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The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.
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Enfermedades de los Peces , FN-kappa B , Ranavirus , Transducción de Señal , Replicación Viral , Animales , FN-kappa B/metabolismo , FN-kappa B/genética , Replicación Viral/fisiología , Enfermedades de los Peces/virología , Ranavirus/fisiología , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Infecciones por Virus ADN/veterinaria , Infecciones por Virus ADN/virología , Proteínas de Peces/metabolismo , Proteínas de Peces/genética , Proteínas I-kappa B/metabolismo , Proteínas I-kappa B/genética , Regulación de la Expresión GénicaRESUMEN
Aesthetic education, conveyed through public art courses, serves as a vital form of humanistic literacy education. It represents an effective approach to fostering innovative and creative thinking among college students. In order to effectively analyze the aesthetic education work of 46 universities, an aesthetic education index evaluation system is constructed, involving indicators including faculty strength, curriculum setting, teaching management, artistic practice, and teaching support. The secondary indicators corresponding to the five indicators are statistically analyzed, and a comprehensive evaluation analysis of the current development status of aesthetic education in 46 universities in Anhui Province is conducted by combining theoretical analysis with empirical analysis. Based on principal component analysis, an integrated evaluation model for the development of aesthetic education in universities in Anhui Province is further constructed. The model designed quantifies the influence weight of each aesthetic education index on the development of aesthetic education in Anhui Province, and forges a theoretical basis for determining the precursors of rapid development of aesthetic education in Anhui Province. Additionally, a novel approach is introduced to gauge the progression of aesthetic education within universities in Anhui Province, considering the dispersion of aesthetic education index data across the province. The comprehensive evaluation model for the development of aesthetic education in Anhui Province exhibits an overall declining trend. Hence, it is suggested to utilize the maximum value of the first derivative of the comprehensive evaluation model as an indicator of the imminent rapid development of aesthetic education in Anhui Province. On this basis, the probability equation of sustainable development of aesthetic education in Anhui Province is defined. Overall, the research results lay a theoretical foundation for the development of aesthetic education in Anhui Province.
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Estética , Análisis de Componente Principal , Humanos , Universidades , Curriculum , China , Estudiantes/psicología , Modelos EducacionalesRESUMEN
INTRODUCTION: Rhizoctonia solani Kühn is a pathogen causing rice sheath blight (ShB). Ammonium transporter 1 (AMT1) promotes resistance of rice to ShB by activating ethylene signaling. However, how AMT1 activates ethylene signaling remains unclear. OBJECTIVE: In this study, the indeterminate domain 10 (IDD10)-NAC079 interaction model was used to investigate whether ethylene signaling is modulated downstream of ammonium signaling and modulates ammonium-mediated ShB resistance. METHODS: RT-qPCR assay was used to identify the relative expression levels of nitrogen and ethylene related genes. Yeast two-hybrid assays, Bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) assay were conducted to verify the IDD10-NAC079-calcineurin B-like interacting protein kinase 31 (CIPK31) transcriptional complex. Yeast one-hybrid assay, Chromatin immunoprecipitation (ChIP) assay, and Electrophoretic mobility shift assay (EMSA) were used to verify whether ETR2 was activated by IDD10 and NAC079. Ethylene quantification assay was used to verify ethylene content in IDD10 transgenic plants. Genetic analysis is used to detect the response of IDD10, NAC079 and CIPK31 to ShB infestation. RESULTS: IDD10-NAC079 forms a transcription complex that activates ETR2 to inhibit the ethylene signaling pathway to negatively regulating ShB resistance. CIPK31 interacts and phosphorylates NAC079 to enhance its transcriptional activation activity. In addition, AMT1-mediated ammonium absorption and subsequent N assimilation inhibit the expression of IDD10 and CIPK31 to activate the ethylene signaling pathway, which positively regulates ShB resistance. CONCLUSION: The study identified the link between ammonium and ethylene signaling and improved the understanding of the rice resistance mechanism.
