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1.
Philos Trans A Math Phys Eng Sci ; 382(2283): 20240014, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39370796

RESUMEN

Recent advances in origami science and engineering have particularly focused on the challenges of dynamics. While research has primarily focused on statics and kinematics, the need for effective and processable dynamic models has become apparent. This paper evaluates various dynamic modelling techniques for rigid-foldable origami, particularly focusing on their ability to capture nonlinear dynamic behaviours. Two primary methods, the lumped mass-spring-damper approach and the energy-based method, are examined using a bistable stacked Miura-origami (SMO) structure as a case study. Through systematic dynamic experiments, we analyse the effectiveness of these models in predicting bistable dynamic responses, including intra- and interwell oscillations, in different loading conditions. Our findings reveal that the energy-based approach, which considers the structure's inertia and utilizes dynamic experimental data for parameter identification, outperforms other models in terms of validity and accuracy. This model effectively predicts the dynamic response types, the rich and complex nonlinear characteristics and the critical frequency where interwell oscillations occur. Despite its relatively increased complexity in model derivation, it maintains computational efficiency and shows promise for broader applications in origami dynamics. By comparing model predictions with experimental results, this study enhances our understanding of origami dynamics and contributes valuable insights for future research and applications. This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

2.
Chemosphere ; : 143367, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306113

RESUMEN

In this study, we fabricated phosphorus-modified carbon felt electrode anodes for chloride oxidation in saline solutions to produce HClO via electrocatalysis, forming a compound fungicide saline applicable for debridement and disinfection. A low-cost phosphorus-modified carbon felt electrode (P@CF) with high chlorine evolution reaction activity was synthesized to address the reduced efficiency of CER and the solution's pH increase. Heteroatoms P and O were introduced into the carbon felt by phosphoric acid activation followed by heat treatment. The maximum active chlorine concentration on the P@CF electrode could reach 616.8 mg/L in 60 minutes under the optimal synthesis conditions of a phosphoric acid mass fraction of 30%, a phosphoric acid impregnation time of 3 h, and a heat treatment temperature of 300°C. The active chlorine concentration was 1.8 times higher on the P@CF electrode compared to the original carbon felt electrode. The optimal reaction conditions for the generation of active chlorine were as follows: salt concentration of 9 g/L, voltage of 7 V, and electrode spacing of 2 cm as verified by response surfaces. This electrolysis reaction follows one-stage reaction kinetics. Subsequently, the disinfection efficacy of the produced disinfectants was examined. The prepared disinfectant was also compared to a commercially available hypochlorite disinfectant, showing similar disinfection effects on E. coli for both.

3.
Toxics ; 12(9)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39330558

RESUMEN

With the rapid development of society, more and more unknown halogenated disinfection byproducts (DBPs) enter into drinking water and pose potential risks to humans. To explore the unknown halogenated DBPs in tap water, a selectively nontargeted analysis (SNTA) method was developed by conducting micro-liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (micro-LC-QTOFMS). In this method, two runs were employed: in the first run, the modes of TOFMS and precursor ion (the fragments were set as Cl35/Cl37, Br79/Br81, and I126.9) were performed, and the molecular ions or precursor ions of the halogenated organics could be obtained; in the second run, the product ion mode was conducted by setting the molecular ion screened above, and the MS/MS spectrums could be acquired to speculate concerning the structure. Two kinds of model DBPs (one kind had an aliphatic structure and the other was an aromatic compound) were used to optimize the parameters of the MS, and their MS characteristics were summarized. With this SNTA method, 15 halogenated DBPs were screened in two tap water samples and their structures were proposed. Of them, six DBPs had not been reported before and were assumed to be new DBPs. Overall, the detected halogenated DBPs were mostly acidic substances.

