Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.802
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 181(5): 997-1003.e9, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32359424

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Teorema de Bayes , COVID-19 , China/epidemiologia , Infecções por Coronavirus/virologia , Monitoramento Epidemiológico , Humanos , Funções Verossimilhança , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Viagem
2.
Nat Immunol ; 20(10): 1348-1359, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31406382

RESUMO

Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the TH17 subset of helper T cells and promoted angiogenesis. Interestingly, the 'angio-lymphokine' PlGF, in turn, specifically induced the differentiation of pathogenic TH17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with TH17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, TH17 cell development and autoimmunity.


Assuntos
Artrite Experimental/imunologia , Encefalomielite Autoimune Experimental/imunologia , Fator de Crescimento Placentário/metabolismo , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Autoimunidade , Diferenciação Celular , Células Cultivadas , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Neovascularização Patológica , Fator de Crescimento Placentário/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
3.
Proc Natl Acad Sci U S A ; 121(10): e2310841121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38412134

RESUMO

Connectomics research has made it more feasible to explore how neural circuits can generate multiple outputs. Female sexual drive provides a good model for understanding reversible, long-term functional changes in motivational circuits. After emerging, female flies avoid male courtship, but they become sexually receptive over 2 d. Mating causes females to reject further mating for several days. Here, we report that pC1 neurons, which process male courtship and regulate copulation behavior, exhibit increased CREB (cAMP response element binding protein) activity during sexual maturation and decreased CREB activity after mating. This increased CREB activity requires the neuropeptide Dh44 (Diuretic hormone 44) and its receptors. A subset of the pC1 neurons secretes Dh44, which stimulates CREB activity and increases expression of the TRP channel Pyrexia (Pyx) in more pC1 neurons. This, in turn, increases pC1 excitability and sexual drive. Mating suppresses pyx expression and pC1 excitability. Dh44 is orthologous to the conserved corticotrophin-releasing hormone family, suggesting similar roles in other species.


Assuntos
Proteínas de Drosophila , Neuropeptídeos , Animais , Masculino , Feminino , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Neuropeptídeos/metabolismo , Copulação/fisiologia , Corte , Hormônios , Comportamento Sexual Animal/fisiologia
4.
N Engl J Med ; 388(18): 1668-1679, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-36876735

RESUMO

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
5.
Hepatology ; 80(5): 1074-1086, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466639

RESUMO

BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. APPROACH AND RESULTS: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05). CONCLUSIONS: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Hepatocelular , Imunoglobulina A , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Fibroblastos Associados a Câncer/imunologia , Imunoglobulina A/metabolismo , Masculino , Feminino , Bevacizumab/uso terapêutico , Bevacizumab/farmacologia , Fenótipo , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Receptor de Morte Celular Programada 1/metabolismo , Intervalo Livre de Progressão
6.
Am J Physiol Cell Physiol ; 326(1): C229-C251, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37899748

RESUMO

This review summarizes methods to study kidney intercalated cell (IC) function ex vivo. While important for acid-base homeostasis, IC dysfunction is often not recognized clinically until it becomes severe. The advantage of using ex vivo techniques is that they allow for the differential evaluation of IC function in controlled environments. Although in vitro kidney tubular perfusion is a classical ex vivo technique to study IC, here we concentrate on primary cell cultures, immortalized cell lines, and ex vivo kidney slices. Ex vivo techniques are useful in evaluating IC signaling pathways that allow rapid responses to extracellular changes in pH, CO2, and bicarbonate (HCO3-). However, these methods for IC work can also be challenging, as cell lines that recapitulate IC do not proliferate easily in culture. Moreover, a "pure" IC population in culture does not necessarily replicate its collecting duct (CD) environment, where ICs are surrounded by the more abundant principal cells (PCs). It is reassuring that many findings obtained in ex vivo IC systems signaling have been largely confirmed in vivo. Some of these newly identified signaling pathways reveal that ICs are important for regulating NaCl reabsorption, thus suggesting new frontiers to target antihypertensive treatments. Moreover, recent single-cell characterization studies of kidney epithelial cells revealed a dual developmental origin of IC, as well as the presence of novel CD cell types with certain IC characteristics. These exciting findings present new opportunities for the study of IC ex vivo and will likely rediscover the importance of available tools in this field.NEW & NOTEWORTHY The study of kidney intercalated cells has been limited by current cell culture and kidney tissue isolation techniques. This review is to be used as a reference to select ex vivo techniques to study intercalated cells. We focused on the use of cell lines and kidney slices as potential useful models to study membrane transport proteins. We also review how novel collecting duct organoids may help better elucidate the role of these intriguing cells.


