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Ginger (Zingiber officinale) is one of the most widely consumed dietary supplements. However, the content of active ingredients varied greatly from place to place. In this study, we first identified and compared the compositions of ginger samples from six different origins. Then, we evaluated the anti-inflammatory activity of different samples in LPS-stimulated RAW264.7 cells. The results indicated that highly variable in chemical composition and activity for ginger from different origin. Further, correlation analysis showed that isoborneol, terpineol, α-curcumene, germacrene D, α-elemol and 8-shogaol exhibited a strong correlation with inflammatory factors, which could be used as potential chemical markers to evaluate quality and distinguish source of ginger. Finally, comprehensive evaluation found that the ginger from Sichuan exerts stronger anti-inflammatory properties. This study will help to select ginger varieties with excellent characteristics, provide theoretical basis for the development and utilization of ginger. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01229-2.
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The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide. A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages, while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells. However, specific T-cell responses remain largely unaffected by the mutations, indicating that T-cell-mediated cellular immunity can still provide protection. Moreover, the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo, which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1. These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies. The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health. The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants. Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2 , Linfócitos B , Anticorpos Neutralizantes/genéticaRESUMO
Due to the boom of Internet of Things (IoT) in recent years, various IoT devices are connected to the Internet and communicate with each other through network protocols such as the Constrained Application Protocol (CoAP). These protocols are typically defined and described in specification documents, such as Request for Comments (RFC), which are written in natural or semi-formal languages. Since developers largely follow the specification documents when implementing web protocols, they have become the de facto protocol specifications. Therefore, it must be ensured that the descriptions in them are consistent to avoid technological issues, incompatibility, security risks, or even legal concerns. In this work, we propose Neural RFC Knowledge Graph (NRFCKG), a neural network-generated knowledge graph based contradictions detection tool for IoT protocol specification documents. Our approach can automatically parse the specification documents and construct knowledge graphs from them through entity extraction, relation extraction, and rule extraction with large language models. It then conducts an intra-entity and inter-entity contradiction detection over the generated knowledge graph. We implement NRFCKG and apply it to the most extensively used messaging protocols in IoT, including the main RFC (RFC7252) of CoAP, the specification document of MQTT, and the specification document of AMQP. Our evaluation shows that NRFCKG generalizes well to other specification documents and it manages to detect contradictions from these IoT protocol specification documents.
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Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.
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Quinases Ciclina-Dependentes , Ciclinas , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologia , Quinase 2 Dependente de CiclinaRESUMO
BACKGROUND: The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy. PURPOSE: To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case. METHODS: Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers. RESULTS: There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP. CONCLUSION: Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.
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BACKGROUND: Leaves are the main medicinal organ in Epimedium herbs, and leaf flavonoid content is an important criterion of Epimedium herbs. However, the underlying genes that regulate leaf size and flavonoid content are unclear, which limits the use of breeding for Epimedium development. This study focuses on QTL mapping of flavonoid and leaf-size related traits in Epimedium. RESULTS: We constructed the first high-density genetic map (HDGM) using 109 F1 hybrids of Epimedium leptorrhizum and Epimedium sagittatum over three years (2019-2021). Using 5,271 single nucleotide polymorphism (SNP) markers, an HDGM with an overall distance of 2,366.07 cM and a mean gap of 0.612 cM was generated by utilizing genotyping by sequencing (GBS) technology. Every year for three years, 46 stable quantitative trait loci (QTLs) for leaf size and flavonoid contents were discovered, including 31 stable loci for Epimedin C (EC), one stable locus for total flavone content (TFC), 12 stable loci for leaf length (LL), and two stable loci for leaf area (LA). For flavonoid content and leaf size, the phenotypic variance explained for these loci varied between 4.00 and 16.80% and 14.95 and 17.34%, respectively. CONCLUSIONS: Forty-six stable QTLs for leaf size and flavonoid content traits were repeatedly detected over three years. The HDGM and stable QTLs are laying the basis for breeding and gene investigation in Epimedium and will contribute to accelerating the identification of desirable genotypes for Epimedium breeding.
