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Cultivated strawberry (Fragaria × ananassa) is a popular, economically important fruit. The ripening of the receptacle (pseudocarp), the main edible part, depends on endogenously produced abscisic acid (ABA) and is suppressed by the high level of auxin produced from achenes (true fruit) during early development. However, the mechanism whereby auxin regulates receptacle ripening through inhibiting ABA biosynthesis remains unclear. Here, we identified AUXIN RESPONSE FACTOR 2 (FaARF2), which showed decreased expression with reduced auxin content in the receptacle, leading to increased ABA levels and accelerated ripening. Dual-luciferase, yeast one-hybrid, and electrophoretic mobility shift assays demonstrated that FaARF2 could bind to the AuxRE element in the promoter of 9-CIS-EPOXYCAROT-ENOID DIOXYGENASE 1 (FaNCED1), a key ABA biosynthetic gene, to suppress its transcriptional activity. Transiently overexpressing FaARF2 in the receptacles decreased FaNCED1 expression and ABA levels, resulting in inhibition of receptacle ripening and of development of quality attributes, such as pigmentation, aroma, and sweetness. This inhibition caused by overexpressing FaARF2 was partially recovered by the injection of exogenous ABA; conversely, transient silencing of FaARF2 using RNA interference produced the opposite results. The negative targeting of FaNCED1 by FaARF2 is a key link between auxin-ABA interactions and regulation of strawberry ripening.
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OBJECTIVES: To explore the current application of high-throughput drug sensitivity (HDS) testing in children with relapsed and refractory acute leukemia (RR-AL) and analyze the feasibility of salvage treatment plans. METHODS: A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted, followed by an analysis of drug sensitivity results and treatment outcomes. RESULTS: A total of 17 children with RR-AL underwent HDS testing, including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia. The detection rate of highly sensitive chemotherapy drugs/regimens was 53% (9/17), while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100% (17/17). Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens, the MOACD regimen (mitoxantrone + vincristine + cytarabine + cyclophosphamide + dexamethasone) accounted for 100%, with the highest inhibition rate for single-agent mitoxantrone (94%, 16/17), and the highest inhibition rate for targeted therapy being bortezomib (94%, 16/17). Nine patients adjusted their chemotherapy based on HDS testing results, with 4 undergoing hematopoietic stem cell transplantation. Four patients achieved disease-free survival, while 5 died. Eight patients received empirical chemotherapy, with 2 undergoing hematopoietic stem cell transplantation; 4 achieved disease-free survival, while 4 died. CONCLUSIONS: HDS testing can identify highly sensitive drugs/regimens for children with RR-AL, improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Feminino , Masculino , Pré-Escolar , Estudos Retrospectivos , Adolescente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva , Ensaios de Triagem em Larga Escala , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia de Salvação , Lactente , Antineoplásicos/uso terapêuticoRESUMO
Multi-drug therapies are common in cardiovascular disease intervention; however, io channel/pump coordination has not been tested electrophysiologically. Apparently, inward currents were not elicited by Yoda1/10 nM or Dobutamine/100 nM alone in Ah-type baroreceptor neurons, but were by their combination. To verify this, electroneurography and the whole-cell patch-clamp technique were performed. The results showed that Ah- and C-volley were dramatically increased by the combination at 0.5 V and 5 V, in contrast to A-volley, as consistent with repetitive discharge elicited by step and ramp with markedly reduced current injection/stimulus intensity. Notably, a frequency-dependent action potential (AP) duration was increased with Iberiotoxin-sensitive K+ component. Furthermore, an increased peak in AP measured in phase plots suggested enhanced Na+ influx, cytoplasmic Ca2+ accumulation through reverse mode of Na+/Ca2+ exchanger, and, consequently, functional KCa1.1 up-regulation. Strikingly, the Yoda1- or Dbtm-mediated small/transient Na+/K+-pump currents were robustly increased by their combination, implying a quick ion equilibration that may also be synchronized by hyperpolarization-induced voltage-sag, enabling faster repetitive firing. These novel findings demonstrate multi-channel/pump collaboration together to integrate neurotransmission at the cellular level for baroreflex, providing an afferent explanation in sexual dimorphic blood pressure regulation, and raising the caution regarding the individual drug concentration in multi-drug therapies to optimize efficacy and minimize toxicity.