4.
Ecol Evol ; 14(8): e70094, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39091326

RESUMEN

This study combined population genetics and parentage analysis to obtain foundational data for the conservation of Magnolia kwangsiensis. M. kwangsiensis is a Class I tree species that occurs in two disjunct regions in a biodiversity hotspot in southwest China. We assessed the genetic diversity and structure of this species across its distribution range to support its conservation management. Genetic diversity and population structure of 529 individuals sampled from 14 populations were investigated using seven nuclear simple sequence repeat (nSSR) markers and three chloroplast DNA (cpDNA) fragments. Parentage analysis was used to evaluate the pollen and seed dispersal distances. The nSSR marker analysis revealed a high genetic diversity in M. kwangsiensis, with an average observed (Ho) and expected heterozygosities (He) of 0.726 and 0.687, respectively. The mean and maximum pollen and seed dispersal distances were 66.4 and 95.7 m and 535.4 and 553.8 m, respectively. Our data revealed two distinct genetic groups, consistent with the disjunct geographical distribution of the M. kwangsiensis populations. Both pollen and seed dispersal movements help maintain genetic connectivity among M. kwangsiensis populations, contributing to high levels of genetic diversity. Both genetically differentiated groups corresponding to the two disjunct regions should be recognized as separate conservation units.

5.
J Pharm Pharm Sci ; 27: 13062, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104461

RESUMEN

Obesity, characterised by excessive fat accumulation, is a complex chronic condition that results from dysfunctional adipose tissue expansion due to prolonged calorie surplus. This leads to rapid adipocyte enlargement that exceeds the support capacity of the surrounding neurovascular network, resulting in increased hypoxia, inflammation, and insulin resistance. Intermittent fasting (IF), a dietary regimen that cycles between periods of fasting and eating, has emerged as an effective strategy to combat obesity and improve metabolic homeostasis by promoting healthy adipose tissue remodeling. However, the precise molecular and cellular mechanisms behind the metabolic improvements and remodeling of white adipose tissue (WAT) driven by IF remain elusive. This review aims to summarise and discuss the relationship between IF and adipose tissue remodeling and explore the potential mechanisms through which IF induces alterations in WAT. This includes several key structural changes, including angiogenesis and sympathetic innervation of WAT. We will also discuss the involvement of key signalling pathways, such as PI3K, SIRT, mTOR, and AMPK, which potentially play a crucial role in IF-mediated metabolic adaptations.


Asunto(s)
Ayuno Intermitente , Animales , Humanos , Tejido Adiposo Blanco/metabolismo , Ayuno Intermitente/metabolismo , Obesidad/dietoterapia , Obesidad/metabolismo , Transducción de Señal
6.
Infect Genet Evol ; 123: 105619, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38906518

RESUMEN

Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.


Asunto(s)
Adenovirus Humanos , COVID-19 , Gastroenteritis , Filogenia , SARS-CoV-2 , Humanos , Gastroenteritis/virología , Gastroenteritis/epidemiología , COVID-19/epidemiología , COVID-19/virología , Adenovirus Humanos/genética , Adenovirus Humanos/clasificación , Adenovirus Humanos/aislamiento & purificación , Preescolar , Niño , China/epidemiología , Lactante , Femenino , Masculino , SARS-CoV-2/genética , Infecciones por Adenovirus Humanos/virología , Infecciones por Adenovirus Humanos/epidemiología , Prevalencia
7.
Front Cell Infect Microbiol ; 14: 1415885, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846351

RESUMEN

Corona Virus Disease 2019 (COVID-19) is a highly prevalent and potent infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until now, the world is still endeavoring to develop new ways to diagnose and treat COVID-19. At present, the clinical prevention and treatment of COVID-19 mainly targets the spike protein on the surface of SRAS-CoV-2. However, with the continuous emergence of SARS-CoV-2 Variants of concern (VOC), targeting the spike protein therapy shows a high degree of limitation. The Nucleocapsid Protein (N protein) of SARS-CoV-2 is highly conserved in virus evolution and is involved in the key process of viral infection and assembly. It is the most expressed viral structural protein after SARS-CoV-2 infection in humans and has high immunogenicity. Therefore, N protein as the key factor of virus infection and replication in basic research and clinical application has great potential research value. This article reviews the research progress on the structure and biological function of SARS-CoV-2 N protein, the diagnosis and drug research of targeting N protein, in order to promote researchers' further understanding of SARS-CoV-2 N protein, and lay a theoretical foundation for the possible outbreak of new and sudden coronavirus infectious diseases in the future.