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Background: Radiotherapy or concurrent chemoradiotherapy is the standard treatment for patients with locally advanced or inoperable cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, treatment failure for CESC patients treated with radical radiotherapy still occurs due to local recurrence and distant metastasis. The previous prediction models were focused on all CESC patients, neglecting the prognostic differences under different treatment modalities. Therefore, there is a pressing demand to explore novel biomarkers for the prognosis and sensitivity of radiotherapy in CESC patients treated with radical radiotherapy. As a single biomarker has limited effect in stratifying these patients, our objective was to identify radioresponse-related mRNAs to ameliorate forecast of the prognosis for CESC patients treated with radical radiotherapy. Methods: Sample data on CESC patients treated with radical radiotherapy were obtained from The Cancer Genome Atlas (TCGA) database. We randomly separated these patients into a training and test cohorts using a 1:1 ratio. Differential expression analysis was carried out to identify radioresponse-related mRNA sets that were significantly dysregulated between complete response (CR) and radiographic progressive disease (RPD) groups, and univariate Cox regression analyses, least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression were performed to identify the radioresponse-related signature in the training cohort. we adopted survival analysis to measure the predictive value of the radioresponse-related signature both in the test and entire cohorts. Moreover, we developed a novel nomogram to predict the overall survival (OS) of CESC patients treated with radical radiotherapy. In addition, immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to preliminarily explore possible mechanisms. Results: This study included a total of 92 CESC patients subjected to radical radiotherapy. We developed and verified a risk score model based on radioresponse-related mRNA. The radioresponse-related mRNA signature and International Federation of Gynecology and Obstetrics (FIGO) stage were served as independent prognostic factors for CESC patients treated with radical radiotherapy. Moreover, a nomogram integrating radioresponse-related mRNA signature with FIGO stage was established to perform better for predicting 1-, 3-, and 5-year survival rates. Mechanically, the low-risk group under the risk score of this model had a better survival status, and the distribution of CD4 T cells was potentially involved in the regulation of radiotherapy response in CESC, leading to a better survival outcome in the low-risk group. Conclusions: This study presents a new radioresponse-related mRNA signature that shows promising clinical efficacy in predicting the prognosis of CESC patients treated with radical radiotherapy.
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ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from Sulfurovum lithotrophicum (SlPPK2). After directed evolution and computation-supported design, we found that SlPPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of SlPPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.IMPORTANCEATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from Sulfurovum lithotrophicum was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.
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Adenosina Trifosfato , Epsilonproteobacteria , Fosfotransferasas (Aceptor del Grupo Fosfato) , Adenosina Trifosfato/metabolismo , Temperatura , Fosfotransferasas (Aceptor del Grupo Fosfato)/genética , Fosfotransferasas (Aceptor del Grupo Fosfato)/metabolismo , NucleótidosRESUMEN
Combining the advantages of energetic heterocycles to achieve high-energy insensitive explosives is a significant challenge. Herein, based on high-energy tetrazole rings and highly stable 1,3,4-oxadiazole rings, a series of novel nitrogen rich energetic compounds 5-9 were successfully constructed. The related compounds were fully characterized by EA, FT-IR, NMR, DSC, and MS, and compounds 6-9 were further confirmed by X-ray single crystal diffraction. Among them, the energetic ion salts 6-8 show high thermal stability (Tdec > 250 °C) and low mechanical sensitivity (IS > 40 J, FS > 360 N), as well as good energy properties (7552-8050 m s-1, 19.4-23.3 GPa). In particular, the azo compound 9 exhibits competent comprehensive performances (Tdec = 226.2 °C, D = 8502 m s-1, P = 28.9 GPa, IS = 32 J, FS = 320 N). These results suggest that the strategy of integrating tetrazole and 1,3,4-oxadiazole and employing an azo structure as a bridging unit are effective approaches to construct high-energy insensitive materials.
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α-Ketoglutarate decarboxylase is a crucial enzyme in the tricarboxylic acid cycle of cyanobacteria, catalyzing the non-oxidative decarboxylation of α-ketoglutarate to produce succinate semialdehyde and CO2. The decarboxylation process is reliant on the cofactor of thiamine diphosphate. However, this enzyme's biochemical and structural properties have not been well characterized. In this work, two α-ketoglutarate decarboxylases encoded by MAE_06010 and MiAbw_01735 genes from Microcystis aeruginosa NIES-843 (MaKGD) and NIES-4325 (MiKGD), respectively, were overexpressed and purified by using an Escherichia coli expression system. It was found that MaKGD exhibited 9.2-fold higher catalytic efficiency than MiKGD, which may be attributed to the absence of glutamate decarboxylase in Microcystis aeruginosa NIES-843. Further biochemical investigation of MaKGD demonstrated that it displayed optimum activity at pH 6.5-7.0 and was most activated by Mg2+. Additionally, MaKGD showed substrate specificity towards α-ketoglutarate. Structural modeling and autodocking results revealed that the active site of MaKGD contained a distinct binding pocket where α-ketoglutarate and thiamine diphosphate interacted with specific amino acid residues via hydrophobic interactions, hydrogen bonds and salt bridges. Furthermore, the mutagenesis study provided strong evidence supporting the importance of certain residues in the catalysis of MaKGD. These findings provide new insights into the structure-function relationships of α-ketoglutarate decarboxylases from cyanobacteria.
