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Cell-cell interactions play an important role in many biological processes, and various methods have been developed for controlling the cell-cell interactions. However, the effective and rapid control of intercellular interactions remains challenging. Herein, we report a novel, rapid, and effective electrochemical strategy without destroying the basic life processes for the dynamic control of intercellular interactions via liposome fusion. In the proposed system, bioorthogonal chemical groups and hydroquinone (HQ)- and aminooxy (AO)-tethered ligands were modified on the surface of living cells on the basis of the liposome fusion, enabling dynamical intercellular assemblies. Upon application of the corresponding oxidative potential, the "off-state" HQ could be oxidized to the "on-state" quinone (Q), which subsequently reacts with AO-tethered ligands to form stable oxime linkages under physiological conditions. This reaction effectively shortens the distance between cells, promoting the formation of cell clusters. When the corresponding reverse reductive potential is applied, the oxime linkage is cleaved, resulting in the release of the cells. Furthermore, we employed HQ- and AO-tethered ligands to modify mitochondria, inducing mitochondrial aggregation. This noninvasive and label-free strategy allows for the dynamic reversible regulation of intercellular interactions, enhancing our understanding of intercellular communication networks, and has the potential for improving the antitumor therapy efficacy.
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Microorganisms are vital for the health of marine invertebrates, and their assembly is driven by both deterministic and stochastic factors that regulate residents (innate to the host) and transients (from ambient water). However, the role of water microbiota and the significance of deterministic and stochastic processes in aquatic hosts facing mortality threats are largely unknown. This study examines the shifts in water microbiota during an oyster mortality event using amplicon sequencing and compared with those of resident oysters to disentangle the balance of the deterministic and stochastic factors involved. Water temperature and dissolved oxygen significantly shape the microbial community with a distinct monthly pattern, and Cyanobacteria blooms might exacerbate oyster mortality. The comparative analysis of microbial communities in oysters and water revealed that ≤ 21% of the genera were shared between oysters and water, implying that water microbiota cannot easily transfer into oysters. Furthermore, these shared genera had different functions, with oysters more involved in promoting host digestion and nutrient acquisition and water bacteria enriched more in functions promoting their own growth and survival. These findings illustrate that oysters may possess specific selection or barrier mechanisms that permit a small percentage of transients, controlled by stochastic factors and having a minimal effect on oyster mortality, to enter, whereas the majority of oyster microbiota are residents governed by deterministic factors. Consequently, oysters exhibit some plasticity in their symbiotic microbiota, enabling them to maintain microbial homeostasis and adapt to complex microbial surroundings. This may be a shared mechanism among marine invertebrates for survival in complex marine environments.IMPORTANCEPacific oysters are widely cultured and play vital ecological roles. However, the summer mortality hinders sustainable oyster farming. Untangling causative mechanisms of oyster mortality is a complex task due to the intricate "interactome" involving environmental factors, hosts, and pathogens. Interactions between hosts and microorganisms offer an ideal avenue for investigating the truth. We systematically investigated the microbial community in water and resident oysters during a summer mortality event and proposed that the assembly of oyster microbiota is primarily governed by deterministic processes independent of mortality. Pathogens mainly originate from resident members of the oyster microbiota, with a limited influence from the microbial community in the water. Additionally, environmental degraders, such as Cyanobacteria blooms, cannot be overlooked as a contributing factor of oyster mortality. This study evaluated the weight of deterministic and stochastic factors in microbial assembly during an oyster mortality event and greatly broadened our understanding of the "interactome" through the interaction between oysters and water in microbiota.