Asunto(s)
COVID-19 , Proteínas de la Nucleocápside de Coronavirus , Fosfoproteínas , SARS-CoV-2 , SARS-CoV-2/genética , Humanos , Proteínas de la Nucleocápside de Coronavirus/genética , Proteínas de la Nucleocápside de Coronavirus/química , Proteínas de la Nucleocápside de Coronavirus/metabolismo , COVID-19/virología , COVID-19/diagnóstico , Fosfoproteínas/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Proteínas de la Nucleocápside/metabolismo , Proteínas de la Nucleocápside/genética
8.
ACS Sens ; 9(6): 3387-3393, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38850514

RESUMEN

Fatty acid amide hydrolase (FAAH) plays a crucial role in the metabolism of the endocannabinoid system by hydrolyzing a series of bioactive amides, whose abnormal levels are associated with neuronal disorders including Alzheimer's disease (AD). However, due to the lack of suitable quantitative sensing tools, real-time and accurate monitoring of the activity of FAAH in living systems remains unresolved. Herein, a novel enzyme-activated near-infrared two-photon ratiometric fluorescent probe (CANP) based on a naphthylvinylpyridine monofluorophore is successfully developed, in which the electron-withdrawing amide moiety is prone to be hydrolyzed to an electron-donating amine group under the catalysis of FAAH, leading to the activation of the intramolecular charge transfer process and the emergence of a new 80 nm red-shifted emission, thereby achieving a ratiometric luminescence response. Benefiting from the high selectivity, high sensitivity, and ratiometric response to FAAH, the probe CANP is successfully used to quantitatively monitor and image the FAAH levels in living neurons, by which an amyloid ß (Aß)-induced upregulation of endogenous FAAH activity is observed. Similar increases in FAAH activity are found in various brain regions of AD model mice, indicating a potential fatty acid amide metabolite-involved pathway for the pathological deterioration of AD. Moreover, our quantitative FAAH inhibition experiments further demonstrate the great value of CANP as an efficient visual probe for in situ and precise assessment of FAAH inhibitors in complex living systems, assisting the discovery of FAAH-related therapeutic agents.


Asunto(s)
Amidohidrolasas , Encéfalo , Colorantes Fluorescentes , Neuronas , Amidohidrolasas/metabolismo , Animales , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Neuronas/metabolismo , Ratones , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/análisis , Humanos , Piridinas/química , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Fotones
9.
PLoS One ; 19(6): e0298610, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38870109

RESUMEN

SUMMARY: Utilizing the Mendelian randomization technique, this research clarifies the putative causal relationship between body mass index (BMI) andbone mineral density (BMD), and the mediating role of low-density lipoprotein (LDL). The implications of these findings present promising opportunities for enhancing our understanding of complex bone-related characteristics and disorders, offering potential directions for treatment and intervention. OBJECTIVE: The objective of this study is to examine the correlation between BMI and BMD, while exploring the intermediary role of LDL in mediating the causal impact of BMI on BMD outcomes via Mendelian randomization. METHODS: In this study, we employed genome-wide association study (GWAS) data on BMI, LDL, and BMD to conduct a comparative analysis using both univariate and multivariate Mendelian randomization. RESULTS: Our study employed a two-sample Mendelian randomization design. Considering BMI as the exposure and BMD as the outcome, our results suggest that BMI may function as a potential protective factor for BMD (ß = 0.05, 95% CI 1.01 to 1.09, P = 0.01). However, when treating LDL as the exposure and BMD as the outcome, our findings indicate LDL as a risk factor for BMD (ß = -0.04, 95% CI 0.92 to 0.99, P = 0.04). In our multivariate Mendelian randomization (MVMR) model, the combined influence of BMI and LDL was used as the exposure for BMD outcomes. The analysis pointed towards a substantial protective effect of LDL on BMD (ß = 0.08, 95% CI 0.85 to 0.97, P = 0.006). In the analysis of mediation effects, LDL was found to mediate the relationship between BMI and BMD, and the effect was calculated at (ß = 0.05, 95% CI 1.052 to 1.048, P = 0.04). CONCLUSION: Our findings suggest that BMI may be considered a protective factor for BMD, while LDL may act as a risk factor. Moreover, LDL appears to play a mediatory role in the causal influence of BMI on BMD.


