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Predicting protein function is crucial for understanding biological life processes, preventing diseases and developing new drug targets. In recent years, methods based on sequence, structure and biological networks for protein function annotation have been extensively researched. Although obtaining a protein in three-dimensional structure through experimental or computational methods enhances the accuracy of function prediction, the sheer volume of proteins sequenced by high-throughput technologies presents a significant challenge. To address this issue, we introduce a deep neural network model DeepSS2GO (Secondary Structure to Gene Ontology). It is a predictor incorporating secondary structure features along with primary sequence and homology information. The algorithm expertly combines the speed of sequence-based information with the accuracy of structure-based features while streamlining the redundant data in primary sequences and bypassing the time-consuming challenges of tertiary structure analysis. The results show that the prediction performance surpasses state-of-the-art algorithms. It has the ability to predict key functions by effectively utilizing secondary structure information, rather than broadly predicting general Gene Ontology terms. Additionally, DeepSS2GO predicts five times faster than advanced algorithms, making it highly applicable to massive sequencing data. The source code and trained models are available at https://github.com/orca233/DeepSS2GO.
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Algoritmos , Biologia Computacional , Redes Neurais de Computação , Estrutura Secundária de Proteína , Proteínas , Proteínas/química , Proteínas/metabolismo , Proteínas/genética , Biologia Computacional/métodos , Bases de Dados de Proteínas , Ontologia Genética , Análise de Sequência de Proteína/métodos , SoftwareRESUMO
BACKGROUND: Dermatomyositis (DM) is a kind of dermatologically associated autoimmune disease that is notably associated with an increased risk of concurrent malignancies, although the underlying mechanisms remain to be fully elucidated. The purpose of this investigation was to examine the immunological parallels between DM and nasopharyngeal carcinoma (NPC), with the aim of identifying pivotal biomarkers that could facilitate a deeper understanding and enhance the predictive capabilities of NPC in DM patients. METHOD: Data for DM and NPC were sourced from the Gene Expression Omnibus (GEO) database. Immune infiltration was analyzed using the "cibersort" R package, differentially expressed genes (DEGs) were identified with the "limma" package, and functional pathways were investigated through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Characteristic genes were determined by Utilizing Protein-Protein Interaction (PPI) and Least Absolute Shrinkage and Selection Operator (LASSO), and their features were validated using the GSE53819 dataset. RESULTS: In comparison to normal samples, significant infiltration of macrophage M1 was observed in both DM and NPC. The analysis revealed 77 DEGs in DM and 1051 DEGs in NPC, with 22 genes found to be co-DEGs. Following PPI and LASSO analysis, six distinctive genes were retained. Notably, CCL8, IFIH1, CXCL10, and CXCL11 exhibited optimal diagnostic efficacy for NPC and displayed significant correlation with macrophage M1 infiltration within the carcinoma. CONCLUSION: Four characteristic genes, CCL8, IFIH1, CXCL10, and CXCL11 are risk factors for both DM and NPC. They exhibit a robust correlation with the incidence of NPC and offer a commendable diagnostic efficacy. Furthermore, they may serve as prospective predictive biomarkers for the emergence of NPC in DM.
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Biologia Computacional , Dermatomiosite , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Dermatomiosite/genética , Dermatomiosite/imunologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/imunologia , Mapas de Interação de Proteínas/genética , Bases de Dados Genéticas , Perfilação da Expressão GênicaRESUMO
Since the discovery of graphene, the development of new two-dimensional (2D) materials has received considerable interest. Recently, as a newly emerging member of the 2D family, 2D metastable-phase oxides that combine the unique advantages of metal oxides, 2D structures, and metastable-phase materials have shown enormous potential in various catalytic reactions. In this review, the potential of various 2D materials to form a metastable-phase is predicted. The advantages of 2D metastable-phase oxides for advanced applications, reliable methods of synthesizing 2D metastable-phase oxides, and the application of these oxides in different catalytic reactions are presented. Finally, the challenges associated with 2D metastable-phase oxides and future perspectives are discussed.