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Epimedium , Epimedium/genética , Melhoramento Vegetal , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Flavonoides/genética , Ligação Genética , Folhas de Planta/genéticaRESUMO
The emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.1.1) has attracted global attention. The numerous mutations in the spike protein suggest that it may have altered susceptibility to immune protection elicited by the existing coronavirus disease 2019 (COVID-19) infection. We used a live virus neutralization test and SARS-CoV-2 pseudotype vesicular stomatitis virus vector-based neutralization assay to assess the degree of immune escape efficiency of the original, Delta (B1.617.2), and Omicron strains against the serum antibodies from 64 unvaccinated patients who had recovered from COVID-19 and the results were strongly correlated. The convalescent serum neutralization was more markedly reduced against the Omicron variant (9.4-57.9-fold) than the Delta variant (2.0-4.5-fold) as compared with the original strain. Our results demonstrate the reduced fusion and notable immune evasion capabilities of the Omicron variants, highlighting the importance of accelerating the development of vaccines targeting them.
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Although the clinical manifestation of COVID-19 is mainly respiratory symptoms, approximately 20% of patients suffer from cardiac complications. COVID-19 patients with cardiovascular disease have higher severity of myocardial injury and poor outcomes. The underlying mechanism of myocardial injury caused by SARS-CoV-2 infection remains unclear. Using a non-transgenic mouse model infected with Beta variant (B.1.351), we found that the viral RNA could be detected in lungs and hearts of infected mice. Pathological analysis showed thinner ventricular wall, disorganized and ruptured myocardial fiber, mild inflammatory infiltration, and mild epicardia or interstitial fibrosis in hearts of infected mice. We also found that SARS-CoV-2 could infect cardiomyocytes and produce infectious progeny viruses in human pluripotent stem cell-derived cardiomyocyte-like cells (hPSC-CMs). SARS-CoV-2 infection caused apoptosis, reduction of mitochondrial integrity and quantity, and cessation of beating in hPSC-CMs. In order to dissect the mechanism of myocardial injury caused by SARS-CoV-2 infection, we employed transcriptome sequencing of hPSC-CMs at different time points after viral infection. Transcriptome analysis showed robust induction of inflammatory cytokines and chemokines, up-regulation of MHC class I molecules, activation of apoptosis signaling and cell cycle arresting. These may cause aggravate inflammation, immune cell infiltration, and cell death. Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics.
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OBJECTIVE: The association between sleep behaviors and gout risk remains uncertain. We aimed to evaluate the relationship of sleep patterns based on a combination of five major sleep behaviors with the risk of new-onset gout, and to explore whether genetic risks of gout may modify this association in the general population. METHODS: 403,630 participants without gout at baseline in UK Biobank were included. A healthy sleep score was created by combining five major sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Genetic risk score for gout was calculated based on 13 single nucleotide polymorphisms (SNPs) with independently significant genome-wide association with gout. The primary outcome was new-onset gout. RESULTS: During a median follow-up duration of 12.0 years, 4270 (1.1%) participants developed new-onset gout. Compared to participants with poor sleep patterns (0 ≤ healthy sleep score ≤ 1), those with healthy sleep patterns (4 ≤ healthy sleep score ≤ 5) had a significantly lower risk of new-onset gout (HR, 0.79; 95% CI: 0.70-0.91). Moreover, the significantly lower risk of new-onset gout associated with healthy sleep patterns were mainly found in those with low (HR, 0.68; 95%CI: 0.53-0.88), or intermediate genetic risks of gout (HR, 0.78; 95%CI: 0.62-0.99), but not in participants with high genetic risks of gout (HR, 0.95; 95%CI: 0.77-1.17) (P for interaction =0.043). CONCLUSIONS: Among the general population, a healthy sleep pattern was associated with a significant lower of new-onset gout risk, especially in those with lower genetic risks of gout.
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Biothiols such as cysteine, homocysteine, and glutathione play significant roles in important biological activities, and their abnormal concentrations have been found to be closely associated with certain diseases, making their detection a critical task. To this end, fluorescent probes have become increasingly popular due to their numerous advantages, including easy handling, desirable spatiotemporal resolution, high sensitivity, fast response, and favorable biocompatibility. As a result, intensive research has been conducted to create fluorescent probes for the detection and imaging of biothiols. This brief review summarizes recent advances in the field of biothiol-responsive fluorescent probes, with an emphasis on rational probe design, including the reaction mechanism, discriminating detection, reversible detection, and specific detection. Furthermore, the challenges and prospects of fluorescence probes for biothiols are also outlined.
