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BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.
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Neoplasias , Neoplasias Gástricas , Animais , Humanos , Antígeno CD47 , Modelos Animais de Doenças , Imunoterapia , Leucócitos Mononucleares/metabolismo , Recidiva Local de Neoplasia , Fagocitose , Fator A de Crescimento do Endotélio VascularRESUMO
Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.
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Clostridiales , Microbiota , Doença de Parkinson , Humanos , Animais , Camundongos , Microglia , Doenças Neuroinflamatórias , NF-kappa B , ButiratosRESUMO
PURPOSE: To investigate the antifungal and anti-inflammatory effects of quercetin in Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: Draize eye test was performed in mice to evaluate the toxicity of quercetin, and the antifungal effects on A. fumigatus were assessed via scanning electron microscopy (SEM), propidium iodide uptake, and adherence assay. In fungal keratitis (FK) mouse models, immunostaining was performed for investigating toll-like receptor 4 (TLR-4) expression and macrophage infiltration. Real-time PCR, ELISA, and Western blot were used to evaluate the expression of pro-inflammatory factors IL-1ß, TNF-α, and IL-6 in infected RAW264.7 cells. Cells were also treated with TLR-4 siRNA or agonist CRX-527 to investigate mechanisms underlying the anti-inflammatory activity of quercetin. RESULTS: Quercetin at 32 µM was non-toxic to corneal epithelial and significantly inhibited A. fumigatus growth and adhesion, and also altered the structure and reduced the number of mycelia. Quercetin significantly reduced macrophage infiltration in the mouse cornea, and attenuated the expression of TLR-4 in the corneal epithelium and stroma of mice with keratitis caused by A. fumigatus. In RAW264.7 cells infected by A. fumigatus, quercetin downregulated TLR-4 along with pro-inflammatory factors IL-1ß, TNF-α, and IL-6. RAW cells with TLR-4 knockdown had reduced expression of factors after A. fumigatus infection, which was decreased even further with quercetin treatment. In contrast, cells with CRX-527 had elevated inflammatory factors compared to control, which was significantly attenuated in the presence of quercetin. CONCLUSION: Quercetin plays a protective role in mouse A. fumigatus keratitis by inhibiting fungal load, disrupting hyphae structure, macrophage infiltration, and suppressing inflammation response in macrophages via TLR-4 mediated signaling pathway.
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Aspergillus fumigatus , Ceratite , Camundongos , Animais , Receptor 4 Toll-Like , Quercetina/farmacologia , Antifúngicos/uso terapêutico , Interleucina-6 , Fator de Necrose Tumoral alfa/uso terapêutico , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos C57BLRESUMO
Bromine is an important resource that is widely used in medical, automotive, and electronic industries. Waste electronic products containing brominated flame retardants can cause serious secondary pollution, which is why catalytic cracking, adsorption, fixation, separation, and purification have gained significant attention. However, the bromine resources have not been effectively reutilized. The application of advanced pyrolysis technology could help solve this problem via converting bromine pollution into bromine resources. Coupled debromination and bromide reutilization during pyrolysis is an important field of research in the future. This prospective paper presents new insights in terms of the reorganization of different elements and adjustment of bromine phase transition. Furthermore, we proposed some research directions for efficient and environmentally friendly debromination and reutilization of bromine: 1) precise synergistic pyrolysis should be further explored for efficient debromination, such as using persistent free radicals in biomass, polymer hydrogen supply, and metal catalysis, 2) rematching of Br elements and nonmetal elements (C/H/O) will be a promising direction for synthesizing functionalized adsorption materials, 3) oriented control of the bromide migration path should be further studied to obtain different forms of bromine resources, and 4) advanced pyrolysis equipment should be well developed.
