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The SARS-CoV-2 Omicron variant exhibits striking immune evasion and is spreading rapidly worldwide. Understanding the structural basis of the high transmissibility and enhanced immune evasion of Omicron is of high importance. Here, using cryo-electron microscopy, we present both the closed and the open states of the Omicron spike (S) protein, which appear more compact than the counterparts of the G614 strain1, potentially related to enhanced inter-protomer and S1-S2 interactions induced by Omicron residue substitution. The closed state showing dominant population may indicate a conformational masking mechanism for the immune evasion of Omicron. Moreover, we captured three states for the Omicron S-ACE2 complex, revealing that the substitutions on the Omicron RBM result in new salt bridges and hydrogen bonds, more favourable electrostatic surface properties, and an overall strengthened S-ACE2 interaction, in line with the observed higher ACE2 affinity of Omicron S than of G614. Furthermore, we determined the structures of Omicron S in complex with the Fab of S3H3, an antibody that is able to cross-neutralize major variants of concern including Omicron, elucidating the structural basis for S3H3-mediated broad-spectrum neutralization. Our findings shed light on the receptor engagement and antibody neutralization or evasion of Omicron and may also inform the design of broadly effective vaccines against SARS-CoV-2.
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COVID-19 , Glicoproteína de la Espiga del Coronavirus , Enzima Convertidora de Angiotensina 2 , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Microscopía por Crioelectrón , Humanos , SARS-CoV-2RESUMEN
Cell identity annotation for single-cell transcriptome data is a crucial process for constructing cell atlases, unraveling pathogenesis, and inspiring therapeutic approaches. Currently, the efficacy of existing methodologies is contingent upon specific data sets. Nevertheless, such data are often sourced from various batches, sequencing technologies, tissues, and even species. Notably, the gene regulatory relationship remains unaffected by the aforementioned factors, highlighting the extensive gene interactions within organisms. Therefore, we propose scHGR, an automated annotation tool designed to leverage gene regulatory relationships in constructing gene-mediated cell communication graphs for single-cell transcriptome data. This strategy helps reduce noise from diverse data sources while establishing distant cellular connections, yielding valuable biological insights. Experiments involving 22 scenarios demonstrate that scHGR precisely and consistently annotates cell identities, benchmarked against state-of-the-art methods. Crucially, scHGR uncovers novel subtypes within peripheral blood mononuclear cells, specifically from CD4+ T cells and cytotoxic T cells. Furthermore, by characterizing a cell atlas comprising 56 cell types for COVID-19 patients, scHGR identifies vital factors like IL1 and calcium ions, offering insights for targeted therapeutic interventions.
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The single-cell proteomics enables the direct quantification of protein abundance at the single-cell resolution, providing valuable insights into cellular phenotypes beyond what can be inferred from transcriptome analysis alone. However, insufficient large-scale integrated databases hinder researchers from accessing and exploring single-cell proteomics, impeding the advancement of this field. To fill this deficiency, we present a comprehensive database, namely Single-cell Proteomic DataBase (SPDB, https://scproteomicsdb.com/), for general single-cell proteomic data, including antibody-based or mass spectrometry-based single-cell proteomics. Equipped with standardized data process and a user-friendly web interface, SPDB provides unified data formats for convenient interaction with downstream analysis, and offers not only dataset-level but also protein-level data search and exploration capabilities. To enable detailed exhibition of single-cell proteomic data, SPDB also provides a module for visualizing data from the perspectives of cell metadata or protein features. The current version of SPDB encompasses 133 antibody-based single-cell proteomic datasets involving more than 300 million cells and over 800 marker/surface proteins, and 10 mass spectrometry-based single-cell proteomic datasets involving more than 4000 cells and over 7000 proteins. Overall, SPDB is envisioned to be explored as a useful resource that will facilitate the wider research communities by providing detailed insights into proteomics from the single-cell perspective.