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BACKGROUND: Limited data indicated the performance of large language model (LLM) taking on the role of doctors. We aimed to investigate the potential for ChatGPT-3.5 and New Bing Chat acting as doctors using thyroid nodules as an example. METHODS: A total of 145 patients with thyroid nodules were included for generating questions. Each question was entered into chatbot of ChatGPT-3.5 and New Bing Chat five times and five responses were acquired respectively. These responses were compared with answers given by five junior doctors. Responses from five senior doctors were regarded as gold standard. Accuracy and reproducibility of responses from ChatGPT-3.5 and New Bing Chat were evaluated. RESULTS: The accuracy of ChatGPT-3.5 and New Bing Chat in answering Q2, Q3, Q5 were lower than that of junior doctors (all P < 0.05), while both LLMs were comparable to junior doctors when answering Q4 and Q6. In terms of "high reproducibility and accuracy", ChatGPT-3.5 outperformed New Bing Chat in Q1 and Q5 (P < 0.001 and P = 0.008, respectively), but showed no significant difference in Q2, Q3, Q4, and Q6 (P > 0.05 for all). New Bing Chat generated higher accuracy than ChatGPT-3.5 (72.41% vs 58.62%) (P = 0.003) in decision making of thyroid nodules, and both were less accurate than junior doctors (89.66%, P < 0.001 for both). CONCLUSIONS: The exploration of ChatGPT-3.5 and New Bing Chat in the diagnosis and management of thyroid nodules illustrates that LLMs currently demonstrate the potential for medical applications, but do not yet reach the clinical decision-making capacity of doctors.
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Microalgae and cyanobacteria are a rich source of carotenoids that are well known for their potent bioactivities, including antioxidant, anti-cancer, anti-proliferative, anti-inflammatory, and anti-obesity properties. Recently, many interests have also been focused on the biological activities of these microalgae/cyanobacteria-derived carotenoids, such as fucoxanthin and ß-carotene potential to be the salutary nutraceuticals, on treating or preventing human common diseases (e.g., cancers). This is due to their special chemical structures that demonstrate unique bioactive functions, in which the biologically active discrepancies might attribute to the different spatial configurations of their molecules. In addition, their abundance and bioaccessibilities make them more popularly applied in food and pharmaceutical industries, as compared to the macroalgal/fungal-derived ones. This review is focused on the recent studies on the bioactivities of fucoxanthin and some carotenoids derived from microalgae and cyanobacteria in relationship with human health and diseases, with emphasis on their potential applications as natural antioxidants. Various biotechnological approaches employed to induce the production of these specific carotenoids from the culture of microalgae/cyanobacteria are also critically reviewed. These well-developed and emerging biotechnologies present promise to be applied in food and pharmaceutical industries to facilitate the efficient manufacture of the bioactive carotenoid products derived from microalgae and cyanobacteria.
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Disturbing cellular redox homeostasis within malignant cells, particularly improving reactive oxygen species (ROS), is one of the effective strategies for cancer therapy. The ROS generation based on nanozymes presents a promising strategy for cancer treatment. However, the therapeutic efficacy is limited due to the insufficient catalytic activity of nanozymes or their high dependence on hydrogen peroxide (H2O2) or oxygen. Herein, we reported a nanozyme (CSA) based on well-defined CuSe hollow nanocubes (CS) uniformly covered with Ag nanoparticles (AgNPs) to disturb cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for the synergistic therapy of breast cancer. In this system, CSA could interact with the thioredoxin reductase (TrxR) and deplete the tumor microenvironment-activated glutathione (GSH), disrupting the cellular antioxidant defense system and augmenting ROS generation. Besides, CSA possessed high peroxidase-mimicking activity toward H2O2, leading to the generation of various ROS including hydroxyl radical (â¢OH), superoxide radicals (â¢O2-), and singlet oxygen (1O2), facilitated by the Cu(II)/Cu(I) redox and H2O2 cycling, and plentiful catalytically active metal sites. Additionally, due to the absorption and charge separation performance of AgNPs, the CSA exhibited excellent photothermal performance in the second near-infrared (NIR-II, 1064 nm) region and enhanced the photocatalytic ROS level in cancer cells. Owing to the inhibition of TrxR activity, GSH depletion, high peroxidase-mimicking activity of CSA, and abundant ROS generation, CSA displays remarkable and specific inhibition of tumor growth.