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Resíduo Eletrônico , Retardadores de Chama , Bromo , Brometos , Pirólise , Estudos Prospectivos , Resíduo Eletrônico/análiseRESUMO
Bromine removal is significant in the recycling of waste printed circuit boards (WPCBs). This study found that the critical factors limiting the debromination efficiency of conventional pyrolysis are the formation of coke impeding mass transfer and conversion of bromine into less volatile species, such as coking-Br and copper bromide. According to frontier molecular orbital analysis and thermodynamic equilibrium analysis, C-O bonds of resin are sites prone to electrophilic reactions and copper bromide in residue may undergo hydrolysis; therefore, introducing H2O during pyrolysis was a feasible method for thorough debromination. Through pyrolysis in a water vapor atmosphere, the diffusion limitation of debromination was overcome, and resin was converted into light components; thereby, rapid and deep removal of bromine was achieved. The result indicated that 99.7% of bromine was removed, and the residue could be used as a clean secondary resource. According to life-cycle assessment, pyrolysis of WPCBs in water vapor could be expected to reduce 77 Kt of CO2 emission and increase financial benefits by 60 million dollars, annually.
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Resíduo Eletrônico , Vapor , Cobre , Bromo/química , Brometos , Pirólise , Reciclagem/métodos , Resíduo Eletrônico/análiseRESUMO
PURPOSE: This study aimed at the population receiving thrombolytic therapy and to explore the optimal time point for neutrophil-to-lymphocyte ratio (NLR) in predicting stroke-associated pneumonia (SAP). METHODS: We assessed patients undergoing intravenous thrombolysis (IVT) for acute ischemic stroke. Blood parameters were sampled before thrombolysis (within 30 min after admission) and within 24-36 h after thrombolysis, respectively. The primary outcome measure was the occurrence of SAP. Multivariate logistic regression analysis was performed to analyze the association between admission blood parameters and the event of SAP. We also used receiver operating characteristic (ROC) curve analysis to assess the discriminative ability of blood parameters measured at different times in predicting SAP. RESULTS: Among the 388 patients, SAP occurred in 60 (15%) patients. Multivariate logistic regression analysis showed that NLR was significantly associated with SAP (NLR before IVT: aOR = 1.288; 95%CI = 1.123-1.476; p < 0.001; NLR after IVT: (aOR = 1.127, 95%CI = 1.017-1.249; p = 0.023). The ROC curve showed that the predictive ability of NLR after IVT was better than NLR before IVT, not only in predicting the occurrence of SAP but also in predicting short-term and long-term functional outcomes, hemorrhagic transformation, and 1-year mortality. CONCLUSION: Increased NLR measured within 24-36 h after IVT has a significant predictive effect on the occurrence of SAP and can be used to predict short-term and long-term poor functional outcomes, hemorrhagic transformation, and 1-year mortality.
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AVC Isquêmico , Pneumonia , Acidente Vascular Cerebral , Humanos , Neutrófilos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , LinfócitosRESUMO
PURPOSE: To investigate the effect of Glabridin (GLD) in Aspergillus fumigatus keratitis and its associated mechanisms. METHODS: Aspergillus fumigatus (A. fumigatus) conidia was inoculated in 96-well plate, and minimal inhibitory concentration (MIC) and biofilm formation ability were evaluated after GLD treatment. Spore adhesion ability was evaluated in conidia infected human corneal epithelial cells (HCECs). Keratitis mouse model was created by corneal intrastromal injection with A. fumigatus conidia, and GLD treatment started at the day after infection. The number of fungal colonies was calculated by plate count, and degree of corneal inflammation was assessed by clinical score. Flow cytometry, myeloperoxidase (MPO), and immunofluorescence staining (IFS) experiments were used to assess neutrophil infiltrations. PCR, ELISA and Western blot were conducted to determine levels of TLR4, Dectin-1 as well as downstream inflammatory factors. RESULTS: GLD treatment suppressed the proliferation, biofilm formation abilities and adhesive capability of A. fumigatus. In mice upon A. fumigatus infection, treatment of GLD showed significantly decreased severity of corneal inflammation, reduced number of A. fumigatus in cornea, and suppressed neutrophil infiltration in cornea. GLD treatment obviously inhibited mRNA and protein levels of Dectin-1, TLR4 and proinflammatory mediators such as IL-1ß, HMGB1, and TNF-α in mice corneas compared to the control group. CONCLUSION: GLD has antifungal and anti-inflammatory effects in fungal keratitis through suppressing A. fumigatus proliferation and alleviating neutrophil infiltration, and repressing the expression of TLR4, Dectin-1 and proinflammatory mediators.
