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Serial dependence has shown seemingly contradictory effects on visual perception and working memory. While serial dependence promotes perpetual and mnemonic stability, it biases behavioral reports toward prior information. The neural mechanisms that drive both biasing and adaptive stabilizing effects are not well understood. We proposed and tested a reactivation and integration mechanism that can account for these contradictory effects. We used multivariate pattern analyses of EEG data (26 human participants, 17 females, 9 males) to examine the reactivation of prior reported orientation during the delay period of a visual working memory task. The reactivation strength of prior reports, but not prior sensory items, was predictive of the magnitude of serial dependency biases. These reactivated representations integrated with the representation of the current memory item and improved the ability to decode the current contents of memory. Overall, our data provide convergent evidence suggesting that prior reports in a visual working memory task are reactivated on the subsequent trial and become integrated with current memory representations. This similarity-dependent reactivation mechanism drives both report biasing and stabilization effects attributed to serial dependence in working memory.
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Eletroencefalografia , Memória de Curto Prazo , Percepção Visual , Humanos , Feminino , Masculino , Memória de Curto Prazo/fisiologia , Adulto , Adulto Jovem , Percepção Visual/fisiologia , Estimulação Luminosa/métodos , AdolescenteRESUMO
Herein, we report concise total syntheses of diterpene natural products (-)-crinipellins A and B with a tetraquinane skeleton, three adjacent all-carbon quaternary centers, and multiple oxygenated and labile functional groups. Our synthesis features a convergent Kozikowski ß-alkylation to unite two readily available building blocks with all the required carbon atoms, an intramolecular photochemical [2 + 2] cycloaddition to install three challenging and adjacent all-carbon quaternary centers and a 5-6-4-5 tetracyclic skeleton, and a controlled Cargill rearrangement to rearrange the 5-6-4-5 tetracyclic skeleton to the desired tetraquinane skeleton. These strategically enabling transformations allowed us to complete total syntheses of (-)-crinipellins A and B in 12 and 13 steps, respectively. The results of quantum chemical computations revealed that the Bronsted acid-catalyzed Cargill rearrangements likely involve stepwise paths to products and the AlR3-catalyzed Cargill rearrangements likely involve a concerted path with asynchronous alkyl shifting events to form the desired product.
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Diterpenos , Diterpenos/síntese química , Diterpenos/química , Estereoisomerismo , Produtos Biológicos/síntese química , Produtos Biológicos/química , Estrutura Molecular , Reação de Cicloadição , AlquilaçãoRESUMO
BACKGROUND: The development of pulmonary fibrosis involves a cascade of events, in which inflammation mediated by immune cells plays a pivotal role. Chemotherapeutic drugs have been shown to have dual effects on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. METHODS: A model of bleomycin-induced pulmonary fibrosis was established, followed by treatment with bortezomib. Tissue samples were collected for analysis of immune cell subsets and functional assessment by flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors, as well as the characteristics of cell populations. RESULTS: Here, we observed that the expression of CXCL16 and CXCR6 was elevated in the lung tissue of a pulmonary fibrosis model. In the context of pulmonary fibrosis or TGF-ß1 stimulation in vitro, macrophages exhibited an M2-polarized phenotype and secreted more CXCL16 than those of the control group. Moreover, flow cytometry revealed increased expression levels of CD69 and CXCR6 in pulmonary CD4 T cells during fibrosis progression. The administration of bortezomib alleviated bleomycin-induced pulmonary fibrosis, accompanied by reduced ratio of M2-polarized macrophages and decreased accumulation of CD4 T cells expressing CXCR6. CONCLUSIONS: Our findings provide insights into the key immune players involved in bleomycin-induced pulmonary fibrosis and offer preclinical evidence supporting the repurposing strategy and combination approaches to reduce lung fibrosis.