Asunto(s)
Índice de Masa Corporal , Densidad Ósea , Estudio de Asociación del Genoma Completo , Lipoproteínas LDL , Análisis de la Aleatorización Mendeliana , Humanos , Densidad Ósea/genética , Lipoproteínas LDL/sangre , Polimorfismo de Nucleótido Simple , Femenino
10.
Plant Divers ; 46(3): 395-405, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38798723

RESUMEN

Stomatal regulation is critical for mangroves to survive in the hyper-saline intertidal zone where water stress is severe and water availability is highly fluctuant. However, very little is known about the stomatal sensitivity to vapour pressure deficit (VPD) in mangroves, and its co-ordination with stomatal morphology and leaf hydraulic traits. We measured the stomatal response to a step increase in VPD in situ, stomatal anatomy, leaf hydraulic vulnerability and pressure-volume traits in nine true mangrove species of five families and collected the data of genome size. We aimed to answer two questions: (1) Does stomatal morphology influence stomatal dynamics in response to a high VPD in mangroves? with a consideration of possible influence of genome size on stomatal morphology; and (2) do leaf hydraulic traits influence stomatal sensitivity to VPD in mangroves? We found that the stomata of mangrove plants were highly sensitive to a step rise in VPD and the stomatal responses were directly affected by stomatal anatomy and hydraulic traits. Smaller, denser stomata was correlated with faster stomatal closure at high VPD across the species of Rhizophoraceae, and stomata size negatively and vein density positively correlated with genome size. Less negative leaf osmotic pressure at the full turgor (πo) was related to higher operating steady-state stomatal conductance (gs); and a higher leaf capacitance (Cleaf) and more embolism resistant leaf xylem were associated with slower stomatal responses to an increase in VPD. In addition, stomatal responsiveness to VPD was indirectly affected by leaf morphological traits, which were affected by site salinity and consequently leaf water status. Our results demonstrate that mangroves display a unique relationship between genome size, stomatal size and vein packing, and that stomatal responsiveness to VPD is regulated by leaf hydraulic traits and stomatal morphology. Our work provides a quantitative framework to better understand of stomatal regulation in mangroves in an environment with high salinity and dynamic water availability.

11.
Transl Oncol ; 44: 101954, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38608405

RESUMEN

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

12.
Anal Methods ; 16(16): 2472-2477, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38606501

RESUMEN

Sialic acids are a family of monosaccharides that share a nine-carbon backbone and a carboxyl group. A recent derivatization method based on 3-nitrophenylhydrazine (3-NPH) provides a mild chemical labeling technique for biomolecules containing carbonyl or carboxyl groups. In this study, we utilized 3-NPH to label sialic acids via a two-step derivatization process. The derivatized species can produce a common reporter ion corresponding to C1-C3 with two labels, and a fragment differentiating between Neu5Ac, Neu5Gc, and KDN. This method is compatible with O-acetylated sialic acids and provides high sensitivity to Neu5Gc and KDN, and since the utilization of dual labeling significantly enhances the hydrophobicity of derivatives, it can effectively mitigate matrix effects when combined with parallel reaction monitoring technology. Negative-ion tandem mass spectrometry (MS/MS) analysis reveals a distinctive fragmentation profile for the 4-O-acetylated species, while the other sialic acids yield similar MS/MS spectra with a high abundance of reporter ions. Using the reporter ion as a transition, this analytical strategy is effective for analyzing complex biological samples. For example, it was successfully employed to quantify sialic acids in the intestinal tissues of several carp species, demonstrating its potential in sialylation research.