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Barorreflexo , Animais , Barorreflexo/efeitos dos fármacos , Masculino , Ratos , Pressorreceptores/efeitos dos fármacos , Pressorreceptores/metabolismo , Pressorreceptores/fisiologia , Potenciais de Ação/efeitos dos fármacos , Ratos Sprague-Dawley , Técnicas de Patch-ClampRESUMO
Auxin response transcription factors (ARFs) form a large gene family, many of whose members operate at the final step of the auxin signaling pathway. ARFs participate directly in many aspects of plant growth and development. Here we summarize recent advances in understanding the roles of ARFs in regulating aspects of fleshy fruit development and ripening. ARFs play a crucial role in regulating fruit size, color, nutrients, texture, yield, and other properties that ultimately influence the ripening and quality of important crops such as tomato, apple, strawberry, and peach. ARFs impact these processes acting as positive, negative, or bidirectional regulators via phytohormone-dependent or -independent mechanisms. In the phytohormone-dependent pathway, ARFs act as a central hub linking interactions with multiple phytohormones generating diverse effects. The three domains within ARFs, namely the DNA-binding domain, the middle region, and the carboxy-terminal dimerization domain, exhibit distinct yet overlapping functions, contributing to a range of mechanisms mediated by ARFs. These findings not only provide a profound understanding of ARF functions, but also raise new questions. Further exploration can lead to a more comprehensive understanding of the regulatory mechanisms of fleshy fruit development and ripening mediated by ARFs.
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Background: The relationship between white matter hyperintensities (WMH) and the core features of Alzheimer's disease (AD) remains controversial. Further, due to the prevalence of co-pathologies, the precise role of WMH in cognition and neurodegeneration also remains uncertain. Methods: Herein, we analyzed 1803 participants with available WMH volume data, extracted from the ADNI database, including 756 cognitively normal controls, 783 patients with mild cognitive impairment (MCI), and 264 patients with dementia. Participants were grouped according to cerebrospinal fluid (CSF) pathology (A/T profile) severity. Linear regression analysis was applied to evaluate the factors associated with WMH volume. Modeled by linear mixed-effects, the increase rates (Δ) of the WMH volume, cognition, and typical neurodegenerative markers were assessed. The predictive effectiveness of WMH volume was subsequently tested using Cox regression analysis, and the relationship between WMH/ΔWMH and other indicators such as cognition was explored through linear regression analyses. Furthermore, we explored the interrelationship among amyloid-ß deposition, cognition, and WMH using mediation analysis. Results: Higher WMH volume was associated with older age, lower CSF amyloid-ß levels, hypertension, and smoking history (all p ≤ 0.001), as well as cognitive status (MCI, p < 0.001; dementia, p = 0.008), but not with CSF tau levels. These results were further verified in any clinical stage, except hypertension and smoking history in the dementia stage. Although WMH could not predict dementia conversion, its increased levels at baseline were associated with a worse cognitive performance and a more rapid memory decline. Longitudinal analyses showed that baseline dementia and positive amyloid-ß status were associated with a greater accrual of WMH volume, and a higher ΔWMH was also correlated with a faster cognitive decline. In contrast, except entorhinal cortex thickness, the WMH volume was not found to be associated with any other neurodegenerative markers. To a lesser extent, WMH mediates the relationship between amyloid-ß and cognition. Conclusion: WMH are non-specific lesions that are associated with amyloid-ß deposition, cognitive status, and a variety of vascular risk factors. Despite evidence indicating only a weak relationship with neurodegeneration, early intervention to reduce WMH lesions remains a high priority for preserving cognitive function in the elderly.