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Kidney, bladder, and prostate cancer are the three major tumor types of the urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding RNAs with a stabile structure and a unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs are widely distributed within the body, with important biologic functions such as sponges for microRNAs, as RNA binding proteins, and as templates for regulation of transcription and protein translation. The abnormal expression of circRNAs in vivo is significantly associated with the development of urologic tumors. CircRNAs have now emerged as potential biomarkers for the diagnosis and prognosis of urologic tumors, as well as targets for the development of new therapies. Although we have gained a better understanding of circRNA, there are still many questions to be answered. In this review, we summarize the properties of circRNAs and detail their function, focusing on the effects of circRNA on proliferation, metastasis, apoptosis, metabolism, and drug resistance in kidney, bladder, and prostate cancers.
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MicroRNAs , Neoplasias Urológicas , Humanos , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Biossíntese de Proteínas , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genéticaRESUMO
In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8+ effector T cells, epithelial-to-mesenchymal transition and pan-fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression-free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/diagnóstico , Nivolumabe , Everolimo/uso terapêutico , Proteômica , China , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glicólise , Microambiente TumoralRESUMO
Upon Mycobacterium tuberculosis (Mtb) infection, protein kinase G (PknG), a eukaryotic-type serine-threonine protein kinase (STPK), is secreted into host macrophages to promote intracellular survival of the pathogen. However, the mechanisms underlying this PknG-host interaction remain unclear. Here, we demonstrate that PknG serves both as a ubiquitin-activating enzyme (E1) and a ubiquitin ligase (E3) to trigger the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-ß-activated kinase 1 (TAK1), thereby inhibiting the activation of NF-κB signaling and host innate responses. PknG promotes the attachment of ubiquitin (Ub) to the ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), rather than the usual C86-Ub thiol-ester bond. PknG induces the discharge of Ub from UbcH7 by acting as an isopeptidase, before attaching Ub to its substrates. These results demonstrate that PknG acts as an unusual ubiquitinating enzyme to remove key components of the innate immunity system, thus providing a potential target for tuberculosis treatment.
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Mycobacterium tuberculosis , Proteínas Quinases Dependentes de GMP Cíclico , Mycobacterium tuberculosis/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
Emulsion gels as soft materials were formulated by insoluble soybean fiber (ISF) assembled from okara in this study. Steam explosion on okara (ISFS) transformed the insoluble fiber in the original okara (ISFU) into soluble fiber. Enzymatic hydrolysis led to a lower protein content, smaller particle size and smaller contact angle of ISF. ISFE, which was obtained by enzymatic hydrolysis of ISFU, was not able to produce stable emulsion gels at 0.50 to 1.50 wt% ISF, whereas the ISF after a combined steam explosion-enzymatic hydrolysis treatment (giving rise to ISFSE) stabilized emulsion gels at varying oil volume fractions (φ) from 10 to 50%. The ζ-potential of emulsion gels was around -19 to -26 mV. The droplet size first decreased (from 43.8 µm to 14.8 µm when at φ = 0.3) with increasing ISF content (from 0.25 wt% to 1.25 wt%) and then remained constant, as also seen from the microstructure. The apparent viscosity and viscoelastic properties were strengthened upon increasing both the ISF concentration and oil volume fraction. The protein and soluble fiber contributed to the interfacial activity of ISF while the insoluble fiber played an important role in the gel-like structured network of emulsion gels, making them maintain physical stability during long term storage. These findings could provide novel information about soybean fiber to fabricate soft materials and the utilization of okara at an industrial-scale.
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Glycine max , Vapor , Emulsões/química , Tamanho da Partícula , Géis/químicaRESUMO
BACKGROUND: Papillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2. METHODS: A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan-Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker. RESULTS: PRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%). CONCLUSIONS: TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Prognóstico , Estudos Retrospectivos , Everolimo/uso terapêutico , China , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
African swine fever virus (ASFV) is a highly contagious nucleocytoplasmic large DNA virus (NCLDV) that causes nearly 100% mortality in swine. The development of effective vaccines and drugs against this virus is urgently needed. pA104R, an ASFV-derived histone-like protein, shares sequence and functional similarity with bacterial HU/IHF family members and is essential for viral replication. Herein, we solved the crystal structures of pA104R in its apo state as well as in complex with DNA. Apo-pA104R forms a homodimer and folds into an architecture conserved in bacterial heat-unstable nucleoid proteins/integration host factors (HUs/IHFs). The pA104R-DNA complex structure, however, uncovers that pA104R has a DNA binding pattern distinct from its bacterial homologs, that is, the ß-ribbon arms of pA104R stabilize DNA binding by contacting the major groove instead of the minor groove. Mutations of the basic residues at the base region of the ß-strand DNA binding region (BDR), rather than those in the ß-ribbon arms, completely abolished DNA binding, highlighting the major role of the BDR base in DNA binding. An overall DNA bending angle of 93.8° is observed in crystal packing of the pA104R-DNA complex structure, which is close to the DNA bending angle in the HU-DNA complex. Stilbene derivatives SD1 and SD4 were shown to disrupt the binding between pA104R and DNA and inhibit the replication of ASFV in primary porcine alveolar macrophages. Collectively, these results reveal the structural basis of pA104R binding to DNA highlighting the importance of the pA104R-DNA interaction in the ASFV replication cycle and provide inhibitor leads for ASFV chemotherapy.