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Bleomicina , Bortezomib , Linfócitos T CD4-Positivos , Quimiocina CXCL16 , Fibrose Pulmonar , Receptores CXCR6 , Animais , Masculino , Camundongos , Antígenos CD , Antígenos de Diferenciação de Linfócitos T/metabolismo , Bleomicina/efeitos adversos , Bortezomib/farmacologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Quimiocina CXCL16/metabolismo , Quimiotaxia/efeitos dos fármacos , Modelos Animais de Doenças , Lectinas Tipo C , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Receptores CXCR6/metabolismoRESUMO
INTRODUCTION: In 2015, the term 'intrinsic capacity' (IC) was proposed by the World Health Organisation to promote healthy aging. However, the factors associated with IC are still discrepant and uncertain. AIM: We aim to synthesise the factors connected with IC. METHODS: This scoping review followed the five-stage framework of Arksey and O'Malley and was reported using PRISMA-ScR guidelines. RESULTS: In all, 29 articles were included. IC of older adults is associated with demographic characteristics, socioeconomic factors, disease conditions, behavioural factors, and biomarkers. Age, sex, marital status, occupation status, education, income/wealth, chronic diseases, hypertension, diabetes, disability, smoking status, alcohol consumption, and physical activity were emerged as important factors related to the IC of older adults. CONCLUSIONS: This review shows that IC is related to multiple factors. Understanding these factors can provide the healthcare personnel with the theoretical basis for intervening and managing IC in older adults. RELEVANCE TO CLINICAL PRACTICE: The influencing factors identified in the review help to guide older adults to maintain their own intrinsic capacity, thereby promoting their health and well-being. The modifiable factors also provide evidence for healthcare personnel to develop targeted intervention strategies to delay IC decline. NO PATIENT OR PUBLIC CONTRIBUTION: As this is a scoping review, no patient or public contributions are required.
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Envelhecimento Saudável , Humanos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Envelhecimento Saudável/fisiologiaRESUMO
Nitrite is one of the most common nitrogenous compounds, which is not only an important indicator of aquaculture water but also widely used as a food additive. Its potential toxicity poses a huge threat to aquatic products and human health. Therefore, it is important to develop a convenient and rapid sensor for the high-efficient onsite detection of nitrite. In this work, a novel electrochemical sensor was developed for the qualitative and quantitative analysis of nitrite. The developed nitrite electrochemical detection system is easily applied in onsite detection. The electrochemical working electrode was constructed based on the combination of Ag-CeO2 and conductive carbon paste (CPE) with excellent electrocatalysis activity and rapid electron transfer ability. By the application of the developed system and under the optimal conditions, the linear range was from 40.0 µM to 500.0 µM, and the detection limit was reduced to 4.3 µM. The recovery was between 92.1% and 108.1%, and the relative standard deviations (RSDs) were 0.49%~9.31%. The sensor exhibited superior reproducibility, high stability sensitivity, and anti-interference ability, confirming its effectiveness for nitrite analysis. Finally, the developed electrochemical sensor was successfully applied to detect nitrite in beverages and aquaculture water samples, indicating that this approach has great potential in onsite food testing and environmental monitoring.
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Aquicultura , Bebidas , Cério , Técnicas Eletroquímicas , Nitritos , Nitritos/análise , Técnicas Eletroquímicas/métodos , Cério/química , Bebidas/análise , Prata/química , Limite de Detecção , Poluentes Químicos da Água/análise , Eletrodos , Reprodutibilidade dos Testes , Água/química , Água/análiseRESUMO
Claudin-2 is a major component of tight junctions (TJs), which play an important role in reovirus entry into host cells. The Bombyx mori cytoplasmic polyhedosis virus (BmCPV) relates to the cypovirus strain of the reovirus family. So far, the role of claudin-2 in the process of BmCPV infection is not known. In the present study, it was observed that increasing expression of the claudin-2 gene (CLDN2) may concomitantly elevate BmCPV infection. Contrarily, knockdown of CLDN2 expression by siRNAs can reduce BmCPV infection. Similarly, antibody-based blockage of claudin-2 could also decrease BmCPV cell entry. These results suggest that claudin-2 can promote BmCPV infection in vitro. Moreover, immunofluorescence (IF) assays showed that claudin-2 can interact with BmCPV during viral infection. Specifically, co-immunoprecipitation experiments indicated that claudin-2 binds the BmCPV VP7 (instead of VP3 proteins). The interaction between VP7 and claudin-2 was further confirmed by bimolecular fluorescence complementation (BIFC). Altogether, our results suggest that BmCPV cell entry can be promoted upon interaction of VP7 with claudin-2. These findings provide new mechanistic insights related to BmCPV infection. KEY POINTS: â¢Claudin-2 could promote BmCPV infection of cells. â¢Claudin-2 interacted with BmCPV during BmCPV infection. â¢Claudin-2 could interact with BmCPV VP7 protein, but not with VP3 proteins.
