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The teleost kidneys are anatomically divided into head kidney and trunk kidney, each performing distinct physiological functions. Although previous research has elucidated the role of the head kidney in immune responses, there is a paucity of literature on the comparative studies of the head and trunk kidney response to bacterial infection. Therefore, an Edwardsiella ictaluri infection model of yellow catfish was constructed to investigate and compare the immune responses between the two kidney types. The findings indicated that E. ictaluri infection induced significant pathological changes in both the head and trunk kidney. Despite variances in structure, both the head and trunk kidney of yellow catfish exhibit robust immune responses following E. ictaluri infection. Unexpectedly, the up-regulation level of IgM was found to be higher in the trunk kidney compared to the head kidney. Additionally, both the IgM+ and IgD+ B cells were increased after bacterial infection. This research elucidates the parallels and distinctions in immune functions between both the head and trunk kidney in fish, enriching the immune theory of the fish kidney, and also providing a theoretical basis for the immune response of teleost kidney against bacterial infections.
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LSD1 (histone lysine-specific demethylase 1) has been gradually disclosed to act as an immunomodulator to enhance antitumor immune response. Despite the identification of numerous potent LSD1 inhibitors, there remains a lack of LSD1 inhibitors approved for marketing. Novel LSD1 inhibitors with different mechanisms are therefore needed. Herein, we reported a series of novel quinazoline-based LSD1 inhibitors. Among them, compound Z-1 exhibited the best LSD1 inhibitory activity (IC50 = 0.108 µM). Z-1 also acted as a selective and cellular active as an LSD1 inhibitor. Furthermore, Z-1 promoted response of gastric cancer cells to T-cell killing effect by decreasing PD-L1 expression and further attenuated the PD-1/PD-L1 interaction. In vivo, Z-1 exhibited significant suppression effect on the growth of gastric cancer cells without obvious toxicity. Therefore, Z-1 represents a potential novel immunomodulator that targets LSD1, providing a lead compound with new function mechanism for gastric cancer treatment.
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As a complex three-phase heterogeneous catalyst, the oxygen reduction reaction (ORR) catalyst activity is determined by the interfacial and surface structures and chemical state of the catalyst support. As a typical biomass carbon-based support, rice husk-based porous carbon (RHPC) has natural unique hierarchical porous structures, which easily regulate the microstructure and surface properties. This study explored the correlative effects of RHPC structure and surface properties on ORR catalytic activity through the typical modification methods, namely, alkali etching, high temperature, oxidation, and ball milling. The various factors for the joint effects are defined as the specific surface area, oxygen-containing functional groups, graphite edge defects, resistivity, and contact angle. The analysis of such joint influences is difficult to quantitatively evaluate due to the large number of experimental factors and small sample sizes. Partial least-squares (PLS) can better deal with such problems. Therefore, a PLS regression model was established to evaluate the relative weight of each factor on the catalytic activity for the RHPC-based support catalysts. The results reveal that the regression coefficients of four factors yield similar magnitude for the effect of the half-wave potential (E1/2). However, graphite edge defects had a more significant impact on the limiting diffusion current density (J) and electron transfer number (n). Furthermore, an optimal support named BM-RHPC-3 was prepared with more defects and oxygen-containing functional groups, which prepared Fe-NS/BM-RHPC-3 presenting the best ORR catalytic activity (E1/2 = 0.880 V, J of 5.15 mA cm-2), superior to Pt/C (E1/2 = 0.844 V, J of 4.99 mA cm-2). The statistical regression model is validated with a relative error of less than 5% between predicted and true values for analyzing RHPC-based ORR catalysts' catalytic performance. It shows the feasibility of experiment-informed learning for data-driven material discovery and design.
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BACKGROUND: Cluster of differentiation 24 (CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a "don't eat me" signaling molecule in tumor immune. This study aimed to investigate the potential features of CD24 in pan-cancer. METHODS: The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package "ESTIMATE" was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman's correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of CD24 in LIHC. RESULTS: CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally, CD24 was overexpressed in most tumors, with high CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally, CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC. CONCLUSION: CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker.
