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Recent work suggests that cholesterol metabolism impacts innate immune responses against infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we have shown that upon DNA and RNA viral infection, macrophages reduced 7-dehydrocholesterol reductase (DHCR7) expression. DHCR7 deficiency or treatment with the natural product 7-dehydrocholesterol (7-DHC) could specifically promote phosphorylation of IRF3 (not TBK1) and enhance type I interferon (IFN-I) production in macrophages. We further elucidated that viral infection or 7-DHC treatment enhanced AKT3 expression and activation. AKT3 directly bound and phosphorylated IRF3 at Ser385, together with TBK1-induced phosphorylation of IRF3 Ser386, to achieve IRF3 dimerization. Deletion of DHCR7 and the DHCR7 inhibitors including AY9944 and the chemotherapy drug tamoxifen promoted clearance of Zika virus and multiple viruses in vitro or in vivo. Taken together, we propose that the DHCR7 inhibitors and 7-DHC are potential therapeutics against emerging or highly pathogenic viruses.
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Deshidrocolesteroles/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Interferón Tipo I/biosíntesis , Macrófagos/inmunología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Estomatitis Vesicular/inmunología , Células A549 , Animales , Línea Celular , Colesterol/metabolismo , Activación Enzimática/inmunología , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Interferencia de ARN , ARN Interferente Pequeño/genética , Virus de la Estomatitis Vesicular Indiana/inmunologíaRESUMEN
Plants are unique with tremendous chemical diversity and metabolic complexity, which is highlighted by estimates that green plants collectively produce metabolites numbering in the millions. Plant metabolites play crucial roles in all aspects of plant biology, like growth, development, stress responses, etc. However, the lack of a reference metabolome for plants, and paucity of high-quality standard compound spectral libraries and related analytical tools, have hindered the discovery and functional study of phytochemicals in plants. Here, by leveraging an advanced LC-MS platform, we generated untargeted mass spectral data from >150 plant species collected across the five major phyla. Using a self-developed computation protocol, we constructed reference metabolome for 153 plant species. A 'Reference Metabolome Database for Plants' (RefMetaPlant) was built to encompass the reference metabolome, integrated standard compound mass spectral libraries for annotation, and related query and analytical tools like 'LC-MS/MS Query', 'RefMetaBlast' and 'CompoundLibBlast' for searches and profiling of plant metabolome and metabolite identification. Analogous to a reference genome in genomic research, RefMetaPlant provides a powerful platform to support plant genome-scale metabolite analysis to promote knowledge/data sharing and collaboration in the field of metabolomics. RefMetaPlant is freely available at https://www.biosino.org/RefMetaDB/.
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Bases de Datos Factuales , Metaboloma , Cromatografía Liquida , Metaboloma/genética , Metabolómica/métodos , Plantas/metabolismo , Espectrometría de Masas en TándemRESUMEN
Air humidity significantly impacts plant physiology. However, the upstream elements that mediate humidity sensing and adaptive responses in plants remain largely unexplored. In this study, we define high humidity-induced cellular features of Arabidopsis plants and take a quantitative phosphoproteomics approach to obtain a high humidity-responsive landscape of membrane proteins, which we reason are likely the early checkpoints of humidity signaling. We found that a brief high humidity exposure (i.e., 0.5 h) is sufficient to trigger extensive changes in membrane protein abundance and phosphorylation. Enrichment analysis of differentially regulated proteins reveals high humidity-sensitive processes such as 'transmembrane transport', 'response to abscisic acid', and 'stomatal movement'. We further performed a targeted screen of mutants, in which high humidity-responsive pathways/proteins are disabled, to uncover genes mediating high humidity sensitivity. Interestingly, ethylene pathway mutants (i.e., ein2 and ein3eil1) display a range of altered responses, including hyponasty, reactive oxygen species level, and responsive gene expression, to high humidity. Furthermore, we observed a rapid induction of ethylene biosynthesis genes and ethylene evolution after high humidity treatment. Our study sheds light on the potential early signaling events in humidity perception, a fundamental but understudied question in plant biology, and reveals ethylene as a key modulator of high humidity responses in plants.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Humedad , Etilenos/metabolismo , Arabidopsis/metabolismo , Proteínas de la Membrana/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Chemical compositions of crops are of great agronomical importance, as crops serve as resources for nutrition, energy, and medicines for human and livestock. For crop metabolomics research, the lack of crop reference metabolome and high-quality reference compound mass spectra, as well as utilities for metabolic profiling, has hindered the discovery and functional study of phytochemicals in crops. To meet these challenging needs, we have developed the Crop Metabolome database (abbreviated as CropMetabolome) that is dedicated to the construction of crop reference metabolome, repository, and dissemination of crop metabolomic data, and profiling and analytic tools for metabolomics research. CropMetabolome contains a metabolomics database for more than 50 crops (belonging to eight categories) that integrated self-generated raw mass spectral data and public-source datasets. The reference metabolome for 59 crop species was constructed, which have functions that parallel those of reference genome in genomic studies. CropMetabolome also contains 'Standard compound mass spectral library', 'Flavonoids library', 'Pesticide library', and a set of related analytical tools that enable metabolic profiling based on a reference metabolome (CropRefMetaBlast), annotation and identification of new metabolites (CompoundLibBlast), deducing the structure of novel flavonoid derivatives (FlavoDiscover), and detecting possible residual pesticides in crop samples (PesticiDiscover). In addition, CropMetabolome is a repository to share and disseminate metabolomics data and a platform to promote collaborations to develop reference metabolome for more crop species. CropMetabolome is a comprehensive platform that offers important functions in crop metabolomics research and contributes to improve crop breeding, nutrition, and safety. CropMetabolome is freely available at https://www.cropmetabolome.com/.