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Homeostase , Peróxido de Hidrogênio , Nanopartículas Metálicas , Oxirredução , Peróxido de Hidrogênio/metabolismo , Humanos , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Homeostase/efeitos dos fármacos , Feminino , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Raios Infravermelhos , Prata/química , Prata/farmacologia , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Glutationa/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Microambiente Tumoral/efeitos dos fármacosRESUMO
Myeloid differentiation factor-88 (MyD88) is a key adaptor of the toll-like receptor (TLR) signaling pathway and plays a crucial role in innate immune signal transduction in animals. However, the MyD88-mediated signal transduction mechanism in shellfish has not been well studied. In this study, a new MyD88 gene, CfMyD88-2, was identified in the Zhikong scallop, Chlamys farreri. The 1779 bp long open reading frame encodes 592 amino acids. The N-terminus of CfMyD88-2 contains a conserved death domain (DD), followed by a TIR (TLR/Interleukin-1 Receptor) domain. The results of the multi-sequence comparison showed that the TIR domain sequences were highly conserved. Phylogenetic analysis revealed that CfMyD88-2 was first associated with Mizuhopecten yessoensis MyD88-4 and Argopecten irradians MyD88-4. CfMyD88-2 mRNA was expressed in all scallop tissues, as detected by qRT-PCR, and the expression level was the highest in the mantle and hepatopancreas. In addition, CfMyD88-2 mRNA expression significantly increased after pathogen-associated molecular patterns (PAMPs, such as lipopolysaccharide, peptidoglycan, or polyinosinic-polycytidylic acid) stimulation. The results of the co-immunoprecipitation experiments in HEK293T cells showed that both CfMyD88-1 and CfMyD88-2 interacted with the TLR protein of scallops, suggesting the existence of more than one functional TLR-MyD88 signaling axis in scallops. Dual luciferase reporter gene assays indicated that the overexpressed CfMyD88-2 in HEK293T cells activated interferon (IFN) α, IFN-ß, IFN-γ, and NF-κB reporter genes, indicating that the protein has multiple functions. The results of the subcellular localization experiment uncovered that CfMyD88-2 was mainly localized in the cytoplasm of human cells. In summary, the novel identified CfMyD88-2 can respond to the challenge of PAMPs, participate in TLR immune signaling, and may activate downstream effector genes such as NF-κB gene. These research results will be useful in advancing the theory of innate immunity in invertebrates and provide a reference for the selection of disease-resistant scallops in the future.
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Sequência de Aminoácidos , Regulação da Expressão Gênica , Imunidade Inata , Fator 88 de Diferenciação Mieloide , Pectinidae , Filogenia , Alinhamento de Sequência , Receptores Toll-Like , Animais , Imunidade Inata/genética , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , Pectinidae/imunologia , Pectinidae/genética , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Receptores Toll-Like/química , Alinhamento de Sequência/veterinária , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Transdução de Sinais/imunologia , Humanos , Células HEK293 , Sequência de BasesRESUMO
The FeOCl-based photo-Fenton heterojunction catalyst holds great promise for effective water pollution treatment. A novel heterojunction FeOCl/MOF-In2S3 (F/M-I) was fabricated by coating hollow MOF-In2S3 nanoflowers onto the surface of FeOCl. Under the optimal conditions, the maximum photo-Fenton degradation rate constants of FeOCl/MOF-In2S3 for oxytetracycline (OTC) within 20 min is 0.88192 L mg-1·min-1, which are 3.2 and 2.5 times that of pure FeOCl (0.27357 L mg-1·min-1) and MOF-In2S3 (0.35222 L mg-1·min-1). Density functional theory (DFT) results confirm that the electron-rich nature of MOF-In2S3 accelerates the cycle between Fe (III)/Fe (II)of FeOCl, promoting H2O2 adsorption by FeOCl/MOF-In2S3 and generating more hydroxyl radicals (·OH) for pollutant degradation. Based on the results of DFT, combined with the results of the reactive oxidation species scavenger (ROSs), electron paramagnetic resonance (EPR) and Mott-Schottky curves, the separation and transfer behavior of photoexcited charges in FeOCl/MOF-In2S3 heterojunction and the possible photocatalytic degradation mechanism were investigated. Finally, a Z-scheme heterostructure is proposed to elucidate the catalytic mechanism. This study provides a new perspective on designing and synthesizing semiconductor materials for water treatment by photo-Fenton catalysis.