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Carboxiliasas , Microcystis , Microcystis/genética , Tiamina Pirofosfato/metabolismo , Ácidos Cetoglutáricos/metabolismo , Carboxiliasas/metabolismoRESUMEN
To seek new high energetic materials, N-methylene-C-bridged nitrogen-rich heterocycle 1-((4,5-diamino-4H-1,2,4-triazol-3-yl)methyl)-1H-1,2,4-triazol-3,5-diamine (DATMTDA) (2) was first synthesized, and two copper coordination compounds ([Cu12(OH)4(ClO4)4(H2O)4(DATMTDA)12](ClO4)16·12H2O (3) and [Cu3(OH)(ClO4)(DATMTDA)3](ClO4)3(NO3) (4)) based on 2 were formed by introducing different anions. These compounds were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction analysis. The crystal structures of compounds 3 and 4 are similar and crystallize in monoclinic systems with the P21/c space group, while the central copper atoms show different coordination behaviors. However, the structure of compounds 3 and 4 is analogous to a three dimensional structure owing to the O atom of OH-, forming coordinate bonds with three copper cations. The NBO charge of 2 was calculated using density functional theory to understand its coordination modes. The Hirshfeld surface calculation reveals that 3 and 4 have strong intermolecular interactions. The thermal decomposition processes, non-isothermal kinetics, and enthalpies of formation and sensitivities of these compounds were investigated. By introducing one NO3- of compound 4 to replace one ClO4- in compound 3, compound 4 shows lower density and lower decomposition peak temperature but lower sensitivity and a higher formation enthalpy than compound 3. The complex 4 possesses an outstanding catalytic effect for the decomposition of AP than that of complex 3. The results illustrate the possibility of introducing various anions into energetic coordination compounds for the regulation of energetic materials.
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The Gannan navel orange (Citrus sinensis Osbeck cv. Newhall) is one of the most widely planted citrus fruit cultivars in Ganzhou City, Jiangxi Province, China. A Gannan navel orange was harvested from an orchard in Yudu County, Ganzhou City, Jiangxi Province, China, in October 2022 (25.95N, 115.41E). Approximately 5% of the fruit rotted after being stored at room temperature for about two weeks.Infected fruits appear brown and rotted with slightly indented edges. Initially symptoms of infected fruits was small circular, light brown, which the rot expands, slightly water-stained halo circle with slightly indented edges. The surface of 10 infected fruits was sterilized with 75% ethanol, and the lesion edge was cut into 5-mm-diameter pieces, and the pieces were then placed on potato dextrose agar (PDA) and incubated at 25°C for five days. A total of eight morphologically similar isolates were obtained. PDA results showed dense white and fluffy aerial mycelia in the center of colonies with sparser edges. Two types of conidia were produced; the alpha conidia were hyaline, ellipsoidal or clavate, and aseptate, with 2 oil drops, 4.8 to 7.5 × 2.1 to 2.7 µm (n=30). The beta conidia were hyaline, aseptate, filiform, smooth, straight to sinuous, 16.9 to 27.5 × 1.3 to 1.6 µm (n=30). These isolates exhibit morphological characteristics similar to those of the Diaporthe genus. Genomic DNA of two representative isolates (JFRL-03-1130 and JFRL-03-1131) was extracted for further confirmation. The internal transcribed spacer (ITS) region, beta-tubulin (TUB), calmodulin (CAL), partial translation elongation factor 1-alpha (TEF1-α), and histone H3 (HIS3) genes were amplified and sequenced using primers ITS1/ITS4, Bt2a/Bt2b, CAL228F/CAL737R, EF1-728F/EF1-986R, and CYLH3F/H3-1b, respectively (Udayanga et al. 2015). These nucleotide sequences were deposited into the GenBank database with accession numbers OQ691637-OQ691638 (ITS), OQ701022-OQ701023 (TUB), OQ701016-OQ701017 (CAL), OQ701018-OQ701019 (TEF1-α) and OQ701020-OQ701021 (HIS3). The maximum likelihood analyses were performed for the combined ITS, TEF1-a, TUB, HIS3, and CAL data set using Phylosuite V1.2.2 (Zhang et al. 2020). The phylogenetic tree showed that the two isolates clustered with D. unshiuensis in a clade with 100% bootstrap support. Therefore, the fungus was identified as D. unshiuensis based on morphological and molecular characteristics. To evaluate pathogenicity, a sterile scalpel was used to wound 10 surface-sterilized fruits, and a 5-mm-diameter mycelial plug of the isolate JFRL 03-1130, cultured on PDA at 25â for 7-days, was put on the wound. Another set of 10 fruits was similarly inoculated with