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BACKGROUND: Optical flow ratio (OFR) is a novel computational fractional flow reserve derived from optical coherence tomography (OCT). However, the impact of combining post-stenting morphology (OCT) and physiology (OFR) remains largely unknown. METHOD: OCT and OFR were analyzed at the independent core laboratory. Target lesion failure (TLF) was defined as the composite of cardiac death, target lesion myocardial infarction and target lesion revascularization. Suboptimal stent deployment was identified with at least one TLF-related OCT or OFR characteristics. RESULTS: A total of 448 ACS patients (459 vessels) were assessed. Stent expansion<80%, MSA<4.5 mm2 and stent edge lipid-rich plaque and OFR<0.90 were independent predictors of TLR (all p value<0.001). Patients with OCT-suboptimal [adjusted hazard ratio (HR): 7.88, 95% CI: 2.73-22.72, p<0.001] or OFR-suboptimal (adjusted HR: 5.78, 95% CI: 2.54-13.14, p<0.001) stent deployment showed significantly higher risk of TLF compared to those with optimal stent deployment with a significant interaction (pinteraction<0.001). OCT and OFR both-suboptimal stent deployment was confirmed as an independent predictor of TLF (adjusted HR: 9.39, 95% CI: 4.25-20.76, p<0.001). CONCLUSION: Combined OCT and OFR conferred an optimal reclassification of stent deployment, which may aid in decision-making regarding a tailored PCI strategy for optimal stent deployment.
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Polymeric immunoglobulin receptor (pIgR) is an important immune factor in the mucosal immune system of fish, which plays a key role in mediating the secretion and transport of immunoglobulin into mucus. In this study, the full-length cDNA sequence of Megalobrama amblycephala pIgR gene was firstly cloned and the immune response to Aeromonas hydrophila was detected. After being challenged by Aeromonas hydrophila at 3 d, significantly pathological features were observed in intestine, head kidney, spleen, liver and gill of Megalobrama amblycephala. The content of lysozyme (Lys) and the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) increased significantly at 1 d and reached the peak at 3 d, and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in serum reached the peak at 5 d and 7 d after infection, respectively. The expression level of IL-1ß gene reached the peak at 3 d in intestine, 5 d in gill and spleen, 7 d in head kidney and liver of Megalobrama amblycephala after infected by Aeromonas hydrophila, respectively. The TNF-α gene expression reached the peak at 3 d in intestine and gill, 5 d in head kidney and spleen, 7 d in liver after infection, respectively. The experimental results showed that the infection of Aeromonas hydrophila caused the pathological changes of immune-related tissues and triggered the inflammation responses. The full-length cDNA sequence of Megalobrama amblycephala pIgR was 1828 bp, and its open reading frame (ORF) was 1023 bp, encoding 340 amino acids. The pIgR of Megalobrama amblycephala has a signal peptide sequence, followed by extracellular region, transmembrane region and intracellular region. The extracellular region includes two Ig-like domains (ILDs), and its tertiary structure is twisted "L". The phylogenetic tree was constructed using the adjacency method, and the pIgR genes of Megalobrama amblycephala and cyprinidae fish were clustered into a single branch. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pIgR gene in different tissues of Megalobrama amblycephala. The expression level of pIgR gene was the highest in liver, followed by intestine, head kidney, skin, middle kidney and spleen, lower in heart, gill and brain, and the lowest in muscle. After being infected by Aeromonas hydrophila, the expression level of Megalobrama amblycephala pIgR gene in intestine, head kidney, spleen, liver and gill showed a trend of increasing first and then decreasing within 28 d. The pIgR gene expression reached the peak in mucosal immune-related tissues (gill and intestine) was earlier than that in systemic immune-related tissues (head kidney and spleen), and the relative expression level of pIgR gene at peak in intestine (12.3 fold) was higher than that in head kidney (3.73 fold) and spleen (7.84 fold). These results suggested that Megalobrama amblycephala pIgR might play an important role in the mucosal immune system to against Aeromonas hydrophila infection.