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AIMS: The early stages of Alzheimer's disease (AD) are no longer insurmountable. Therefore, identifying at-risk individuals is of great importance for precise treatment. We developed a model to predict cognitive deterioration in patients with mild cognitive impairment (MCI). METHODS: Based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we constructed models in a derivation cohort of 761 participants with MCI (138 of whom developed dementia at the 36th month) and verified them in a validation cohort of 353 cognitively normal controls (54 developed MCI and 19 developed dementia at the 36th month). In addition, 1303 participants with available AD cerebrospinal fluid core biomarkers were selected to clarify the ability of the model to predict AD core features. We assessed 32 parameters as candidate predictors, including clinical information, blood biomarkers, and structural imaging features, and used multivariable logistic regression analysis to develop our prediction model. RESULTS: Six independent variables of MCI deterioration were identified: apolipoprotein E ε4 allele status, lower Mini-Mental State Examination scores, higher levels of plasma pTau181, smaller volumes of the left hippocampus and right amygdala, and a thinner right inferior temporal cortex. We established an easy-to-use risk heat map and risk score based on these risk factors. The area under the curve (AUC) for both internal and external validations was close to 0.850. Furthermore, the AUC was above 0.800 in identifying participants with high brain amyloid-ß loads. Calibration plots demonstrated good agreement between the predicted probability and actual observations in the internal and external validations. CONCLUSION: We developed and validated an accurate prediction model for dementia conversion in patients with MCI. Simultaneously, the model predicts AD-specific pathological changes. We hope that this model will contribute to more precise clinical treatment and better healthcare resource allocation.
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Disfunção Cognitiva , Demência , Proteínas tau , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico por imagem , Estudos de Coortes , Demência/sangue , Demência/diagnóstico por imagem , Progressão da Doença , Imageamento por Ressonância Magnética , Neuroimagem , Valor Preditivo dos Testes , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidianoRESUMO
The active role of "Shen" (mind) in the process of disease treatment has always been valued by scholars of traditional Chinese medicine (TCM). "Tiaoshen" (mind-regulating) is regarded as the fundamental component of TCM therapy. "Mind-regulating" acupuncture and moxibustion therapy, as a treatment method for both body and mind, is consistent with the present bio-psycho-social medical model. In recent years, a large number of clinical studies have confirmed the exact efficacy of "mind-regulating" acupuncture and moxibustion therapy. This article reviewed the clinical applications of that in psychosomatic diseases, neurological diseases, and digestive diseases over the last decade. This article also summarized the research progress of various "mind-regulating" acupuncture and moxibustion methods, investigated the theoretical connotations of "Tongdu Tiaoshen" (dredging Governor Vessel and regulating mind) acupuncture, "Shugan Tiaoshen" (soothing liver and regulating mind) acupuncture, and the "Tiaoshen needling technique" (mind-regulating needling technique), and generalized the main acupoint selection rules. Lastly, future development directions were provided for the theoretical basis of clinical application of "mind-regulating" acupuncture and moxibustion therapy for further improvement.
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Terapia por Acupuntura , Moxibustão , Humanos , Pontos de Acupuntura , Medicina Tradicional Chinesa , Doenças do Sistema Nervoso/terapiaRESUMO
The epidemic and outbreaks of influenza B Victoria lineage (Bv) during 2019-2022 led to an analysis of genetic, epitopes, charged amino acids and Bv outbreaks. Based on the National Influenza Surveillance Network (NISN), the Bv 72 strains isolated during 2019-2022 were selected by spatio-temporal sampling, then were sequenced. Using the Compare Means, Correlate and Cluster, the outbreak data were analyzed, including the single nucleotide variant (SNV), amino acid (AA), epitope, evolutionary rate (ER), Shannon entropy value (SV), charged amino acid and outbreak. With the emergence of COVID-19, the non-pharmaceutical interventions (NPIs) made Less distant transmission and only Bv outbreak. The 2021-2022 strains in the HA genes were located in the same subset, but were distinct from the 2019-2020 strains (P < 0.001). The codon G â A transition in nucleotide was in the highest ratio but the transversion of C â A and T â A made the most significant contribution to the outbreaks, while the increase in amino acid mutations characterized by polar, acidic and basic signatures played a key role in the Bv epidemic in 2021-2022. Both ER and SV were positively correlated in HA genes (R = 0.690) and NA genes (R = 0.711), respectively, however, the number of mutations in the HA genes was 1.59 times higher than that of the NA gene (2.15/1.36) from the beginning of 2020 to 2022. The positively selective sites 174, 199, 214 and 563 in HA genes and the sites 73 and 384 in NA genes were evolutionarily selected in the 2021-2022 influenza outbreaks. Overall, the prevalent factors related to 2021-2022 influenza outbreaks included epidemic timing, Tv, Ts, Tv/Ts, P137 (B â P), P148 (B â P), P199 (P â A), P212 (P â A), P214 (H â P) and P563 (B â P). The preference of amino acid mutations for charge/pH could influence the epidemic/outbreak trends of infectious diseases. Here was a good model of the evolution of infectious disease pathogens. This study, on account of further exploration of virology, genetics, bioinformatics and outbreak information, might facilitate further understanding of their deep interaction mechanisms in the spread of infectious diseases.