sterile agar plugs as controls. The fruits were cultured at 25°C and 85% relative humidity, and the test was repeated twice. These fruits inoculated with D. unshiuensis showed similar rot symptoms after 10 days, while the control group remained symptomless. In order to prove Koch's postulates, the pathogen was re-isolated from the inoculated fruits and confirmed as D. unshiuensis by molecular techniques, but never from the control fruits. Diaporthe unshiuensis has been reported as an endophyte associated with citrus and a pathogen that causes melanose disease in citrus (Chaisiri et al. 2020; Huang et al. 2015). However, to the best of our knowledge, this is the first reported case of D. unshiuensis causing postharvest fruit rot on Citrus sinensis. In the past, D. sojae has also been reported causing postharvest fruit brown rot disease on Citrus sinensis in China (Xiao, et al. 2023); Therefore, managers should pay more attention to postharvest fruit rot disease caused by Diaporthe species and implement storage strategies to control and reduce losses.
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The enzyme encoded by slr1022 gene from Synechocystis sp. PCC6803 was reported to function as N-acetylornithine aminotransferase, γ-aminobutyric acid aminotransferase, and ornithine aminotransferase, which played important roles in multiple metabolic pathways. Among these functions, N-acetylornithine aminotransferase catalyzes the reversible conversion of N-acetylornithine to N-acetylglutamate-5-semialdehyde with PLP as cofactor, which is a key step in the arginine biosynthesis pathway. However, the investigation of the detailed kinetic characteristics and catalytic mechanism of Slr1022 has not been carried out yet. In this study, the exploration of kinetics of recombinant Slr1022 illustrated that Slr1022 mainly functioned as N-acetylornithine aminotransferase with low substrate specificity to γ-aminobutyric acid and ornithine. Kinetic assay of Slr1022 variants and the model structure of Slr1022 with N-acetylornithine-PLP complex revealed that Lys280 and Asp251 residues were the key amino acids of Slr1022. The respective mutation of the above two residues to Ala resulted in the activity depletion of Slr1022. Meanwhile, Glu223 residue was involved in substrate binding and it served as a switch between the two half reactions. Other residues such as Thr308, Gln254, Tyr39, Arg163, and Arg402 implicated a substrate recognition and catalytic process of the reaction. The results of this study further enriched the understanding of the catalytic kinetics and mechanism of N-acetylornithine aminotransferase, especially from cyanobacteria.
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Synechocystis , Synechocystis/genética , Synechocystis/metabolismo , Transaminasas/metabolismo , Ornitina-Oxo-Ácido Transaminasa , Ácido gamma-AminobutíricoRESUMEN
BACKGROUND: Eucommia ulmoides leaf (EUL), as a medicine and food homology plant, is a high-quality industrial raw material with great development potential for a valuable economic crop. There are many factors affecting the quality of EULs, such as different drying methods and regions. Therefore, quality and safety have received worldwide attention, and there is a trend to identify medicinal plants with artificial intelligence technology. In this study, we attempted to evaluate the comparison and differentiation for different drying methods and geographical traceability of EULs. As a superior strategy, the two-dimensional correlation spectroscopy (2DCOS) was used to directly combined with residual neural network (ResNet) based on Fourier transform near-infrared spectroscopy. RESULTS: (1) Each category samples from different regions could be clustered together better than different drying methods through exploratory analysis and hierarchical clustering analysis; (2) A total of 3204 2DCOS images were obtained, synchronous 2DCOS was more suitable for the identification and analysis of EULs compared with asynchronous 2DCOS and integrated 2DCOS; (3) The superior ResNet model about synchronous 2DCOS used to identify different drying method and regions of EULs than the partial least squares discriminant model that the accuracy of train set, test set, and external verification was 100%; (4) The Xinjiang samples was significant differences than others with correlation analysis of 19 climate data and different regions. CONCLUSIONS: This study verifies the superiority of the ResNet model to identify through this example, which provides a practical reference for related research on other medicinal plants or fungus.