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Vírus da Febre Suína Africana/efeitos dos fármacos , Vírus da Febre Suína Africana/fisiologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/efeitos dos fármacos , DNA/química , Estilbenos/farmacologia , Febre Suína Africana/prevenção & controle , Vírus da Febre Suína Africana/genética , Animais , Sequência de Bases , Proteínas de Ligação a DNA/metabolismo , Escherichia coli , Histonas/química , Modelos Moleculares , Conformação Proteica , Suínos , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: E. coli ST131 is the predominant lineage among extraintestinal pathogenic E. coli isolates worldwide and is an important pathogen associated with all kinds of human infections. The aim of this study was to investigate the prevalence and molecular characteristics of E. coli ST131 and non-ST131 isolates that cause bloodstream infections and evaluate the risk factors for E. coli ST131. METHODS: A total of 103 E. coli isolates associated with bloodstream infection were collected between August 2014 and August 2015 at a Chinese university hospital. The isolates were classified into ST131 and non-ST131 E. coli groups by multilocus sequence typing. Phylogenetic analysis, susceptibility testing, virulence genotyping, PCR-based O typing, and pulsed-field gel electrophoresis (PFGE) were performed, and the clinical features of patients in both groups were compared. RESULTS: Overall, 12 isolates (11.7%) were identified as ST131 isolates, including 10 O25b-ST131 (83.3%) and 2 O16-ST131 (16.7%) clones. All 103 E. coli isolates were divided into four phylogenetic groups: B2 was the predominant phylogenetic group (n = 39, 37.9%), and it was followed in descending order by D (n = 33, 32.0%), A (n = 20, 19.4%), and B1 (n = 11, 10.7%). Compared with the non-ST131 isolates, the E. coli ST131 isolates harbored more virulence factors and were associated with a significantly higher incidence of urinary tract infection (p = 0.040) and a significantly greater length of hospital stay (p = 0.045). According to PFGE analysis, the molecular features of the E. coli ST131 isolates were highly diverse, and there was no dominant clone. CONCLUSIONS: The ST131 isolates collected from Southeast China in this study exhibited strong virulence and multiple drug resistance, and the main serotype was O25b-ST131. Therefore, future studies should focus on O16-ST131 subclones in order to better understand the prognosis of patients with bloodstream infection caused by E. coli ST131.
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Infecções por Escherichia coli , Sepse , Escherichia coli/genética , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/epidemiologia , Genótipo , Humanos , Epidemiologia Molecular , Filogenia , Fatores de Risco , beta-Lactamases/genéticaRESUMO
BACKGROUND: To identify the malignant potential and prognostic indicators of renal epithelioid angiomyolipoma (eAML), clinicopathological and molecular features as well as the drug efficacy of 67 eAML cases were analyzed. MATERIALS AND METHODS: Sixty-seven renal eAML patients were enrolled and the immunohistochemical features of these patients were examined. FFPE slides of all patients were re-examined. 21 patients with metastasis received Everolimus 10 mg orally once daily. Responses were evaluated with RECIST criteria by three authors. A risk stratification model was constructed using the following factors: pT3 and pT4, presence of necrosis, mitotic count ≥ 2; the presence of atypical mitoses; severe nuclear atypia, SMA negative, Ki-67 ≥ 10%. RESULTS: The average percentage of the epithelioid component was 85.6% (range 80-95%). Immunohistochemically, Ki-67 ≥ 10% and negative SMA staining were significantly correlated with malignant characteristics (Ki-67: p < 0.001; SMA: p = 0.001). Survival analysis suggested that pT3-pT4 stage, presence of necrosis, severe nuclear atypia, presence of atypical mitoses, mitotic count ≥ 2, Ki-67 ≥ 10% and negative SMA expression were significantly associated with poorer PFS and OS (p < 0.05). The risk model sufficiently discriminated recurrence/metastasis (AUC = 0.897) and cancer-specific mortality (AUC = 0.932) of renal eAML patients in different risk groups. 21 patients had received Everolimus targeted therapy after recurrence/metastasis. The best response for Everolimus treatment was 8/21 (38.1%) partial responses (PR), 9/21 (42.9%) stable disease (SD) and 4/21 (19.0%) progressive disease (PD). CONCLUSION: The risk stratification model could well distinguish eAML patients at high risk of recurrence/metastasis. Everolimus targeted treatment showed good efficacy in patients with recurrence/metastasis.