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Peróxido de Hidrogênio , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Adsorção , Poluentes Químicos da Água/química , Catálise , Estruturas Metalorgânicas/química , Ferro/química , Purificação da Água/métodosRESUMO
Increasing evidence suggests the importance of CD24 in tumor progression, but its role and mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. The present study aims to explore the potential of CD24 as a novel predictive biomarker in ESCC, as well as its mechanism and therapeutic implications in metastasis and 5-FU chemoresistance. By using tissue microarray and immunohistochemistry, we found that CD24 expression was higher in ESCC tumor tissues than paired non-tumor tissues, further indicating that CD24 was markedly associated with poor prognosis. CD24 significantly promoted metastasis and 5-FU chemoresistance in vitro and in vivo. Mechanistically, CD24 competes with GIT2 to bind to Arf6, and stabilizes Arf6-GTP to activate the subsequent ERK pathway, thus promoting cancer progression. In addition, a significant positive correlation between CD24 and p-ERK was observed in clinical ESCC tissues. In summary, this study not only reveals CD24 as a regulatory factor for Arf6 activity, but also uncovers CD24-Arf6-ERK signaling axis as a novel mechanism of ESCC progression. Our findings suggest CD24 as a promising biomarker and therapeutic target in ESCC.
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Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP , Antígeno CD24 , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Antígeno CD24/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Animais , Linhagem Celular Tumoral , Masculino , Feminino , Camundongos , Sistema de Sinalização das MAP Quinases , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Prognóstico , Pessoa de Meia-Idade , Camundongos NusRESUMO
It still remains challenging to design multifunctional therapeutic reagents for effective cancer therapy under a unique tumor microenvironment including insufficient endogenous H2O2 and O2, low pH, and a high concentration of glutathione (GSH). In this work, a CO-based phototherapeutic system triggered by photogenerated holes, which consisted of ionic liquid (IL), the CO prodrug Mn2(CO)10, and iridium(III) porphyrin (IrPor) modified carbonized ZIF-8-doped graphitic carbon nitride nanocomposite (IL/ZCN@Ir(CO)), was designed for cascade hypoxic tumors. Upon light irradiation, the photogenerated holes on IL/ZCN@Ir(CO) oxidize water into H2O2, which subsequently induces Mn2(CO)10 to release CO. Meanwhile, IrPor can convert H2O2 to hydroxyl radical (â¢OH) and subsequent singlet oxygen (1O2), which further triggers CO release. Moreover, the degraded MnO2 shows activity for glutathione (GSH) depletion and mimics peroxidase, leading to GSH reduction and â¢OH production in tumors. Thus, this strategy can in situ release high concentrations of CO and reactive oxygen species (ROS) and deplete GSH to efficiently induce cell apoptosis under hypoxic conditions, which has a high inhibiting effect on the growth of tumors, offering an attractive strategy to amplify CO and ROS generation to meet therapeutic requirements in cancer treatment.