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Bombyx , Reoviridae , Animais , Claudina-2 , Claudinas/genética , Interações Hospedeiro-Patógeno , Proteínas de Insetos , Internalização do Vírus , Proteína da Zônula de Oclusão-2RESUMO
Despite the exciting breakthroughs in medical technology, cancer still accounts for one of the principle triggers of death and conventional therapeutic modalities often fail to attain an effective cure. Recently, nanobiotechnology has made huge advancement in cancer therapy with gigantic application potential because of their ability in achieving precise and controlled drug release, elevating drug solubility and reducing adverse effects. Carbon nanotubes (CNTs), one of the most promising carbon-related nanomaterials, have already achieved much success in biomedical field. Due to their excellent optical property, thermal and electronic conductivity, easy functionalization ability and high drug loading capacity, CNTs can be applied in a multifunctional way for cancer treatment and diagnosis. In this review, we will give an overview of the recent progress of CNT-based drug delivery systems in cancer theranostics, which emphasizes their targetability to intracellular components of tumor cells and extracellular elements in tumor microenvironment. Moreover, a detailed introduction on how CNTs penetrate inside the tumor cells to reach their sites of action and achieve the therapeutic effects, as well as their diagnostic applications will be highlighted.
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Nanotubos de Carbono/química , Neoplasias/terapia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/uso terapêutico , Microambiente TumoralRESUMO
This paper proposes and studies the characteristics of a laser-driven optothermal microactuator (OTMA) directly operated in water. A theoretical model of optothermal temperature rise and expansion is established, and simulations on a 1000 µm long OTMA are conducted, revealing that its arm is able to expand and contract in response to the laser pulses in a water environment. Microactuating experiments are further carried out using a microfabricated OTMA. The results demonstrate that the OTMA can be practically actuated in water by a 650 nm laser beam and that the OTMA's deflection amplitude increases linearly with laser power. When irradiated by laser pulses with 9.9 mW power and 0.9-25.6 Hz frequencies, the OTMA achieves deflection amplitude ranging from 3.9 to 3.2 µm, respectively. The experimental results match well with theoretical model when taking the damping effect of water into account. This research may be conducive to developing particular micro-electromechanical systems or micro-optoelectromechanical devices such as underwater optothermal micromotors, micro-pumps, micro-robots, and other underwater microactuators.
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Control of selectivity is one of the central topics in organic chemistry. Although unprecedented alkoxyl-radical-induced transformations have drawn a lot of attention, compared to selective C-H activation, selective radical O-H activation remains less explored. Herein, we report a novel selective radical O-H activation strategy of diols by combining spatial effects with proton-coupled electron transfer (PCET). It was found that DMSO is an essential reagent that enables the regioselective transformation of diols. Mechanistic studies indicated the existence of the alkoxyl radical and the selective interaction between DMSO and hydroxyl groups. Moreover, the distal C-C cleavage was realized by this selective alkoxyl-radical-initiation protocol.