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Proteínas , Proteómica , Anticuerpos , Bases del Conocimiento , Espectrometría de Masas , Humanos , Animales , Análisis de la Célula IndividualRESUMEN
Advanced multi-omics technologies offer much information that can uncover the regulatory mechanisms from genotype to phenotype. In soybean, numerous multi-omics databases have been published. Although they cover multiple omics, there are still limitations when it comes to the types and scales of omics datasets and analysis methods utilized. This study aims to address these limitations by collecting and integrating a comprehensive set of multi-omics datasets. This includes 38 genomes, transcriptomes from 435 tissue samples, 125 phenotypes from 6686 accessions, epigenome data involving histone modification, transcription factor binding, chromosomal accessibility and chromosomal interaction, as well as genetic variation data from 24 501 soybean accessions. Then, common analysis pipelines and statistical methods were applied to mine information from these multi-omics datasets, resulting in the successful establishment of a user-friendly multi-omics database called SoyMD (https://yanglab.hzau.edu.cn/SoyMD/#/). SoyMD provides researchers with efficient query options and analysis tools, allowing them to swiftly access relevant omics information and conduct comprehensive multi-omics data analyses. Another notable feature of SoyMD is its capability to facilitate the analysis of candidate genes, as demonstrated in the case study on seed oil content. This highlights the immense potential of SoyMD in soybean genetic breeding and functional genomics research.
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Bases de Datos Factuales , Glycine max , Programas Informáticos , Genómica/métodos , Glycine max/genética , Multiómica , FitomejoramientoRESUMEN
The Animal Meta-omics landscape database (AnimalMetaOmics, https://yanglab.hzau.edu.cn/animalmetaomics#/) is a comprehensive and freely available resource that includes metagenomic, metatranscriptomic, and metaproteomic data from various non-human animal species and provides abundant information on animal microbiomes, including cluster analysis of microbial cognate genes, functional gene annotations, active microbiota composition, gene expression abundance, and microbial protein identification. In this work, 55 898 microbial genomes were annotated from 581 animal species, including 42 924 bacterial genomes, 12 336 virus genomes, 496 archaea genomes and 142 fungi genomes. Moreover, 321 metatranscriptomic datasets were analyzed from 31 animal species and 326 metaproteomic datasets from four animal species, as well as the pan-genomic dynamics and compositional characteristics of 679 bacterial species and 13 archaea species from animal hosts. Researchers can efficiently access and acquire the information of cross-host microbiota through a user-friendly interface, such as species, genomes, activity levels, expressed protein sequences and functions, and pan-genome composition. These valuable resources provide an important reference for better exploring the classification, functional diversity, biological process diversity and functional genes of animal microbiota.
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Bases de Datos Genéticas , Microbiota , Multiómica , Animales , Bacterias/genética , Genoma Microbiano , Metagenoma/genética , Microbiota/genéticaRESUMEN
Glucose is a major energy substrate for porcine adipocytes and also serves as a regulatory signal for adipogenesis and lipid metabolism. In this study, we combined transcriptome and metabolome analyses to reveal the underlying regulatory mechanisms of high glucose (HG) on adipogenesis by comparing differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) identified in porcine adipocytes. Results showed that HG (20 mmol/L) significantly increased fat accumulation in porcine adipocytes compared to low glucose (LG, 5 mmol/L). A total of 843 DEGs and 365 DAMs were identified. Functional enrichment analyses of DEGs found that multiple pathways were related to adipogenesis, lipid metabolism, and immune-inflammatory responses. PPARγ, C/EBPα, ChREBP, and FOS were identified as the key hub genes through module 3 analysis, and PPARγ acted as a central regulator by linking genes involved in lipid metabolism and immune-inflammatory responses. Gene-metabolite networks found that PPARγ-13-HODE was the most important interaction relationship. These results revealed that PPARγ could mediate the cross-talk between adipogenesis and the immune-inflammatory response during adipocyte maturation. This work provides a comprehensive view of the regulatory mechanisms of glucose on adipogenesis in porcine adipocytes.