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Anti-Inflamatórios/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/fisiologia , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Isoflavonas/uso terapêutico , Fenóis/uso terapêutico , Animais , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Western Blotting , Úlcera da Córnea/microbiologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Fúngicas/microbiologia , Feminino , Citometria de Fluxo , Lectinas Tipo C/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Infiltração de Neutrófilos , Reação em Cadeia da Polimerase , Receptor 4 Toll-Like/metabolismoRESUMO
As a kind of typical veterinary drug, fluoroquinolone antibiotics (FQs) are widely used in the field of livestock and poultry breeding, but these FQs escape to surrounding soil through various pathways, polluting soil through long-term accumulation. Current study proposed a clean technology named thermal desorption to deal with FQs contaminated soils. It was observed that time, temperature and soil particle size were the critical factors in FQs thermal desorption. Results of the study showed that higher temperature was more effective in the removal of FQs, while removal of FQs attached with finer particles was more difficult compared to coarse particles. Fine soil particles (0.6-0.85 mm) were decontaminated up 99.4% when treated with 400 °C for 60min. Thermal desorption of FQs from contaminated soil was governed by first-order kinetics. Based on the detection of exhaust gas components, a possible thermal desorption mechanism was proposed. Study suggested that thermal desorption was a clean and effective remediation method to treat FQs-contaminated soils without generating any further waste.
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Recuperação e Remediação Ambiental , Poluentes do Solo , Animais , Fluoroquinolonas/análise , Gado , Aves Domésticas , Solo , Poluentes do Solo/análiseRESUMO
The increasingly large stream of e-waste is seriously threatening the environment; meanwhile, global energy shortage is on the rise. Based on the principles of energy regeneration and waste utilization, we introduced a win-win approach to utilize waste capacitors for construction of magnetic and core-shell Z-scheme Nb-Pb-codoped BaTiO3/Ni-Pd@graphite-like carbon nitride (g-C3N4) photocatalysts for H2 evolution. Using simple ball-milling, waste capacitors were transformed to Nb-Pb-codoped BaTiO3/Ni-Pd-Ag-Sn nanoparticles and g-C3N4 was coated on the nanoparticles, forming a core-shell structure. The Ni-Pd acted as the electron mediator in the Z-scheme, and Ag-Sn also facilitated the electron transfer. Moreover, Ni made the Z-scheme magnetically separable. The Z-scheme showed a remarkably enhanced photocatalytic H2 evolution rate, which was 22.2 times higher than that of g-C3N4. Such an enhanced photocatalytic performance was attributed to the special Z-scheme and core-shell structure, improving the light adsorption, increasing the Brunauer-Emmett-Teller (BET) surface area, facilitating the efficient separation of electron-hole pairs, and maintaining the strong redox ability of charge carriers. Furthermore, the photoluminescence analysis combined with density functional theory (DFT) calculations provided the basis for the Z-scheme mechanism. This study adequately utilized the composition of e-waste to construct a highly efficient and magnetically separable Z-scheme for H2 generation, which realizes energy regeneration, waste recycling, and environmental protection.
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Resíduo Eletrônico , Catálise , Luz , Fenômenos FísicosRESUMO
Glaucoma has been the leading cause of irreversible blindness worldwide. High intraocular pressure (IOP) is a high-risk factor of glaucoma, repression of which has been the important treatment of glaucoma in clinic. Trabecular meshwork is crucial for maintaining IOP in aqueous humour out-flow system. It is urgent to reveal the molecular mechanism of trabecular meshwork in glaucoma. Previous studies found that some pathways were related to glaucoma, such as extracellular matrix (ECM)-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and apoptosis. To identify novel molecules in glaucoma, we performed high-throughput transcriptome and proteome analysis to immortal human trabecular meshwork cells (iHTM) and glaucomatous human trabecular meshwork cells (GTM3 ), respectively. Twenty-six up-regulated genes/proteins and 59 down-regulated genes/proteins were identified as the high-risk factors based on differential analysis, including some known factors of glaucoma. Furthermore, a glaucoma-related protein-protein interaction (PPI) network was constructed for investigating the function roles of risk factors. Some genes were identified as potential regulator in the pathogenesis of glaucoma based on the topology analysis and module analysis to the network. Importantly, we identified and demonstrated that CD9 played key roles in glaucoma by biological experiment. CD9 is down-regulated in glaucoma, overexpression of CD9 can active integrin α4 (ITGA4), PI3K and Akt, which lead to the decreased apoptosis and attenuate glaucoma. All these results provide a novel molecular therapy of glaucoma.