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Productos Agrícolas , Bases de Datos Factuales , Metaboloma , Metabolómica , Productos Agrícolas/metabolismo , Productos Agrícolas/genética , Metabolómica/métodos , Flavonoides/metabolismo , Espectrometría de MasasRESUMEN
Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine-fed mice showed better cold tolerance. In mice with diet-induced obesity, the asparagine-fed group was more responsive to ß3-adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and 13 C-glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis.
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Asparagina/farmacología , Glucólisis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Termogénesis/efectos de los fármacos , Animales , Células Cultivadas , Frío , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Metabolómica , RatonesRESUMEN
Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following T. gondii infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in T. gondii-infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab in vitro, the expression levels of Arg-1, IL-10, C/EBPß, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C/EBPß to the promoters of ARG1 and IL10 was decreased in human decidual MDSCs with T. gondii infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by T. gondii infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after T. gondii infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C/EBPß signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes.
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Células Supresoras de Origen Mieloide , Toxoplasma , Toxoplasmosis , Animales , Femenino , Humanos , Ratones , Embarazo , Receptor 2 Celular del Virus de la Hepatitis A/genética , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Células Supresoras de Origen Mieloide/metabolismo , Resultado del Embarazo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Toxoplasma/metabolismo , Toxoplasmosis/metabolismoRESUMEN
Reproduction, a fundamental feature of all known life, closely correlates with energy homeostasis. The control of synthesizing and mobilizing lipids are dynamic and well-organized processes to distribute lipid resources across tissues or generations. However, how lipid homeostasis is precisely coordinated during insect reproductive development is poorly understood. Here we describe the relations between energy metabolism and reproduction in the silkworm, Bombyx mori, a lepidopteran model insect, by using CRISPR/Cas9-mediated mutation analysis and comprehensively functional investigation on two major lipid lipases of Brummer (BmBmm) and hormone-sensitive lipase (BmHsl), and the sterol regulatory element binding protein (BmSrebp). BmBmm is a crucial regulator of lipolysis to maintain female fecundity by regulating the triglyceride (TG) storage among the midgut, the fat body, and the ovary. Lipidomics analysis reveals that defective lipolysis of females influences the composition of TG and other membrane lipids in the BmBmm mutant embryos. In contrast, BmHsl mediates embryonic development by controlling sterol metabolism rather than TG metabolism. Transcriptome analysis unveils that BmBmm deficiency significantly improves the expression of lipid synthesis-related genes including BmSrebp in the fat body. Subsequently, we identify BmSrebp as a key regulator of lipid accumulation in oocytes, which promotes oogenesis and cooperates with BmBmm to support the metabolic requirements of oocyte production. In summary, lipid homeostasis plays a vital role in supporting female reproductive success in silkworms.
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Bombyx , Animales , Femenino , Bombyx/genética , Bombyx/metabolismo , Oogénesis , Ovario , Desarrollo Embrionario , Lípidos , Proteínas de Insectos/metabolismoRESUMEN
In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis.