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Aeromonas hydrophila , Sequência de Aminoácidos , Cyprinidae , Doenças dos Peixes , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas , Imunidade Inata , Filogenia , Receptores de Imunoglobulina Polimérica , Animais , Aeromonas hydrophila/fisiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Cyprinidae/imunologia , Cyprinidae/genética , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Receptores de Imunoglobulina Polimérica/genética , Receptores de Imunoglobulina Polimérica/imunologia , Receptores de Imunoglobulina Polimérica/química , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Alinhamento de Sequência/veterinária , Perfilação da Expressão Gênica/veterinária , Sequência de BasesRESUMO
SLAMF9, a member of the conserved lymphocyte activation molecules family (SLAMF), has been less investigated compared to other SLAMs, especially concerning its implications across various cancer types. In our systematic pan-cancer investigation, we observed elevated SLAMF9 expression in various tumor tissues, which was correlated with reduced patient survival across most malignancies. Correlation analyses further revealed significant associations between SLAMF9 expression and immune cell infiltrates, immune checkpoint inhibitors, tumor mutation load, microsatellite instability, and epithelial-mesenchymal transition (EMT) scores. Cell-based assays demonstrated that SLAMF9 knockdown attenuated the proliferative, motile, and invasive capacities of colorectal cancer (CRC) cells. In a nude mouse xenograft model, suppression of SLAMF9 expression substantially inhibited tumor growth. These findings highlight the potential of SLAMF9 as a prognostic and therapeutic biomarker across tumors, with notable implications for CRC cell proliferation and migration.
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Proliferação de Células , Neoplasias Colorretais , Família de Moléculas de Sinalização da Ativação Linfocitária , Animais , Feminino , Humanos , Camundongos , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Instabilidade de Microssatélites , Prognóstico , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/genéticaRESUMO
How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The resistance mechanism of platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis and develop resistance to chemotherapy drugs through metabolic variability. In addition, due to the lack of histone protection and a relatively weak damage repair ability, mitochondrial DNA (mtDNA) is more susceptible to damage, which in turn affects mitochondrial OXPHOS and can become a potential target for platinum-based drugs. Therefore, mitochondria, as targets of anticancer drugs, have become a hot topic in tumor resistance research. This study constructed a self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. ß-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles can target CD44 on the tumor surface and further deliver the prodrug to intracellular mitochondria through a triphenylphosphine group (TPP+). Disulfide bonds can be selectively degraded by glutathione (GSH) in mitochondria, releasing lonidamine (LND) and the cisplatin prodrug (Pt(IV)). Under the action of GSH and ascorbic acid, Pt(IV) is further reduced to cisplatin (Pt(II)). Cisplatin can cause mtDNA damage, induce mitochondrial dysfunction and mitophagy, and then affect mitochondrial OXPHOS. Meanwhile, LND can reduce the hexokinase II (HK II) level, induce destruction of mitochondria, and block energy supply by glycolysis inhibition. Ultimately, this self-assembled nano targeted delivery system can synergistically kill cisplatin-resistant lung cancer cells, which supplies an overcome cisplatin resistance choice via the disrupt mitochondria therapy.
