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关键词： Bimetallic electrocatalysts   Degradation mechanisms   Oxygen reduction reaction   Identical location transmission electron microscopy   Nitrogen-doped carbon support   Pt-based catalysts  

摘要： The widespread adoption of devices based on proton-exchange membrane fuel cells directly depends on advances in the development of oxygen reduction reaction catalysts. A bimetallic PtCu/C-N catalyst using a facile, surfactant-free liquid-phase method was synthesized. The catalyst exhibits excellent uniformity in size and distribution, with an average nanoparticle diameter of 2.9 nm attributed to the intercalation of nitrogen atoms into the carbon support. The mass activity has reached 1.4 A/mgPt, which exceeds commercial Pt/C by 5.5 times. Stability tests have been performed under three accelerated stress testing (AST) protocols, revealing distinct degradation mechanisms such as nanoparticle dissolution and Ostwald ripening. The structural stability for the home-made catalyst has been proven by identical location transmission electron microscopy (IL-TEM), including scanning transmission electron microscopy and secondary electron imaging. The IL-TEM analysis has indicated exceptional morphological stability, with an average nanoparticle size variation of only 0.4 nm during stress testing. Following 30,000 cycles under the DOE-recommended protocol, mass activity of the catalyst retains 67 % stability. The study conducted emphasizes the need for comprehensive analysis of bimetallic catalysts as degradation mechanisms may vary widely. The combined electrochemical-structural analysis offers insights into the stability mechanisms of bimetallic catalysts on heteroatom-doped supports.

关键词： ACE2   Angiotensin-Converting Enzyme 2   ALI   Air-liquid Interface   AMs   Alveolar Macrophages   AP-1   Activating Protein-1   APCs   antigen presenting cells   APN   AminoPeptidase N   ASL   Airway Surface Liquid   AT-I   Type I Alveolar epithelial cell = type I pneumocyte   AT-II   Type II Alveolar epithelial cell = type II pneumocyte   BAL   BronchoAlveolar Lavage   CCL   C-C motif Chemokine Ligand   CDCs   conventional DCs   CDHR3   Cadherin-Related family member 3   CAR   Coxsackievirus B and Adenovirus Receptor   CaV1.2   voltage-dependent calcium channel   CCSP   Club Cell Secretory Protein   COPD   Chronic Obstructive Pulmonary Disease   CXCL10/IP-10   C-X-C motif chemokine ligand 10/Interferon gamma-induced protein 10   CYP1A1   Cytochrome P450, family 1, subfamily A, polypeptide 1   DAMPs   Damage-Associated Molecular Patterns   DCs   Dendritic Cells   DC-SIGN   Dendritic Cell-Specific C-type lectin ICAM-3 Grabbing Nonintegrin   DE   Diesel Exhaust   DEP   Diesel Exhaust Particles   DPP4   DiPeptidyl Peptidase-4   Ds   Double-Stranded   DSG2   Desmoglein 2   EC   Elemental Carbon   EGFR   Epidermal Growth Factor Receptor   EPFR   Environmental Particles containing Free-Radicals   F protein   Fusion protein   FP   Fine Particles   GAGs   GlycosAminoGlycans   GM-CSF   Granulocyte-Macrophage Colony-Stimulating Factor   GSH   glutathione   HA   hemagglutinin   HAdVs   Human mastadenoviruses   HBECs   Human Bronchial Epithelial Cells   HBoV   ex human bocaviruses   HE   Hemagglutinin Esterase   HEF   Hemagglutinin Esterase Fusion protein   HPIV   Human ParaInfluenza Virus   HS   Heparan Sulfate a GAG   HSPGs   Heparan Sulfate ProteoGlycans   IAV   Influenza A Virus   ICAM-1   InterCellular Adhesion Molecule-1   ICTV 2023   International Committee on taxonomy of viruses, Virus Taxonomy, 2023 Release   IFIT1   InterFeron-Induced protein with Tetratricopeptide repeats 1   IFN   Interferon   IL   InterLeukin   ILCs   Innate Lymphoid Cells   IPS-1   Interferon-β Promoter Stimulator 1   IRF   Interferon Regulatory Factors   ISG   Interferon-Stimulated Genes   ISRE   Interferon-Stimulated Response Element   JAK/STAT   Janus Kinase/ Signal Transducer and Activator of Transcription   KC   Keratinocyte-derived chemokine CXCL1   KGF   Keratin  