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OBJECTIVES: This study aimed to investigate the value of a deep learning (DL) model based on greyscale ultrasound (US) images for precise assessment and accurate diagnosis of primary Sjögren's syndrome (pSS). METHODS: This was a multicentre prospective analysis. All pSS patients were diagnosed according to 2016 ACR/EULAR criteria. 72 pSS patients and 72 sex- and age-matched healthy controls recruited between January 2022 and April 2023, together with 41 patients and 41 healthy controls recruited from June 2023 to February 2024 were used for DL model development and validation, respectively. DL model was constructed based on the ResNet 50, input with preprocessed all participants' bilateral submandibular glands (SMGs), parotid glands (PGs), and lacrimal glands (LGs) greyscale US images. Diagnostic performance of the model was compared with two radiologists. The accuracy of prediction and identification performance of DL model were evaluated by calibration curve. RESULTS: 864 and 164 greyscale US images of SMGs, PGs, and LGs were collected for development and validation of the model. The AUCs of DL model in the SMG, PG, and LG were 0.92, 0.93, 0.91 in the model cohort, and were 0.90, 0.88, 0.87 in the validation cohort respectively, outperforming both radiologists. Calibration curves showed the prediction probability of DL model were consistent with the actual probability in both model cohort and validation cohort. CONCLUSION: DL model based on greyscale US images showed diagnostic potential in the precise assessment of pSS patients in the SMG, PG, and LG, outperforming conventional radiologist evaluation.
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BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.
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Biomarcadores , Desensibilización Inmunológica , Pyroglyphidae , Rinitis Alérgica , Humanos , Rinitis Alérgica/terapia , Rinitis Alérgica/inmunología , Masculino , Desensibilización Inmunológica/métodos , Animales , Femenino , Adulto , Pyroglyphidae/inmunología , Resultado del Tratamiento , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Persona de Mediana Edad , Adulto Joven , Alérgenos/inmunología , Alérgenos/administración & dosificación , Antígenos Dermatofagoides/inmunología , Inyecciones Subcutáneas , Adolescente , PronósticoRESUMEN
Acute myeloid leukemia (AML) is a notably lethal disease, characterized by malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study seeks to unveil potential therapeutic targets for AML, using a combined approach of microarray analysis and Mendelian randomization (MR). We collected data samples from the Gene Expression Omnibus (GEO) database and extracted pQTL data from genome-wide association studies (GWAS) to identify overlapping genes between the DEGs and GWAS data. Gene enrichment and pathway annotation analyses were performed on these genes. Furthermore, we validated gene expression levels and assessed their clinical relevance. By taking the intersection of these gene sets, we obtained a list of co-expressed genes, including four upregulated genes (REC8, TPM2, ZMIZ1, CD82) and two downregulated genes (IFNAR1, TMCO3). MR analysis demonstrated that genetically predicted protein levels of CD82, REC8, ZMIZ1, and TPM2 were significantly associated with increased odds of AML, while IFNAR1 and TMCO3 showed a protective effect. Gene ontology and KEGG pathway analyses revealed significant enrichment in functions related to female gamete generation, meiosis, p53 signaling pathway, and cardiac muscle contraction. Differences in immune cell profiles were observed between AML survivors and those with poor prognosis, including lower levels of neutrophils and higher levels of follicular helper T cells in the latter group. This study identifies a causal relationship between gene expression and AML and highlights the potential role of REC8 in leukemogenesis, possibly through its impact on gametocyte meiotic abnormalities. The findings provide new insights into the prevention and treatment of leukemia.
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Metabolism of polyamines is of critical importance to physiological processes. Ornithine decarboxylase (ODC) antizyme inhibitors (AZINs) are capable of interacting with antizymes (AZs), thereby releasing ODC from ODC-AZs complex, and promote polyamine biosynthesis. AZINs regulate reproduction, embryonic development, fibrogenesis and tumorigenesis through polyamine and other signaling pathways. Dysregulation of AZINs has involved in multiple human diseases, especially malignant tumors. Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans. Additionally, the high frequencies of RNA-edited AZIN1 in human cancers correlates with increase of cancer cell proliferation, enhancement of cancer cell stemness, and promotion of tumor angiogenesis. In this review, we summarize the current knowledge on the various contribution of AZINs related with potential cancer promotion, cancer stemness, microenvironment and RNA modification, especially underlying molecular mechanisms, and furthermore explored its promising implication for cancer diagnosis and treatment.