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Apoptose , Glaucoma/patologia , Integrinas/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tetraspanina 29/metabolismo , Malha Trabecular/patologia , Células Cultivadas , Glaucoma/genética , Glaucoma/metabolismo , Humanos , Integrinas/genética , Fosfatidilinositol 3-Quinase/genética , Proteoma/análise , Proteoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Tetraspanina 29/genética , Malha Trabecular/metabolismo , TranscriptomaRESUMO
This paper explores a novel method to produce ultrafine ZnS particles, a high value-added product, from waste zinc-manganese battery through evaporation-separation, sulfurization and inert gas condensation process. The heating temperature, condensation temperature, nitrogen gas pressure and condensation distance were identified as the main factors influencing the morphology of ZnS nanoparticles produced. Ultrafine ZnS particles can be prepared when the heating temperature is 873 K, the condensation temperature is 723 K and the nitrogen gas pressure is 1000-1500 Pa at the condensation distance of 30 cm. Size of ZnS particles was between 10 and 100 nm with average size of about 40 nm. Based on the scientific graphing and statistical analysis, the size of ZnS particles follows the log-normal distribution. This study not only provides the theoretical fundamentals for preparing ultrafine ZnS particles, but also provides a simple and efficient method to recycle the high value-added ZnS products from waste zinc-manganese batteries.
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BACKGROUND Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) that is particularly prevalent in school-aged children. This study explored the potential involvement of cytokines in children with Mycoplasma pneumoniae pneumonia (MPP) infection. MATERIAL AND METHODS Children aged 3-7 years who were hospitalized due to CAP infection were enrolled and divided into 2 groups: an MPP group (n=33) and a NMPP group (n=38), along with 21 age-matched healthy controls. Clinical characteristics and laboratory data were recorded. Serum levels of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were assessed using Luminex xMAP technology. Correlation analysis and ROC curves analysis were also performed to further explore the role of these detected cytokines in CAP. RESULTS Compared with the healthy controls, the serum expression of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were significantly higher in the MPP and NMPP groups. Furthermore, serum IL-18 expression was found to be significantly correlated with lgE, FeNO, IL-5, IL-8, and IL-13 concentrations. Significant differences were also observed between the MPP group and NMPP group patients in levels of IL-18, IL-5, and IL-6, and further ROC analysis showed that the area under the curve (AUC) of IL-18 and IL-5 were 0.813 (95% CI: 0.710-0.917; P<0.01) and 0.844 (95% CI: 0.756-0.933; P<0.01), respectively. CONCLUSIONS IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 serum levels showed significant differences in children with CAP. IL-18 and IL-5 were much higher in the MPP group compared to the NMPP group patients, whereas IL-6 levels were significantly lower in these 2 groups.