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Surtos de Doenças , Evolução Molecular , Influenza Humana , Mutação , Polimorfismo de Nucleotídeo Único , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/genética , Vírus da Influenza B/genética , Aminoácidos/genética , Epitopos/genética , Filogenia , Substituição de Aminoácidos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genéticaRESUMO
BACKGROUND: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. RESULTS: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. CONCLUSION: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract.
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Febre de Chikungunya , Vírus Chikungunya , Fezes , Microbioma Gastrointestinal , Macaca mulatta , Animais , Fezes/microbiologia , Febre de Chikungunya/virologia , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Disbiose/microbiologia , Inflamação , Inflamassomos/metabolismo , Modelos Animais de Doenças , Interleucina-17/metabolismo , Trato Gastrointestinal/microbiologia , Citocinas/metabolismoRESUMO
Radioactive nuclides and highly toxic organophosphates are typical deadly threats. Materials with the function of radioactive substances adsorption and organophosphates degradation provide double protection. Herein, dual-functional polyamide (PA)/polyethyleneimine (PEI)@Zr-MOF fiber composite membranes, fabricated by in-situ solvothermal growth of Zr-MOF on PA/PEI electrospun fiber membranes, are designed for protection against two typical model compounds of iodine and dimethyl 4-nitrophenyl phosphate (DMNP). Benefiting from the unique core-sheath structure composed of inner nitrogen-rich fibers and outer porous Zr-MOF, the composite membranes rapidly enrich iodine through abundant active sites of the outer sheath and form complexes with the amine of inner PEI, exhibiting a highly competitive adsorption capacity of 609 mg g-1. Moreover, it can adsorb and degrade DMNP with the synergy of PEI component and Zr-MOF, achieving an 80 % removal of DMNP within 7 min without any additional co-catalyst. This work provides a feasible strategy to fabricate dual-functional materials that protect against radioactive and organophosphorus contaminants.
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Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin-like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.
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COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , COVID-19/virologia , COVID-19/metabolismo , COVID-19/genética , Animais , Camundongos , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , Células HEK293 , Mutação , Mutação de Sentido Incorreto , Chlorocebus aethiopsRESUMO
Solid polymer electrolytes (SPEs) are crucial in the development of lithium metal batteries. Recently, metal-organic frameworks (MOFs) with open metal sites (OMSs) have shown promise as solid fillers to improve the performance of SPEs. However, the number of OMS-containing MOFs is quite limited, comprising less than 5% of the total MOFs. When considering yield, cost, and processability, the commonly used OMS-containing MOFs are no more than 10â types, causing great limitations. Herein, we reported a simple and universal methodology that converted OMS-free MOFs to OMS-rich quasi-MOFs for developing high-performance SPEs, and explored the underlying mechanism. The "OMS-polymer" and "OMS-ion" interactions were investigated in detail to elucidate the role of quasi-MOFs on battery performance. It was found that quasi-MOFs, functioning as ion sieves, can effectively regulate ion migration, thus promoting uniform Li deposition and enabling an ultra-stable interface. As a result, the Li symmetric cell stably ran over 3000â h at 0.3â mA cm-2, while the full cell retained 85 % of its initial capacity after 1500â cycles at 1.0â C. Finally, universal testing was performed using other MOFs, confirming the generalizability and effectiveness of our design concept.