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Ornitina Descarboxilasa , Investigación Biomédica Traslacional , Humanos , Ornitina Descarboxilasa/genética , Ornitina Descarboxilasa/metabolismo , Poliaminas/metabolismo , Transformación Celular Neoplásica , ARN , Microambiente TumoralRESUMEN
BACKGROUND: Cerebral palsy is a severe motor disability in childhood that poses challenges for children, families, and society. Rhesus macaques are the preferred animals for cerebral palsy model, but surgical excision of motor cortex has low success rate and high cost. In this work, we created cerebral palsy rhesus macaque models by intrathecal injection of bilirubin. METHODS: The puncture point for injection was identified as the intervertebral disc space two, located below the intersection of the iliac crest line and the posterior median line. RESULTS: The models showed abnormal posture and increased muscle tension. Diffuse deposits of bilirubin were found in the basal ganglia from the magnetic resonance imaging. Pathological slides also revealed the presence of brain lesions, such as vacuole formation, contraction of neuronal nuclei, and deep staining of nuclei in the histopathological sections of the hippocampus and basal ganglia. CONCLUSION: The model's symptoms closely resemble those observed in humans with spastic cerebral palsy.
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Parálisis Cerebral , Personas con Discapacidad , Trastornos Motores , Humanos , Animales , Parálisis Cerebral/veterinaria , Parálisis Cerebral/patología , Macaca mulatta , Análisis Costo-BeneficioRESUMEN
This research elucidates the potential of Lycium barbarum residue (LBR), a by-product rich in bioactive substances, as a dietary supplement in aquaculture, especially for herbivorous fish like grass carp. In a detailed 120-day feeding trial, the impacts of varying LBR levels on juvenile grass carp were assessed, focusing on growth performance, survival rate, biochemical markers, and liver health. The study identified a 6% inclusion rate of LBR as optimal for enhancing survival and growth while mitigating hepatic lipid accumulation. Composition analysis of this diet revealed high concentrations of polysaccharides and flavonoids. Notably, the intake of LBR was found to enhance the antioxidant and immune-related enzymatic activities in the liver. Furthermore, it contributed to a reduction in hepatic fat deposition by decreasing the levels of triglycerides (TG) and total cholesterol (T-CHO) both in the liver and serum. Transcriptomic analysis of the liver highlighted LBR's substantial influence on lipid metabolism pathways, including the PPAR signaling pathway, primary bile acid biosynthesis, cholesterol metabolism, bile secretion, fat digestion and absorption, fatty acid degradation and fatty acid biosynthesis. Further, the expression level of genes pinpointed significant downregulation of fasn and dgat2, alongside upregulation of genes like pparda, cpt1b, cpt1ab and abca1b, in response to LBR supplementation. Overall, the findings present LBR as a promising enhancer of growth and survival in grass carp, with significant benefits in promoting fat metabolism and liver health, offering valuable insights for aquacultural nutrition strategies.
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Alimentación Animal , Carpas , Dieta , Suplementos Dietéticos , Hígado , Animales , Carpas/crecimiento & desarrollo , Carpas/inmunología , Alimentación Animal/análisis , Hígado/metabolismo , Suplementos Dietéticos/análisis , Dieta/veterinaria , Metabolismo de los Lípidos/efectos de los fármacos , Lycium/químicaRESUMEN
miRNAs are increasingly recognized for their crucial role in autophagy processes. Recent research has highlighted the significant function of autophagy in modulating immune responses. Within this context, specific miRNAs have been identified as indirect mediators of immune functions through their modulation of autophagy. In this study, we verified that miR-193b-5p simultaneously targeted the grass carp autophagy-related gene deptor, thereby reducing autophagy levels in CIK cells. Moreover, we found the expression levels of miR-193b-5p and deptor responding to pathogen infections in the GCRV-infected CIK cells. Notably, the overexpression of miR-193b-5p was found to induce the GCRV replication and reduce the irf3, irf7 and IFN1 expression. These findings also demonstrated that grass carp miR-193b-5p impacted the proliferation, migration, and antiapoptotic abilities of CIK cells. All the above results indicated that miR-193b-5p was linked to grass carp autophagy and played a vital role in antiviral immunity by targeting deptor. Our study may provide important insights into autophagy-related miRNAs and their roles in defense and immune mechanisms against pathogens in teleost.
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Carpas , Enfermedades de los Peces , MicroARNs , Infecciones por Reoviridae , Reoviridae , Animales , Reoviridae/fisiología , Carpas/metabolismo , Autofagia , MicroARNs/metabolismo , Proteínas de Peces/genéticaRESUMEN
Recent studies have increasingly linked miRNAs with the modulation of inflammatory responses and immunosuppressive activities. This investigation reveals that mir-30e-3p selectively binds to and modulates gimap8, as demonstrated by luciferase reporter assays and qPCR analyses. Upon LPS stimulation of CIK cells, mir-30e-3p expression was notably elevated, inversely correlating with a decrease in gimap8 mRNA levels. Overexpression of mir-30e-3p attenuated the mRNA levels of pro-inflammatory cytokines beyond the effect of LPS alone, suggesting a regulatory role of mir-30e-3p in inflammation mediated by the gimap8 gene. These insights contribute to our understanding of the complex mechanisms governing inflammatory and immune responses.
