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Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform. Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.
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Glioblastoma , Ribonucleoproteínas Nucleares Heterogêneas , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Proteína cdc42 de Ligação ao GTP , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Humanos , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Linhagem Celular Tumoral , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , Splicing de RNA , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Septic tanks are widely adopted in decentralized household wastewater treatment systems serving billions of people globally. Due to the lack of effective electron acceptors, insufficient nutrient removal and the emission of harmful gases, e. g. H2S, CH4, etc., are the common drawbacks. In the present work, we attempted to supplement nitrite into septic tanks as an electron acceptor, via nitrifying human urine source-separated from blackwater, to overcome these drawbacks. Partial or complete nitritation of source-separated urine was achieved in a sequencing batch reactor. The addition of nitrified urine into septic tanks improved organic and nitrogen removals in blackwater up to 90 % and 70 %, respectively. The emission of harmful gases from the septic tanks was stably diminished, with more than 75 % of CH4, CO2 and H2S reductions. Nitrite addition significantly reduced the abundance of hydrogenotrophic methanogens in septic tanks. Though the activity of sulfate-reducing bacteria recovered after the initial inhibition upon nitrite addition, the bio-generated H2S was retained in water since the increased wastewater pH after nitrite addition promoted the disassociation of H2S in aqueous solution.
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Porcine reproductive and respiratory syndrome (PRRS) remains a formidable challenge for the global pig industry. Caused by PRRS virus (PRRSV), this disease primarily affects porcine reproductive and respiratory systems, undermining effective host interferon and other immune responses, resulting in vaccine ineffectiveness. In the absence of specific antiviral treatments for PRRSV, vaccines play a crucial role in managing the disease. The current market features a range of vaccine technologies, including live, inactivated, subunit, DNA, and vector vaccines, but only modified live virus (MLV) and killed virus (KV) vaccines are commercially available for PRRS control. Live vaccines are promoted for their enhanced protective effectiveness, although their ability to provide cross-protection is modest. On the other hand, inactivated vaccines are emphasized for their safety profile but are limited in their protective efficacy. This review updates the current knowledge on PRRS vaccines' interactions with the host interferon system, and other immunological aspects, to assess their current status and evaluate advents in PRRSV vaccine development. It presents the strengths and weaknesses of both live attenuated and inactivated vaccines in the prevention and management of PRRS, aiming to inspire the development of innovative strategies and technologies for the next generation of PRRS vaccines.
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The environmental risks of fluorinated alternatives are of great concern with the phasing out of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate. Here, multi-omics (i.e., metabolomics and transcriptomics) coupled with physiological and biochemical analyses were employed to investigate the stress responses of wheat seedings (Triticum aestivum L.) to perfluorobutanoic acid (PFBA), one of the short-chain per- and polyfluoroalkyl substances (PFAS) and PFOA alternatives, at environmentally relevant concentrations (0.1-100 ng/g). After 28 days of soil exposure, PFBA boosted the generation of OH and O2- in wheat seedlings, resulting in lipid peroxidation, protein perturbation and impaired photosynthesis. Non-enzymatic antioxidant defense systems (e.g., glutathione, phenolics, and vitamin C) and enzymatic antioxidant copper/zinc superoxide dismutase were strikingly activated (p < 0.05). PFBA-triggered oxidative stress induced metabolic and transcriptional reprogramming, including carbon and nitrogen metabolisms, lipid metabolisms, immune responses, signal transduction processes, and antioxidant defense-related pathways. Down-regulation of genes related to plant-pathogen interaction suggested suppression of the immune-response, offering a novel understanding on the production of reactive oxygen species in plants under the exposure to PFAS. The identified MAPK signaling pathway illuminated a novel signal transduction mechanism in plant cells in response to PFAS. These findings provide comprehensive understandings on the phytotoxicity of PFBA to wheat seedlings and new insights into the impacts of PFAS on plants.