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AIM: The study objective was to evaluate the primary feasibility of endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) to treat small bowel subepithelial lesions (SELs). METHOD: A retrospective case series study was performed. The first fifteen consecutive patients who underwent ESD (n = 10) and EFTR (n = 5) via BAE to remove small bowel SELs from November 2016 to December 2023 were included. The main outcome measures were the technique success rate, operative time and complication rate. RESULTS: This research focused on 15 cases of jejunoileal SELs, four cases of lipomyoma, three cases of ectopic pancreas, two cases of NETs, three cases of benign fibrous tumours and three cases of angioma. The overall technique success rate was 86.7%, with 100% (10/10) and 60% (3/5) for BAE-ESD and BAE-EFTR, respectively, in removing small bowel SELs. Two cases of EFTR failed, as the BAE operation was unsuitable for tumour resection and suture repair of a perforated wound. No serious bleeding or any postoperative complications occurred. The median time of endoscopic resection via BAE for SELs was 44 min (range 22-68 min). CONCLUSION: ESD and EFTR via BAE might be alternative choices for treating small SELs in the small bowel, with the advantages of clear and accurate positioning and minimal invasiveness. However, its superiority over surgery still needs to be further investigated.
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Enteroscopia de Balão , Ressecção Endoscópica de Mucosa , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Enteroscopia de Balão/métodos , Ressecção Endoscópica de Mucosa/métodos , Estudos de Viabilidade , Neoplasias Intestinais/cirurgia , Neoplasias Intestinais/patologia , Intestino Delgado/cirurgia , Duração da Cirurgia , Resultado do TratamentoRESUMO
Reversed-phase liquid chromatography (RPLC) represents an effective separation method, and is widely employed as the second dimension in most 2D-LC systems. Nevertheless, the solvent effect of the eluent from the first dimension on RPLC presents a challenge to the online coupling of RPLC with other separation modes, particularly normal phase liquid chromatography (NPLC). To address this issue, a comprehensive understanding of the solvent effect is essential. Following a comprehensive investigation into the influence of diverse solvents on RPLC separations, it was observed that alkane solvents, such as n-hexane, exhibited a pronounced tendency to be retained during RPLC separations. Such solvents do not affect the analysis of samples with weaker retention abilities than themselves, even when a large injection volume is used. The solvent effect was thus reduced by employing n-hexane-based solvent dilution. Leveraging the markedly enhanced solvent tolerance and extensive injection volume in RPLC, a versatile integration of the NPLC and RPLC was devised, necessitating merely a purge pump and a 10 port 2 position valve in conjunction with two sample loops. The novel 2D-LC system was then deployed for the analysis of propolis, a naturally occurring complex sample, and demonstrated remarkable separation efficiency.
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Produtos Biológicos , Cromatografia de Fase Reversa , Hexanos , Solventes , Hexanos/química , Solventes/química , Cromatografia de Fase Reversa/métodos , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Cromatografia Líquida/métodosRESUMO
Accurate on-site detection of nitrite in complex matrices remains a significant challenge. Herin, we construct a self-ratio optical bimodal portable kit via co-assembling NaErF4:0.5%Tm@NaYF4@NaYbF4:0.5%Tm@NaYF4 (Er:Tm@Yb:Tm) and nitrogen-doped carbon platinum nanomaterials (Pt/CN) in sodium alginate (SA) hydrogel. Pt/CN nanomaterials are synthesized by high-temperature sintering using a zinc-based zeolite imidazolium framework as a sacrificial template. The Pt/CN nanozyme possesses excellent oxidase-like activity to produce the oxidation state 3,3',5,5'-tetramethylbenzidine (oxTMB). Nitrite mediates diazotization of oxTMB to trigger the change of absorption signals, accompanying the ratio fluorescence response of the Er:Tm@Yb:Tm. Crucially, Er:Tm@Yb:Tm and Pt/CN are embedded in SA hydrogel to fabricate a portable kit with efficient and sensitive performance. An image processing algorithm is used to analyze the nitrite-induced signal change of the portable hydrogel kit, resulting in detection limits of 0.63 µM. This method has great potential for point-of-care applications due to its reliability, long-term stability, accuracy, sensitivity, and portability.