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Cisteína , Corantes Fluorescentes , Glutationa , Homocisteína , Espectrometria de Fluorescência/métodosRESUMO
N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes, and it participates in the regulation of pathophysiological processes in various diseases, including malignant tumors, by regulating the expression and function of both coding and non-coding RNAs (ncRNAs). More and more studies demonstrated that m6A modification regulates the production, stability, and degradation of ncRNAs and that ncRNAs also regulate the expression of m6A-related proteins. Tumor microenvironment (TME) refers to the internal and external environment of tumor cells, which is composed of numerous tumor stromal cells, immune cells, immune factors, and inflammatory factors that are closely related to tumors occurrence and development. Recent studies have suggested that crosstalk between m6A modifications and ncRNAs plays an important role in the biological regulation of TME. In this review, we summarized and analyzed the effects of m6A modification-associated ncRNAs on TME from various perspectives, including tumor proliferation, angiogenesis, invasion and metastasis, and immune escape. Herein, we showed that m6A-related ncRNAs can not only be expected to become detection markers of tumor tissue samples, but can also be wrapped into exosomes and secreted into body fluids, thus exhibiting potential as markers for liquid biopsy. This review provides a deeper understanding of the relationship between m6A-related ncRNAs and TME, which is of great significance to the development of a new strategy for precise tumor therapy.
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Exossomos , Microambiente Tumoral , Microambiente Tumoral/genética , Adenosina , Transporte Biológico , Exossomos/genéticaRESUMO
The R294K mutation in neuraminidase (NA) causes resistance to oseltamivir in the avian influenza virus H7N9. Reverse transcription droplet digital polymerase chain reaction (RT-dd PCR) is a novel technique for detecting single-nucleotide polymorphisms. This study aimed to develop an RT-dd PCR method for detecting the R294K mutation in H7N9. Primers and dual probes were designed using the H7N9 NA gene and the annealing temperature was optimized at 58.0 °C. The sensitivity of our RT-dd PCR method was not significantly different from that of RT-qPCR (p = 0.625), but it could specifically detect R294 and 294K in H7N9. Among 89 clinical samples, 2 showed the R294K mutation. These two strains were evaluated using a neuraminidase inhibition test, which revealed that their sensitivity to oseltamivir was greatly reduced. The sensitivity and specificity of RT-dd PCR were similar to those of RT-qPCR and its accuracy was comparable to that of NGS. The RT-dd PCR method had the advantages of absolute quantitation, eliminating the need for a calibration standard curve, and being simpler in both experimental operation and result interpretation than NGS. Therefore, this RT-dd PCR method can be used to quantitatively detect the R294K mutation in H7N9.
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Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Influenza Humana , Animais , Humanos , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Subtipo H7N9 do Vírus da Influenza A/genética , Neuraminidase/genética , Neuraminidase/metabolismo , Transcrição Reversa , Reação em Cadeia da Polimerase , Mutação , Aves/genéticaRESUMO
Background: During the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited. Methods: In this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4+ and CD8+ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose. Results: The booster dose elevated cytokine response in CD4+ and CD8+ T cells as well as expression of cytotoxic marker CD107a in CD8+ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4+ and CD8+ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4+ and CD8+ T cell responses. In addition, booster vaccination produced similar spike-specific AIM+CD4+ and AIM+CD8+ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4+ and CD8+ T cells. Conclusions: These data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Linfócitos T CD8-Positivos , Células T de Memória , COVID-19/prevenção & controle , SARS-CoV-2 , Citocinas , Vacinas de Produtos InativadosRESUMO
Plant vacuoles serve as the primary intracellular compartments for inorganic phosphate (Pi) storage. Passage of Pi across vacuolar membranes plays a critical role in buffering the cytoplasmic Pi level against fluctuations of external Pi and metabolic activities. To gain new insights into the proteins and processes, vacuolar Pi level regulated by vacuolar phosphate transporter 1 (VPT1) in Arabidopsis, we carried out tandem mass tag labeling proteome and phosphoproteome profiling of Arabidopsis WT and vpt1 loss-of-function mutant plants. The vpt1 mutant had a marked reduced vacuolar Pi level and a slight increased cytosol Pi level. The mutant was stunted as reflected in the reduction of the fresh weight compared with WT plants and bolting earlier under normal growth conditions in soil. Over 5566 proteins and 7965 phosphopeptides were quantified. About 146 and 83 proteins were significantly changed at protein abundance or site-specific phosphorylation levels, but only six proteins were shared between them. Functional enrichment analysis revealed that the changes of Pi states in vpt1 are associated with photosynthesis, translation, RNA splicing, and defense response, consistent with similar studies in Arabidopsis. Except for PAP26, EIN2, and KIN10, which were reported to be associated with phosphate starvation signal, we also found that many differential proteins involved in abscisic acid signaling, such as CARK1, SnRK1, and AREB3, were significantly changed in vpt1. Our study illuminates several new aspects of the phosphate response and identifies important targets for further investigation and potential crop improvement.