Asunto(s)
Fenilhidrazinas , Ácidos Siálicos , Animales , Acetilación , Cromatografía Líquida con Espectrometría de Masas , Fenilhidrazinas/química , Ácidos Siálicos/química , Ácidos Siálicos/análisis
13.
J Virol ; 98(5): e0157323, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38572974

RESUMEN

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-ß). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and production, and inhibited the RIG-I-like receptor (RLR) signaling pathway through selectively interacting with mitochondrial antiviral-signaling protein (MAVS). MAVS439-466 region and MAVS Lys461 were essential for the physical association between MAVS and ORF7b, and the inhibition of the RLR signaling pathway by ORF7b. MAVSK461/K63 ubiquitination was essential for the RLR signaling regulated by the MAVS-ORF7b complex. ORF7b interfered with the recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) and the activation of the RLR signaling pathway by MAVS. Furthermore, interfering peptides targeting the ORF7b complex reversed the ORF7b-suppressed MAVS-RLR signaling pathway. The most potent interfering peptide V disrupts the formation of ORF7b tetramers, reverses the levels of the ORF7b-inhibited physical association between MAVS and TRAF6, leading to the suppression of viral growth and infection. Overall, this study provides a mechanism for the suppression of innate immunity by SARS-CoV-2 infection and the mechanism-based approach via interfering peptides to potentially prevent SARS-CoV-2 infection.IMPORTANCEThe pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and continues to be a threat to public health. It is imperative to understand the biology of SARS-CoV-2 infection and find approaches to prevent SARS-CoV-2 infection and ameliorate COVID-19. Multiple SARS-CoV-2 proteins are known to function on the innate immune response, but the underlying mechanism remains unknown. This study shows that ORF7b inhibits the RIG-I-like receptor (RLR) signaling pathway through the physical association between ORF7b and mitochondrial antiviral-signaling protein (MAVS), impairing the K63-linked MAVS polyubiquitination and its recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) to MAVS. The most potent interfering peptide V targeting the ORF7b-MAVS complex may reverse the suppression of the MAVS-mediated RLR signaling pathway by ORF7b and prevent viral infection and production. This study may provide new insights into the pathogenic mechanism of SARS-CoV-2 and a strategy to develop new drugs to prevent SARS-CoV-2 infection.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , COVID-19 , SARS-CoV-2 , Transducción de Señal , Animales , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Apoptosis , COVID-19/virología , COVID-19/inmunología , COVID-19/metabolismo , Proteína 58 DEAD Box/metabolismo , Células HEK293 , Inmunidad Innata , Interferón beta/metabolismo , Receptores Inmunológicos/metabolismo , SARS-CoV-2/inmunología , SARS-CoV-2/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ubiquitinación , Proteínas Reguladoras y Accesorias Virales/metabolismo , Proteínas Reguladoras y Accesorias Virales/genética
14.
J Exp Psychol Hum Percept Perform ; 50(5): 479-497, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38546626

RESUMEN

How compound words are processed remains a central question in research on Chinese reading. The Chinese reading model assumes that all possible words sharing characters are activated during word processing and these activated words compete for a winner (Li & Pollatsek, 2020). The present studies aimed to examine whether embedded component words compete with whole compound words in Chinese reading. In Study 1, we analyzed two existing lexical decision databases and revealed inhibitory effects of component-word frequency and facilitative effects of character frequency on the first components. In Study 2, we conducted two factorial experiments to further examine the effects of first component-word frequency, with character frequencies controlled. The results consistently indicated significant inhibitory effects of component-word frequency. Collectively, these findings support the theoretical proposition that both component words and compound words are activated and engage in competition during word processing. This provides a new approach to compound word processing in Chinese reading and a possible solution to mixed results of character frequency effects reported in the literature. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Reconocimiento Visual de Modelos , Procesamiento de Texto , Humanos , China , Lectura
15.
Microbiol Spectr ; 12(4): e0341023, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38376366

RESUMEN

The nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer's stability, a circular bivalent form, cb-N-Apt17, was designed and evaluated. Our findings demonstrated that cb-N-Apt17 exhibited improved stability, enhanced binding affinity, and superior inhibition of N protein LLPS; thus, it has the potential inhibition ability on viral replication. These results provide valuable evidence supporting the potential of cb-N-Apt17 as a promising candidate for the development of antiviral therapies against COVID-19.IMPORTANCEVariants of SARS-CoV-2 pose a significant challenge to currently available COVID-19 vaccines and therapies due to the rapid epitope changes observed in the viral spike protein. However, the nucleocapsid (N) protein of SARS-CoV-2, a highly conserved structural protein, offers promising potential as a target for inhibiting viral replication. The N protein forms complexes with genomic RNA, interacts with other viral structural proteins during virion assembly, and plays a critical role in evading host innate immunity by impairing interferon production during viral infection. In this investigation, we discovered a single-stranded DNA aptamer, designated as N-Apt17, exhibiting remarkable affinity and specificity for the N protein. Notably, N-Apt17 disrupts the liquid-liquid phase separation (LLPS) of the N protein. To enhance the stability and molecular recognition capabilities of N-Apt17, we designed a circular bivalent DNA aptamer termed cb-N-Apt17. In both in vivo and in vitro experiments, cb-N-Apt17 exhibited increased stability, enhanced binding affinity, and superior LLPS disrupting ability. Thus, our study provides essential proof-of-principle evidence supporting the further development of cb-N-Apt17 as a therapeutic candidate for COVID-19.


Asunto(s)
COVID-19 , Proteínas de la Nucleocápside , Humanos , SARS-CoV-2/genética , ADN de Cadena Simple/farmacología , Vacunas contra la COVID-19 , Antivirales/farmacología
16.
J Proteomics ; 297: 105128, 2024 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-38382841

RESUMEN

Investigating site-specific protein phosphorylation remains a challenging task. The present study introduces a two-step chemical derivatization method for accurate identification of phosphopeptides. Methylamine neutralizes carboxyl groups, thus reducing the adsorption of non-phosphorylated peptides during enrichment, while dimethylamine offers a cost-effective reagent for stable isotope labeling of phosphorylation sites. The derivatization improves the mass spectra obtained through liquid chromatography-tandem mass spectrometry. The product ions at m/z 58.07 and 64.10 Da, resulting from dimethylamine-d0 and dimethylamine-d6 labeled phosphorylation sites respectively, can serve as report ions. Derivatized phosphopeptides from casein demonstrate enhanced ionization and formation of product ions, yielding a significant increase in the number of identifiable peptides. When using the parallel reaction monitoring technique, it is possible to distinguish isomeric phosphopeptides with the same amino acid sequence but different phosphorylation sites. By employing a proteomic software and screening the report ions, we identified 29 endogenous phosphopeptides in 10 µL of human saliva with high reliability. These findings indicate that the two-step derivatization strategy has great potential in site-specific phosphorylation and large-scale phosphoproteomics research. SIGNIFICANCE: There is a significant need to improve the accuracy of identifying phosphoproteins and phosphopeptides and analyzing them quantitatively. Several chemical derivatization techniques have been developed to label phosphorylation sites, thus enabling the identification and relative quantification of phosphopeptides. Nevertheless, these methods have limitations, such as incomplete conversion or the need for costly isotopic reagents. Building upon previous contributions, our study moves the field forward due to high efficiency in site-specific labeling, cost-effectiveness, improved sensitivity, and comprehensive product ion coverage. Using the two-step derivatization approach, we successfully identified 29 endogenous phosphopeptides in 10 µL of human saliva with high reliability. The outcomes underscore the possibility of the method for site-specific phosphorylation and large-scale phosphoproteomics investigations.


Asunto(s)
Fosfopéptidos , Proteómica , Humanos , Fosfopéptidos/análisis , Marcaje Isotópico/métodos , Proteómica/métodos , Reproducibilidad de los Resultados , Indicadores y Reactivos , Fosforilación , Iones , Dimetilaminas
17.
iScience ; 27(1): 108726, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38235327

RESUMEN

The tight coupling between electricity and gas has put the US New England region at constant risk of electricity price spikes due to a shortage of gas supplies, especially in the wake of limited natural gas supply in 2022. Here, we investigate the electricity-gas price couplings in the six states in New England from 2006 to 2022. We found that the price coupling in New England has been high and consistent in the past five years across all states, despite varying levels of gas-fired power generation. Additionally, we anticipate it will remain high even with increasing renewables by 2030. Furthermore, the price coupling exhibits an asymmetrical influence with electricity prices closely tracking gas prices, while gas prices are weakly affected by electricity price variations. Our findings also suggest that promoting electricity-gas cooperations could potentially mitigate the asymmetrical influence and electricity price spikes in New England.

18.
J Med Virol ; 95(11): e29182, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37909805

RESUMEN

INTRODUCTION: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. METHODS: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. RESULTS: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). CONCLUSIONS: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.


Asunto(s)
Infecciones por Adenovirus Humanos , Adenovirus Humanos , Infecciones Comunitarias Adquiridas , Neumonía Viral , Neumonía , Niño , Humanos , Femenino , Lactante , Adenovirus Humanos/genética , Proteómica , Factores de Riesgo
19.
Pancreatology ; 23(8): 949-956, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37968184

RESUMEN

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed in non-HTG-induced acute pancreatitis (AP), such as in the early stage of acute biliary pancreatitis (ABP). There is overlap in the etiologies of ABP, HTG-AP, and biliary-hypertriglyceridemia acute pancreatitis (BHAP), which may be perplexing for clinicians. METHODS: We retrospectively analyzed 394 AP patients. The patients were divided into three groups based on etiology. We analyzed the differences among the three groups of patients in terms of general information, laboratory parameters, and prognosis. RESULTS: The mean age of patients in the ABP group was significantly higher than that in the HTG-AP and BHAP groups (p < 0.001). Females made up a greater percentage of the ABP group, whereas males made up the majority in the HTG-AP and BHAP groups. The ABP group had the highest PCT, AMS, LPS, ALT, AST, GGT, TBIL, DBIL, APACHE II, and BISAP scores. TG and BMI were highest in the HTG-AP group. AST and GGT levels were substantially greater in BHAP patients than those in HTG-AP. The BHAP group had the greatest incidence of organ failure, systemic complications, and local complications. CONCLUSION: ABP usually develops in people aged 50-59 years. HTG-AP primarily affects people aged 30-39 years. However, the peak incidence age of BHAP falls between the two aforementioned age groups (40-49 years). We also found that patients with BHAP seem to be in an intermediate state in terms of some biochemical markers and demographic characteristics. Furthermore, BHAP may have the worst clinical outcomes compared with HTG-AP and ABP.


Asunto(s)
Hipertrigliceridemia , Pancreatitis , Masculino , Femenino , Humanos , Pancreatitis/complicaciones , Pancreatitis/epidemiología , Estudios Retrospectivos , Enfermedad Aguda , Triglicéridos , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/epidemiología
20.
Nature ; 623(7988): 752-756, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37853128

RESUMEN

Subduction related to the ancient supercontinent cycle is poorly constrained by mantle samples. Sublithospheric diamond crystallization records the release of melts from subducting oceanic lithosphere at 300-700 km depths1,2 and is especially suited to tracking the timing and effects of deep mantle processes on supercontinents. Here we show that four isotope systems (Rb-Sr, Sm-Nd, U-Pb and Re-Os) applied to Fe-sulfide and CaSiO3 inclusions within 13 sublithospheric diamonds from Juína (Brazil) and Kankan (Guinea) give broadly overlapping crystallization ages from around 450 to 650 million years ago. The intracratonic location of the diamond deposits on Gondwana and the ages, initial isotopic ratios, and trace element content of the inclusions indicate formation from a peri-Gondwanan subduction system. Preservation of these Neoproterozoic-Palaeozoic sublithospheric diamonds beneath Gondwana until its Cretaceous breakup, coupled with majorite geobarometry3,4, suggests that they accreted to and were retained in the lithospheric keel for more than 300 Myr during supercontinent migration. We propose that this process of lithosphere growth-with diamonds attached to the supercontinent keel by the diapiric uprise of depleted buoyant material and pieces of slab crust-could have enhanced supercontinent stability.

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