摘要： The respiratory tract is the primary entry point for inhaled particles from anthropogenic or biological origin such as respiratory viruses. Ambient particulate matter (PM) has adverse effects on the respiratory tract through mechanisms eliciting inflammatory responses, oxidative stress, and other pathophysiological effects. At the same time, respiratory viruses cause a range of infections. By compromising the integrity of the respiratory barrier and by modulating the host immune response, PM may facilitate viral entry and replication, thereby enhancing the pathogenicity of respiratory viruses. While epidemiological studies suggest that PM exposure may influence susceptibility to and severity of viral infection, the underlying mechanisms are not fully understood. This review aims to synthesise experimental studies that investigate how PM exposure may modulate virus infection and antiviral defence. These findings will be contextualised by an overview of the characteristics and effects of PM, the major respiratory viruses, and innate lung immunity.

关键词： MRI   Structure   Neuroanatomy   Late effects   Cancer survivorship   Mouse model   Doxorubicin   Cytokines   Inflammation   Histology  

摘要： Purpose: Doxorubicin (DXR) treatment is linked to cognitive impairments in cancer patients, including pediatric survivors. However, since DXR does not readily cross the blood-brain barrier, systemic mechanisms such as DXRinduced elevations of pro-inflammatory cytokines may be key in mediating neurotoxicity. Using a mouse model of pediatric cancer treatment, we investigated cytokine levels following DXR treatment and evaluated its effects on brain toxicity through genetic knockout. Experimental design: Mice were treated with DXR at a childhood-equivalent age (P17 and P19) and sacrificed at P20 to measure cytokine levels in plasma and brain tissue. IL-6 was significantly elevated in both after DXR treatment. We assessed brain volume alterations using longitudinal in vivo MRI (from P14 to P98) and performed histological analysis to further explore DXR impact on the brain in wildtype and Il-6 knockout mice. Results: DXR treatment caused widespread brain volume reductions. The volume reductions were partially rescued in Il-6 knockout mice treated with DXR, which showed progressive brain volume improvements over time. Additionally, histological analysis revealed an increase in the pro-inflammatory microglial marker CD68 in wildtype mice treated with DXR, a response that was mitigated in Il-6 knockout mice. Conclusions: Our results indicate that IL-6 plays a role in DXR-induced brain toxicity, offering a potential mechanism by which DXR affects the brain despite its limited penetration of the blood-brain barrier. This study also provides evidence that targeting IL-6 may alleviate side effects of chemotherapy associated with structural brain changes, such as cognitive deficits in cancer survivors treated with DXR.

摘要： Rationale: Tumor necrosis factor inhibitors (TNFi) infliximab and adalimumab are commonly used third-line treatments for chronic or refractory sarcoidosis. The utility of monitoring TNFi levels and anti-drug antibody (ADA) formation in sarcoidosis is unclear. This study aimed to identify factors associated with TNFi trough levels and ADA prevalence in real-world sarcoidosis patients. Methods: We included sarcoidosis patients treated with TNFi for >= 3 months at an academic specialty clinic who had trough drug and ADA levels assessed due to suboptimal therapeutic response. Associations between TNFi levels and dosing, patient characteristics, concomitant medications, and presence of ADAs were analyzed by univariate analysis. Results: 90 patients (median age 51 years, 66 % female, 60 % Black) met inclusion criteria (64 infliximab, 26 adalimumab). 66 % of patients were on at least 1 additional anti-sarcoidosis medication. The most common infliximab dose was 5 mg/kg every 6 weeks and adalimumab 40 mg weekly. Mean trough levels were 14.6ug/ml and 13.1ug/ml, respectively. ADAs were more prevalent in those on adalimumab (30.8 % vs 19.0 %). ADA presence was significantly associated with low infliximab (p < 0.001) and adalimumab levels (p < 0.001). For infliximab, concurrent use of second-line medications was associated with reduced prevalence of ADAs (8 % vs 38.9 %, p = 0.013) compared to patients on no additional immunosuppression. Discussion: This is the largest reported cohort assessing TNFi drug and ADA levels in sarcoidosis to date. Prevalence of ADAs was high, particularly against adalimumab. Second-line therapy may reduce ADA formation. Monitoring TNFi drug and ADA levels may aid clinicians in managing patients with a suboptimal response to therapy.