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Técnicas Biossensoriais , Hidrogéis , Limite de Detecção , Nitritos , Smartphone , Técnicas Biossensoriais/métodos , Nitritos/análise , Hidrogéis/química , Humanos , Benzidinas/química , Nanoestruturas/química , Platina/químicaRESUMO
Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.
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Citocinas , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Replicação Viral , Infecção por Zika virus , Zika virus , Animais , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia , Replicação Viral/efeitos dos fármacos , Camundongos , Citocinas/metabolismo , Taxa de Sobrevida , Receptor de Interferon alfa e beta/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Receptor de Interferon gama , Células VeroRESUMO
Quaternary ammonium salt bactericides are broad-spectrum bactericides often used in oral care products because of their high antibacterial efficacy, strong penetration, and low toxicity. However, the excessive use of quaternary ammonium salt bactericides may cause contact dermatitis, scalding poisoning, and even death. Existing methods to determine quaternary ammonium salt bactericides are unable to meet current requirements owing to the lack of determination components. Therefore, establishing a simple and accurate method for the simultaneous detection of more quaternary ammonium salt bactericides is necessary. In this study, a method that couples sample pretreatment with high performance liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) was developed for the simultaneous determination of quaternary ammonium salt bactericides in oral care products, including dodecyltrimethylammonium chloride, dodecyldimethylbenzylammonium chloride, benzethonium chloride, tetradecyl trimethyl ammonium chloride, tetradecyldimethylbenzylammonium chloride, N-hexadecyltrimethylammonium chloride, benzyldimethylhexadecylammonium chloride, trimethylstearylammonium chloride, stearyldimethylbenzylammonium chloride, and docosyltrimethylammonium chloride. Some of these bactericides do not absorb ultraviolet light, so a universal evaporative light-scattering detector was used owing to testing cost and stability concerns. The paste samples contained thickening agents, which are highly soluble in water but insoluble in organic solvents; these agents can seriously affect the results of sample pretreatment and damage the chromatographic column. Hence, sample dehydration was necessary. In this study, four dehydration methods were compared. Anhydrous sodium sulfate (Na2SO4) was selected, and the amount of Na2SO4 was optimized. Based on the solubility of the 10 target compounds and extraction efficiency, three extraction solvents were compared, and ethanol was selected. Ultrasonic extraction was the primary extraction process used in this study. The effects of different ultrasonication times, temperatures, and powers on the extraction recoveries were also investigated. Ultimately, the optimized conditions were as follows: extraction of the dehydrated paste and powder samples using ethanol at room temperature (25 â) for 20 min under 100 W ultrasound power, and dilution of the liquid sample with ethanol. After extraction, the samples were separated on an Acclaim Surfactant column (150 mm×4.6 mm, 5 µm) with 50 mmol/L ammonium acetate aqueous solution (pH=5.5) (A) and acetonitrile (B) as mobile phases. The gradient elution program were as follows: 0-5.0 min, 75%A-35%A, 5.0-15.0 min, 35%A-20%A, 15.0-20.0 min, 20%A, 20.0-21.0 min, 20%A-75%A, 21.0-25.0 min, 75%A. An external standard method was used for quantitative determination. The 10 compounds were analyzed within 25 min. Linear equations, correlation coefficients, and linear ranges were obtained by analyzing a series of mixed standard working solutions. The limits of detection (LODs, S/N=3) and quantification (LOQs, S/N=10) of the 10 components were determined. Stearyldimethylbenzylammonium chloride and docosyltrimethylammonium chloride showed good linear relationships in the range of 10-200 mg/L, while the other compounds demonstrated good linear relationships in the range of 5-100 mg/L. In all cases, correlation coefficients (R2) of no less than 0.9992 were obtained. The LODs and LOQs were in the range of 1.42-3.31 mg/L and 4.25-9.94 mg/L, respectively. Ten analytes were spiked in blank matrices, such as toothpaste (paste), mouthwash (liquid), and dentifrice powder (powder) at three levels, and the recoveries and precisions were calculated. The average recoveries were 87.9%-103.1%, and the corresponding relative standard deviations (RSDs) did not exceed 5.5% (n=6). The developed method was used to detect 109 oral care products. Benzyldimethylhexadecylammonium chloride and stearyldimethylbenzylammonium chloride revealed high detection rates. Moreover, the amount of stearyldimethylbenzylammonium chloride in one toothpaste sample exceeded regulatory requirements. Given its advantages of good precision and accuracy, the developed method is suitable for the quantitative analysis of the 10 aforementioned compounds in typical oral care products. The study findings can serve as a reference for the quality and safety monitoring of oral care products.