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The D620N mutation in vacuolar protein sorting protein 35 (VPS35) gene has been identified to be linked to late onset familial Parkinson disease (PD). However, the pathophysiological roles of VPS35-D620N in PD remain unclear. Here, we generated the transgenic Caenorhabditis elegans overexpressing either human wild type or PD-linked mutant VPS35-D620N in neurons. C. elegans expressing VPS35-D620N, compared with non-transgenic controls, showed movement disorders and dopaminergic neuron loss. VPS35-D620N worms displayed more swimming induced paralysis but showed no defects in BSR assays, thus indicating the disruption of dopamine (DA) recycling back inside neurons. Moreover, VPS35 formed a protein interaction complex with DA transporter (DAT), RAB5, RAB11 and FAM21. In contrast, the VPS35-D620N mutant destabilized these interactions, thus disrupting DAT transport from early endosomes to recycling endosomes, and decreasing DAT at the cell surface. These effects together increased DA in synaptic clefts, and led to dopaminergic neuron degeneration and motor dysfunction. Treatment with reserpine significantly decreased the swimming induced paralysis in VPS35-D620N worms, as compared with vehicle treated VPS35-D620N worms. Our studies not only provide novel insights into the mechanisms of VPS35-D620N-induced dopaminergic neuron degeneration and motor dysfunction via disruption of DAT function and the DA signaling pathway but also indicate a potential strategy to treat VPS35-D620N-related PD and other disorders.
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Dopamina , Enfermedad de Parkinson , Animales , Humanos , Dopamina/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Transporte de Proteínas , Neuronas Dopaminérgicas/metabolismo , Enfermedad de Parkinson/metabolismo , Degeneración Nerviosa/patología , Parálisis/genética , Parálisis/metabolismo , Parálisis/patologíaRESUMEN
Simultaneous detection of multiple breast cancer-associated miRNAs significantly raises the accuracy and reliability of early diagnosis. In this work, disposable carbon fiber paper serves as the biosensing interface, linking DNA probes via click chemistry to efficiently capture targets and signals efficiently. DNA probes have multiple recognition domains that trigger a cascade reaction through the helper probes and targets, resulting in two signals output. The signals are centrally encapsulated in the pore of the MIL-88(Fe)-NH2. The signal carriers are directed by signal probes to the recognition domains that correspond to the DNA probes. The biosensor is selective and stable, and it can quantify miRNA-21 and miRNA-155 simultaneously with detection limits of 0.64 and 0.54 fmol/L, respectively. Furthermore, it demonstrates satisfactory performance in tests conducted with normal human serum and cell lysate. Overall, this method makes a satisfactory exploration to realize an inexpensive and sensitive biosensor for multiple biomarkers.
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Técnicas Biosensibles , Química Clic , MicroARNs , Técnicas Biosensibles/métodos , Humanos , MicroARNs/análisis , MicroARNs/sangre , Sondas de ADN/química , Neoplasias de la Mama/diagnóstico , Límite de DetecciónRESUMEN
BACKGROUND: Hydrogen gas (H2), a novel and beneficial gaseous molecule, plays a significant role in plant growth and development processes. Hydrogen-rich water (HRW) is regarded as a safe and easily available way to study the physiological effects of H2 on plants. Several recent research has shown that HRW attenuates stress-induced seed germination inhibition; however, the underlying modes of HRW on seed germination remain obscure under non-stress condition. RESULTS: In this current study, we investigated the possible roles of gibberellin (GA) and abscisic acid (ABA) in HRW-regulated seed germination in wax gourd (Benincasa hispida) through pharmacological, physiological, and transcriptome approaches. The results showed that HRW application at an optimal dose (50% HRW) significantly promoted seed germination and shortened the average germination time (AGT). Subsequent results suggested that 50% HRW treatment stimulated GA production by regulating GA biosynthesis genes (BhiGA3ox, BhiGA2ox, and BhiKAO), whereas it had no effect on the content of ABA and the expression of its biosynthesis (BhiNCED6) and catabolism genes (BhiCYP707A2) but decreased the expression of ABA receptor gene (BhiPYL). In addition, inhibition of GA production by paclobutrazol (PAC) could block the HRW-mediated germination. Treatment with ABA could hinder HRW-mediated seed germination and the ABA biosynthesis inhibitor sodium tungstate (ST) could recover the function of HRW. Furthermore, RNA-seq analysis revealed that, in the presence of GA or ABA, an abundance of genes involved in GA, ABA, and ethylene signal sensing and transduction might involve in HRW-regulated germination. CONCLUSIONS: This study portrays insights into the mechanism of HRW-mediated seed germination, suggesting that HRW can regulate the balance between GA and ABA to mediate seed germination through ethylene signals in wax gourd.
