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Embryonic development is a key developmental event in plant sexual reproduction; however, regulatory networks of plant early embryonic development, particularly the effects and functional mechanisms of phospholipid molecules are still unknown due to the limitation of sample collection and analysis. We innovatively applied the microspore-derived in vitro embryogenesis of Brassica napus and revealed the dynamics of phospholipid molecules, especially phosphatidic acid (PA, an important second messenger that plays an important role in plant growth, development, and stress responses), at different embryonic developmental stages by using a lipidomics approach. Further analysis of Arabidopsis mutants deficiency of CDS1 and CDS2 (cytidinediphosphate diacylglycerol synthase, key protein in PA metabolism) revealed the delayed embryonic development from the proembryo stage, indicating the crucial effect of CDS and PA metabolism in early embryonic development. Decreased auxin level and disturbed polar localization of auxin efflux carrier PIN1 implicate that CDS-mediated PA metabolism may regulate early embryogenesis through modulating auxin transport and distribution. These results demonstrate the dynamics and importance of phospholipid molecules during embryo development, and provide informative clues to elucidate the regulatory network of embryogenesis.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Diglicéridos , Desarrollo Embrionario , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Ácidos Fosfatidicos/metabolismoRESUMEN
Autophagy, a highly conserved process of protein and organelle degradation, has emerged as a critical regulator in various diseases, including cancer progression. In the context of liver cancer, the predictive value of autophagy-related genes remains ambiguous. Leveraging chip datasets from the TCGA and GTEx databases, we identified 23 differentially expressed autophagy-related genes in liver cancer. Notably, five key autophagy genes, PRKAA2, BIRC5, MAPT, IGF1, and SPNS1, were highlighted as potential prognostic markers, with MAPT showing significant overexpression in clinical samples. In vitro cellular assays further demonstrated that MAPT promotes liver cancer cell proliferation, migration, and invasion by inhibiting autophagy and suppressing apoptosis. Subsequent in vivo studies further corroborated the pro-tumorigenic role of MAPT by suppressing autophagy. Collectively, our model based on the five key genes provides a promising tool for predicting liver cancer prognosis, with MAPT emerging as a pivotal factor in tumor progression through autophagy modulation.
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Autofagia , Neoplasias Hepáticas , Proteínas tau , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Autofagia/genética , Proteínas tau/genética , Proteínas tau/metabolismo , Pronóstico , Línea Celular Tumoral , Survivin/genética , Survivin/metabolismo , Proliferación Celular , Animales , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Biomarcadores de Tumor/genética , Movimiento Celular , Ratones , Apoptosis , Regulación Neoplásica de la Expresión Génica , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismoRESUMEN
How mutations impact protein stability and structure dynamics is crucial for understanding the pathological process and rational drug design. Herein, we establish a time-resolved native mass spectrometry (TR-nMS) platform via a rapid-mixing capillary apparatus for monitoring the acid-initiated protein unfolding process. The molecular details in protein structure unfolding are further profiled by a 193 nm ultraviolet photodissociation (UVPD) analysis of the structure-informative photofragments. Compared with the wild-type dihydrofolate reductase (WT-DHFR), the M42T/H114R mutant (MT-DHFR) exhibits a significant stability decrease in TR-nMS characterization. UVPD comparisons of the unfolding intermediates and original DHFR forms indicate the special stabilization effect of cofactor NADPH on DHFR structure, and the M42T/H114R mutations lead to a significant decrease in NADPH-DHFR interactions, thus promoting the structure unfolding. Our study paves the way for probing the mutation-induced subtle changes in the stability and structure dynamics of drug targets.