关键词： IL-21   shRNA   CCR2   Melanoma   Immunotherapy  

摘要： Interleukin-21 (IL-21), a pivotal immune molecule, exerts an antitumor effect by regulating immune responses in vivo. Nevertheless, the short half-life of IL-21 protein and the difficulty of intratumoral injection of recombinant proteins for the majority of patients present obstacles. We have engineered an IL-21 gene expression vector and confirmed its ability to stably express IL-21 in tumor tissue, exhibiting a certain anti-melanoma effect. Meanwhile, the chemokine CCL2 (chemokine (C-C motif) ligand 2) promotes tumor progression in various cancers by binding to its receptor CCR2 (C-C Chemokine Receptor Type 2), potentially serving as an important target for tumor therapy. However, whether it can synergistically function with IL-21 in antitumor activity remains uncertain. This comprehensive study employed diverse methodologies to validate the anti-melanoma efficacy of an IL-21 and shRNA-CCR2 co-expression plasmid, administered via attenuated Salmonella. By inhibiting CCR2 and augmenting IL-21 levels, this innovative therapy markedly inhibited tumor growth and extended survival in vivo. Mechanistically, it suppressed melanoma cell proliferation, downregulated migration-associated proteins like MMP2 (Matrix Metallopeptidase 2), c-Myc (cellular myelocytomatosis viral oncogene homolog), and CyclinD1 (Cyclin-dependent kinase 4 regulatory subunit 1), and induced apoptosis. Furthermore, it triggered apoptosis in tumor cells while enhancing the presence and infiltration of symbolscript symbolscript T cells, and NK cells (Natural Killer Cells) within the spleen and the tumor microenvironment. This groundbreaking research introduces a novel combinatorial treatment strategy for melanoma, which is expected to transform clinical management.

关键词： Lung cancer   neutrophils   IL-8   PD-L1   immune escape   tumor microenvironment  

摘要： Background Lung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer *** Employing in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-gamma secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and *** Lung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-gamma secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell *** This study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.

关键词： Spent lithium-ion batteries   Ionic liquid   Solvent extraction   Cyanex 272   Cyphos IL 101  

摘要： Spent lithium-ion batteries (LIBs) contain a significant amount of valuable metals, representing a precious secondary resource. Solvent extraction is an effective method for recovering valuable metal ions from these batteries. This study proposes the use of a traditional extractant, Cyanex 272, combined with the ionic liquid Cyphos IL 101, to extract and recover leachate from lithium cobalt oxide (LiCoO2) batteries. With an organic-to-aqueous (O/A) phase ratio of 1:1 and a temperature of 25 degrees C, 97.12 % of Co was extracted, only 2.37 % of Li were coextracted. The separation factor of Co and Li (beta Co/Li) was 1390.1. Stripping was accomplished using pure water, achieving nearly 100 % efficiency, with the extractant demonstrating excellent recyclability and stability. Due to the low viscosity of the organic phase, the extraction system exhibits excellent performance even at room temperature (25 degrees C), eliminating the need for additional heat input. Using Fourier-transform infrared spectroscopy (FTIR), Ultraviolet-visible spectroscopy (UV-Vis), and Nuclear Magnetic Resonance (NMR), it was confirmed that a tetrahedral Co-Cyanex 272 complex is generated during the cobalt extraction process, following a cation exchange mechanism. Concurrently, Cyphos IL 101 facilitates the extraction of Co2 + by transferring them as [CoCl4]2- complexes from the aqueous phase into the organic phase. The novel extraction system reduces raw material costs for recycling spent lithium cobalt oxide batteries. This research highlights the feasibility of solvent extraction methods for processing spent LIBs, offering an efficient approach to recover lithium cobalt oxide batteries.

关键词： Coronavirus disease of 2019   IL-8 polymorphism   Clinical outcomes   Platelet counts   CRP   Serum creatinine  

摘要： Background: COVID-19 presents with a wide spectrum of clinical outcomes, ranging from asymptomatic infection to critical illness. The cytokine storm is a hallmark of severe COVID-19 and is associated with elevated levels of pro-inflammatory cytokines, often observed in severe cases. Genetic polymorphisms in the IL-8 gene may influence individual responses to SARS-CoV-2 infection and the severity of the disease. Methods: A case-control study was conducted involving 200 COVID-19 patients and 201 healthy controls. Two IL-8 gene polymorphisms,-251T/A and +1633T/C, were genotyped using the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique. Results: The IL-8-251TA genotype and-251A allele were significantly associated with COVID-19 patients (P = 0.02, OR = 2.31;P = 0.03, OR = 1.38). The AT haplotype (-251A/+1633C) showed a non-significant trend toward increased risk for COVID-19 (P = 0.11, OR = 2.24). The IL-8 +1633 TT genotype was associated with impaired platelet counts among COVID-19 patients (P = 0.05, OR = 2.42). The IL-8-251TA genotype was significantly associated with all stages of COVID-19 severity-critical (P = 0.05, OR = 8.15), severe (P = 0.002, OR = 2.74), moderate (P = 0.008, OR = 2.16), and mild (P = 0.01, OR = 2.89). In contrast, the IL-8-251AA genotype was significantly associated with the critical stage (P = 0.04, OR = 2.53). A marginally significant association was observed between the IL-8 +1633CT genotype and the severe stage of COVID-19 (P = 0.07, OR = 2.13). Additionally, a borderline significant association was noted between elevated serum creatinine levels and the IL-8-251AA genotype (P = 0.07, OR = 2.45). Conclusion: The IL-8-251T/A polymorphism may serve as a potential risk factor for severe disease progression;the +1633 TT genotype may be linked to thrombocytopenia and poor clinical outcomes;and the-251AA genotype may be associated with elevated serum creatinine levels and an increased risk of renal dysfunct