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BACKGROUND: The aim of this study was to investigate the effect of citrulline on the pyroptosis of mouse macrophage RAW264.7 and the mechanism. We investigated the effect of citrulline on pyroptosis of RAW264.7 cell induced by lipopolysaccharide (LPS), and the modulation of nuclear factor-kappaB (NF-κB) signaling. METHODS: Pyroptosis was evaluated using flow cytometry and caspase-1/sytox double staining. Cell counting kit-8 assay was performed to evaluate cell viability. RESULTS: Citrulline promoted cell viability and inhibited the pyroptosis of RAW264.7 cell stimulated by LPS. Furthermore, citrulline inactivated NF-κb/p65 signaling pathway by suppressing p65 nuclear translocation induced by LPS. An NF-κb signaling pathway activator, betulinic acid, reversed the inhibition of pyroptosis induced by citrulline. CONCLUSION: Citrulline inhibited LPS-induced pyrophosis, which may be closely related to the inactivation of NF-κB/p65 signaling pathway.
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Citrulina , NF-kappa B , Animais , Camundongos , Citrulina/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , NF-kappa B/metabolismo , Piroptose , Transdução de SinaisRESUMO
The demand for multicomponent foods to meet human energy and nutritional needs has been increasing; however, few studies have addressed the theoretical basis for their preparation. We investigated the effect of the nanoscale polymerization index (DPw) of amylose on the logarithm of slope plot-based kinetics and the mechanism of digestion of starch-lauric acid-ß-lactoglobulin protein complexes. Amylose from each of the five Chinese seedless breadfruit species was mixed with breadfruit amylopectin with the highest resistant starch (RS) content to form starch ternary complexes with various amylose DPws. All five complexes exhibited V-type crystalline diffraction and rod-like molecular configuration. Characteristic X-ray diffraction peaks and Fourier transform-infrared spectra of the ternary complexes revealed similar molecular configurations. As the amylose DPw increased, the complexing index, relative crystallinity, short-range order, weight-average molar mass, molecular density index, gelatinization temperature, decomposition temperature, RS, slowly digestible starch (SDS), and speed rate constants at the second hydrolysis stage (k2) increased, whereas the semicrystalline lamellae thickness, mass fractal structure parameter, average characteristic crystallite unit length, radius of gyration, fractal dimension and cavities of granule surface microstructure, final viscosity, interval speed rate from SDS to RS, equilibrium concentration, and glycemic index decreased. The digestion kinetics exhibited highly significant variation according to the physiochemical properties and multiscale supramolecular structure (r > 0.99 or r < -0.99, p < 0.01). Together, these results identify amylose DPw as an important structural factor that markedly affects the kinetics and mechanism of ternary complex digestion and provide a new theoretical direction for the production of starch-based multicomponent foods.
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E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, suggesting that the activation of GmMPK3 is most likely responsible for the activated immunity observed in the GmSAUL1a/1b-silenced plants. Furthermore, we provided evidence that GmSAUL1a is a bona fide E3 ligase. Collectively, our results indicated that GmSAUL1 plays a negative role in regulating cell death and immunity in soybean.