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Ácido Abscísico , Germinación , Giberelinas , Hidrógeno , Reguladores del Crecimiento de las Plantas , Semillas , Transducción de Señal , Giberelinas/metabolismo , Germinación/efectos de los fármacos , Ácido Abscísico/metabolismo , Semillas/crecimiento & desarrollo , Semillas/efectos de los fármacos , Semillas/genética , Semillas/fisiología , Reguladores del Crecimiento de las Plantas/metabolismo , Hidrógeno/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacosRESUMEN
Fluorescent elastomers are predominantly fabricated through doping fluorescent components or conjugating chromophores into polymer networks, which often involves detrimental effects on mechanical performance and also makes large-scale production difficult. Inspired by the heteroatom-rich microphase separation structures assisted by intensive hydrogen bonds in natural organisms, an ultra-robust fluorescent polyurethane elastomer is reported, which features a remarkable fracture strength of 87.2 MPa with an elongation of 1797%, exceptional toughness of 678.4 MJ m-3 and intrinsic cyan fluorescence at 445 nm. Moreover, the reversible fluorescence variation with temperature could in situ reveal the microphase separation of the elastomer in real time. By taking advantage of mechanical properties, intrinsic fluorescence and hydrogen bonds-promoted interfacial bonding ability, this fluorescent elastomer can be utilized as an auxetic skeleton for the elaboration of an integrated auxetic composite. Compared with the auxetic skeleton alone, the integrated composite shows an improved mechanical performance while maintaining auxetic deformation in a large strain below 185%, and its auxetic process can be visually detected under ultraviolet light by the fluorescence of the auxetic skeleton. The concept of introducing hydrogen-bonded heteroatom-rich microphase separation structures into polymer networks in this work provides a promising approach to developing fluorescent elastomers with exceptional mechanical properties.
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Triboelectric Nanogenerator (TENG) has proven highly effective in converting mechanical energy into electrical energy. Previous research on manipulating microstructure for performance enhancement primarily focused on the surface of TENGs. In this study, an innovative bottom-up strategic design to control the internal nano-architecture for the enhanced output of TENG is proposed. This multiscale structural design strategy consists of defect chemistry (angstrom-scale), surface modification (nano-scale), and spatial regulation of nanoparticles (meso-scale), which helps explore the optimal utilization of TENG's internal structure. After fine-tuning the nano-architecture, the output voltage is significantly increased. This optimized TENG serves as a robust platform for developing self-powered systems, including self-powered electrochemical chlorination systems for sterilization. Additionally, through the utilization of multiscale simulations (density functional theory, all-atom molecular dynamics, and dissipative particle dynamics), the underlying mechanisms governing how the optimized nanoparticle-polymer interface and spatial arrangement of nanoparticles influence the storage and transfer of charges are comprehensively elucidated. This study not only demonstrates the effectiveness of manipulating internal nano-architecture to enhance TENG performance for practical applications but also provides invaluable insights into structural engineering for TENG advancement.