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Monóxido de Carbono , Glutationa , Monóxido de Carbono/metabolismo , Monóxido de Carbono/química , Monóxido de Carbono/farmacologia , Humanos , Glutationa/metabolismo , Glutationa/química , Animais , Linhagem Celular Tumoral , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/radioterapia , Hipóxia Tumoral/efeitos dos fármacos , Camundongos , Irídio/química , Irídio/farmacologia , Grafite/química , Grafite/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Nanocompostos/química , Nanocompostos/uso terapêutico , Compostos de NitrogênioRESUMO
A significant challenge in direct seawater electrolysis is the rapid deactivation of the cathode due to the large scaling of Mg(OH)2. Herein, we synthesized a Pt-coated highly disordered NiCu alloy (Pt-NiCu alloy) electrode with superior solidophobic behavior, enabling stable hydrogen generation (100 mA cm-2, >1000 h durability) and simultaneous production of Mg(OH)2 (>99.0% purity) in electrolyte enriched with Mg2+ and Ca2+. The unconventional solidophobic property primarily stems from the high surface energy of the NiCu alloy substrate, which facilitates the adsorption of surface water and thereby compels the bulk formation of Mg(OH)2 via homogeneous nucleation. The discovery of this solidophobic electrode will revolutionarily simplify the existing techniques for seawater electrolysis and increase the economic viability for seawater electrolysis.
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E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.
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Multimerização Proteica , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/genética , Humanos , Ubiquitina/metabolismo , Ubiquitina/química , Ubiquitinação , Modelos Moleculares , Cristalografia por Raios X , Proteínas Oncogênicas Virais/metabolismo , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Ligação Proteica , Conformação Proteica em alfa-HéliceRESUMO
Introduction: CARD11 is a lymphoid lineage-specific scaffold protein regulating the NF-κB activation downstream of the antigen receptor signal pathway. Defective CARD11 function results in abnormal development and differentiation of lymphocytes, especially thymic regulatory T cells (Treg). Method: In this study, we used patients' samples together with transgenic mouse models carrying pathogenic CARD11 mutations from patients to explore their effects on Treg development. Immunoblotting and a GFP receptor assay were used to evaluate the activation effect of CARD11 mutants on NF-κB signaling. Then the suppressive function of Tregs carrying distinct CARD11 mutations was measured by in vitro suppression assay. Finally, we applied the retroviral transduced bone marrow chimeras to rescue the Treg development in an NF-κB independent manner. Results and discuss: We found CARD11 mutations causing hyper-activated NF-κB signals also gave rise to compromised Treg development in the thymus, similar to the phenotype in Card11 deficient mice. This observation challenges the previous view that CARD11 regulates Treg lineage dependent on the NF-kB activation. Mechanistic investigations reveal that the noncanonical function CARD11, which negatively regulates the AKT/ FOXO1 signal pathway, is responsible for regulating Treg generation. Moreover, primary immunodeficiency patients carrying CARD11 mutation, which autonomously activates NF-κB, also represented the reduced Treg population in their peripheral blood. Our results propose a new regulatory function of CARD11 and illuminate an NF-κB independent pathway for thymic Treg lineage commitment.
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Proteínas Adaptadoras de Sinalização CARD , Guanilato Ciclase , Mutação , NF-kappa B , Transdução de Sinais , Linfócitos T Reguladores , Timo , Animais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , NF-kappa B/metabolismo , Humanos , Camundongos , Timo/imunologia , Timo/citologia , Timo/metabolismo , Camundongos Transgênicos , Diferenciação Celular/imunologia , Doenças da Imunodeficiência Primária/imunologia , Doenças da Imunodeficiência Primária/genética , MasculinoRESUMO
Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.