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Antineoplásicos , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Mitocôndrias , Pró-Fármacos , Cisplatino/farmacologia , Cisplatino/química , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Nanopartículas/química , Animais , Camundongos , Sistemas de Liberação de Medicamentos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Reprogramação MetabólicaRESUMO
Background: Otopetrin 2 (OTOP2) is a conserved ion channel protein that regulates cell signaling, growth, and development. Although the role of OTOP2 in tumor suppression has been reported in several studies of colon adenocarcinoma (COAD), characterized its immunomodulatory effects on tumors. Methods: We conducted a thorough analysis of OTOP2 expression and its association with clinicopathological characteristics, immune-related pathways, and immune-related molecules in individuals with COAD using data from The Cancer Genome Atlas (TCGA) and confirmed the findings with tissue microarrays (TMAs). We conducted in vitro assays to demonstrate the tumor suppressive effect of OTOP2 in COAD cells. Results: OTOP2 expression was abnormal in multiple types of tumors and was significantly downregulated in patients with COAD (P<0.001). Moreover, the presence of OTOP2 was linked to enhanced survival in individuals diagnosed with COAD. In vitro experiments showed that OTOP2 suppressed cell proliferation, migration, invasion, and adhesion. Gene set enrichment analysis of the TCGA database indicated that OTOP2 was positively correlated with antigen presentation pathways and T cell responses. The immunophenoscore (IPS) indicated a positive correlation between OTOP2 expression and MHC molecule expression (P<0.001) as well as between OTOP2 expression and the number of effector cells (P<0.01). Immunohistochemical analysis of the TMAs revealed strong associations between OTOP2 expression and MHC-I, TAP1, and TAP2 expression, and between OTOP2 expression and CD8+ T cell infiltration in COAD patients. Conclusion: In summary, our research emphasizes the role of OTOP2 as a tumor suppressor, suggesting its use as a prognostic indicator and predictor of response to immunotherapy in COAD patients.
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BACKGROUND: Postpartum depression (PPD) has received widespread attention. Shenzhen has been running a large-scale program for PPD since 2013. The program requires mothers to self-assess when applying information technology to PPD screening beginning in 2021. The purpose of this study was to conduct a longitudinal analysis of the impact of mHealth apps on the health-seeking behaviors of PPD patients. METHODS: Longitudinal data from districts in the Shenzhen Maternal and Child Health Management Information System (MCHMIS) for ten years was used in this study. Referral success rate (RSR, successful referrals to designated hospitals as a percentage of needed referrals) was used to assess health-seeking behavior. Trend χ2 tests were used to assess the overall trend of change after the implementation of mHealth in ten districts in Shenzhen. Interrupted Time Series Analysis (ITSA) was employed to assess the role of the mHealth app in changing patient health-seeking behaviors. RESULTS: For the results of the trend χ2 tests, the ten districts of Shenzhen showed an upward trend. For the ITSA results, different results were shown between districts. Nanshan district, Longhua district, and Longgang district all demonstrated an upward trend in the first-year application of the mHealth app. Nanshan district and Longgang district both exhibited an upward trend in terms of sustained effects. CONCLUSIONS: There is a difference in the performance of the mHealth app across the ten districts. The results show that the three districts with better health resource allocation, Nanshan, Longgang, and Longhua districts, demonstrated more significant mHealth app improvements. The mHealth app's functions, management systems, and health resource allocation may be potential factors in the results. This suggests that when leveraging mHealth applications, the first step is to focus on macro-level area resource allocation measures. Secondly, there should be effective process design and strict regulatory measures. Finally, there should also be appropriate means of publicity.
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Depressão Pós-Parto , Aplicativos Móveis , Encaminhamento e Consulta , Telemedicina , Humanos , Feminino , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/terapia , Estudos Longitudinais , China , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Análise de Séries Temporais Interrompida , Programas de Rastreamento/métodos , Gravidez , Política de SaúdeRESUMO
Oxidative dehydrogenation of propane (ODHP) is a reaction with significant practical significance. As for the industrial application of ODHP, it is challenging to achieve high activity and high propylene selectivity simultaneously. In this study, to overcome this obstacle, we designed a series of Cu/BN catalysts with unique morphologies for establishing a photothermal ODHP system with high efficiency and selectivity. Characterization and evaluation results revealed that Cu/BN-NS and Cu/BN-NF with enlarged specific surface areas exhibited higher catalytic activities. The localized surface plasmon resonance (LSPR) effect of Cu nanoparticles further enhanced the photothermal catalytic performances of Cu/BN catalysts under visible light irradiation. To the best of our knowledge, it is the first time to establish a BN-based photothermal ODHP catalytic system. This study is expected to pave pathways to realize high activity and propylene selectivity for the practical application of ODHP.