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Escherichia coli , Desplegamiento Proteico , Escherichia coli/metabolismo , NADP/metabolismo , Estabilidad Proteica , Mutación , Espectrometría de Masas , Tetrahidrofolato Deshidrogenasa/metabolismoRESUMEN
Covering: up to August 2023Terpenoids, which are widely distributed in animals, plants, and microorganisms, are a large group of natural products with diverse structures and various biological activities. They have made great contributions to human health as therapeutic agents, such as the anti-cancer drug paclitaxel and anti-malarial agent artemisinin. Accordingly, the biosynthesis of this important class of natural products has been extensively studied, which generally involves two major steps: hydrocarbon skeleton construction by terpenoid cyclases and skeleton modification by tailoring enzymes. Additionally, fungi (Ascomycota and Basidiomycota) serve as an important source for the discovery of terpenoids. With the rapid development of sequencing technology and bioinformatics approaches, genome mining has emerged as one of the most effective strategies to discover novel terpenoids from fungi. To date, numerous terpenoid cyclases, including typical class I and class II terpenoid cyclases as well as emerging UbiA-type terpenoid cyclases, have been identified, together with a variety of tailoring enzymes, including cytochrome P450 enzymes, flavin-dependent monooxygenases, and acyltransferases. In this review, our aim is to comprehensively present all fungal terpenoid cyclases identified up to August 2023, with a focus on newly discovered terpenoid cyclases, especially the emerging UbiA-type terpenoid cyclases, and their related tailoring enzymes from 2015 to August 2023.
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Hongos , Terpenos , Terpenos/metabolismo , Terpenos/química , Hongos/metabolismo , Hongos/química , Estructura Molecular , Productos Biológicos/metabolismo , Productos Biológicos/química , Sistema Enzimático del Citocromo P-450/metabolismoRESUMEN
The microscopic visualization of large-scale three-dimensional (3D) samples by optical microscopy requires overcoming challenges in imaging quality and speed and in big data acquisition and management. We report a line-illumination modulation (LiMo) technique for imaging thick tissues with high throughput and low background. Combining LiMo with thin tissue sectioning, we further develop a high-definition fluorescent micro-optical sectioning tomography (HD-fMOST) method that features an average signal-to-noise ratio of 110, leading to substantial improvement in neuronal morphology reconstruction. We achieve a >30-fold lossless data compression at a voxel resolution of 0.32 × 0.32 × 1.00 µm3, enabling online data storage to a USB drive or in the cloud, and high-precision (95% accuracy) brain-wide 3D cell counting in real time. These results highlight the potential of HD-fMOST to facilitate large-scale acquisition and analysis of whole-brain high-resolution datasets.
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Encéfalo/diagnóstico por imagen , Imagenología Tridimensional/métodos , Microscopía/métodos , Microtomía/métodos , Relación Señal-Ruido , Tomografía/métodosRESUMEN
Autoimmune regulator (Aire) and TGF-ß signaling play important roles in central tolerance and peripheral tolerance, respectively, by eliminating or suppressing the activity of autoreactive T cells. We previously demonstrated that dnTGFßRII mice develop a defect in peripheral tolerance and a primary biliary cholangitis (PBC)-like disease. We hypothesized that by introducing the Aire gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrated that, while dnTGFßRII Aire-/- mice do manifest key histological and serological features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA sequencing (RNA-seq) and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFßRII Aire-/- mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti-CD8α antibody significantly alleviated hepatic inflammation and prolonged the life span of these mice. Finally, RNA-seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice developed an autoreactive CD8+ T-cell-mediated autoimmune cholangitis with concurrent hepatitis that exhibited key histological and serological features of the AIH-PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease. © 2023 The Pathological Society of Great Britain and Ireland.