Assuntos
Túbulos Renais Coletores , Túbulos Renais Coletores/metabolismo , Cultura Primária de Células , Rim/metabolismo , Linhagem Celular , Células Epiteliais/metabolismo , Organoides
7.
Clin Infect Dis ; 78(3): 646-650, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-37555762

RESUMO

Here, we report on a case of human infection with the H3N8 avian influenza virus. The patient had multiple myeloma and died of severe infection. Genome analysis showed multiple gene mutations and reassortments without mammalian-adaptive mutations. This suggests that avian influenza (A/H3N8) virus infection could be lethal for immunocompromised persons.


Assuntos
Vírus da Influenza A Subtipo H3N8 , Influenza Humana , Humanos , China , Vírus da Influenza A Subtipo H3N8/genética
8.
J Am Chem Soc ; 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39463343

RESUMO

Magnetic anisotropy is a crucial characteristic for enhancing the spintronic device performance. The synthesis of SmCrGe3 single crystals through a high-temperature solution method has led to the determination of uniaxial magnetocrystalline anisotropy. Phase verification was achieved by using scanning transmission electron microscopy (STEM), powder, and single-crystal X-ray diffraction techniques. Electrical transport and specific heat measurements indicate a Curie temperature (TC) of approximately 160 K, while magnetization measurements were utilized to determine the anisotropy fields and constants. Curie-Weiss fitting applied to magnetization data suggests the contribution of both Sm and Cr in the paramagnetic phase. Additionally, density functional theory (DFT) calculations explored the electronic structures and magnetic properties of SmCrGe3, revealing a significant easy-axis single-ion Sm magnetocrystalline anisotropy of 16 meV/fu. Based on the magnetization measurements, easy-axis magnetocrystalline anisotropy at 20 K is 13 meV/fu.

9.
Anal Chem ; 96(21): 8356-8364, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38753674

RESUMO

Lipids are essential for various cellular functions, including energy storage, membrane flexibility, and signaling molecule production. Maintaining proper lipid levels is important to prevent health problems such as cancer, neurodegenerative disorders, cardiovascular diseases, obesity, and diabetes. Monitoring cellular lipid droplets (LDs) in real-time with high resolution can provide insights into LD-related pathways and diseases owing to the dynamic nature of LDs. Fluorescence-based imaging is widely used for tracking LDs in live cells and animal models. However, the current fluorophores have limitations such as poor photostability and high background staining. Herein, we developed a novel fluorogenic probe based on a push-pull interaction combined with aggregation-induced emission enhancement (AIEE) for dynamic imaging of LDs. Probe 1 exhibits favorable membrane permeability and spectroscopic characteristics, allowing specific imaging of cellular LDs and time-lapse imaging of LD accumulation. This probe can also be used to examine LDs in fruit fly tissues in various metabolic states, serving as a highly versatile and specific tool for dynamic LD imaging in cellular and tissue environments.


Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Animais , Humanos , Imagem Óptica , Compostos de Boro/química , Camundongos , Células HeLa , Drosophila melanogaster
10.
Hum Brain Mapp ; 45(2): e26619, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339822

RESUMO

The prefrontal cortex (PFC) has been extensively studied in relation to various cognitive abilities, including executive function, attention, and memory. Nevertheless, there is a gap in our scientific knowledge regarding the functionally dissociable neural dynamics across the PFC during a cognitive task and their individual differences in performance. Here, we explored this possibility using a delayed match-to-sample (DMTS) working memory (WM) task using NIRSIT, a high-density, wireless, wearable functional near-infrared spectroscopy (fNIRS) system. First, upon presentation of the sample stimulus, we observed an immediate signal increase in the ventral (orbitofrontal) region of the anterior PFC, followed by activity in the dorsolateral PFC. After the DMTS test stimulus appeared, the orbitofrontal cortex activated once again, while the rest of the PFC showed overall disengagement. Individuals with higher accuracy showed earlier and sustained activation of the PFC across the trial. Furthermore, higher network efficiency and functional connectivity in the PFC were correlated with individual WM performance. Our study sheds new light on the dynamics of PFC subregional activity during a cognitive task and its potential applicability in explaining individual differences in experimental, educational, or clinical populations. PRACTITIONER POINTS: Wearable functional near-infrared spectroscopy (fNIRS) captured dissociable temporal dynamics across prefrontal subregions during a delayed match-to-sample task. Anterior regions of the orbitofrontal cortex (OFC) activated first during the delay period, followed by the dorsolateral prefrontal cortex (PFC). PFC disengaged overall after the delay, but the OFC reactivated to the test stimulus. Earlier and sustained activation of PFC was associated with better accuracy. Functional connectivity and network efficiency also varied with task performance.


Assuntos
Memória de Curto Prazo , Dispositivos Eletrônicos Vestíveis , Humanos , Memória de Curto Prazo/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cognição/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia
11.
BMC Plant Biol ; 24(1): 284, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627650

RESUMO

BACKGROUND: Lipids found in plant seeds are essential for controlling seed dormancy, dispersal, and defenses against biotic and abiotic stress. Additionally, these lipids provide nutrition and energy and are therefore important to the human diet as edible oils. Acer truncatum, which belongs to the Aceaceae family, is widely cultivated around the world for its ornamental value. Further because its seed oil is rich in unsaturated fatty acids (UFAs)- i.e. α-linolenic acid (ALA) and nervonic acid (NA)- and because it has been validated as a new food resource in China, the importance of A. truncatum has greatly risen. However, it remains unknown how UFAs are biosynthesized during the growth season, to what extent environmental factors impact their content, and what areas are potentially optimal for their production. RESULTS: In this study, transcriptome and metabolome of A. truncatum seeds at three representative developmental stages was used to find the accumulation patterns of all major FAs. Cumulatively, 966 metabolites and 87,343 unigenes were detected; the differential expressed unigenes and metabolites were compared between stages as follows: stage 1 vs. 2, stage 1 vs. 3, and stage 2 vs. 3 seeds, respectively. Moreover, 13 fatty acid desaturases (FADs) and 20 ß-ketoacyl-CoA synthases (KCSs) were identified, among which the expression level of FAD3 (Cluster-7222.41455) and KCS20 (Cluster-7222.40643) were consistent with the metabolic results of ALA and NA, respectively. Upon analysis of the geographical origin-affected diversity from 17 various locations, we found significant variation in phenotypes and UFA content. Notably, in this study we found that 7 bioclimatic variables showed considerable influence on FAs contents in A. truncatum seeds oil, suggesting their significance as critical environmental parameters. Ultimately, we developed a model for potentially ecological suitable regions in China. CONCLUSION: This study provides a comprehensive understanding of the relationship between metabolome and transcriptome in A. truncatum at various developmental stages of seeds and a new strategy to enhance seed FA content, especially ALA and NA. This is particularly significant in meeting the increasing demands for high-quality edible oil for human consumption. The study offers a scientific basis for A. truncatum's novel utilization as a woody vegetable oil rather than an ornamental plant, potentially expanding its cultivation worldwide.