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Angiomiolipoma , Neoplasias Renais , Células Epitelioides/metabolismo , Células Epitelioides/patologia , Everolimo/uso terapêutico , Humanos , Antígeno Ki-67 , Neoplasias Renais/patologia , Necrose , Estudos RetrospectivosRESUMO
BACKGROUND: The role of protein-polysaccharide interactions and their mixtures has been a vital factor affecting the formation and stability of food emulsions. Okara protein (OP), which is extracted from the by-product of soybean processing, has received much attention because of its abundant sources and potential attributes with respect to food formulation. Carboxymethyl cellulose (CMC), a well-known food-grade polysaccharide additive, has been widely utilized in the protein-polysaccharide system, whereas, among the proteins, the role of OP has not yet been explored. RESULTS: The present study first assessed the ζ-potential and hydrodynamic diameter of aqueous mixtures containing OP (1.0 wt%) and CMC (0-0.5 wt%), followed by the investigation of OP-CMC mixtures stabilized O/W emulsions. As CMC increased, oil droplet size, surface protein adsorption, apparent viscosity and storage modulus increased, whereas the loss tangent decreased. CONCLUSION: CMC resulted in emulsion destabilization compared to emulsions without CMC, whereas a higher concentration of CMC promoted emulsion stability against creaming for emulsions in the presence of CMC. The results provide information with respect to OP and CMC being incorporated into food formulations and also strengthen our understanding of the related mechanism, in addition to facilitating the further utilization of OP. © 2020 Society of Chemical Industry.
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Carboximetilcelulose Sódica/química , Emulsões/química , Proteínas de Plantas/química , Polissacarídeos/química , Óleos/química , Reologia , Alimentos de Soja , Viscosidade , Água/químicaRESUMO
Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. Besides that, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes (ISGs) in response to ZIKV infection. In particular, we found that AZM upregulates the expression of MDA5 and RIG-I, pathogen recognition receptors (PRRs) induced by ZIKV infection, and increases the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulates phosphorylation of TBK1, without inducing phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and prevent ZIKV associated devastating clinical outcomes, such as congenital microcephaly.
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The pearl oyster Pinctada maxima exhibits great difficulty to culture pearls through nuclear insertion with an allograft, but it is easy for P. fucata to culture pearls after allografting. If P. fucata could be used as a surrogate mother to culture P. maxima pearls, it would benefit the pearl culture industry of P. maxima. However, this is blocked by the immune rejection of P. fucata against P. maxima mantle grafts. In this study, the immune responses of P. fucata hemocyte to allograft and xenograft were investigated after transplantation by transcriptome analysis. In total, 107.93 Gb clean reads were produced and assembled using the reference genome of P. fucata. Gene Ontology Term enrichment and KEGG enrichment analyses indicated that apoptosis, hippo signaling pathway, oxidation-reduction, MAPK signaling pathway, ribosome, protein processing in endoplasmic reticulum, purine metabolism, NF-kappa B signaling pathway, oxidative phosphorylation, Ras signaling pathway, and ubiquitin mediated proteolysis were involved in response to transplantation. Many genes related to oxidation-reduction reactions, the MAPK signaling pathway, and apoptosis were identified by comparison of the allograft group and the xenograft group at 0 h, 6 h, 12 h, 24 h, 48 h, 72 h, and 96 h post-transplantation. Among them, the expression levels of NADH dehydrogenase, succinate dehydrogenase and other dehydrogenases were increased significantly in the xenograft groups compared with allograft groups at 0 h post transplantation, indicating that a respiratory burst of neutrophils occurred immediately after xenograft transplantation. Additionally, HSP70 was highly expressed from 0 h to 96 h in the xenograft groups, indicating an oyster immune response to the xenograft. The genes enriched in the ribosome and hippo-signaling pathways were also identified, and expression patterns of these DEGs were different as compared between transplantation and control groups. Finally, altered expression levels of 10 randomly selected immune-related DEGs were confirmed by quantitative real-time PCR. These results indicated that oxidation-reduction is likely the key factor responsible for immune rejection to transplantation. The findings should provide some new insight into the molecular mechanism of immune rejection of the host against xenograft, and thus benefit to development of immunosuppressive reagents to facilitate effective xenograft pearling.