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Colangitis , Hepatitis Autoinmune , Cirrosis Hepática Biliar , Ratones , Animales , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/metabolismo , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/metabolismo , Linfocitos T CD8-positivos , Colangitis/genética , Colangitis/metabolismoRESUMEN
Discovering novel NDM-1 inhibitors is an urgent task for treatment of 'superbug' infectious diseases. In this study, we found that naturally occurring houttuynin and its sulfonate derivatives might be effective NDM-1 inhibitors with novel mechanism, i.e. the attribute of partially covalent inhibition of sulfonate derivatives of houttuynin against NDM-1. Primary structure-activity relationship study showed that both the long aliphatic side chain and the warhead of aldehyde group are vital for the efficiency against NDM-1. The homologs with longer chains (SNH-2 to SNH-5) displayed stronger inhibitory activities with IC50 range of 1.1-1.5 µM, while the shorter chain the weaker inhibition. Further synergistic experiments in cell level confirmed that all these 4 compounds (at 32 µg/mL) recovered the antibacterial activity of meropenem (MER) against E. coli BL21/pET15b-blaNDM-1.
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Antibacterianos , Relación Dosis-Respuesta a Droga , Escherichia coli , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Estructura Molecular , beta-Lactamasas/metabolismo , Inhibidores de beta-Lactamasas/farmacología , Inhibidores de beta-Lactamasas/química , Inhibidores de beta-Lactamasas/síntesis química , Productos Biológicos/farmacología , Productos Biológicos/química , Productos Biológicos/síntesis química , Humanos , Proteínas de Escherichia coliRESUMEN
KEY MESSAGE: Calcium polypeptide plays a key role during cadmium stress responses in rice, which is involved in increasing peroxidase activity, modulating pectin methylesterase activity, and regulating cell wall by reducing malondialdehyde content. Cadmium (Cd) contamination threatens agriculture and human health globally, emphasizing the need for sustainable methods to reduce cadmium toxicity in crops. Calcium polypeptide (CaP) is a highly water-soluble small molecular peptide acknowledged for its potential as an organic fertilizer in promoting plant growth. However, it is still unknown whether CaP has effects on mitigating Cd toxicity. Here, we investigated the effect of CaP application on the ability to tolerate toxic Cd in rice. We evaluated the impact of CaP on rice seedlings under varying Cd stress conditions and investigated the effect mechanism of CaP mitigating Cd toxicity by Fourier transform infrared spectroscopy (FTIR), fluorescent probe dye, immunofluorescent labeling, and biochemical analysis. We found a notable alleviation of Cd toxicity by reduced malondialdehyde content and increased peroxidase activity. In addition, our findings reveal that CaP induces structural alterations in the root cell wall by modulating pectin methylesterase activity. Altogether, our results confirm that CaP not only promoted biomass accumulation but also reduced Cd concentration in rice. This study contributes valuable insights to sustainable strategies for addressing Cd contamination in agricultural ecosystems.
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Cadmio , Malondialdehído , Oryza , Estrés Oxidativo , Pectinas , Oryza/efectos de los fármacos , Oryza/metabolismo , Cadmio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Pectinas/metabolismo , Malondialdehído/metabolismo , Proteínas de Plantas/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/metabolismo , Plantones/crecimiento & desarrollo , Péptidos/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
OBJECTIVE: Research has previously established connections between the intestinal microbiome and the progression of some cancers. However, there is a noticeable gap in the literature in regard to using Mendelian randomisation (MR) to delve into potential causal relationships between the gut microbiota (GM) and basal cell carcinoma (BCC). Therefore, the purpose of our study was to use MR to explore the causal relationship between four kinds of GM (Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae) and BCC. METHODS: We used genome-wide association study (GWAS) data and MR to explore the causal relationship between four kinds of GM and BCC. This study primarily employed the random effect inverse variance weighted (IVW) model for analysis, as complemented by additional methods including the simple mode, weighted median, weighted mode and MRâEgger methods. We used heterogeneity and horizontal multiplicity to judge the reliability of each analysis. MR-PRESSO was mainly used to detect and correct outliers. RESULTS: The random-effects IVW results showed that Bacteroides (OR = 0.936, 95% CI = 0.787-1.113, p = 0.455), Streptococcus (OR = 0.974, 95% CI = 0.875-1.083, p = 0.629), Proteobacteria (OR = 1.113, 95% CI = 0.977-1.267, p = 0.106) and Lachnospiraceae (OR = 1.027, 95% CI = 0.899-1.173, p = 0.688) had no genetic causal relationship with BCC. All analyses revealed no horizontal pleiotropy, heterogeneity or outliers. CONCLUSION: We found that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae do not increase the incidence of BCC at the genetic level, which provides new insight for the study of GM and BCC.