Assuntos
Citocinas/imunologia , Óxido Nítrico/metabolismo , Pneumonia por Mycoplasma/imunologia , Testes Respiratórios , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas , Feminino , Humanos , Imunoglobulina E/imunologia , Interferon gama/imunologia , Interleucina-13/imunologia , Interleucina-18/imunologia , Interleucina-33/imunologia , Interleucina-5/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Masculino , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia por Mycoplasma/metabolismoRESUMO
Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the respiratory syncytial virus (RSV) F glycoprotein, is the only prophylactic agent approved for use for the treatment of RSV infection. However, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high-potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F protein trimer. We compared in vitro and in vivo the potency and protective efficacy of 5C4 and the murine precursor of palivizumab, antibody 1129. Both antibodies were synthesized on identical murine backbones as either an IgG1 or IgG2a subclass and evaluated for binding to multiple F protein conformations, in vitro inhibition of RSV infection and propagation, and protective efficacy in mice. Although 1129 and 5C4 had similar pre-F protein binding affinities, the 5C4 neutralizing activity was nearly 50-fold greater than that of 1129 in vitro In BALB/c mice, 5C4 reduced the peak titers of RSV 1,000-fold more than 1129 did in both the upper and lower respiratory tracts. These data indicate that antibodies specific for antigenic site Ø are more efficacious at preventing RSV infection than antibodies specific for antigenic site II. Our data also suggest that site Ø-specific antibodies may be useful for the prevention or treatment of RSV infection and support the use of the pre-F protein as a vaccine antigen.IMPORTANCE There is no vaccine yet available to prevent RSV infection. The use of the licensed antibody palivizumab, which recognizes site II on both the pre-F and post-F proteins, is restricted to prophylaxis in neonates at high risk of severe RSV disease. Recommendations for using passive immunization in the general population or for therapy in immunocompromised persons with persistent infection is limited because of cost, determined from the high doses needed to compensate for its relatively low neutralizing potency. Prior efforts to improve the in vitro potency of site II-specific antibodies did not translate to significant in vivo dose sparing. We isolated a pre-F protein-specific, high-potency neutralizing antibody (5C4) that recognizes antigenic site Ø and compared its efficacy to that of the murine precursor of palivizumab (antibody 1129) matched for isotype and pre-F protein binding affinities. Our findings demonstrate that epitope specificity is an important determinant of antibody neutralizing potency, and defining the mechanisms of neutralization has the potential to identify improved products for the prevention and treatment of RSV infection.
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Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Antivirais/administração & dosagem , Palivizumab/administração & dosagem , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/imunologia , Proteínas Virais de Fusão/imunologia , Animais , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/isolamento & purificação , Linhagem Celular , Modelos Animais de Doenças , Humanos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Ligação Proteica , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Vírus Sinciciais Respiratórios/crescimento & desenvolvimento , Resultado do TratamentoRESUMO
The association between ATP-binding cassette subfamily B member 1 (ABCB1) C3435T and C1236T polymorphisms and the risk for childhood acute lymphoblastic leukemia (ALL) is inconclusive. We conducted a meta-analysis of all published studies to determine the association of ABCB1 C3435T and C1236T polymorphisms and pediatric ALL risk. A systematic retrieval of relevant publications from the PubMed and Web of Science databases was performed. Data were calculated and statistical analysis was performed using STATA version 12.0 software. Metaanalysis results showed no significant association between C3435T polymorphism and pediatric ALL risk (TT vs. CC: odds ratio [OR] = 1.20, 95% confidence interval [CI] = 0.95-1.52; CT vs. CC: OR = 1.00, 95% CI = 0.82-1.23; the dominant model: OR = 1.07, 95% CI = 0.89-1.29; the recessive model: OR = 1.17, 95% CI = 0.84-1.62). Similarly, there was no association found for the C1236T polymorphism (TT vs. CC: OR = 1.18, 95% CI= 0.82-1.70; CT vs. CC: OR = 1.08, 95% CI = 0.80-1.45; the dominant model: OR = 1.10, 95% CI= 0.83-1.46; the recessive model: OR = 0.98, 95% CI = 0.61-1.58). Similar results were observed in the subgroup analyses on ethnicity and Hardy-Weinberg equilibrium. The present meta-analysis found no evidence for ABCB1 C3435T and C1236T polymorphisms as risk factors for pediatric ALL.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMO
Glutamatergic transmission converging on calcium signaling plays a key role in dendritic differentiation. In early development, AMPA receptor (AMPAR) transcripts are extensively spliced and edited to generate subunits that differ in their biophysical properties. Whether these subunits have specific roles in the context of structural differentiation is unclear. We have investigated the role of nine GluA variants and revealed a correlation between the expression of flip variants and the period of major dendritic growth. In interneurons, only GluA1(Q)-flip increased dendritic length and branching. In pyramidal cells, GluA2(Q)-flop, GluA2(Q)-flip, GluA3(Q)-flip and calcium-impermeable GluA2(R)-flip promoted dendritic growth, suggesting that flip variants with slower desensitization kinetics are more important than receptors with elevated calcium permeability. Imaging revealed significantly higher calcium signals in pyramidal cells transfected with GluA2(R)-flip as compared with GluA2(R)-flop, suggesting a contribution of voltage-activated calcium channels. Indeed, dendritic growth induced by GluA2(R)-flip in pyramidal cells was prevented by blocking NMDA receptors (NMDARs) or voltage-gated calcium channels (VGCCs), suggesting that they act downstream of AMPARs. Intriguingly, the action of GluA1(Q)-flip in interneurons was also dependent on NMDARs and VGCCs. Cell class-specific effects were not observed for spine formation, as GluA2(Q)-flip and GluA2(Q)-flop increased spine density in pyramidal cells as well as in interneurons. The results suggest that AMPAR variants expressed early in development are important determinants for activity-dependent dendritic growth in a cell type-specific and cell compartment-specific manner.