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Hemócitos/imunologia , Imunidade Inata , Pinctada/imunologia , Transcriptoma , Animais , Perfilação da Expressão Gênica , Xenoenxertos , Pinctada/genéticaRESUMO
The mantle piece from the donor pearl oyster would be rejected by the immune system of recipient oyster in pearl culture practice, especially in the case that the donor and receptor are different species. Thus, investigation of the immune response of recipient oyster to grafted mantle pieces, particularly to xenografts, is of importance in creating xenograft transplantation technology for pearl culture industry. The humoral immune responses of P. fucata to allograft (mantle piece of P. fucata) and xenografts (mantle pieces of P. maxima and P. margaritifera, respectively) were studied in this paper. The oysters receiving no transplantations were served as the control group. The serum was collected from recipient P. fucata at 1 d, 2 d, 3 d, 4 d, 5 d, 7 d, 9 d, 11 d, 13 d, and 15 d, respectively after transplantation, and the serum antibacterial activity, lysozyme activity (LZM), alkaline phosphatase (AKP), acid phosphatase (ACP), total antioxidant capacity (TAC), and agglutination to rabbit red blood cells were investigated. The result indicated that serum of both the experimental groups and the control group can agglutinate rabbit red blood cells, with variation between groups and between time points, respectively. The antibacterial activity in the experimental group was significantly higher than that in the control group at 2-4 d, but lower at 5-11 d and returned back to normal at 15 d, with significant differences among experimental groups (P < 0.05). The LZM in the experimental group was significantly higher than that in the control group at 3-7 d, with significant differences in bacteriolytic activity among various groups (P < 0.05). Both the ACP and AKP activity levels in the experimental groups were higher than those in the control group at 2-9 d, with significant differences among various groups at 3-9 d (P < 0.05). The TAC level in the experimental groups was higher than that in the control group at 1-7 d, with significant differences among various groups at 4-7 d (P < 0.05). The above results indicated that all of the humoral immune factors investigated showed immune responses to both allografts and xenografts, with no specific to any of them. Thus, it is necessary to further screen immune rejection factors specific to xenografts, including cellular immune components.
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Imunidade Humoral , Pinctada/imunologia , Testes de Aglutinação , Aloenxertos/imunologia , Animais , Antioxidantes/metabolismo , Escherichia coli/imunologia , Xenoenxertos/imunologia , Pinctada/enzimologiaRESUMO
The pearl oyster Pinctada fucata is commonly cultured for marine pearls in China. To culture pearls, a mantle piece from a donor pearl oyster is grafted with a nucleus into a receptor. This transplanted mantle piece may be rejected by the immune system of the recipient oyster, thus reducing the success of transplantation. However, there have been limited studies about the oyster's immune defense against allograft. In this study, hemocyte transcriptome analysis was performed to detect the immune responses to allograft in P. fucata at 0 h and 48 h after a transplant. The sequencing reaction produced 92.5 million reads that were mapped against the reference genome sequences of P. fucata. The Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify all immune-related differentially expressed genes (DEGs). Compared with patterns at 0 h, a total of 798 DEGs were identified, including 410 up-regulated and 388 down-regulated genes at 48 h. The expression levels of interleukin receptor and toll-like receptor in hemocytes were increased significantly 48 h post-transplant, indicating that the oyster immune response was induced. Finally, altered levels of 18 randomly selected immune-related DEGs were confirmed by quantitative real-time PCR (qRT-PCR). Our results provide the basis for further analysis of the immune rejection of allotransplantation.