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Carcinoma Basocelular , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neoplasias Cutáneas , Humanos , Carcinoma Basocelular/genética , Carcinoma Basocelular/microbiología , Microbioma Gastrointestinal/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/microbiología , Streptococcus/genética , Proteobacteria/genética , Bacteroides/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Due to the adjustable hybridization activity, antinuclease digestion stability, and superior endocytosis, spherical nucleic acids (SNAs) have been actively developed as probes for molecular imaging and the development of noninvasive diagnosis and image-guided surgery. However, since highly expressed biomarkers in tumors are not negligible in normal tissues, an inevitable background signal and the inability to precisely release probes at the chosen region remain a challenge for SNAs. Herein, we proposed a rationally designed, endogenous enzyme-activatable functional SNA (Ep-SNA) for spatiotemporally controlled signal amplification molecular imaging and combinational tumor therapy. The self-assembled amphiphilic polymer micelles (SM-ASO), which were obtained by a simple and rapid copper-free strain-promoted azide-alkyne cycloaddition click reaction between dibenzocyclooctyne-modified antisense oligonucleotide and azide-containing aliphatic polymer polylactic acid, were introduced as the core elements of Ep-SNA. This Ep-SNA was then constructed by connecting two apurinic/apyrimidinic (AP) site-containing trailing DNA hairpins, which could occur via a hybridization chain reaction in the presence of low-abundance survivin mRNA to SM-ASO through complementary base pairing. Notably, the AP site-containing trailing DNA hairpins also empowered the SNA with the feasibility of drug delivery. Once this constructed intelligent Ep-SNA nanoprobe was specifically cleaved by the highly expressed cytoplasmic human apurinic/apyrimidinic endonuclease 1 in tumor cells, three key elements (trailing DNA hairpins, antisense oligonucleotide, and doxorubicin) could be released to enable subsequent high-sensitivity survivin mRNA imaging and combinational cancer therapy (gene silencing and chemotherapy). This strategy shows great application prospects of SNAs as a precise platform for the integration of disease diagnosis and treatment and can contribute to basic biomedical research.
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Azidas , Neoplasias , Humanos , Survivin , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , ADN , Oligonucleótidos , Oligonucleótidos Antisentido , Imagen Molecular , ARN MensajeroRESUMEN
The chloroplast is a semi-autonomous organelle with a double membrane structure, and its structural stability is a prerequisite for its correct function. Chloroplast development is regulated by known nuclear-encoded chloroplast proteins or proteins encoded within the chloroplast itself. However, the mechanism of chloroplast development regulated by other organelles remains largely unknown. Here, we report that the nuclear-localized DEAD-box RNA helicase 13 (RH13) is essential for chloroplast development in Arabidopsis thaliana. RH13 is widely expressed in tissues and localized to the nucleolus. A homozygous rh13 mutant shows abnormal chloroplast structure and leaf morphogenesis. Proteomic analysis showed that the expression levels of photosynthesis-related proteins in chloroplasts were reduced due to loss of RH13. Furthermore, RNA-sequencing and proteomics data revealed decreases in the expression levels of these chloroplast-related genes, which undergo alternative splicing events in the rh13 mutant. Taken together, we propose that nucleolus-localized RH13 is critical for chloroplast development in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , ARN Helicasas/genética , Proteómica , Cloroplastos/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Gilteritinib is currently approved in China for relapsed/refractory FLT3-mutated acute myeloid leukemia, and it is very important to monitor and report its adverse drug reaction (ADR) after post-marketing. This case report describes a patient who was diagnosed with acute myeloid leukemia harboring FLT3 mutations and developed a severe suspected immune-related enteritis during treatment with gilteritinib for maintenance therapy following allo-hematopoietic stem cell transplantation. According to the Naranjo probability scale, gilteritinib was defined as a 'possible' cause of ADR. Another suspicious inducement, graft-versus-host disease, can not be eluted and might represent a limitation in this case. To the best of our knowledge, this is the first report on gilteritinib-induced severe enteritis and will help physicians to keep vigilant, and detect and deal with time for possible ADR.