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Besides the scattering structures, the energy transfer (ET) process in the gain medium plays a significant role in the competition between coherent (comprising strongly coherent components) and incoherent (consisting of weakly coherent or "hidden" coherent components) modes of random lasers. In this study, bichromatic emission random lasers were successfully created using polydimethylsiloxane (PDMS) replicas with grooved structures that imitate the inner surface of abalone shells as scattering substrates. The influence mechanism of the ET process from the monomer to dimer in the Rhodamine 640 dye on the competition of random laser modes was thoroughly investigated from both spectral and temporal dimensions. It was confirmed that the ET process can reduce the gain of monomers while amplifying the gain of dimers. By considering the dominant high-efficiency ET processes, an energy transfer factor associated with the pump energy density was determined. Notably, for the first time, it was validated that the statistical distribution characteristics of the time sequence variations in the coherent random laser generated by dimers closely resemble a normal distribution. This finding demonstrates the feasibility of producing high-quality random number sequences.
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High-power all-solid-state continuous-wave (CW) single-frequency laser with high linear polarization is a significant source for quantum optics and precision measurement. In this Letter, a high-power linearly polarized CW single-frequency laser based on the single-crystal fiber (SCF) master-oscillator power amplifier (MOPA) is presented, in which a homemade 140 W low-noise CW single-frequency laser and a Nd:YAG SCF are firstly employed as the seed laser and the medium of the MOPA, respectively. The mode-matching between the pump laser propagated with waveguide form and the freely propagated seed laser is optimized by considering the influence of the degradations of the polarization and the beam quality. Finally, when the incident powers of the pump and seed lasers are 262.6 W and 126.3 W, respectively, the seed waist radius is optimized to 200 µm. In this case, the output power of the linearly polarized laser reaches up to 208 W, which is the highest output power, to the best of our knowledge. The presented results provide a good reference for implementing a high power and high degree of the polarization and good beam quality laser based on the SCF MOPA.
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Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.
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Natural killer/T-cell lymphoma (NKTCL) is an aggressive and malignant condition with a high mortality rate. Prognostic factors may assist to evaluate the outcome of the disease and may also be useful in selecting appropriate therapeutic strategies for patients. The study aims to describe NKTCL in terms of its clinical features, laboratory examinations, and immunophenotypes and to analyze relevance affecting patient survival outcomes. The patients diagnosed as NKTCL in Jinling Hospital from Jan. 2012 to Dec. 2022 were reviewed retrospectively in this study basing on histopathology. The analysis was performed to evaluate overall survival (OS). A total of 125 NKTCL patients were included, which mainly affected male more than female with the onset median age of 51.00 years old (range, 14 ~ 85 y). NKTCL commonly affects the nasopharynx and upper aerodigestive tract, intestines, and skin. The median overall survival was 13.00 months (range, 2-156 m), and the 5-year survival rate was 9.8%. Under univariable analysis revealed the following factors at diagnosis age: serum total IgEAb ≥ 54.6 IU/mL, IL-6 ≥ 32.445 ng/L, elevated PINK score, smoking, and extranasopharyngeal site were statistically significant predictors for OS. Compared to the patients who received radiotherapy alone or chemotherapy alone, the patients who received combined chemoradiotherapy had longer OS. We found that IL-6 and total IgEAb were significant prognostic factors in NKTCL patients. Also, extranasopharyngeal site was correlated with advanced disease.
