remodeling by activating the FGF/FGFR1 pathway, thereby maintaining stable vascular permeability, and diminishing pulmonary edema. This study provides a promising therapeutic target for the treatment of HPS.
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Permeabilidad Capilar , Síndrome Hepatopulmonar , Monocitos , Oncostatina M , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Transducción de Señal , Bazo , Animales , Humanos , Síndrome Hepatopulmonar/metabolismo , Masculino , Monocitos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Bazo/metabolismo , Oncostatina M/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Ratas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Esplenectomía , Ratas Sprague-Dawley , Pulmón/metabolismo , Pulmón/irrigación sanguínea , Femenino , Persona de Mediana Edad , Adulto , Glicocálix/metabolismoRESUMEN
BACKGROUND: Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma (NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of NPC cells to IR remains poorly understood. OBJECTIVE: This study aimed to explore the association between IR and ferroptosis in NPC, as well as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells. METHODS: CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells. JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined the levels of Fe2+, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione (GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate its impact on the ferroptosis of these cells. RESULTS: IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4, COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione levels, and elevated Fe2+ levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR. CONCLUSION: IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.
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Sistema de Transporte de Aminoácidos y+ , Ferroptosis , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radiación Ionizante , Especies Reactivas de Oxígeno , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Ferroptosis/efectos de la radiación , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Línea Celular Tumoral , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a Radiación , Potencial de la Membrana Mitocondrial/efectos de la radiación , Supervivencia Celular/efectos de la radiaciónRESUMEN
This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.
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Ciego , Ácido Pantoténico , Animales , Ácido Butírico , Diferenciación Celular , Suplementos Dietéticos , PorcinosRESUMEN
BACKGROUND: The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN). METHODS: A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment. RESULTS: (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3-CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3-CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers. CONCLUSIONS: RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production. TRIAL REGISTRATION: The research was registered at the First Affiliated Hospital of Soochow University. REGISTRATION NUMBER: MR-32-23-016211. Registration Date: May 31, 2023.
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Glomerulonefritis Membranosa , Humanos , Rituximab/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Subgrupos de Linfocitos T , Linfocitos T Reguladores , Linfocitos B , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19RESUMEN
In this work, an investigation on the Zn-Cu alloy coated with heparin was conducted in order to explore the potentiality of its application as a feasible alternative for biodegradable implants, with the specific goal of addressing the issue of encrustation in the urinary system. The stability of the nanoparticles were characterized by dynamic light scattering. Typical surface characterization such as X-ray photoelectron spectroscopy, scanning electron microscopy, and atomic force microscopy were used to demonstrate a successful immobilization of the NPs. The in vitro corrosion behavior was studied by potentiodynamic polarization and immersion tests in artificial urine (AU) at 37 °C. The 8 weeks in vivo degradation, encrustation resistance, hemocompatibility, and histocompatibility were investigated by means of implantation into the bladders of rats. Both in vitro and in vivo degradation tests exhibited a higher degradation rate for Zn-Cu and NPs groups when compared to pure Zn. Histological evaluations and hemocompatibility revealed that there was no tissue damage or pathological alterations caused by the degradation process. Furthermore, antiencrustation performance and urinalysis results confirmed that the modified alloy demonstrated significant encrustation inhibitory properties and bactericidal activity compared to the pure Zn control. Our findings highlight the potential of this modified alloy as an antiencrustation biodegradable ureteral stent.
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Heparina , Nanopartículas , Animales , Ratas , Heparina/farmacología , Prótesis e Implantes , Aleaciones , ZincRESUMEN
Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments with 18 replicates per treatment and one pig per replicate. The control group was fed with a basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet had no significant effect on the growth performance of weaned piglets (p > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (p < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (p > 0.05) but increased the content of glutathione in plasma (p < 0.05). Tea residue had no significant effect on the morphology of the jejunum and ileum of piglets (p > 0.05), but it could significantly reduce the content of chloride ions in feces (p < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of TMEM16A and CFTR mRNA in the colon of weaned piglets (p > 0.05). The whole-cell patch clamp recording showed that the TMEM16A and CFTR ion channels could be activated by ionomycin and forskolin, respectively. However, when HT-29 cells transfected with TMEM16A and CFTR channels were treated with tea residue extract, it could significantly inhibit the chloride current of the TMEM16A and CFTR ion channels (p < 0.05).