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Compuestos de Anilina , Leucemia Mieloide Aguda , Humanos , Mutación , Compuestos de Anilina/uso terapéutico , Pirazinas/efectos adversos , Leucemia Mieloide Aguda/genéticaRESUMEN
Covalent organic polymers are an emerging class of amorphous microporous materials that have raised increasing concerns in analytical chemistry due to their unique structural and surface chemical properties. However, the application of covalent organic polymers as mixed-mode stationary phases in chromatographic separations has rarely been reported. Herein, novel spherical silica hydroxyl-functionalized covalent organic polymer composites were successfully prepared via a layer-by-layer approach. The structure and morphology of the materials were carefully characterized by elemental analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, Brunauer-Emmett-Teller, and contact angle measurements. Baseline separations of various alkylbenzenes, polycyclic aromatic hydrocarbons, and nucleosides and bases were achieved on the prepared stationary phase under reversed-phase/hydrophilic interaction mode. The column efficiencies of 23 853 and 36 580 plates/m were obtained for butylbenzene and uracil, respectively, and the relative standard deviation of the retention time for continuous injections was less than 1.38% (n = 10), suggesting satisfactory column efficiency and repeatability. Additionally, this novel stationary phase realized the complete separation of the endocrine-disrupting chemicals in river water. This work affords a new route for synthesizing covalent organic polymers-based mixed-mode stationary phase and further reveals their great potential in chromatographic separation.
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Cisplatin is highly effective for killing tumor cells. However, as one of its side effects, ototoxicity limits the clinical application of cisplatin. The mechanisms of cisplatin-induced ototoxicity have not been fully clarified yet. SIRT3 is a deacetylated protein mainly located in mitochondria, which regulates a variety of physiological processes in cells. The role of SIRT3 in cisplatin-induced hair cell injury has not been founded. In this study, primary cultured cochlear explants exposed to 5 µM cisplatin, as well as OC-1 cells exposed to 10 µM cisplatin, were used to establish models of cisplatin-induced ototoxicity in vitro. We found that when combined with cisplatin, metformin (75 µM) significantly up-regulated the expression of SIRT3 and alleviated cisplatin-induced apoptosis of hair cells. We regulated the expression of SIRT3 to explore the role of SIRT3 in cisplatin-induced auditory hair cell injury. Overexpression of SIRT3 promoted the survival of auditory hair cells and alleviated the apoptosis of auditory hair cells. In contrast, knockdown of SIRT3 impaired the protective effect of metformin and exacerbated cisplatin injury. In addition, we found that the protective effect of SIRT3 may be achieved by regulating GLUT4 translocation and rescuing impaired glucose uptake caused by cisplatin. Our study confirmed that upregulation of SIRT3 may antagonize cisplatin-induced ototoxicity, and provided a new perspective for the study of cisplatin-induced ototoxicity.