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Fluorocarbonos , Plântula , Poluentes do Solo , Triticum , Triticum/efeitos dos fármacos , Fluorocarbonos/toxicidade , Plântula/efeitos dos fármacos , Poluentes do Solo/toxicidade , Estresse OxidativoRESUMO
Lysosomal enzymes degrade cellular macromolecules, while their inactivation causes human hereditary metabolic disorders. Mucopolysaccharidosis IVA (MPS IVA; Moquio A syndrome) is one of the lysosomal storage disorders caused by a defective Galactosamine-6-sulfatase (GalN6S) enzyme. In several populations, disease incidence is elevated due to missense mutations brought on by non-synonymous allelic variation in the GalN6S enzyme. Here, we studied the effect of non-synonymous single nucleotide polymorphism (nsSNPs) on the structural dynamics of the GalN6S enzyme and its binding with N-acetylgalactosamine (GalNAc) using all-atom molecular dynamics simulation and an essential dynamics approach. Consequently, in this study, we have identified three functionally disruptive mutations in domain-I and domain-II, that is, S80L, R90W, and S162F, which presumably contribute to post-translational modifications. The study delineated that both domains work cooperatively, and alteration in domain II (S80L, R90W) leads to conformational changes in the catalytic site in domain-I, while mutation S162F mainly provokes higher residual flexibility of domain II. These results show that these mutations impair the hydrophobic core, implying that Morquio A syndrome is caused by misfolding of the GalN6S enzyme. The results also show the instability of the GalN6S-GalNAc complex upon substitution. Overall, the structural dynamics resulting from point mutations give the molecular rationale for Moquio A syndrome and, more importantly, the Mucopolysaccharidoses (MPS) family of diseases, re-establishing MPS IVA as a protein-folding disease.Communicated by Ramaswamy H. Sarma.
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Mucopolissacaridose IV , Humanos , Mucopolissacaridose IV/genética , Acetilgalactosamina , Galactosamina , Dobramento de Proteína , SulfatasesRESUMO
The extensive use of florfenicol in poultry industry results in the emergence of optrA gene, which also confers resistance to clinically important antibiotic linezolid. This study investigated the occurrence, genetic environments, and removal of optrA in enterococci in mesophilic (37 °C) and thermophilic (55 °C) anaerobic digestion systems, and a hyper-thermophilic (70 °C) anaerobic pretreatment system for chicken waste. A total of 331 enterococci were isolated and analyzed for antibiotic resistance against linezolid and florfenicol. The optrA gene was frequently detected in enterococci from chicken waste (42.7%) and effluents from mesophilic (72%) and thermophilic (56.8%) reactors, but rarely detected in the hyper-thermophilic (5.8%) effluent. Whole-genome sequencing revealed that optrA-carrying Enterococcus faecalis sequence type (ST) 368 and ST631 were the dominant clones in chicken waste, and they remained dominant in mesophilic and thermophilic effluents, respectively. The plasmid-borne IS1216E-fexA-optrA-erm(A)-IS1216E was the core genetic element for optrA in ST368, whereas chromosomal Tn554-fexA-optrA was the key one in ST631. IS1216E might play a key role in horizontal transfer of optrA due to its presence in different clones. Hyper-thermophilic pretreatment removed enterococci with plasmid-borne IS1216E-fexA-optrA-erm(A)-IS1216E. A hyper-thermophilic pretreatment is recommended for chicken waste to mitigate dissemination of optrA from animal waste to the environment.