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Poly-drug therapy is now recognized as a crucial treatment, and the analysis of drug-drug interactions (DDIs) offers substantial theoretical support and guidance for its implementation. Predicting potential DDIs using intelligent algorithms is an emerging approach in pharmacological research. However, the existing supervised models and deep learning-based techniques still have several limitations. This paper proposes a novel DDI analysis and prediction framework called the Multi-View Semi-supervised Graph-based (MVSG) framework, which provides a comprehensive judgment by integrating multiple DDI features and functions without any time-consuming training process. Unlike conventional approaches, MVSG can search for the most suitable similarity (or distance) measurement among DDI data and construct graph structures for each feature. By employing a parameter self-tuning strategy, MVSG fuses multiple graphs according to the contributions of features' information. The actual anticancer drug data are extracted from the authoritative public database for evaluating the effectiveness of our framework, including 904 drugs, 7730 DDI records and 19 types of drug interactions. Validation results indicate that the prediction is more accurate when multiple features are adopted by our framework. In comparison to conventional machine learning techniques, MVSG can achieve higher performance even with less labeled data and without a training process. Finally, MVSG is employed to narrow down the search for potential valuable combinations.
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Algoritmos , Aprendizaje Automático , Interacciones FarmacológicasRESUMEN
To investigate the potential functions and regulatory mechanism of circRSU1 on septic acute lung injury (sepsis-ALI) progression. We used lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) to establish the cell model of sepsis-ALI in vitro. qRT-PCR and Western blotting were used for the detection of genes and proteins. The migration and tubulogenesis of HPMECs were assessed by transwell, wound healing, and tube formation assays. Inflammatory factors were detected by ELISA analysis. Cell permeability (PA) was determined by transendothelial resistance (TEER) and fluorescein isothiocyanate (FITC) with transwell assay. The interaction between miR-1224-5p and circRSU1 or ITGA5 (Integrin Subunit Alpha 5) was studied by dual-luciferase reporter and RNA pull-down assays. CircRSU1 expression was decreased after LPS treatment in HPMECs. Functionally, re-expression of circRSU1 in HPMECs could alleviate LPS-induced inflammatory response, the inhibition of cell migration and tube formation and enhancement of cell permeability. Mechanistically, circRSU1 acted as a sponge for miR-1224-5p. LPS treatment enhanced miR-1224-5p expression, and inhibition of miR-1224-5p reversed LPS-evoked HPMEC dysfunction mentioned above. Moreover, miR-1224-5p could abolish the protective effects of circRSU1 on HPMECs. In addition, miR-1224-5p directly targeted ITGA5, and circRSU1 was able to regulate ITGA5 expression via interacting with miR-1224-5p. CircRSU1 could alleviate LPS-induced HPMEC injury by miR-1224-5p/ITGA5 axis, indicating the potential molecular contribution of circRSU1 in sepsis-ALI.
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Lesión Pulmonar Aguda , MicroARNs , ARN Circular , Sepsis , Humanos , Lesión Pulmonar Aguda/inducido químicamente , Apoptosis , Células Endoteliales , Lipopolisacáridos , MicroARNs/genética , ARN Circular/genéticaRESUMEN
Objectives: Inadequate cytotrophoblast migration and invasion are speculated to result in preeclampsia, which is a pro-inflammatory condition. Sodium dichloroacetate (DCA) exerts anti-inflammatory actions. Thus,we sought to investigate the effect of DCA on the migration function of the lipopolysaccharide (LPS)-stimulated human-trophoblast-derived cell line (HTR-8/SVneo). Materials and Methods: HTR-8/SVneo cells were treated with LPS to suppress cell migration. Cell migration was examined by both scratch wound healing assay and transwell migration assay. Western blotting was used to analyze the expression levels of toll-like receptor-4 (TLR4), nuclear factor-κB (NF-κB), TNF-α, IL-1ß, and IL-6 in the cells. Results: DCA reversed LPS-induced inhibition of migration in HTR-8/SVneo cells. Furthermore, DCA significantly suppressed LPS-induced activation of TLR4, phosphorylation of NF-κB (p65), translocation of p65 into the nucleus, and the production of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). Treatment with inhibitors of TLR4 signal transduction (CLI095 or MD2-TLR-4-IN-1) reduced LPS-induced overexpression of pro-inflammatory cytokines, and a synergistic effect was found between TLR4 inhibitors and DCA in HTR-8/SVneo cells. Conclusion: DCA improved trophoblast cell migration function by suppressing LPS-induced inflammation, at least in part, via the TLR4/NF-κB signaling pathway. This result indicates that DCA might be a potential therapeutic candidate for human pregnancy-related complications associated with trophoblast disorder.