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Carpas , Proteínas de Peces , Inflamación , Lipopolisacáridos , MicroARNs , Animales , MicroARNs/genética , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Lipopolisacáridos/farmacología , Carpas/genética , Carpas/inmunología , Inflamación/genética , Inflamación/inmunología , Regulación de la Expresión Génica/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Riñón/inmunología , Inmunidad Innata/genética , Línea CelularRESUMEN
Recent research has highlighted complex and close interaction between miRNAs, autophagy, and viral infection. In this study, we observed the autophagy status in CIK cells infected with GCRV at various time points. We found that GCRV consistently induced cellar autophagy from 0 h to 12 h post infection. Subsequently, we performed deep sequencing on CIK cells infected with GCRV at 0 h and 12 h respectively, identifying 38 DEMs and predicting 9581 target genes. With the functional enrichment analyses of GO and KEGG, we identified 35 autophagy-related target genes of these DEMs, among which akt3 was pinpointed as the most central hub gene using module assay of the PPI network. Then employing the miRanda and Targetscan programs for prediction, and verification through a double fluorescent enzyme system and qPCR method, we confirmed that miR-193 b-3p could target the 3'-UTR of grass carp akt3, reducing its gene expression. Ultimately, we illustrated that grass carp miR-193 b-3p could promote autophagy in CIK cells. Above results collectively indicated that miRNAs might play a critical role in autophagy of grass carp during GCRV infection and contributed significantly to antiviral immunity by targeting autophagy-related genes. This study may provide new insights into the intricate mechanisms involved in virus, autophagy, and miRNAs.
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Autofagia , Carpas , Enfermedades de los Peces , MicroARNs , Proteínas Proto-Oncogénicas c-akt , Infecciones por Reoviridae , Reoviridae , Animales , MicroARNs/genética , MicroARNs/inmunología , Carpas/inmunología , Carpas/genética , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Infecciones por Reoviridae/inmunología , Infecciones por Reoviridae/veterinaria , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/inmunología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reoviridae/fisiología , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Línea Celular , Regulación de la Expresión Génica/inmunologíaRESUMEN
Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.
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Quimiometría , Metaboloma , Extractos Vegetales , Espectrometría de Masas , Cromatografía Liquida , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Dual-source drinking water distribution systems (DWDS) over single-source water supply systems are becoming more practical in providing water for megacities. However, the more complex water supply problems are also generated, especially at the hydraulic junction. Herein, we have sampled for a one-year and analyzed the water quality at the hydraulic junction of a dual-source DWDS. The results show that visible changes in drinking water quality, including turbidity, pH, UV254, DOC, residual chlorine, and trihalomethanes (TMHs), are observed at the sample point between 10 and 12 km to one drinking water plant. The average concentration of residual chlorine decreases from 0.74 ± 0.05 mg/L to 0.31 ± 0.11 mg/L during the water supplied from 0 to 10 km and then increases to 0.75 ± 0.05 mg/L at the end of 22 km. Whereas the THMs shows an opposite trend, the concentration reaches to a peak level at hydraulic junction area (10-12 km). According to parallel factor (PARAFAC) and high-performance size-exclusion chromatography (HPSEC) analysis, organic matters vary significantly during water distribution, and tryptophan-like substances and amino acids are closely related to the level of THMs. The hydraulic junction area is confirmed to be located at 10-12 km based on the water quality variation. Furthermore, data-driven models are established by machine learning (ML) with test R2 higher than 0.8 for THMs prediction. And the SHAP analysis explains the model results and identifies the positive (water temperature and water supply distance) and negative (residual chlorine and pH) key factors influencing the THMs formation. This study conducts a deep understanding of water quality at the hydraulic junction areas and establishes predictive models for THMs formation in dual-sources DWDS.
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Agua Potable , Aprendizaje Automático , Calidad del Agua , Abastecimiento de Agua , Agua Potable/química , Agua Potable/análisis , Trihalometanos/análisis , Modelos Teóricos , Contaminantes Químicos del Agua/análisis , Cloro/análisisRESUMEN
Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.