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Circular RNAs (circRNAs) with regulatory potency activity was identified from varieties of species. Crucian carp (Carassius auratus gibelio) is one of the most freshwater aquaculture species in China. Every year, huge economic damage to the farming was caused by the virus and bacterial infection. Until now, there is any information about circRNA reported from the Crucian carp. In this study, the expression pattern of circRNA in Crucian carp was investigated with transcriptomic analysis. The results showed that only 37 circRNAs were identified from the Crucian carp, and these circRNAs biogenesis was formed with canonical GU-AG splicing mechanism with unevenly distributed on the chromosomes. Wherein, most of the circRNAs were derived from the sense overlapping strategy. Reverse transcript PCR and Sanger sequencing data indicated that these circRNAs were existed authenticity in Crucian carp. The bioinformatics analysis indicated that circRNAs identified from the Crucian carp with potential miRNA sponge regulate the expression level of mRNAs. GO annotation and KEGG pathway analysis of these circRNAs showed that more than 20% circRNAs were related with catalytic activity and binding in the category of molecular function, and these circRNAs were enriched in 9 signaling pathways, such as, Wnt signaling pathway, MAPK signaling pathway, Ubiquitin mediated proteolysis et al. 220 mRNAs would be regulated by the circRNAs via miRNAs mediation. These target mRNAs were further analyzed with functional annotation and KEGG analysis. GO annotation analysis showed that several genes were related with function of nucleotide binding, transcription regulatory activity. KEGG pathway analysis showed that 5 genes were enriched in the pathway of Endocytosis. The circRNA-miRNA-mRNA regulation network indicated that one miRNA can link one or more circRNA and one or more mRNA. Overall, these results will not only help us to further understand the novel RNA transcripts in Crucian carp, but also provide the novel clue to investigate the interaction between host and pathogens from this novel circRNA molecule.
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Carpas/genética , RNA Circular/genética , Transdução de Sinais/imunologia , Animais , Sequência de Bases , Carpas/imunologia , Biologia Computacional , Perfilação da Expressão Gênica/veterinária , RNA Circular/imunologia , RNA Circular/metabolismo , Transdução de Sinais/genéticaRESUMO
Plastic waste is a growing global pollutant. Plastic degradation by microorganisms has captured attention as an earth-friendly tactic. Although the mechanisms of plastic degradation by bacteria, fungi, and algae have been explored over the past decade, a large knowledge gap still exists regarding the identification, sorting, and cultivation of efficient plastic degraders, primarily because of their uncultivability. Advances in sequencing techniques and bioinformatics have enabled the identification of microbial degraders and related enzymes and genes involved in plastic biodegradation. In this review, we provide an outline of the situation of plastic degradation and summarize the methods for effective microbial identification using multidisciplinary techniques such as multiomics, meta-analysis, and spectroscopy. This review introduces new strategies for controlling plastic pollution in an environmentally friendly manner. Using this information, highly efficient and colonizing plastic degraders can be mined via targeted sorting and cultivation. In addition, based on the recognized rules and plastic degraders, we can perform an in-depth analysis of the associated degradation mechanism, metabolic features, and interactions.
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Bactérias , Plásticos , Plásticos/metabolismo , Bactérias/genética , Bactérias/metabolismo , Biodegradação Ambiental , Fungos/genética , Fungos/metabolismoRESUMO
OBJECTIVE: To assess the effect of different noninvasive ventilation interfaces on preventing the facial pressure injury. METHODS: This network meta-analysis was conducted following the PRISMA reporting guidelines. Seven electronic databases were systematically searched for randomised controlled trials about the comparative effectiveness of different interfaces in preventing facial pressure injury with noninvasive ventilation in adults and newborns from inception to June 2023. The acronym of PICOS was used and the keywords as well as inclusion/exclusion criteria were determined. Study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias assessment tool was used to assess the methodological quality. RESULTS: A total of 78 randomised controlled trials involving 7,291 patients were included. The results of network meta-analysis showed that the effectiveness of the eight noninvasive ventilation interfaces on the prevention of facial pressure injury was in the order of: nasal cannula > full-face mask > rotation of nasal mask with nasal prongs > helmet > nasal mask > oronasal mask > nasal prongs > face mask. The use of full-face mask in adults and nasal cannula in newborns had the best effect on preventing the incidence of facial pressure injury. CONCLUSIONS: The use of full-face mask in adults and nasal cannula in newborns had the most clinical advantage in preventing the incidence of facial pressure injury and were worthy promoting in clinical practice. IMPLICATIONS FOR CLINICAL PRACTICE: This study provides a certain theoretical basis for the selection of appropriate interface for patients with noninvasive ventilation. Clinical practitioners should choose the appropriate interfaces based on the patient's specific condition to reduce the incidence of facial pressure injury, enhance patient comfort, and improve the effectiveness of respiratory therapy.