Assuntos
Compostos de Amônio Quaternário , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/análise , Cromatografia Líquida de Alta Pressão , Antibacterianos/análise , Luz , Espalhamento de RadiaçãoRESUMO
Fluorescence imaging technology is a versatile and essential tool in the field of biomedical research. To obtain excellent imaging results, the precise labeling of fluorescent probes is an important prerequisite. Nevertheless, the labeling selectivity of most fluorescent probes is not satisfactory, new design concepts are desperately needed. In this context, two isomeric lipid droplets (LDs) fluorescent probes Lipi-Cz-1 and Lipi-Cz-2 have been sophisticatedly developed with TICT and ICT-emitting characteristic, respectively. The more environmentally sensitive TICT-emitting Lipi-Cz-1 exhibits a significantly enhanced labeling selectivity in LDs imaging compared to the ICT-emitting Lipi-Cz-2, sufficiently illustrating the effectiveness of TICT-emitting characteristic in improving labeling selectivity. Additionally, Lipi-Cz-1 displays high photostability and biocompatibility. These advantages enable Lipi-Cz-1 to be finely applied in multimode fluorescence imaging, e.g. time-lapse 3D confocal imaging to monitor changes of the number and size of LDs during starvation, two-photon 3D imaging to compare the variations of LDs in various liver tissues, and STED super-resolution imaging to visualize the nanoscale LDs with the resolution of 65 nm. Overall, these imaging findings validate the effectiveness of the new strategy for improving the labeling selectivity.
Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Imagem Óptica , Corantes Fluorescentes/química , Gotículas Lipídicas/química , Humanos , Imagem Óptica/métodos , Animais , Técnicas Biossensoriais/métodos , CamundongosRESUMO
Caffeic acid (CA) is a natural polyphenol that can have various positive effects on human health. However, its extraction and processing can cause significant ecological issues. Therefore, it is crucial to detect and degrade CA effectively in the environment. In this study, we have developed a multifunctional magnetic luminescent nanozyme, Fe3O4@CeO2/Tb-MOF, which combines peroxidase activity to detect and degrade CA. The fluorescence of the nanozyme was significantly attenuated due to the specific nucleophilic reaction between its boronic acid moiety and the o-diphenol hydroxyl group of CA, energy competition absorption and photo-induced electron transfer (PET) effect. This nanozyme demonstrates a linear detection range from 50 nM to 500 µM and an exceptionally low detection limit of 18.9 nM, along with remarkable selectivity and stability. Moreover, the synergistic catalysis of Fe3O4 and CeO2 within Fe3O4@CeO2/Tb-MOF fosters peroxidase activity, leading to the generation of substantial free radicals catalyzed by H2O2, which ensures the efficient degradation of CA (â¼95%). The superparamagnetic property of Fe3O4 further enables the efficient reuse and recycling of the nanozyme. This research provides a novel approach for the concurrent detection and remediation of environmental contaminants.