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BACKGROUND: The dimerizable Cre recombinase system (DiCre) exhibits increased leaky activity in Cryptosporidium, leading to unintended gene editing in the absence of induction. Therefore, optimization of the current DiCre technique is necessary for functional studies of essential Cryptosporidium genes. METHODS: Based on the results of transcriptomic analysis of Cryptosporidium parvum stages, seven promoters with different transcriptional capabilities were screened to drive the expression of Cre fragments (FKBP-Cre59 and FRB-Cre60). Transient transfection was performed to assess the effect of promoter strength on leakage activity. In vitro and in vivo experiments were performed to evaluate the leaky activity and cleavage efficiency of the optimized DiCre system by polymerase chain reaction (PCR), nanoluciferase, and fluorescence analyses. RESULTS: The use of promoters with lower transcriptional activity, such as pcgd6_4110 and pcgd3_260, as opposed to strong promoters such as pActin, pα-Tubulin, and pEnolase, reduced the leakage rate of the system from 35-75% to nearly undetectable levels, as verified by transient transfection. Subsequent in vitro and in vivo experiments using stable lines further demonstrated that the optimized DiCre system had no detectable leaky activity. The system achieved 71% cleavage efficiency in vitro. In mice, a single dose of the inducer resulted in a 10% conditional gene knockout and fluorescent protein expression in oocysts. These fluorescently tagged transgenic oocysts could be enriched by flow sorting for further infection studies. CONCLUSIONS: A DiCre conditional gene knockout system for Cryptosporidium with good cleavage efficiency and reduced leaky activity has been successfully established.
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Cryptosporidium parvum , Edição de Genes , Integrases , Regiões Promotoras Genéticas , Edição de Genes/métodos , Animais , Camundongos , Integrases/genética , Integrases/metabolismo , Cryptosporidium parvum/genética , Cryptosporidium parvum/enzimologia , Criptosporidiose/parasitologia , Cryptosporidium/genéticaRESUMO
OBJECTIVE: To investigate the anti- chronic myelogenous leukemia (CML) activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression, and explore the potential role of its signaling pathway. METHODS: Firstly, CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B, imatinib, and their combination on the proliferation and migration of K562 cells. Furthermore, the apoptosis rate of K562 cells treated with Csn-B, imatinib, and their combination was detected by flow cytometry. The expression levels of Nur77, Pim-1, Drp1, p-Drp1 S616, Bcl-2 and Bax in K562 cells were detected by Western blot. Finally, the expression levels of reactive oxygen species (ROS) in K562 cells treated with Csn-B, imatinib and their combination were detected by immunofluorescence assay. RESULTS: The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754 (P < 0.001). Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells (both P < 0.001), and induce apoptosis (P < 0.001). Csn-B promoted Nur77 expression in K562 cells, and synergistically enhanced imatinib sensitivity when combined with imatinib. Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment (both P < 0.001). CONCLUSION: Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.
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Apoptose , Proliferação de Células , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Proteínas Proto-Oncogênicas c-pim-1 , Humanos , Mesilato de Imatinib/farmacologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Apoptose/efeitos dos fármacos , Células K562 , Proliferação de Células/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Dinaminas , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Movimento CelularRESUMO
Mounting evidence suggests that intraplaque angiogenesis is associated with the progression of atherosclerotic plaques and the development of intraplaque hemorrhage. The specificity of intraplaque immune cell infiltration may be associated with abnormalities in the structure and function of the nascent capillaries. Here, we analyzed expression levels of angiogenesis-associated genes in early and advanced carotid atheromatous plaque tissues as well as in stable and intraplaque hemorrhage plaques. Expression profiles of advanced arterial plaques based on angiogenesis-associated genes were classified into subtypes by performing a consensus clustering analysis. The correlation between the immune microenvironment of plaques and expression of angiogenesis-associated genes was also explored using the single sample gene set enrichment analysis method and the CIBERSORT algorithm. We identified hub angiogenesis-associated genes showing similar expression patterns throughout plaque adverse progression, and constructed a prediction model using the random forest algorithm. Receiver operating curves were constructed to evaluate efficacy in identification of intraplaque hemorrhage in a plaque. Our results suggest that heterogeneity of angiogenesis-related genes may promote the malignant development of plaques and cause plaque rupture. In conclusion, we propose a model based on expression of angiogenesis-related genes to predict the risk of plaque rupture.