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Within human-influenced landscapes, pesticides cooccur with a variety of antibiotic stressors. However, the relationship between pesticides removal process and antibiotic resistance gene variation are not well understood. This study explored pesticide (topramezone, TPZ) and antibiotic (polymyxin E, PME) co-contamination using liquid chromatography-tandem mass spectrometry (LC-MS/MS), bacterial-16 S rRNA sequencing and high-throughput quantitative polymerase chain reaction (HT-qPCR) in a soil-earthworm-maize system. After incubating soil for 28 days with TPZ and PME (10 mg kg-1 dry weight), earthworm weight-gain, mortality rates, and maize plant weight-gain only differed slightly, but height-gain significantly decreased. PME significantly increased TPZ-removal in the soil. Accumulation of TPZ in earthworm's tissues may pose potential risks in the food chain. Combined pollution altered the microbial community structure and increased the abundance of functional microorganisms involved in aromatic compound degradation. Furthermore, maize rhizosphere can raise resistance genes, however earthworms can reduce resistance genes. Co-contamination increased absolute abundance of mobile genetic elements (MGEs) in bulk-soil samples, antibiotic resistance genes (ARGs) in skin samples and number of ARGs in bulk-soil samples, while decreased absolute abundance of transposase gene in bulk-soil samples and number of ARGs in rhizosphere-soil samples. Potential hosts harbouring ARGs may be associated with the antagonistic effect during resistance and detoxification of TPZ and PMB co-occurrence. These findings provide insights into the mechanism underlining pesticide removal regarding occurrence of ARGs in maize agroecosystem.
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Oligoquetos , Plaguicidas , Animales , Humanos , Suelo/química , Genes Bacterianos , Oligoquetos/genética , Zea mays , Plaguicidas/análisis , Cromatografía Liquida , Microbiología del Suelo , Espectrometría de Masas en Tándem , Antibacterianos/análisis , Farmacorresistencia Microbiana/genética , Aumento de PesoRESUMEN
Under the influence of intensive human activities and global climate change, the sources and compositions of dissolved organic matter (DOM) in the eastern plain lake (EPL) region in China have fluctuated sharply. It has been successfully proven that the humification index (HIX), which can be derived from three-dimensional excitation-emission matrix fluorescence spectroscopy, can be an effective proxy for the sources and compositions of DOM. Therefore, combined with remote sensing technology, the sources and compositions of DOM can be tracked on a large scale by associating the HIX with optically active components. Here, we proposed a novel HIX remote sensing retrieval (IRHIX) model suitable for Landsat series sensors based on the comprehensive analysis of the covariation mechanism between HIX and optically active components in different water types. The validation results showed that the model runs well on the independent validation dataset and the satellite-ground synchronous sampling dataset, with an uncertainty ranging from 30.85 % to 36.92 % (average ± standard deviation = 33.6 % ± 3.07 %). The image-derived HIX revealed substantial spatiotemporal variations in the sources and compositions of DOM in 474 lakes in the EPL during 1986-2021. Subsequently, we obtained three long-term change modes of the HIX trend, namely, significant decline, gentle change, and significant rise, accounting for 74.68 %, 17.09 %, and 8.23 % of the lake number, respectively. The driving factor analysis showed that human activities had the most extensive influence on the DOM humification level. In addition, we also found that the HIX increased slightly with increasing lake area (R2 = 0.07, P < 0.05) or significantly with decreasing trophic state (R2 = 0.83, P < 0.05). Our results provide a new exploration for the effective acquisition of long-term dynamic information about the sources and compositions of DOM in inland lakes and provide important support for lake water quality management and restoration.
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Materia Orgánica Disuelta , Calidad del Agua , Humanos , Lagos/química , China , Espectrometría de Fluorescencia/métodosRESUMEN
The accurate measurement of an object's motion requires knowledge of both its position and its velocity. The commonly used photonic Doppler velocimetry and broadband laser ranging techniques are ideal for conducting simultaneous dynamic experiments. Instead of employing two distinct measurement systems, we developed a hybrid system that can simultaneously measure velocity and distance in dynamic experiments. This reduces cost and complexity, particularly for multi-channel tests, by using only one probe, photodetector, and oscilloscope channel. By precisely synchronizing the velocity and distance data in time, the system can assist with interpreting the target's position and orientation.
RESUMEN
Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI), remains a daunting task. Cell transplantation is a promising strategy to facilitate nerve restoration in SCI. In this research, a pro-regeneration system is developed, namely miR-26a@SPIONs-OECs, for olfactory ensheathing cells (OECs), a preferred choice for promoting nerve regeneration in SCI patients. These entities show high responsiveness to external magnetic fields (MF), leading to synergistic multimodal cues to enhance nerve regeneration. First, an MF stimulates miR-26a@SPIONs-OECs to release extracellular vesicles (EVs) rich in miR-26a. This encourages axon growth by inhibiting PTEN and GSK-3ß signaling pathways in neurons. Second, miR-26a@SPIONs-OECs exhibit a tendency to migrate and orientate along the direction of the MF, thereby potentially facilitating neuronal reconnection through directional neurite elongation. Third, miR-26a-enriched EVs from miR-26a@SPIONs-OECs can interact with host astrocytes, thereby diminishing inhibitory cues for neurite growth. In a rat model of SCI, the miR-26a@SPIONs-OECs system led to significantly improved morphological and motor function recovery. In summary, the miR-26a@SPIONS-OECs pro-regeneration system offers innovative insights into engineering exogenous cells with multiple additional cues, augmenting their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar in SCI.