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Oxazolidinonas , Animais , Enterococcus/genética , Linezolida , Anaerobiose , Genes Bacterianos , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Enterococcus faecalis/genéticaRESUMO
Owing to the high contents of organics and nitrogen in vacuum toilet wastewater (VTW) generated from high-speed trains, onsite pretreatment is usually required before VTW can be discharged into municipal sewers. In this study, a partial nitritation process was stably established in a sequential batch reactor to efficiently utilize the organics in synthetic and real VTWs for nitrogen removal and to produce an effluent suitable for anaerobic ammonia oxidation. In spite of the high fluctuations of COD and nitrogen in VTW, the organics used for nitrogen removal stabilized at 1.97 ± 0.18 mg COD mg N-1 removed, and the effluent NO2--N/NH4+-N ratios were maintained at 1.26 ± 0.13. The removal efficiencies of nitrogen and COD were 31.8 ± 3.5% and 65.2 ± 5.3% under the volumetric loading rates of 1.14 ± 0.15 kg N m-3 d-1 and 1.03 ± 0.26 kg COD m-3 d-1 for real VTW, respectively. Microbial community analysis revealed that Nitrosomonas (0.95%-1.71%) was the dominant autotrophic ammonium-oxidizing bacterial genus, but nitrite-oxidizing bacteria, Nitrolancea, was severely inhibited, with a relative abundance less than 0.05%. The relative abundance of denitrifying bacteria increased by 7.34% when the influent was switched to real VTW. Functional profile predictions of the biomass showed that the decrease in the COD/N ratio and the switch of reactor influent from synthetic to real VTW increased the relative abundance of enzymes and modules involved in carbon and nitrogen metabolisms.
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Compostos de Amônio , Aparelho Sanitário , Águas Residuárias , Desnitrificação , Nitrogênio/metabolismo , Vácuo , Oxirredução , Reatores Biológicos/microbiologia , Bactérias/metabolismo , Esgotos/microbiologiaRESUMO
BACKGROUND: Roughly 50% of adult gliomas harbor isocitrate dehydrogenase (IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized. METHODS: Using bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers. RESULTS: Genes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas. CONCLUSIONS: Our studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/metabolismo , Isocitrato Desidrogenase/genética , Glioma/metabolismo , Diferenciação Celular/genética , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Cromatina , MutaçãoRESUMO
Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
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Neoplasias Encefálicas , Glioma , Células-Tronco Neurais , Células Precursoras de Oligodendrócitos , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/metabolismo , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Células-Tronco Neurais/patologia , Células Precursoras de Oligodendrócitos/patologia , Microambiente TumoralRESUMO
Genetic variations in APOC2 and APOA5 genes involve activating lipoprotein lipase (LPL), responsible for the hydrolysis of triglycerides (TG) in blood and whose impaired functions affect the TG metabolism and are associated with metabolic diseases. In this study, we investigate the biological significance of genetic variations at the DNA sequence and structural level using various computational tools. Subsequently, 8 (APOC2) and 17 (APOA5) non-synonymous SNPs (nsSNPs) were identified as high-confidence deleterious SNPs based on the effects of the mutations on protein conservation, stability, and solvent accessibility. Furthermore, based on our docking results, the interaction of native and mutant forms of the corresponding proteins with LPL depicts differences in root mean square deviation (RMSD), and binding affinities suggest that these mutations may affect their function. Furthermore, in vivo, and in vitro studies have shown that differential expression of these genes in disease conditions due to the influence of nsSNPs abundance may be associated with promoting the development of cancer and cardiovascular diseases. Preliminary screening using computational methods can be a helpful start in understanding the effects of mutations in APOC2 and APOA5 on lipid metabolism; however, further wet-lab experiments would further strengthen the conclusions drawn from the computational study.