Assuntos
Acer , Transcriptoma , Humanos , Perfilação da Expressão Gênica , Acer/genética , Acer/metabolismo , Ácidos Graxos Insaturados/metabolismo , Sementes , Metaboloma , Óleos de Plantas/metabolismo
12.
Small ; 20(26): e2311391, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38233208

RESUMO

Guided by a superb dual-ions cosubstitution strategy, two novel, highly optically anisotropic hybrid bismuth halides are designed and synthesized. The first compound, Gu3Bi2NO3Cl8 (Gu = C(NH2)3), is developed using the 2D perovskite halide Cs3Bi2Cl9 as the maternal structure. This involved substituting all Cs+ cations with organic Gu+ and replacing some Cl- anions with [NO3]-. Further substitution of Cl- with additional [NO3]- resulted in the formation of nitrate-rich Gu2Bi(NO3)3Cl2 crystal, exhibiting a 3.4-fold increase in [NO3]- per unit volume. Both compounds have a structurally 0D nature, comprising bismuth-centered polyhedra formed by coordinated chlorides and monodentate/bidentate nitrate moieties, with Gu+ serving as a separator and linker. Notably, the presence of superb optically anisotropic dual-ions, i.e., planar Gu+ and [NO3]-, enables these crystals to possess sharply enhanced optical anisotropy, with birefringence values more than 1 order of magnitude higher than that of the initial crystal Cs3Bi2Cl9 (0.162/0.186vs 0.011 at 546 nm). The discovery and characterization of Gu3Bi2NO3Cl8 and Gu2Bi(NO3)3Cl2 crystals provide new insights into achieving expected modifications in optical properties through the utilization of a dual-ions cosubstitution strategy.

13.
Small ; : e2405618, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264000

RESUMO

Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

14.
Liver Transpl ; 30(9): 877-886, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38809243

RESUMO

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.


Assuntos
Hepatite Alcoólica , Linfócitos T Reguladores , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Masculino , Hepatite Alcoólica/imunologia , Hepatite Alcoólica/sangue , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Índice de Gravidade de Doença , Resultado do Tratamento , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/sangue , Doença Hepática Terminal/tratamento farmacológico , Análise de Célula Única , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos
15.
J Med Virol ; 96(9): e29871, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39221474

RESUMO

The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment. Although N121T and N121S substitutions are not currently major SARS-CoV-2 variants of concern, this study could provide fundamental information to prepare for potential future mutations at the N121 site of SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Testes de Neutralização , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Humanos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Camundongos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Substituição de Aminoácidos , Mutação
16.
Bioconjug Chem ; 35(9): 1324-1334, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39197031

RESUMO

Inhibitors of the epithermal growth factor receptor (EGFR) were screened from an autodisplayed Fv-antibody library using an anti-EGF antibody. The Fv-antibody library was expressed on the outer membrane of Escherichia coli, which corresponds to the heavy chain VH region of immunoglobulin G. The library was constructed by randomizing the CDR3 region of expressed VH regions (11 amino acid residues) by site-directed mutagenesis. Using an anti-EGF antibody as a screening probe, amino acid sequences (CDR3 region) with antibody binding affinity were screened from the Fv-antibody library. These amino acid sequences were considered to have similar chemical properties to EGF, which can bind to EGFR. Two autodisplayed clones with Fv-antibodies against EGFR were screened from the Fv-antibody library, and the screened Fv-antibodies were expressed as soluble proteins. The binding affinity (KD) was estimated using an SPR biosensor, and the inhibitory activity of expressed Fv-antibodies was observed for PANC-1 pancreatic tumor cells and T98G glioblastoma cells using Western blot analysis of proteins in the EGFR-mediated signaling pathway. The viability of PANC-1 and T98G cells was observed to decrease via the inhibitory activity of expressed Fv-antibodies. Finally, interactions between Fv-antibodies and EGFR were analyzed by using molecular docking simulations.