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Isquemia Encefálica , Fator Neurotrófico Derivado do Encéfalo , Proteína GAP-43 , Glucosídeos , Microglia , Neurônios , Fármacos Neuroprotetores , Fenóis , Ratos Sprague-Dawley , Receptor trkB , Transdução de Sinais , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fármacos Neuroprotetores/farmacologia , Glucosídeos/farmacologia , Fenóis/farmacologia , Masculino , Ratos , Proteína GAP-43/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Receptor trkB/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Neurogênese/efeitos dos fármacos , CamundongosRESUMO
Background: Data with fine granularity about COVID-19-related outcomes and risk factors were still limited in the idiopathic inflammatory myopathies (IIMs) population. This study aimed to investigate clinical factors associated with hospitalized and severe COVID-19 in patients with IIMs, particularly those gauged by myositis-specific antibodies. Methods: This retrospective cohort study was conducted in the Renji IIM cohort in Shanghai, China, under an upsurge of SARS-CoV-2 omicron variant infections from December 2022 to January 2023. Clinical data were collected and analyzed by multivariable logistic regression to determine risk factors. High-dimensional flow cytometry analysis was performed to outline the immunological features. Results: Among 463 infected patients in the eligible cohort (n=613), 65 (14.0%) were hospitalized, 19 (4.1%) suffered severe COVID-19, and 10 (2.2%) died. Older age (OR=1.59/decade, 95% CI 1.18 to 2.16, p=0.003), requiring family oxygen supplement (2.62, 1.11 to 6.19, 0.028), patients with anti-synthetase syndrome (ASyS) (2.88, 1.12 to 7.34, 0.027, vs. other dermatomyositis), higher IIM disease activity, and prednisone intake >10mg/day (5.59, 2.70 to 11.57, <0.001) were associated with a higher risk of hospitalization. Conversely, 3-dose inactivated vaccination reduced the risk of hospitalization (0.10, 0.02 to 0.40, 0.001, vs. incomplete vaccination). Janus kinase inhibitor (JAKi) pre-exposure significantly reduced the risk of severe COVID-19 in hospitalized patients (0.16, 0.04 to 0.74, 0.019, vs. csDMARDs). ASyS patients with severe COVID-19 had significantly reduced peripheral CD4+ T cells, lower CD4/CD8 ratio, and fewer naive B cells but more class-switched memory B cells compared with controls. Conclusion: ASyS and family oxygen supplement were first identified as risk factors for COVID-19-related hospitalization in patients with IIMs. JAKi pre-exposure might protect IIM patients against severe COVID-19 complications.
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COVID-19 , Miosite , Humanos , Estudos Retrospectivos , Ligases , COVID-19/terapia , COVID-19/complicações , SARS-CoV-2 , China/epidemiologia , Miosite/complicações , Miosite/epidemiologia , OxigênioRESUMO
Lesion segmentation in ultrasound images is an essential yet challenging step for early evaluation and diagnosis of cancers. In recent years, many automatic CNN-based methods have been proposed to assist this task. However, most modern approaches often lack capturing long-range dependencies and prior information making it difficult to identify the lesions with unfixed shapes, sizes, locations, and textures. To address this, we present a novel lesion segmentation framework that guides the model to learn the global information about lesion characteristics and invariant features (e.g., morphological features) of lesions to improve the segmentation in ultrasound images. Specifically, the segmentation model is guided to learn the characteristics of lesions from the global maps using an adversarial learning scheme with a self-attention-based discriminator. We argue that under such a lesion characteristics-based guidance mechanism, the segmentation model gets more clues about the boundaries, shapes, sizes, and positions of lesions and can produce reliable predictions. In addition, as ultrasound lesions have different textures, we embed this prior knowledge into a novel region-invariant loss to constrain the model to focus on invariant features for robust segmentation. We demonstrate our method on one in-house breast ultrasound (BUS) dataset and two public datasets (i.e., breast lesion (BUS B) and thyroid nodule from TNSCUI2020). Experimental results show that our method is specifically suitable for lesion segmentation in ultrasound images and can outperform the state-of-the-art approaches with Dice of 0.931, 0.906, and 0.876, respectively. The proposed method demonstrates that it can provide more important information about the characteristics of lesions for lesion segmentation in ultrasound images, especially for lesions with irregular shapes and small sizes. It can assist the current lesion segmentation models to better suit clinical needs.