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Doenças Cardiovasculares , Neoplasias , Humanos , Apolipoproteína A-V/genética , Apolipoproteína C-II/genética , Doenças Cardiovasculares/genética , Polimorfismo de Nucleotídeo Único , Proteínas de TransporteRESUMO
Erythromycin fermentation residue (EFR) is a solid waste generated from the fermentation process of erythromycin A production. Some byproducts are produced during the fermentation process of erythromycin A production, and erythromycin A can also undergo hydrolysis and biodegradation reactions in the environment with the formation of transformation products. Herein, an accurate analytical method was established and validated to quantify erythromycin A, two byproducts and five hydrolysis or biodegradation products, in solid or semi-solid media of waste EFR and the amended soil. The method mainly included ultrasonic solvent extraction, solid phase extraction, and ultra-performance liquid chromatography-tandem mass spectrometry quantification. All analytes could be effectively extracted in a single process, and the recoveries ranged from 76% to 122% for different matrices. Low matrix effects and excellent precision were achieved by optimizing the mass spectrometry parameters, extraction solution, number of extractions and eluent. This method was applied to evaluate the residual analytes in EFR, treated EFR after industrial-scale hydrothermal treatment, and the subsequent soil application. Seven analytes were detected in the EFR, while six were found in the treated EFR and amended soils. The concentration of erythromycin A in EFR was 1,629 ± 100 mg/kg·TS, and the removal efficiency of hydrothermal treatment (180 °C, 60 min) was about 99.6%. Three hydrolysis products were the main residuals in treated EFR, with anhydroerythromycin A showing the highest concentration. The concentrations of the analytes in soil ranged from 2.17 ± 1.04 to 92.33 ± 20.70 µg/kg·TS, and anhydroerythromycin A contributed 65%-77% of the total concentration. Erythromycin B, a byproduct, was still detected in soil. This work provides an accurate analytical method which would be useful to evaluate the potential risk of byproducts and transformation products of erythromycin A in environment.
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Solo , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Solo/química , Fermentação , Eritromicina , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta PressãoRESUMO
Previous studies have shown that interferon-mediated antiviral activity is subtype-dependent. Using a whole transcriptome procedure, we aimed to characterize the small RNA transcriptome (sRNA-Seq) and specifically the differential microRNA (miRNA) responses in porcine alveolar macrophages (PAMs) upon antiviral activation during viral infection and interferon (IFN) stimulation. Data showed that near 90% of the qualified reads of sRNA were miRNAs, and about 10% of the other sRNAs included rRNA, snoRNA, snRNA, and tRNA in order of enrichment. As the majority of sRNA (>98%) were commonly detected in all PAM samples under different treatments, about 2% sRNA were differentially expressed between the different antiviral treatments. Focusing on miRNA, 386 miRNA were profiled, including 331 known and 55 novel miRNA sequences, of which most were ascribed to miRNA families conserved among vertebrates, particularly mammalian species. Of the miRNA profiles comparably generated across the different treatments, in general, significantly differentially expressed miRNA (SEM) demonstrated that: (1) the wild-type and vaccine strains of a porcine arterivirus (a.k.a., PRRSV) induced nearly reversed patterns of up- or down-regulated SEMs; (2) similar SEM patterns were found among the treatments by the vaccine strain and antiviral IFN-α1/-ω5 subtypes; and (3) the weak antiviral IFN-ω1, however, remarked a suppressive SEM pattern as to SEMs upregulated in the antiviral treatments by the vaccine and IFN-α1/-ω5 subtypes. Further articulation identified SEMs commonly or uniquely expressed in different treatments, and experimentally validated that some SEMs including miR-10b and particularly miR-9-1 acted significantly in regulation of differential antiviral reactions stimulated by different IFN subtypes. Therefore, this study provides a general picture of porcine sRNA composition and pinpoints key SEMs underlying antiviral regulation in PAMs correlated to a typical respiratory RNA virus in pigs.