Assuntos
Receptores ErbB , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Humanos , Linhagem Celular Tumoral , Biblioteca de Peptídeos
17.
Opt Lett ; 49(13): 3830-3833, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950279

RESUMO

We developed analytical expressions for the Wigner distribution function of partially coherent fields generated by the scattering of beams with a particular phase structure, namely perfect optical vortex beams. In addition, we provide the modal decomposition of the field correlations and evaluate the evolution of Shannon entropy associated with the partially coherent field.

18.
Phys Rev Lett ; 132(23): 236702, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38905652

RESUMO

Orbital currents have recently emerged as a promising tool to achieve electrical control of the magnetization in thin-film ferromagnets. Efficient orbital-to-spin conversion is required in order to torque the magnetization. Here, we show that the injection of an orbital current in a ferrimagnetic Gd_{y}Co_{100-y} alloy generates strong orbital torques whose sign and magnitude can be tuned by changing the Gd content and temperature. The effective spin-orbital Hall angle reaches up to -0.25 in a Gd_{y}Co_{100-y}/CuO_{x} bilayer compared to +0.03 in Co/CuO_{x} and +0.13 in Gd_{y}Co_{100-y}/Pt. This behavior is attributed to the local orbital-to-spin conversion taking place at the Gd sites, which is about 5 times stronger and of the opposite sign relative to Co. Furthermore, we observe a manyfold increase in the net orbital torque at low temperature, which we attribute to the improved conversion efficiency following the magnetic ordering of the Gd and Co sublattices.

19.
Biotechnol Bioeng ; 121(7): 2057-2066, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38650386

RESUMO

High hydrostatic pressure stabilized galactose oxidase (GaOx) at 70.0-80.0°C against thermal inactivation. The pseudo-first-order rate constant of inactivation kinact decreased by a factor of 8 at 80°C and by a factor of 44 at 72.5°C. The most pronounced effect of pressure was at the lowest studied temperature of 70.0°C with an activation volume of inactivation ΔV‡ of 78.8 cm3 mol-1. The optimal pressure against thermal inactivation was between 200 and 300 MPa. Unlike other enzymes, as temperature increased the ΔV‡ of inactivation decreased, and as pressure increased the activation energy of inactivation Eai increased. Combining the results for GaOx with earlier research on the pressure-induced stabilization of other enzymes suggests that ΔV‡ of inactivation correlates with the total molar volume of cavities larger than ~100 Å3 in enzyme monomers for enzymes near the optimal pH and whose thermal unfolding is not accompanied by oligomer dissociation.


Assuntos
Estabilidade Enzimática , Galactose Oxidase , Pressão Hidrostática , Galactose Oxidase/química , Galactose Oxidase/metabolismo , Temperatura Alta , Temperatura
20.
Langmuir ; 40(41): 21533-21546, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39370649

RESUMO

Microplastic pollution has become a primary global concern in the 21st century. Recyclable magnetic particles with micro-nanostructures are considered an efficient and economical way to remove microplastics from water. In this study, superhydrophobic magnetic cobalt ferrite particles were prepared by using a simple coprecipitation method combined with surface functionalization. The micromorphology, chemical composition, hysteresis loop, and surface contact angle of the functionalized cobalt ferrite were characterized. The separation efficiency and absorption capacity of cobalt ferrite particles in water-oil separation and microplastic removal were investigated. The results showed that the saturation magnetic field intensity of cobalt ferrite was 65.52 emu/g, the residual magnetization intensity (Mr) was 18.79 emu/g, and the low coercivity was 799.83 Oe. Cobalt ferrites had stable superhydrophobicity in the pH range of 1-13. The separation efficiency of cobalt ferrite powder for four oil-water mixture separations was higher than 94.2%. The separation efficiency was as high as 99.6% in the separation of the hexane and water mixtures. Due to the synergistic effect of the hydrophobic effect and van der Waals force, the functionalized magnetic cobalt ferrite had a high and stable microplastic removal efficiency and capture capacity. The removal efficiency of microplastics was close to 100%, and the capture capacity was 2.56 g/g. After ten microplastic removal cycles, the removal efficiency reached more than 98%, and the surface contact angle was still greater than 150°.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA