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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.
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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.
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Jejum Intermitente , Animais , Humanos , Tecido Adiposo Branco/metabolismo , Jejum Intermitente/metabolismo , Obesidade/dietoterapia , Obesidade/metabolismo , Transdução de SinaisRESUMO
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.
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COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , Fosfoproteínas , SARS-CoV-2 , SARS-CoV-2/genética , Humanos , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/química , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , COVID-19/virologia , COVID-19/diagnóstico , Fosfoproteínas/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Proteínas do Nucleocapsídeo/metabolismo , Proteínas do Nucleocapsídeo/genéticaRESUMO
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.
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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.
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Amidoidrolases , Encéfalo , Corantes Fluorescentes , Neurônios , Amidoidrolases/metabolismo , Animais , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neurônios/metabolismo , Camundongos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/análise , Humanos , Piridinas/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , FótonsRESUMO
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.
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Índice de Massa Corporal , Densidade Óssea , Estudo de Associação Genômica Ampla , Lipoproteínas LDL , Análise da Randomização Mendeliana , Humanos , Densidade Óssea/genética , Lipoproteínas LDL/sangue , Polimorfismo de Nucleotídeo Único , FemininoRESUMO
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.
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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.
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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.
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Proteínas Adaptadoras de Transdução de Sinal , COVID-19 , SARS-CoV-2 , Transdução de Sinais , Animais , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose , COVID-19/virologia , COVID-19/imunologia , COVID-19/metabolismo , Proteína DEAD-box 58/metabolismo , Células HEK293 , Imunidade Inata , Interferon beta/metabolismo , Receptores Imunológicos/metabolismo , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitinação , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Virais Reguladoras e Acessórias/genéticaRESUMO
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.
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Fenil-Hidrazinas , Ácidos Siálicos , Animais , Acetilação , Espectrometria de Massa com Cromatografia Líquida , Fenil-Hidrazinas/química , Ácidos Siálicos/química , Ácidos Siálicos/análiseRESUMO
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).
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Reconhecimento Visual de Modelos , Processamento de Texto , Humanos , China , LeituraRESUMO
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.
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Fosfopeptídeos , Proteômica , Humanos , Fosfopeptídeos/análise , Marcação por Isótopo/métodos , Proteômica/métodos , Reprodutibilidade dos Testes , Indicadores e Reagentes , Fosforilação , Íons , DimetilaminasRESUMO
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.
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COVID-19 , Proteínas do Nucleocapsídeo , Humanos , SARS-CoV-2/genética , DNA de Cadeia Simples/farmacologia , Vacinas contra COVID-19 , Antivirais/farmacologiaRESUMO
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.
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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.
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Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções Comunitárias Adquiridas , Pneumonia Viral , Pneumonia , Criança , Humanos , Feminino , Lactente , Adenovírus Humanos/genética , Proteômica , Fatores de RiscoRESUMO
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.
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Hipertrigliceridemia , Pancreatite , Masculino , Feminino , Humanos , Pancreatite/complicações , Pancreatite/epidemiologia , Estudos Retrospectivos , Doença Aguda , Triglicerídeos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/epidemiologiaRESUMO
Norepinephrine (NE) is a key neurotransmitter in the central and sympathetic nervous systems, whose content fluctuates dynamically and rapidly in various brain regions during different physiological and pathophysiological processes. However, it remains a great challenge to directly visualize and precisely quantify the transient NE dynamics in living systems with high accuracy, specificity, sensitivity, and, in particular, high temporal resolution. Herein, we developed a series of small-molecular probes that can specifically detect NE through a sequential nucleophilic substitution-cyclization reaction, accompanied by a ratiometric near-infrared fluorescence response, within an impressively short time down to 60 ms, which is 3 orders of magnitude faster than that of present small-molecular probes. A unique water-promoted intermolecular proton transfer mechanism is disclosed, which dramatically boosted the recognition kinetics by â¼680 times. Benefiting from these excellent features, we quantitatively imaged the transient endogenous NE dynamics under external stimuli at the single living neuron level and further revealed the close correlations between NE fluctuations and Parkinson's disease pathology at the level of acute brain slices and live mouse brains in vivo.
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Encéfalo , Norepinefrina , Animais , Camundongos , Encéfalo/diagnóstico por imagem , Sondas Moleculares , Imagem Óptica , NeurôniosRESUMO
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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Recently, interventional ablation techniques have gained prominence in tumor treatment guidelines and complement traditional approaches, such as surgery, chemotherapy, and radiotherapy. Conventional ablation techniques, such as microwave, radiofrequency, and cryoablation, have been used; however, they have certain limitations, including the risk of damaging surrounding normal tissues and the heat sink effect caused by tumor blood flow.1 Irreversible electroporation (IRE), an ablation technology independent of thermal energy, is a promising alternative.2 Clinical studies have demonstrated IRE's efficacy in treating tumors, such as pancreatic and liver tumors.3 Recent research has shown that IRE can elicit specific anti-tumor immune responses in the body.5 IRE also plays a crucial role in eliminating residual tumor cells postoperatively and preventing tumor recurrence.
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PURPOSE: As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy. METHODS: This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses. RESULTS: Difficult laryngoscopy was indicated in 49 patients (CL grade â ¢ - â £) and easy laryngoscopy in 453 patients (CL grade â - â ¡). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups. CONCLUSION: Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.