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BACKGROUND: Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain. METHODS: Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1. RESULTS: CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression. CONCLUSIONS: CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.
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Neoplasias de la Próstata , ARN Circular , Microambiente Tumoral , Línea Celular Tumoral , Proliferación Celular , Quimiocina CCL20 , Quimiocinas CC , Humanos , Hibridación Fluorescente in Situ , Ligandos , Masculino , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , ARN Circular/genética , Receptores CCR6/genética , Transducción de Señal , Microambiente Tumoral/genética , Macrófagos Asociados a TumoresRESUMEN
Objective: To explore the efficacy and safety of gemcitabine (GEM) combined with cisplatin (DDP) in the treatment of recurrent/metastatic nasopharyngeal carcinoma (NPC). Methods: A total of 100 patients with recurrent/metastatic NPC treated in the First Affiliated Hospital, Hengyang Medical School, University of South China from January 2018 to March 2020 were retrospectively enrolled. Based on different chemotherapy schemes, they were assigned to an observation (Obs) group (DDP + GEM, n = 55) and a control (Con) group [DDP + FU (fluorouracil), n = 45]. The two groups were compared regarding the following items: therapeutic efficacy; serum levels of platelet-derived growth factor-BB (PDGF-BB), soluble epithelial cadherin (SE-CAD), and inflammation-related factors before and after treatment; toxic and side effects; 1-year survival rate; and quality of life (QOL) 6 months after treatment. Results: The Obs group outperformed the Con group in therapeutic efficacy (P < 0.05). There were no significant differences in the levels of PDGF-BB, SE-CAD, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α between the two groups before treatment (P > 0.05). After treatment, better improvements in PDGF-BB, SE-CAD and inflammatory factors were observed in the Obs group (P < 0.05). The toxic and side effects were significantly lower and the 1-year survival rate and patients' QOL after 6 months of treatment were significantly higher in the Obs group compared with the Con group (P < 0.05). Conclusion: GEM combined with DDP can provide more clinical benefits for patients with recurrent/metastatic advanced NPC, with less side effects, high tolerance and significant efficacy, which can be further promoted in clinical use.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Becaplermina , Cisplatino , Desoxicitidina/análogos & derivados , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Fluorouracilo , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento , GemcitabinaRESUMEN
Exploring novel hypergolic fuels for modern space propulsion is highly desired. However, the analysis and understanding of the structure and hypergolic performance at the molecular level are still insufficient. To understand the factors that dictate hypergolicity, we conducted a comparative study on a series of metal-organic frameworks (MOFs) characterized by the same topology but with varied ligand structures. The ignition delay (ID) time trend was found to be imidazole < triazole < tetrazole, and the rapid ID time was 8 ms. By combining experimental studies and density functional theory (DFT) calculations, we found that propargyl and cyanoborohydride groups that functioned as dual hypergolic triggers contributed to the hypergolicity, and a distinct electronic structure was detrimental to ID time. The structure-performance relationships presented herein can potentially provide some fundamental insights into the field of developing high-performance hypergolic fuels.
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Hypoxia frequently occurs in aquatic environments, especially in aquaculture areas. However, research on the relationship between hypoxic aquatic environments with viral diseases outbreak is limited, and its underlying mechanisms remain elusive. Herein, we demonstrated that hypoxia directly triggers the outbreak of infectious spleen and kidney necrosis virus (ISKNV) disease. Hypoxia or activated hypoxia-inducible factor (HIF) pathway could remarkably increase the levels of viral genomic DNA, titers, and gene expression, indicating that ISKNV can response to hypoxia and HIF pathway. To reveal the mechanism of ISKNV respond to HIF pathway, we identified the viral hypoxia response elements (HREs) in ISKNV genome. Fifteen viral HREs were identified, and four related viral genes responded to the HIF pathway, in which the hre-orf077r promoter remarkably responded to the HIF pathway. The level of orf077r mRNA dramatically increased after the infected cells were treated with dimethyloxalylglycine (DMOG) or the infected cells/fish subjected to hypoxic conditions, and overexpressed orf077r could remarkably increase the ISKNV replication. These finding shows that hypoxic aquatic environments induce the expression of viral genes through the viral HREs to promote ISKNV replication, indicating that viral HREs might be important biomarkers for the evaluation of the sensitivity of aquatic animal viral response to hypoxia stress. Furthermore, the frequencies of viral HREs in 43 species aquatic viral genomes from 16 families were predicted and the results indicate that some aquatic animal viruses, such as Picornavirdea, Dicistronviridae, and Herpesviridae, may have a high risk to outbreak when the aquatic environment encounters hypoxic stress.