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Interferons , MicroRNAs , Suínos , Animais , Interferons/genética , Macrófagos Alveolares , Transcriptoma , Antivirais , MicroRNAs/genética , Mamíferos/genéticaRESUMO
Water resources are a major factor in the spatial layout of agricultural production and urban construction, which is an important part of China's ongoing territorial spatial planning. In order to assess the constraining and guiding effects of water resources on territorial spatial planning, water resources suitability evaluation needs to be carried out at the grid scale. Traditional basin or regional-scale indicators of water resources cannot satisfy the requirements with high spatial accuracy in territorial spatial planning, because the internal differences could not be described. In this study, irrigation water supply cost index (CIA) and urban water supply cost index (CIU) were evaluated to characterize the affordability of potential water supply costs by simulating of optimal water supply path. Further, grid-scale indexes of water resource suitability for agricultural production (WRSA) and for urban construction (WRSU) were constructed. The grades of WRSA and WRSU were classified at a 20 m grid scale in Baiyin City. The areas of water resources that were suitable, relatively suitable, less suitable, and unsuitable for agricultural production were 381.0 km2, 3354.7 km2, 3663.9 km2, and 12,700.7 km2, respectively, accounting for 1.9%, 16.7%, 18.2%, and 63.2% of the total area of Baiyin City. The areas of water resources that were suitable, relatively suitable, less suitable, and unsuitable for urban construction were 1657.7 km2, 4184.5 km2, 1177.7 km2, and 13,075.7 km2, respectively, accounting for 8.2%, 20.8%, 5.9%, and 65.1% of the total area of Baiyin City. Coupling analysis with land use and land resources suitability were carried out in this study, which showed that the grid-scale WRSA and WRSU could well characterize the spatial differences of water resources suitability for agricultural production and urban construction. The results of the Geodetector-based study show that the WRSA and WRSU indicators have better explanatory power for the land-use spatial distribution compared to indicators such as water distance. Therefore, the indexes could provide scientific support to delimit agricultural space and urban space, and are effective means of "determining regional functions by water resources" in territorial spatial planning. Furthermore, the indexes could be applied to other arid and semi-arid areas, and also hilly areas, where water supply suitability plays a restrictive role in agricultural production and urban construction.
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Conservação dos Recursos Naturais , Recursos Hídricos , China , Cidades , Planejamento de Cidades , Água , Abastecimento de ÁguaRESUMO
Soybean is widely used as a kind of bean for daily consumption. Chickpea is increasingly utilised because of its good healthcare function. At present, using chickpeas could have better results than soybeans in some areas. Previous studies of the two legumes focused on certain components and failed to fully reveal the differences between the two legumes. Thus, understanding the comprehensive similarities and differences between the two legumes is necessary to apply and develop these legumes effectively. In this study, we performed a UPLC-ESI-MS/MS-based widely targeted metabolomics analysis on two legumes. A total of 776 metabolites (including primary metabolites and secondary metabolites) were detected, which were divided into more than a dozen broad categories. The differential analysis of these metabolites showed that there were 480 metabolites with significant differences in relative contents between the two legumes. Compared with soybean, the expression of 374 metabolites of chickpea was down-regulated and that of 106 metabolites was up-regulated. The metabolic pathway analysis showed significant differences in the flavonoids biosynthesis, phenylpropanoid biosynthesis, linoleic acid metabolism and alkaloid biosynthesis between the two legumes. The advantages and applicability of the two kinds of legumes were confirmed through the analysis of anti-diabetic components. Moreover, some novel compounds (with contents higher than that of soybean) with hypoglycaemic activity were found in chickpea. This study provides an important reference for the in-depth study and comparative application of soybean and chickpea.
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Cicer , Diabetes Mellitus , Fabaceae , Metabolômica/métodos , Glycine max , Espectrometria de Massas em TandemRESUMO
Background: Thioesterase superfamily member 6 (THEM6) has been implicated in the development and progression of various cancers. However, prior research emphasized on its regulatory role merely, we aim to investigate the effect of THEM6 gene on the immunological role and its relationship with molecular subtype in bladder cancer (BLCA). Methods: Through pan-cancer analysis, we explored the THEM6 expression pattern and immunological role using The Cancer Genome Atlas (TCGA) database. In addition, we performed a correlation of THEM6 and its immunological functions, including immunomodulators, immune checkpoints, cancer immunity cycles, T cell inflamed score, and tumor-infiltrating immune cells in the BLCA tumor microenvironment (TME) based on TCGA and BLCA microarray cohort from Xiangya Hospital. We also assessed the accuracy of THEM6 in predicting the molecular subtype and its response to different interventions in BLCA. Finally, we computed and validated a prediction model established by THEM6-related different expressed immune-related genes that might help in BLCA prognosis. Results: THEM6 led to immunosuppression in BLCA TME. Furthermore, there was a downregulation in the immunological functions. Besides, THEM6 could effectively distinguish BLCA molecular subtypes, and THEM6 low expression implied basal subtype that was more effective to several interventions, such as immune checkpoint blockade (ICB) therapies, neoadjuvant chemotherapy, and radiotherapy. While THEM6 high expression indicated luminal subtype, hyperprogression and better response to targeted therapies, such as blocking THEM6 and several immune-inhibited oncogenic pathways. Conclusions: THEM6 may be with potential immune-modulating properties and may become a potential new immunotherapy target for BLCA. THEM6 could accurately predict the molecular subtype of BLCA, which was helpful for guiding the treatment. Simultaneously, the prediction model may exhibit an excellent predictive value in patients with BLCA.