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Processamento de Imagem Assistida por Computador , Nódulo da Glândula Tireoide , Humanos , Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia , MamaRESUMO
Creativity, a high-order cognitive ability, has received wide attention from researchers and educators who are dedicated to promoting its development throughout one's lifespan. Currently, creativity is commonly assessed with divergent thinking tasks, such as the Alternative Uses Task. Recent advancements in neuroimaging techniques have enabled the identification of brain markers for high-order cognitive abilities. One such brain structure of interest in this regard is the hippocampus, which has been found to play an important role in generating creative thoughts in adulthood. However, such role of the hippocampus in childhood is not clear. Thus, this study aimed to investigate the associations between creativity, as measured by divergent thinking, and both the volume of the hippocampus and its resting-state functional connectivity in 116 children aged 8-12 years. The results indicate significant relations between divergent thinking and the volume of the hippocampal head and the hippocampal tail, as well as the volume of a subfield comprising cornu ammonis 2-4 and dentate gyrus within the hippocampal body. Additionally, divergent thinking was significantly related to the differences between the anterior and the posterior hippocampus in their functional connectivity to other brain regions during rest. These results suggest that these two subregions may collaborate with different brain regions to support diverse cognitive processes involved in the generation of creative thoughts. In summary, these findings indicate that divergent thinking is significantly related to the structural and functional characteristics of the hippocampus, offering potential insights into the brain markers for creativity during the developmental stage.
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Encéfalo , Imageamento por Ressonância Magnética , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Criatividade , Cognição , Mapeamento Encefálico/métodos , Hipocampo/diagnóstico por imagemRESUMO
Herein, a type of light- and heat-driven flexible supramolecular polymer with reversibly long-lived phosphorescence and photochromism is constructed from acrylamide copolymers with 4-phenylpyridinium derivatives containing a cyano group (P-CN, P-oM, P-mM), sulfobutylether-ß-cyclodextrin (SBCD), and polyvinyl alcohol (PVA). Compared to their parent solid polymers, these flexible supramolecules based on the non-covalent cross-linking of copolymers, SBCD, and PVA efficiently boost the phosphorescence lifetimes (723.0 ms for P-CN, 623.0 ms for P-oM, 945.8 ms for P-mM) through electrostatic interaction and hydrogen bonds. The phosphorescence intensity/lifetime, showing excellent responsiveness to light and heat, sharply decreased after irradiation with a 275 nm flashlight or sunlight and gradually recovered through heating. This is accompanied by the occurrence and fading of visible photochromism, manifesting as dark green for P-CN and pink for P-oM and P-mM. These reversible photochromism and phosphorescence behaviors are mainly attributed to the generation and disappearance of organic radicals in the 4-phenylpyridinium derivatives with a cyano group, which can guide tunable luminescence and photochromism.
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Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis. Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint. On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity. Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation. More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.
Assuntos
Ouro , Morte Celular Imunogênica , Azul de Metileno , Microambiente Tumoral , Animais , Ouro/química , Azul de Metileno/química , Azul de Metileno/farmacologia , Camundongos , Morte Celular Imunogênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Feminino , Ferro/químicaRESUMO
Seawater electrolysis for hydrogen production is a sustainable and economical approach that can mitigate the energy crisis and global warming issues. Although various catalysts/electrodes with excellent activities have been developed for high-efficiency seawater electrolysis, their unsatisfactory durability, especially for anodes, severely impedes their industrial applications. In this review, attention is paid to the factors that affect the stability of anodes and the corresponding strategies for designing catalytic materials to prolong the anode's lifetime. In addition, two important aspects-electrolyte optimization and electrolyzer design-with respect to anode stability improvement are summarized. Furthermore, several methods for rapid stability assessment are proposed for the fast screening of both highly active and stable catalysts/electrodes. Finally, perspectives on future investigations aimed at improving the stability of seawater electrolysis systems are outlined.