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Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Dendritos/metabolismo , Receptores de AMPA/metabolismo , Processamento Alternativo , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Interneurônios/metabolismo , Neurônios/metabolismo , Edição de RNA , Splicing de RNA , Ratos , Ratos Long-Evans , Receptores de N-Metil-D-Aspartato/metabolismo , Fatores de TempoRESUMO
In recent era, more and more electric and electronic equipment wastes (e-wastes) are generated that contain both toxic and valuable materials in them. Most studies focus on the extraction of valuable metals like Au, Ag from e-wastes. However, the recycling of metals such as Pb, Cd, Zn, and organics has not attracted enough attentions. Vacuum metallurgy separation (VMS) processes can reduce pollution significantly using vacuum technique. It can effectively recycle heavy metals and organics from e-wastes in an environmentally friendly way, which is beneficial for both preventing the heavy metal contaminations and the sustainable development of resources. VMS can be classified into several methods, such as vacuum evaporation, vacuum carbon reduction and vacuum pyrolysis. This paper respectively reviews the state-of-art of these methods applied to recycling heavy metals and organics from several kinds of e-wastes. The method principle, equipment used, separating process, optimized operating parameters and recycling mechanism of each case are illustrated in details. The perspectives on the further development of e-wastes recycling by VMS are also presented.
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Resíduo Eletrônico , Metalurgia/métodos , Reciclagem/métodos , Carbono/química , Conservação dos Recursos Naturais/métodos , Poluentes Ambientais/isolamento & purificação , Metais Pesados/isolamento & purificação , VácuoRESUMO
Vacuum metallurgy separation (VMS) is a technically feasible method to recover Pb, Cd and other heavy metals from crushed e-wastes. To further determine the environmental impacts and safety of this method, heavy metals exposure, noise and thermal safety in the ambiance of a vacuum metallurgy separation system are evaluated in this article. The mass concentrations of total suspended particulate (TSP) and PM10 are 0.1503 and 0.0973 mg m(-3) near the facilities. The concentrations of Pb, Cd and Sn in TSP samples are 0.0104, 0.1283 and 0.0961 µg m(-3), respectively. Health risk assessments show that the hazard index of Pb is 3.25 × 10(-1) and that of Cd is 1.09 × 10(-1). Carcinogenic risk of Cd through inhalation is 1.08 × 10(-5). The values of the hazard index and risk indicate that Pb and Cd will not cause non-cancerous effects or carcinogenic risk on workers. The noise sources are mainly the mechanical vacuum pump and the water cooling pump. Both of them have the noise levels below 80 dB (A). The thermal safety assessment shows that the temperatures of the vacuum metallurgy separation system surface are all below 303 K after adopting the circulated water cooling and heat insulation measures. This study provides the environmental information of the vacuum metallurgy separation system, which is of assistance to promote the industrialisation of vacuum metallurgy separation for recovering heavy metals from e-wastes.