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Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Microambiente Tumoral/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
One of the largest impediments for commercial swine production is the presence of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a devastating RNA viral infection that is responsible for over $1 billion in loss in the U.S. annually. The challenge with combating PRRSV is a combination of the effect of an extraordinary rate of mutation, the ability to infect macrophages, and subversion of host immune response through a series of actions leading to both immunomodulation and immune evasion. Currently there are a handful of commercial vaccines on the market that have been shown to be effective against homologous infections, but struggle against heterologous or mixed strain infections. However, vaccination is the current best strategy for combating PRRSV, making research into new vaccine technology key. To address these issues with PRRSV and host antiviral functions a novel modified-live vaccine (MLV) able to stimulate known antiviral interferons was created and examined for its ability to potentiate effective immunity and better protection. Here, we examine gene expression in the liver of pigs vaccinated with our novel vaccine, given the liver's large role in antiviral responses and vaccine metabolism. Our study indicated that pigs administered the novel vaccine experience homeostatic gene expression consistent with less inflammation and T-cell depletion risk than pigs administered the commercial vaccine.
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BACKGROUND: Sepsis is the leading cause of death in intensive care units and is characterized by multiple organ failure, including dysfuction of the immune system and brain. This study aims to determine the differential effect of sepsis on specific circulating immune cell subsets compared with brain transcriptome and identify the genes co-expressed by them, so as to identify key genes and regulatory factors involved in the pathogenesis of sepsis induced brain injury and identify novel therapeutic targets. METHODS: The GSE133822 and GSE135838 datasets were obtained from the Gene Expression Omnibus (GEO) database and utilized for bioinformatics analyses. Functional enrichment analysis was used to identify commonly expressed genes that were differentially expressed between sepsis patients and non-sepsis patients with critical illness; protein-protein interaction (PPI) networks were also generated. Then, key transcriptomic biomarkers were further validated in an external dataset from the GEO. We also investigated the expression of key mRNAs in peripheral blood mononuclear cells (PBMCs) from sepsis patients by quantitative PCR (qPCR) and an in-vitro model stimulated by lipopolysaccharide (LPS) was generated in brain cell lines. RESULTS: The transcriptomic profiles of brain tissue were relatively similar as those of specific immune cells. In addition, our validation showed that these key genes were up regulated both in PBMCs in sepsis patients and LPS-treated brain cells. CONCLUSION: Brain injury in sepsis was correlated with circulating immune responses, and the expression of DEFA3, MMP8, MMP9 and LCN2 might be potential diagnostic biomarkers as well as therapeutic target in septic brain dysfunction.
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Encéfalo/metabolismo , Sepse/sangue , Sepse/genética , Transcriptoma , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular , Bases de Dados Genéticas , HumanosRESUMO
The sorption isotherms of polychlorinated biphenyls (PCBs) on carbons (coal based activated carbon named AC and hardwood derived biochar named BC) and natural organic matter (NOM) loaded carbons were examined and carbon-water partition coefficients (KC-W-PCB) were calculated. The purpose was to accurately predict the effectiveness of in-situ carbon treatments on the sediment impacted with hydrophobic organic chemicals (HOCs). For 1 month sorption, AC KC-W-PCB values were significantly higher than BC, corresponding to the much larger surface area (particularly in mesopores) for AC. BC KC-W-PCB values were correlated with PCB total surface area (TSA) and octanol-water partition coefficient (logKow). After loading with NOM, AC adsorption to PCBs strongly reduced and the fitted Freundlich exponents (n) decreased with increasing NOM level. However, NOM loading slightly impacted BC sorption and exhibited an opposite effect on BC n values. It is illustrated that the sorption mechanisms are different between AC and BC thereby the influences of NOM on sorption characteristics differ vastly. As the sorption time increased from 1 month to 6 months, an increase is observed in BC sorption extent but simultaneously NOM reduction effect on BC sorption increases, implying that more accurately evaluating BC application as an in-situ sorbent amendment for HOC impacted sediment need further investigation. On the contrary, AC adsorption attenuation caused by NOM coating greatly decreases over time, encouraging AC application as a sediment amendment.
Assuntos
Bifenilos Policlorados , Adsorção , Carvão Vegetal , Sedimentos Geológicos , Bifenilos Policlorados/análiseRESUMO
Per- and polyfluoroalkyl substances (PFASs) are artificial persistent organic pollutants ubiquitous in ecosystem, and their bioaccumulation and adverse outcomes in plants have attracted extensive concerns. Here, we review the toxic effects of PFASs encountered by various plants from physiological, biochemical and molecular perspectives. The exposure routes and bioaccumulation of PFASs in plants from contaminated sites are also summarized. The bioaccumulation of PFASs in plants from contaminated sites varied between ng/g and µg/g levels. The 50% inhibition concentration of PFASs for plant growth is often several orders of magnitude higher than the environmentally relevant concentrations (ERCs). ERCs of PFASs rarely lead to obvious phenotypic/physiological damages in plants, but markedly perturb some biological activities at biochemical and molecular scales. PFAS exposure induces the over-generated reactive oxygen species and further damages plant cell structure and organelle functions. A number of biochemical activities in plant cells are perturbed, such as photosynthesis, gene expression, protein synthesis, carbon and nitrogen metabolisms. To restore the desire states of cells exposed to PFASs, plants initiate several detoxifying mechanisms, including enzymatic antioxidants, non-enzymatic antioxidants, metallothionein genes and metabolic reprogramming. Future challenges and opportunities in PFAS phytotoxicity studies are also proposed in the review.
Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Bioacumulação , Ecossistema , Fluorocarbonos/análise , Fluorocarbonos/toxicidade , Plantas , Poluentes Químicos da Água/análiseRESUMO
The ß2-adrenergic receptor (ß2AR) is a G-protein-coupled receptor (GPCR) that responds to the hormone adrenaline and is an important drug target in the context of respiratory diseases, including asthma. ß2AR function can be regulated by post-translational modifications such as phosphorylation and ubiquitination at the C-terminus, but access to the full-length ß2AR with well-defined and homogeneous modification patterns critical for biochemical and biophysical studies remains challenging. Here, we report a practical synthesis of differentially modified, full-length ß2AR based on a combined native chemical ligation (NCL) and sortase ligation strategy. An array of homogeneous samples of full-length ß2ARs with distinct modification patterns, including a full-length ß2AR bearing both monoubiquitination and octaphosphorylation modifications, were successfully prepared for the first time. Using these homogeneously modified full-length ß2AR receptors, we found that different phosphorylation patterns mediate different interactions with ß-arrestin1 as reflected in different agonist binding affinities. Our experiments also indicated that ubiquitination can further modulate interactions between ß2AR and ß-arrestin1. Access to full-length ß2AR with well-defined and homogeneous modification patterns at the C-terminus opens a door to further in-depth mechanistic studies into the structure and dynamics of ß2AR complexes with downstream transducer proteins, including G proteins, arrestins, and GPCR kinases.