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Antineoplásicos , Metformina , Ototoxicidad , Sirtuina 3 , Humanos , Cisplatino/toxicidad , Antineoplásicos/toxicidad , Sirtuina 3/genética , Ototoxicidad/etiología , Ototoxicidad/prevención & control , Metformina/farmacología , ApoptosisRESUMEN
The indole-3-pyruvic acid (IPA) pathway is the main auxin biosynthesis pathway in the plant kingdom. Local control of auxin biosynthesis through this pathway regulates plant growth and development and the responses to biotic and abiotic stresses. During the past decades, genetic, physiological, biochemical, and molecular studies have greatly advanced our understanding of tryptophan-dependent auxin biosynthesis. The IPA pathway includes two steps: Trp is converted to IPA by TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS/TRYPTOPHAN AMINOTRANSFERASE RELATED PROTEINs (TAA1/TARs), and then IPA is converted to IAA by the flavin monooxygenases (YUCCAs). The IPA pathway is regulated at multiple levels, including transcriptional and post-transcriptional regulation, protein modification, and feedback regulation, resulting in changes in gene transcription, enzyme activity and protein localization. Ongoing research indicates that tissue-specific DNA methylation and miRNA-directed regulation of transcription factors may also play key roles in the precise regulation of IPA-dependent auxin biosynthesis in plants. This review will mainly summarize the regulatory mechanisms of the IPA pathway and address the many unresolved questions regarding this auxin biosynthesis pathway in plants.
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Ácidos Indolacéticos , Plantas , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Plantas/metabolismo , Triptófano-Transaminasa/genética , Triptófano-Transaminasa/metabolismoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a complex disease with several risk factors. The effects of blood metabolites on RA remains elusive. We conducted a genetic correlation scan to explore the relevance of blood metabolism with RA. METHOD: The genome-wide association study (GWAS) dataset of RA(2014) was obtained from a large scale meta-analysis, including 29,880 RA cases and 73,758 controls. The GWAS datasets of 529 blood metabolites were derived from a recently published study. Linkage disequilibrium score regression (LDSC) analysis was performed to evaluate the genetic correlation between each of the blood metabolite and RA(2014). Then we used another GWAS data of RA(2021) and blood metabolites for LDSC analysis to verify whether the same blood metabolites were genetically correlated with RA. Mendelian randomization (MR) analysis was then applied to assess the causal relationship between the significant blood metabolites identified by LDSC and RA(2014). RESULT: Six suggestive blood metabolites were identified for RA(2014), including 10-Undecenoate (correlation coefficient = -0.1686, p value = 0.0394), isovalerylcarnitine (correlation coefficient = 0.1660 p value = 0.0273), proline (correlation coefficient = 0.1647, p value = 0.0145), pantothenate (correlation coefficient = -0.3311, p value = 0.0078), tyrosine (correlation coefficient = 0.1735, p value = 0.0010), X-14057 (correlation coefficient = 0.2695, p value = 0.0373). We identified four blood metabolites may have genetic correlations with RA(2021), including oleoylcarnitine (correlation coefficient = 0.1927, p value = 0.0432), levulinate (correlation coefficient = 0.1008, p value = 0.0413), pantothenate (correlation coefficient = -0.2311, p value = 0.0180), tyrosine (correlation coefficient = 0.1301, p value = 0.0078). There are two identical blood metabolites were found to be related with RA: pantothenate and tyrosine. It was found that there was a significant positive causal relationship between RA (exposure) and 10-Undecenoate (outcome) (ß = 0.0077, SE = 0.0033, p = 0.0192) by MR analysis. CONCLUSION: We investigated the genetic correlation and causal relationship between RA and blood metabolites by LDSC and MR analysis. These results may provide novel insights into the genetic mechanism of RA.