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Serine/threonine kinase receptor-associated protein (STRAP) serves as a scaffold protein and is engaged in a variety of cellular activities, although its importance in antiviral innate immunity is unknown. We discovered that STRAP works as an interferon (IFN)-inducible positive regulator, facilitating type I IFN signaling during pseudorabies virus infection. Mechanistically, STRAP interacts with TBK1 to activate type I IFN signaling. Both the CT and WD40 7 - 6 domains contribute to the function of STRAP. Furthermore, TBK1 competes with PRV-UL50 for binding to STRAP, and STRAP impedes the degradation of TBK1 mediated by PRV-UL50, thereby increasing the interaction between STRAP and TBK1. Overall, these findings reveal a previously unrecognized role for STRAP in innate antiviral immune responses during PRV infection. STRAP could be a potential therapeutic target for viral infectious diseases.
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Herpesvirus Suídeo 1 , Imunidade Inata , Interferon Tipo I , Proteínas Serina-Treonina Quinases , Animais , Linhagem Celular , Herpesvirus Suídeo 1/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Pseudorraiva/imunologia , Pseudorraiva/virologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
Psychrophilic bacteria, the dominant spoilage organisms in raw milk, secrete heat-stable extracellular proteases and lipases that lead to the decomposition of milk and dairy products. In this study, we investigated psychrophilic bacteria in 165 raw milk samples collected across four seasons and six regions in China using shotgun metagenomic sequencing and traditional culture methods. The isolated psychrophilic bacteria were classified into 40 genera and 185 species. Pseudomonas was the most prevalent, accounting for 51.13 % of the genera, while Lactococcus and Chryseobacterium were also notably abundant (> 6.0 %). Metagenomic sequencing revealed that Pseudomonas (47.9 %), Stenotrophomonas (9.75 %), Sphingomonas (6.73 %), Latilactobacillus (6.38 %) and Lactococcus (5.16 %) were the dominant genera in the raw milk samples. The diversity of psychrophilic bacteria in raw milk was strongly influenced by seasonal variations, with the sampling region being a less significant factor. KEGG annotation indicated that carbohydrate and amino acid metabolism were the primary metabolic pathways in these bacteria. Metagenomic sequencing not only accurately identifies species but also provides functional insights into psychrophilic bacteria in raw milk, aiding in understanding their activities, promoting their control on farms, and ultimately improving raw milk quality.
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ETHNOPHARMACOLOGICAL RELEVANCE: Depression impairs not only central nervous system, but also peripheral systems of the host. Gut microbiota have been proved to be involved in the pathogenesis of depression. Xiaoyaosan (XYS) has a history of over a thousand years in China for treating depression, dramatically alleviating anxiety, cognitive disorders, and especially gastrointestinal dysfunctions. Yet, it still just scratches the surface of the anti-depression mechanisms of XYS. AIM OF THE STUDY: This study aims to elucidate the mechanism of actions of XYS from the perspective of "microbiota-gut-brain" axis. MATERIALS AND METHODS: We firstly evaluated the effects of XYS on the macroscopic behaviors of depressed rats that induced by chronic unpredictable mild stress (CUMS). Secondly, the effects of XYS on intestinal homeostasis of depressed rats were revealed by using dysbacteriosis model. Subsequently, the underlying mechanisms were demonstrated by 16S rRNA gene sequencing technology and molecular biology methods. Finally, correlation analysis and visualization of the anti-depression effects of XYS were performed from the "microbiota - gut - brain" perspective. RESULTS: Our data indicated that XYS ameliorated the depression-like symptoms of CUMS rats, partly depending on the presence of gut microbiota. Furthermore, we illustrated that XYS reversed CUMS-induced gut dysbiosis of depressed rats in terms of decreasing the Bacteroidetes/Firmicutes ratio and the abundances of Bacteroides, and Corynebacterium, while increasing the abundances of Lactobacillus and Adlercreutzia. The significant enrichment of Bacteroides and the level of lipopolysaccharides (LPS) suggested that depression damaged the immune responses and gut barrier. Mechanistically, XYS significantly down-regulated the expression levels of factors that involved in TLR4/NLRP3 signaling pathway in the colon and brain tissues of depressed rats. In addition, XYS significantly increased the levels of claudin 1 and ZO-1, showing that XYS positively maintained the integrity of gut and blood-brain barriers (BBB). CONCLUSION: Our study offers insights into the anti-depression effects of XYS through a lens of "microbiota-TLR4/NLRP3 signaling pathway-barriers", providing a foundation for enhancing clinical efficiency and enriching drug selection, and contributing to our understanding of the mechanisms of traditional Chinese medicines (TCMs) in treating depression.