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Enfermedades de los Peces , Iridoviridae , Animales , ADN Viral , Enfermedades de los Peces/epidemiología , Enfermedades de los Peces/genética , Humanos , Hipoxia/genética , Iridoviridae/genética , Elementos de RespuestaRESUMEN
BACKGROUND: More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. RESULTS: Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. CONCLUSIONS: Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Próstata/genética , Interferencia de ARN , ARN Circular/genética , Proteínas de Unión al ARN/genética , Anciano , Anciano de 80 o más Años , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Estabilidad del ARN , Proteínas de Unión al ARN/metabolismoRESUMEN
DDX41 is an intracellular DNA sensor that evokes type I interferon (IFN-I) production via the adaptor stimulator of interferon gene (STING), triggering innate immune responses against viral infection. However, the regulatory mechanism of the DDX41-STING pathway in teleost fish remains unclear. The mandarin fish (Siniperca chuatsi) is a cultured freshwater fish species that is popular in China because of its high market value. With the development of a high-density cultural mode in mandarin fish, viral diseases have increased and seriously restricted the development of aquaculture, such as ranavirus and rhabdovirus. Herein, the role of mandarin fish DDX41 (scDDX41) and its DEAD and HELIC domains in the antiviral innate immune response were investigated. The level of scDDX41 expression was up-regulated following treatment with poly(dA:dT) or Mandarin fish ranavirus (MRV), suggesting that scDDX41 might be involved in fish innate immunity. The overexpression of scDDX41 significantly increased the expression levels of IFN-I, ISGs, and pro-inflammatory cytokine genes. Co-immunoprecipitation and pull-down assays showed that the DEAD domain of scDDX41 recognized the IFN stimulatory DNA and interacted with STING to activate IFN-I signaling pathway. Interestingly, the HELIC domain of scDDX41 could directly interact with the N-terminal of STING to induce the expression levels of IFN-I and ISGs genes. Furthermore, the scDDX41 could enhance the scSTING-induced IFN-I immune response and significantly inhibit MRV replication. Our work would be beneficial to understand the roles of teleost fish DDX41 in the antiviral innate immune response.
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Enfermedades de los Peces , Interferón Tipo I , Ranavirus , Virosis , Animales , Ranavirus/genética , Peces , Inmunidad Innata/genética , ADN , AntiviralesRESUMEN
Two new species of the genus Pseudopoda Jäger, 2000 are reported from Yunnan Province, China: Pseudopoda mingshengi sp. nov. (male, female) and P. uncata sp. nov. (male, female). The male of P. physematosa Zhang, Jäger & Liu, 2019 is described for the first time.
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Arañas , Animales , Femenino , Masculino , ChinaRESUMEN
In this article, the H∞ filtering issue is considered for discrete-time nonlinear networked systems subject to event-triggered communication scheme, dynamic quantization, and stochastic cyber attacks. The considered nonlinear networked system is described by the Takagi-Sugeno (T-S) fuzzy model. The event-triggered policy and the dynamic quantizer will be considered to realize the effective use of the restricted network bandwidth resources. Moreover, a stochastic variable that satisfies the Bernoulli random binary distribution is employed to characterize the effects of stochastic cyber attacks. This paper focus on the design of full- and reduced-order event-triggered H∞ filters and the dynamic parameter of the quantizer such that the filtering error system is stochastically stable and satisfies a predefined H∞ filtering performance. The sufficient design conditions for the event-triggered H∞ filters and the dynamic parameter of the quantizer are proposed based on linear matrix inequalities (LMIs). Finally, an example based on practical application will be used to verify the effectiveness of the presented design methods.