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Ventilação não Invasiva , Úlcera por Pressão , Adulto , Humanos , Recém-Nascido , Ventilação não Invasiva/efeitos adversos , Ventilação não Invasiva/métodos , Úlcera por Pressão/prevenção & controle , Úlcera por Pressão/etiologia , Metanálise em Rede , Máscaras/efeitos adversos , Incidência , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Foundation models pretrained on large-scale datasets via self-supervised learning demonstrate exceptional versatility across various tasks. Due to the heterogeneity and hard-to-collect medical data, this approach is especially beneficial for medical image analysis and neuroscience research, as it streamlines broad downstream tasks without the need for numerous costly annotations. However, there has been limited investigation into brain network foundation models, limiting their adaptability and generalizability for broad neuroscience studies. In this study, we aim to bridge this gap. In particular, (1) we curated a comprehensive dataset by collating images from 30 datasets, which comprises 70,781 samples of 46,686 participants. Moreover, we introduce pseudo-functional connectivity (pFC) to further generates millions of augmented brain networks by randomly dropping certain timepoints of the BOLD signal. (2) We propose the BrainMass framework for brain network self-supervised learning via mask modeling and feature alignment. BrainMass employs Mask-ROI Modeling (MRM) to bolster intra-network dependencies and regional specificity. Furthermore, Latent Representation Alignment (LRA) module is utilized to regularize augmented brain networks of the same participant with similar topological properties to yield similar latent representations by aligning their latent embeddings. Extensive experiments on eight internal tasks and seven external brain disorder diagnosis tasks show BrainMass's superior performance, highlighting its significant generalizability and adaptability. Nonetheless, BrainMass demonstrates powerful few/zero-shot learning abilities and exhibits meaningful interpretation to various diseases, showcasing its potential use for clinical applications.
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Glioblastoma (GBM) is an aggressive brain cancer that is highly resistant to treatment including chimeric antigen receptor (CAR)-T cells. Tumor-associated microglia and macrophages (TAMs) are major contributors to the immunosuppressive GBM microenvironment, which promotes tumor progression and treatment resistance. Hence, the modulation of TAMs is a promising strategy for improving the immunotherapeutic efficacy of CAR-T cells against GBM. Molecularly targeting drug pexidartinib (PLX) has been reported to re-educate TAMs toward the antitumorigenic M1-like phenotype. Here, we developed a cell-drug integrated technology to reversibly conjugate PLX-containing liposomes (PLX-Lip) to CAR-T cells and establish tumor-responsive integrated CAR-T cells (PLX-Lip/AZO-T cells) as a combination therapy for GBM. We used a mouse model of GBM to show that PLX-Lip was stably maintained on the surface of PLX-Lip/AZO-T cells in circulation and these cells could transmigrate across the blood-brain barrier and deposit PLX-Lip at the tumor site. The uptake of PLX-Lip by TAMs effectively re-educated them into the M1-like phenotype, which in turn boosted the antitumor function of CAR-T cells. GBM tumor growth was completely eradicated in 60% of the mice after receiving PLX-Lip/AZO-T cells and extended their overall survival time beyond 50 days; in comparison, the median survival time of mice in other treatment groups did not exceed 35 days. Overall, we demonstrated the successful fusion of CAR-T cells and small-molecule drugs with the cell-drug integrated technology. These integrated CAR-T cells provided a superior combination strategy for GBM treatment and presented a reference for the construction of integrated cell-based drugs.