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Artritis Reumatoide , Estudio de Asociación del Genoma Completo , Artritis Reumatoide/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Polimorfismo de Nucleótido Simple , Tirosina/genéticaRESUMEN
Ultraviolet (UV) laser photolysis of hydrogen peroxide (H2O2) for the in situ generation of hydroxyl radicals (â¢OH) is a widely utilized strategy in the oxidation footprinting of native proteins and mass spectrometry (MS)-based structural analysis. However, it remains challenging to realize peroxide-free photochemical oxidation footprinting. Herein, we describe the footprinting of native proteins by chloride-mediated peroxide-free photochemical oxidation of proteins (PPOP). The protein samples are prepared within biocompatible phosphate-buffered saline (PBS) containing 10 mM Gln as radical scavengers and oxidized in a capillary flow reactor directly under a single-pulse (10 ns) irradiation of a 193 nm ArF UV laser. The main oxidized protein residues are CMYWFHLI. We demonstrate that the PPOP-MS strategy is highly sensitive to the protein high-order structures and can be applied to monitor the protein-drug interfaces, which provides a promising footprinting alternative for protein structure-function explorations.
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Cloruros , Peróxido de Hidrógeno , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Espectrometría de Masas/métodos , Oxidación-Reducción , Peróxidos , Proteínas/análisisRESUMEN
Solid-stabilized high internal phase emulsions have received extensive attention. Many previous studies have confirmed that solid emulsifiers in high internal phase Pickering emulsions (HIPPEs) provide a great interface mechanical barrier. With the development of research, novel solid-stabilized emulsions have emerged. These emulsions are stabilized by the electrostatic repulsion between the surfactants and hydrophilic solid particles. They are distinct from Pickering emulsions in that the solid particles do not exist at the oil-water interface, but are dispersed in the continuous phase, so it is called a non-Pickering emulsion. However, high internal phase non-Pickering emulsions (HIPNPEs) are rarely reported. Herein, HIPNPEs that are synergistically stabilized by anionic surfactants with dynamic covalent bonds and negatively charged nano-SiO2 particles were prepared. In the presence of dodecylamine, the acidity causes the dynamic covalent bonds to break and the surfactant to be inactivated. Additionally, the long-chain amine is protonated and adsorbed on nano-SiO2 particles to form a new surfactant for stabilizing HIPPEs. However, alkalinity causes the HIPNPEs to form again. In addition, rheological tests confirmed that the HIPNPEs and HIPPEs had similar rheological behaviors, which were typical gel-like fluids. The emulsion can quickly respond to realize the conversion between the different types of high internal phase emulsion by simple stimulation, which provides a new direction for stimulus-responsive high internal phase emulsions.
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Auxin, primarily indole-3-acetic acid (IAA), is a versatile signal molecule that regulates many aspects of plant growth, development, and stress response. Recently, microRNAs (miRNAs), a type of short non-coding RNA, have emerged as master regulators of the auxin response pathways by affecting auxin homeostasis and perception in plants. The combination of these miRNAs and the autoregulation of the auxin signaling pathways, as well as the interaction with other hormones, creates a regulatory network that controls the level of auxin perception and signal transduction to maintain signaling homeostasis. In this review, we will detail the miRNAs involved in auxin signaling to illustrate its in planta complex regulation.
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MicroARNs/metabolismo , Desarrollo de la Planta , Plantas/metabolismo , Transducción de Señal , Proteínas de Arabidopsis/metabolismo , Proteínas F-Box/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas/genética , Receptores de Superficie Celular/metabolismoRESUMEN
In recent years, fluorescent probes, as an analytical tool that can target and rapidly detect analytes, have been increasingly used for applications related to medical treatment, detection, and bioimaging. Researchers are interested in hemicyanine-based fluorescent probes because of their high quantum yield, tunable spectrum characteristics, absorption and emission in the near-infrared (NIR) region, and good photo-stability. The development of these dyes and their derivatives as NIR fluorescent probes for biological applications has advanced significantly in the last ten years. This review introduces processes for making hemicyanine dyes and the methodology for creating functional activity-based fluorescent probes. A variety of hemicyanine-based probes have been systematically developed for the detection of small biomolecules in various illnesses. Finally, the potential drawbacks of hemicyanine-based functional probes, and the prospects for future research and translation into clinical medicine, are also discussed. This study is intended to provide strategies for the development and design of novel fluorescence probes.