Assuntos
Antidepressivos , Eixo Encéfalo-Intestino , Depressão , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/psicologia , Estresse Psicológico/metabolismo , Disbiose/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de DoençasRESUMO
Herein, a new dual-model photoelectrochemical (PEC)/electrochemical (EC) sensor based on Z-scheme titanium dioxide (TiO2) disk/methylene blue (MB) sensibilization for the detection of kanamycin (Kana) was developed. Metal-organic framework-derived porous TiO2 disks were synthesized and exhibited excellent anodic photocurrent under visible light excitation. Subsequently, amino-labeled double-stranded DNA (dsDNA) was introduced into the modified electrode. Photocurrent was enhanced with MB embedded in dsDNA to form Z-scheme TiO2/MB sensibilization. When the target, Kana, was present, it specifically bound to the aptamer in the dsDNA, leading to the disruption of the dsDNA structure and the release of MB. This release of MB and the increase in target spatial resistance resulted in a significant weakening of PEC signal and a decreased oxidation peak current of MB. The PEC sensor successfully detected Kana in the range of 2-1000 pM with an LOD of 0.17 pM. Meanwhile, the EC sensor for Kana detection showed a linear range of 5-500 pM with an LOD of 1.8 pM. Additionally, the sensor exhibited excellent selectivity, reproducibility, stability, and good recoveries when applied to milk and honey samples. As a result, this method has the potential for application in ensuring food safety through the rapid determination of antibiotics in food.
Assuntos
Técnicas Eletroquímicas , Canamicina , Azul de Metileno , Leite , Titânio , Titânio/química , Canamicina/análise , Canamicina/química , Azul de Metileno/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Leite/química , Animais , Limite de Detecção , Técnicas Biossensoriais/métodos , Mel/análise , Antibacterianos/análise , Antibacterianos/química , Processos Fotoquímicos , Reprodutibilidade dos Testes , EletrodosRESUMO
O2-Assisted oxidative dehydrogenation of propane (O2-ODHP) could convert abundant shale gas into propylene as an important chemical raw material, meaning O2-ODHP has practical significance. Thermodynamically, high temperature is beneficial for O2-ODHP; however, high reaction temperature always causes the overoxidation of propylene, leading to a decline in its selectivity. In this regard, it is crucial to achieve low temperatures while maintaining high efficiency and selectivity during O2-ODHP. The use of catalytic technology provides more opportunities for achieving high-efficiency O2-ODHP under mild conditions. Up to now, many kinds of catalytic systems have been elaborately designed, including transition metal oxide catalysts (such as vanadium-based catalysts, molybdenum-based catalysts, etc.), transition metal-based catalysts (such as Pt nanoclusters), rare earth metal oxide catalysts (especially CeO2 related catalysts), and non-metallic catalysts (BN, other B-containing catalysts, and C-based catalysts). In this review, we have summarized the development progress of mainstream catalysts in O2-ODHP, aiming at providing a clear picture to the catalysis community and advancing this research field further.