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Aminopiridinas , Neoplasias Encefálicas , Glioblastoma , Microglia , Receptores de Antígenos Quiméricos , Glioblastoma/terapia , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/tratamento farmacológico , Animais , Camundongos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Humanos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/tratamento farmacológico , Lipossomos/química , Pirróis/química , Pirróis/farmacologia , Imunoterapia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Imunoterapia Adotiva , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
Lithium-sulfur batteries (LSBs) are promising next-generation energy storage systems because of their high energy densities and high theoretical specific capacities. However, most catalysts in the LSBs are based on carbon materials, which can only improve the conductivity and are unable to accelerate lithium-ion transport. Therefore, it would be worthwhile to develop a catalytic electrode exhibiting both ion and electron conductivity. Herein, a triple-phase interface using lithium lanthanum titanate/carbon (LLTO/C) nanofibers to construct ion/electron co-conductive materials was used to afford enhanced adsorption of lithium polysulfides (LiPSs), high conductivity, and fast ion transport in working LSBs. The triple-phase interface accelerates the kinetics of the soluble LiPSs and promotes uniform Li2S precipitation/dissolution. Additionally, the LLTO/C nanofibers decrease the reaction barrier of the LiPSs, significantly improving the conversion of LiPSs to Li2S and promoting rapid conversion. Specifically, the LLTO promotes ion transport owing to its high ionic conductivity, and the carbon enhances the conductivity to improve the utilization rate of sulfur. Therefore, the LSBs with LLTO/C functional separators deliver stable life cycles, high rates, and good electrocatalytic activities. This strategy is greatly important for designing ion/electron conductivity and interface engineering, providing novel insight for the development of the LSBs.
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Cell necroptosis has presented great potential, acting as an effective approach against tumor apoptotic resistance, and it could be further enhanced via accompanying reactive oxygen species (ROS) overexpression. However, whether overproduced ROS assists the necroptotic pathway remains unclear. Thus, iron-palladium nanozyme (FePd NZ)- and shikonin (SKN)-encapsulated functional lipid nanoparticles (FPS-LNPs) were designed to investigate the ROS overexpression-enhanced SKN-induced necroptosis. In this system, SKN acts as an effective necroptosis inducer for cancer cells, and FePd NZ, a sensitive Fenton reaction catalyst, produces extra-intracellular ROS to reinforce the necroptotic pathway. Both in vitro and in vivo antitumor evaluation revealed that FPS-LNPs presented the best tumor growth inhibition efficacy compared with FP-LNPs or SKN-LNPs alone. Meanwhile, induced necroptosis by FPS-LNPs can further trigger the release of damage-associated molecular patterns (DAMPs) and antigens from dying tumor cells to activate the innate immune response. Taking biosafety into consideration, this study has provided a potential nanoplatform for cancer nanotherapy via inducing necroptosis to avoid apoptosis resistance and activate CD8+ T cell immune response.