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Resíduo Eletrônico/análise , Temperatura Alta/efeitos adversos , Metalurgia/instrumentação , Metais Pesados/efeitos adversos , Ruído/efeitos adversos , Exposição Ocupacional , Reciclagem/métodos , Cádmio/efeitos adversos , Chumbo/efeitos adversos , Tamanho da Partícula , Material Particulado/efeitos adversos , Medição de Risco , Segurança , Estanho/efeitos adversos , VácuoRESUMO
Molten salt pyrolysis technology stands out as a potent approach for achieving efficient degradation and energy recovery of composite organic materials. Nevertheless, challenges such as the high melting point of molten salt, product destruction, and the complexities of treating waste salt pose significant limitations to the widespread application and popularization of this technology. To tackle these issues, this study proposes a salt-assisted pyrolysis method based on capillary heat transfer called permeable liquid salt pyrolysis. Focusing on abandoned power industry insulators, the research delves into the thermal and mass transfer model of cluster-embedded materials under non-molten salt conditions. The investigation reveals that the capillary between glass fiber and resin proves beneficial in enhancing heat transfer conditions by creating a novel phase known as permeate liquid. Results demonstrate that salt-assisted pyrolysis can substantially lower the required temperature and enhance the pyrolysis reaction rate, achieving a maximum degradation efficiency of 98.99 %. Additionally, the pyrolysis products undergo in-situ modification, with a notable reduction in benzene series compounds ranging from 68 % to 85 %. Furthermore, an erosion diffusion capillary mode is established. This study presents an environmentally-friendly approach to recycle and modify products derived from waste resin-based composite materials generated in the electric power industry.
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Microplastics (MPs) is a novel and significant pollution due to its eco-environmental hazards and ubiquity. In end-of-life vehicle (ELV) recycling base, MPs are widely distributed but have rare reported in scientific literature. In this study, a comprehensive analysis of MPs was conducted in a typical ELV recycling base. MPs were found in all samples at different sampling sites and environmental mediums. A total of 34 polymer types were detected by µ-FTIR, and the main polymers include PE-PP, ABS, polyester resin, nylon, and PEU plastic. MPs were released from the crushing, tearing, and breaking of plastic parts in ELVs. They were in high content in ground dust, with the abundance of 737-29,021 p/5 g D (the average abundance of 5552 ± 6435 p/5 g D). The abundance, shape, color, and size of MPs are related with functional areas of ELV recycling. Heavy metals could be adsorbed on MPs, and their contents on MPs have a significant correlation with those in the corresponding dust samples. At last, some specific MPs control measures, such as changing transportation mode, using dust-proof cloths, and equipping dust removal equipment, have been put forward.
RESUMO
Purpose: To characterize the efficiency of glabridin alone and in combination with clinical antifungals in Aspergillus fumigatus keratitis. Methods: The broth microdilution method was performed to investigate whether glabridin exerted an antifungal role on planktonic cells and immature and mature biofilm. Antifungal mechanism was evaluated by Sorbitol and Ergosterol Assays. The synergistic effect of glabridin and antifungals was assessed through the checkerboard microdilution method and time-killing test. Regarding anti-inflammatory role, inflammatory substances induced by A. fumigatus were assessed by real-time quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. Drug toxicity was assessed by Draize test in vivo. Macrophage phenotypes were examined by flow cytometry. Results: Regarding antifungal activity, glabridin destroyed fungal cell wall and membrane on planktonic cells and suppressed immature and mature biofilm formation. After combining with natamycin or amphotericin B, glabridin possessed a potent synergistic effect against A. fumigatus. Regarding anti-inflammatory aspects, Dectin-1, tolllike receptor (TLR)-2 and TLR-4 expression of human corneal epithelial cells were significantly elevated after A. fumigatus challenge and reduced by glabridin. The elevated expression of interleukin-1ß and tumor necrosis factor-alpha induced by A. fumigatus or corresponding agonists were reversed by glabridin, equivalent to the effect of corresponding inhibitors. Glabridin could also contribute to anti-inflammation by downregulating inflammatory mediator expression to suppress macrophage infiltration. Conclusions: Glabridin contributed to fungal clearance by destroying fungal cell wall and membrane, and disrupting biofilm. Combining glabridin with clinical antifungals was superior in reducing A. fumigatus growth. Glabridin exerted an anti-inflammatory effect by downregulating proinflammatory substance expression and inhibiting macrophage infiltration, which provide a potential agent and treatment strategies for fungal keratitis.