关键词： TNF   TNFR2   Long-term potentiation   Synaptic failure   Memory   Caspase-1   Neuroinflammation   Alzheimer's disease  

摘要： Alzheimer's disease (AD) is a critical health problem with a projected increase in prevalence, demanding more efforts to find an effective treatment. AD is characterized by amyloid-(3 (A(3) accumulation, which drives neuroinflammation. A(3-mediated Caspase-1-dependent neuroinflammation fuels memory loss through pro-inflammatory cytokines signaling. For instance, TNF promotes synaptic plasticity dysfunction impairing longterm potentiation (LTP), an early hallmark of AD. Thus, targeting TNF receptors (TNFR1 and TNFR2) with antagonists/agonists is a promising therapeutic strategy. Here, we found that intrahippocampal administration of a TNFR2-specific blocking antibody improved recognition memory, spatial memory, and synaptic potentiation in response to chemically induced LTP (cLTP) in 5xFAD mice. Additionally, we found that TNFR2 predominates over TNFR1 on the surface of hippocampal synaptosomes from wild-type mice and that TNFR2 levels increased on the synaptosomal surface of 5xFAD mice in a Caspase-1-dependent manner. Notably, Caspase-1 deletion and TNFR2 blocking improved synaptic potentiation of hippocampal synaptosomes from 5xFAD mice in response to cLTP. TNF signaling via TNFR2 also reduced cell viability and impaired BDNF-mediated neurite outgrowth in SN56 cholinergic cells. Thus, our data reveal that TNFR2 contributes to neuron-and synapse-specific deleterious effects, impacting the memory of 5xFAD mice, suggesting that TNFR2-dependent signaling at the synapsis should be considered for AD treatment.

关键词： Squaliobarbus curriculus   IL-10   Molecular characteristics   Functional differentiation   Anti-inflammatory  

摘要： Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays crucial roles in balancing excessive inflammation in fish during infectious diseases. In this study, we identified two IL-10 gene copies in barbel chub (Squaliobarbus curriculus), designated as ScIL-10A and ScIL-10B. Gene collinearity analysis revealed that ScIL-10A and ScIL-10B were located on different chromosomes, and only ScIL-10A shared a conserved gene block with IL-10s from other vertebrates. Both ScIL-10A and ScIL-10B possessed a typical IL-10 protein domain and showed substantial sequence homology with their counterparts in other cyprinid species. Subcellular localization analysis and CHOS cell expression experiments indicated that ScIL-10A was secreted, whereas ScIL-10B was membrane-localized. Tissue-specific expression profiling manifested that ScIL-10A was predominantly expressed in immune-related tissues, including the spleen, kidney, and head kidney, while ScIL-10B exhibited ubiquitous expression across all examined tissues. Following LPS challenge, both ScIL-10A and ScIL-10B showed the significantly upregulated mRNA expression levels and the similar expression patterns in S. curriculus kidney (ScK) cells. Transcriptomic data revealed that overexpression of ScIL-10A and ScIL-10B induced two distinct lists of differentially expressed genes in ScK cells. Specifically, ScIL-10B overexpression significantly downregulated the expression of multiple pro-inflammatory factors, including CXCL8, CXCL11, IL-8, and IL-34, while ScIL-10A overexpression showed minimal impact on these pro-inflammatory factors expression. In LPS-stimulated ScK cells, however, Western blot analysis demonstrated that both ScIL-10A and ScIL-10B overexpression significantly reduced the protein levels of key pro-inflammatory cytokines TNF-alpha and IL-1(3, suggesting their potential synergistic role in inflammation regulation. This study first discovers the molecular characteristics and functional differentiation of two copied IL