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Aloenxertos , Hemócitos/imunologia , Imunidade Inata , Pinctada/genética , Pinctada/imunologia , Transcriptoma , Animais , Perfilação da Expressão Gênica , Anotação de Sequência Molecular , Pinctada/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
A putative regulatory gene ttmRIV located in the tetramycin biosynthetic gene cluster was found in Streptomyces ahygroscopicus. In-frame deletion of ttmRIV led to abolishment of tetramycin and significant enhancement of nystatin A1, whose production reached 2.1-fold of the H42 parental strain. Gene complementation by an integrative plasmid carrying ttmRIV restored tetramycin biosynthesis revealed that ttmRIV was indispensable to tetramycin biosynthesis. Gene expression analysis of the H42 strain and its mutant strain ΔttmRIV via reverse transcriptase-PCR of the tetramycin gene cluster demonstrated that the expression levels of most biosynthetic genes were reduced in ΔttmRIV. Results of electrophoretic mobility shift assays showed that TtmRIV bound the putative promoters of several genes in the tetramycin pathway. Thus, TtmRIV is a pathway-specific positive regulator activating the transcription of the tetramycin gene cluster in S. ahygroscopicus. Providing an additional copy of ttmRIV under the control of the ermEp* promoter in the H42 strain boosted tetramycin A production to 3.3-fold.
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Antibacterianos/biossíntese , Macrolídeos/metabolismo , Nistatina/biossíntese , Streptomyces/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Reatores Biológicos , Vias Biossintéticas , Sequência Consenso , Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Dados de Sequência Molecular , Família Multigênica , Plasmídeos , Regiões Promotoras Genéticas , Streptomyces/genéticaRESUMO
BACKGROUND: 2,4-Dichlorophenoxyacetic acid (2,4-D) is reported to be the most widely used herbicide in home and garden environments, rendering it commonly encountered in daily life. Despite being ubiquitous, there is a scarcity of studies that have comprehensively assessed the relationship between 2,4-D exposure and cognition using multiple models. OBJECTIVE: To explore the association between 2,4-D exposure and cognition among older American people. METHODS: This was a cross-sectional study that included 3 cycles of data from the National Health and Nutrition Examination Survey. Generalized linear models (GLMs), restricted cubic spline (RCS) regression, and generalized additive models (GAMs) were used to assess the relationship between exposure to 2,4-D and cognitive performance by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word learning sub-test, Digit Symbol Substitution Test (DSST), and Animal Fluency Test (AFT). RESULTS: A total of 1364 older U.S. adults (60+ years) were included in the study. The GLMs revealed a negative association between median high levels (0.315-0.566 µg/L) of 2,4-D and cognitive impairment on the DSST and AFT, with multivariate-adjusted ORs of 0.403 (95% CI: 0.208-0.781, P = 0.009) and 0.396 (95% CI: 0.159-0.986, P = 0.047); the RCS regression and GAMs revealed a "U" shaped curve, the left part of which is consistent with the result of the GLMs. IMPACT STATEMENT: There is a U-shaped relationship between human urinary 2,4-D concentrations and cognitive impairment in older U.S. adults, especially in males, so controlling 2,4-D exposure within an appropriate range is particularly important for cognitive function.
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Ácido 2,4-Diclorofenoxiacético , Disfunção Cognitiva , Exposição Ambiental , Herbicidas , Inquéritos Nutricionais , Humanos , Estudos Transversais , Masculino , Feminino , Idoso , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Cognição/efeitos dos fármacos , Modelos LinearesRESUMO
Anthocidaris crassispina is a very popular edible sea urchin distributed along the coast of the South China Sea. In this study, we performed whole-genome sequencing and generated a chromosome-level assembly of this species. The total length of the genomic contig sequence was 891.02 Mb, and contig N50 was 808.15 kb when Hifiasm was used for assembly. The Hi-C library was constructed and sequenced, yielding approximately 68.61 Gb of data. After Hi-C assembly, approximately 886.72 Mb of sequence was able to be mapped onto 21 chromosomes, accounting for 99.52% of the total genome length. Among the sequences located on the chromosomes, those for which the order and direction could be determined accounted for approximately 826.82 Mb, or 93.24% of the total length. These results provide valuable resources for further study of A. crassispina at the genetic level.