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Lipossomos , Nanopartículas , Naftoquinonas , Necroptose , Neoplasias , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , ApoptoseRESUMO
BACKGROUND AND AIMS: T cells are master effectors of anti-tumor immunity in cancer. Recent studies suggest that altered lipid metabolism imposed by the tumor microenvironment constrains anti-tumor immunity. However, the tumor-associated lipid species changes that dampen T cell ability to control tumor progression are not fully understood. Here, we plan to clarify the influences of distinctly altered lipid components in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) on T-cell function, aiming to seek lipid metabolic targets for improving T cell anti-tumor effects. METHODS: Tumor tissues and non-tumor liver from HCC patients were collected for RNA-sequencing, lipid profiling and T cell characterizing, followed by correlation analysis. Additionally, the effects of significantly changed lipid components on anti-tumor potential of T cells were tested by in vitro cell experiments and/or in vivo tumor inoculated model. RESULTS: Altered lipid metabolism coincides with impaired T cell response in HBV-related HCC. Characteristic lipid composition, significantly marked by accumulation of long-chain acylcarnitines (LCACs) and reduction of lysophosphatidylcholines (LPCs), are found in the tumor tissue. Notably, LCACs accumulated are associated with T cells exhaustion and deficient functionality, while LPCs correlate to anti-tumor effects of T cells. In particular, supplement of LPCs, including LPC (20:0) and LPC (22:0), directly promote the activation and IFN-γ secretion of T cells in vitro, and suppress tumor growth in vivo. CONCLUSIONS: Our study highlights the distinctly changed lipid components closely related to T cell dysregulation in HCC, and suggests a promising strategy by decreasing LCACs and increasing LPCs for anti-tumor immunotherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linfócitos T , Imunoterapia , Lipídeos , Microambiente TumoralRESUMO
Pesticides promote the stable development of intensive global agriculture. Nevertheless, their residues in the soil can cause ecological and human health risks. Glyphosate is a popular herbicide and is generally thought to be ecologically safe and nontoxic, but this conclusion has been questioned. Herein, we investigated the interaction among soil fauna (Enchytraeus crypticus) exposed to glyphosate and found that glyphosate induced oxidative stress and detoxification responses in E. crypticus and disturbed their lipid metabolism and digestive systems. We further demonstrated that glyphosate disordered the gut microbiota of E. crypticus and increased the abundance of resistance determinants with significant human health risks. Empirical tests and structural equation models were then used to confirm that glyphosate could cause E. crypticus to generate reactive oxygen species, indirectly interfering with their gut microbiota. Our study provides important implications for deciphering the mechanisms of the ecotoxicity of pesticides under the challenge of worldwide pesticide contamination.
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Microbioma Gastrointestinal , Oligoquetos , Praguicidas , Poluentes do Solo , Animais , Humanos , Microbioma Gastrointestinal/fisiologia , Glifosato , Solo/química , Resistência Microbiana a Medicamentos , Poluentes do Solo/toxicidade , Poluentes do Solo/análiseRESUMO
Can we use attentional control to ignore known distractor features? Providing cues before a visual search trial about an upcoming distractor color (negative cue) can lead to reaction time benefits compared with no cue trials. This suggests top-down control may use negative templates to actively suppress distractor features, a notion that challenges the mechanisms of top-down control provided in many theories of attention. However, there is currently mixed support for this mechanism in the literature. Alternative explanations have been proposed, which do not require suppression within top-down control but instead involve recoding the negative cue into a positive template based on color or spatial layouts. In three experiments, we contrasted the predictions of active suppression and the recoding strategies. Across experiments, we found consistent evidence against a color recoding account. We also found evidence of accuracy, reaction time, and eye movement benefits when location recoding was not possible. These results suggest that prior benefits from negative cues cannot be explained exclusively by spatial or color recoding. The results indicate that active suppression likely plays a role in the attentional benefits following negative cues. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Atenção , Tecnologia de Rastreamento Ocular , Humanos , Tempo de Reação , Sinais (Psicologia) , Movimentos Oculares , Percepção VisualRESUMO
Perceptual distraction distorts visual working memory representations. Previous research has shown that memory responses are systematically biased toward visual distractors that are similar to the memoranda. However, it remains unclear whether the prioritization of one working memory representation over another reduces the impact of perceptual distractors. In five behavioral experiments, we used different forms of retrospective cues (indicating the likelihood of testing each item and/or the reward for responding correctly to each item) to manipulate the prioritization of items in working memory before visual distraction. We examined the effects of distraction with nonparametric analyses and a novel distractor intrusion model. We found that memory responses were more precise (lower absolute response errors and stronger memory signals) for items that were prioritized. However, these prioritized items were not immune to distraction, and their memory responses were biased toward the visual distractors to the same degree as were unprioritized items. Our findings demonstrate that the benefits associated with prioritization in working memory do not include protection from distraction biases. (PsycInfo Database Record (c) 2023 APA, all rights reserved).