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Interleucina-6 , Linfoma Extranodal de Células NK-T , Humanos , Masculino , Femenino , Adolescente , Pronóstico , Estadificación de Neoplasias , Estudios Retrospectivos , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/terapia , Linfoma Extranodal de Células NK-T/patología , Células Asesinas Naturales/patologíaRESUMEN
Carbon dioxide (CO2) injection in unconventional gas-bearing shale reservoirs is a promising method for enhancing methane recovery efficiency and mitigating greenhouse gas emissions. The majority of methane is adsorbed within the micropores and nanopores (≤50 nm) of shale, which possess extensive surface areas and abundant adsorption sites for the sequestration system. To comprehensively discover the underlying mechanism of enhanced gas recovery (EGR) through CO2 injection, molecular dynamics (MD) provides a promising way for establishing the shale models to address the multiphase, multicomponent fluid flow behaviors in shale nanopores. This study proposes an innovative method for building a more practical shale matrix model that approaches natural underground environments. The grand canonical Monte Carlo (GCMC) method elucidates gas adsorption and sequestration processes in shale gas reservoirs under various subsurface conditions. The findings reveal that previously overlooked pore slits have a significant impact on both gas adsorption and recovery efficiency. Based on the simulation comparisons of absolute and excess uptakes inside the kerogen matrix and the shale slits, it demonstrates that nanopores within the kerogen matrix dominate the gas adsorption while slits dominate the gas storage. Regarding multiphase, multicomponent fluid flow in shale nanopores, moisture negatively influences gas adsorption and carbon storage while promoting methane recovery efficiency by CO2 injection. Additionally, saline solution and ethane further impede gas adsorption while facilitating displacement. Overall, this work elucidates the substantial effect of CO2 injection on fluid transport in shale formations and advances the comprehensive understanding of microscopic gas flow and recovery mechanisms with atomic precision for low-carbon energy development.
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OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.
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Lupus Eritematoso Sistémico , Receptores de Antígenos de Linfocitos T gamma-delta , Humanos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Subgrupos de Linfocitos T , FenotipoRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases. METHOD: We comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary-level data from genome-wide association studies. The analysis results mainly came from the random-effects model of inverse variance weighted (IVW-RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables. RESULTS: The IVW-RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01-1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01-1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00-1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01-1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = 2E-05), AAS (OR = 1.05, 95% CI = 1.02-1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00-1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98-1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis. CONCLUSION: This Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hipersensibilidad , Enfermedades Inflamatorias del Intestino , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/epidemiología , Hipersensibilidad/genética , Hipersensibilidad/epidemiología , Polimorfismo de Nucleótido Simple , Asma/genética , Asma/epidemiología , Enfermedad de Crohn/genética , Enfermedad de Crohn/epidemiología , Dermatitis Atópica/genética , Dermatitis Atópica/epidemiología , Colitis Ulcerosa/genética , Colitis Ulcerosa/epidemiología , Factores de Riesgo , Índice de Masa CorporalRESUMEN
C-O bond formation via C-H alkoxylation remains a challenge, especially coupling with a secondary alcohol, due to its low activity and sterically encumbered property. Here, we report a general and effective cobalt-catalyzed oxidative cross-coupling of benzamides with secondary alcohols via C-H alkoxylation reaction under solvothermal conditions, enabled by a salicylaldehyde/cobalt complex. The protocol features easy operation without additives, broad substrate scope, and excellent functional tolerance. The applicability is proven by the gram-scale synthesis and modification of natural products.
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Sensitive and convenient strategy of tyrosinase (TYR) and its inhibitor atrazine is in pressing demand for essential research as well as pragmatic application. In this work, an exquisite label-free fluorometric assay with high sensitivity, convenience and efficiency was described for detecting TYR and the herbicide atrazine on the basis of fluorescent nitrogen-doped carbon dots (CDs). The CDs were prepared via one-pot hydrothermal reaction starting from citric acid and diethylenetriamine. TYR catalyzed the oxidation of dopamine to dopaquinone derivative which could quench the fluorescence of CDs through a fluorescence resonance energy transfer (FRET) process. Thus, a sensitive and selective quantitative evaluation of TYR can be constructed on the basis of the relationship between the fluorescence of CDs and TYR activity. Atrazine, a typical inhibitor of TYR, inhibited the catalytic activity of TYR, leading to the reduced dopaquinone and the fluorescence was retained. The strategy covered a broad linear range of 0.1-150 U/mL and 4.0-80.0 nM for TYR and atrazine respectively with a low detection limit of 0.02 U/mL and 2.4 nM/mL. It is also demonstrated that the assay can be applied to detect TYR and atrazine in spiked complex real samples, which provides infinite potential in application of disease monitoring along with environmental analysis.