Search Results (1,365)

Methane combustion over palladium-based catalysts is a critical process for reducing greenhouse gas emissions from lean-burn engines and natural gas installations, yet the role of oxide support in controlling both the population and the intrinsic reactivity of Pd active centres remains incompletely understood. In this work, Pd catalysts at two series of higher and lower loading were prepared on five oxide supports—Al₂O₃, CeO₂, SiO₂, TiO₂, and ZrO₂—and characterised by a complementary suite of techniques including SEM-EDX, XRD, BET, AAS, in situ CO-FTIR, DRIFTS with methanol as a probe molecule, and Raman spectroscopy. Catalytic activity testing revealed the order Pd/CeO₂ > Pd/ZrO₂ > Pd/Al₂O₃ > Pd/TiO₂ > Pd/SiO₂. In situ CO-FTIR site quantification showed that active site density spans nearly an order of magnitude across the series, with Pd/CeO₂ reaching 105.44 µmol g⁻¹ and Pd/Al₂O₃ only 11.63 µmol g⁻¹. Turnover frequency analysis revealed a striking inversion: Pd/Al₂O₃ exhibited the highest TOF (0.1327 s⁻¹), approximately six times greater than Pd/CeO₂ (0.0226 s⁻¹). DRIFTS/methanol profiling demonstrated that CeO₂ and ZrO₂ expose cooperative redox and basic centres that promote methane activation, while SiO₂ supports only weakly bound methoxy species, consistent with its lowest activity. These results establish that the oxide support simultaneously governs Pd dispersion—and hence site density—and the electronic environment of each Pd centre, thereby modulating intrinsic reactivity. High specific surface area alone does not guarantee catalytic performance, and rational support selection is therefore the decisive lever for optimising methane combustion catalysts at ultra-low Pd loadings. In all, our findings provide a quantitative, molecular-level framework that disentangles support-controlled site density from intrinsic site reactivity under identical reaction conditions. By combining in situ CO-FTIR, DRIFTS, and Raman spectroscopy with kinetic analysis on well-defined, high-purity oxide supports, this work transforms previously qualitative “support effects” in Pd-catalysed methane combustion into predictive structure–activity relationships. Full article

Background: Hospital-acquired infections (HAIs) represent the most significant complications in patients hospitalized for severe burn injuries, after the immediate post-burn resuscitation phase, and are associated with substantial morbidity and mortality. Methods: This is a narrative review. Evidence was extracted mainly with an in-depth search of MEDLINE, focusing on guidelines, randomized controlled trials, and relevant observational studies published in the last 25 years. The reference lists of the most relevant publications were screened to retrieve additional relevant information. Results: Wound infections, bloodstream infections, pneumonia, and urinary tract infections account for the majority of infectious complications. Their diagnosis can be challenging, particularly in the context of wound infections and sepsis. Burn severity and the resulting disruption of tissue and organ homeostasis can alter the pharmacokinetic and pharmacodynamic (PK/PD) properties of antibiotics, rendering standard dosing and administration strategies inadequate. Higher doses, prolonged or continuous infusions, and therapeutic drug monitoring may be required to optimize antibiotic exposure. The emergence of multidrug-resistant (MDR) pathogens (particularly MDR Gram-negative bacilli) has been widely reported across diverse epidemiological settings and occurs frequently in patients with prolonged hospitalization, further complicating treatment. As a result, the use of broad-spectrum antibiotics is substantial, both for empirical therapy and for targeted treatment. Although antimicrobial stewardship programs can promote more appropriate antibiotic use, evidence on how to effectively implement these strategies in Burn Intensive Care Units remains limited. Conclusions: HAIs in burn patients represent a highly complex clinical scenario. Clinical severity is often significant, diagnosis can be challenging, and MDR pathogens are very prevalent, with high consumption of broad-spectrum antibiotics. Moreover, PK/PD properties of antibiotics can be altered. Antimicrobial stewardship can promote appropriate antimicrobial use, but implementation in this setting has not been adequately studied. Close multidisciplinary collaboration between burn specialists and infectious diseases physicians is essential to ensure effective patient management. Full article

α-synuclein (α-syn) aggregation in dopaminergic neurons is a central event in Parkinson’s disease (PD) pathogenesis. Immunotherapeutic strategies targeting α-syn, including passive and active approaches, aim to inhibit aggregation, propagation, and toxicity of pathological species while promoting their clearance via immune mechanisms. This review summarizes α-syn directed immunotherapies evaluated in in silico, in vitro, and in vivo models, as well as early phase clinical trials, focusing on how epitope selection and antibody formats influence efficacy, safety, and target engagement. Data on monoclonal antibody, peptide, and protein-based vaccines, and structure-guided immunogens were analyzed, integrating behavioral, neuropathological, proteomic, and structural outcomes alongside biomarker development for α-syn species in cerebrospinal fluid and peripheral compartments. Clinical evidence indicates that several candidates induce sustained anti-α-syn antibody responses with acceptable safety profiles and signs of pharmacodynamic engagement, including reductions in free or oligomeric α-syn. However, consistent long-term clinical benefits remain unproven, highlighting the gap between preclinical success and disease modification in humans. Advances in structural biology and proteomics support rational epitope selection and improved immunogen design, reinforcing α-syn-targeted immunotherapy as a promising yet experimental strategy for PD, and highlighting the need for mechanistically oriented, biomarker-driven clinical trials initiated in well-characterized prodromal and early-stage cohorts. Full article

Background: Cutaneous melanoma (CM) is a highly immunogenic malignant neoplasm. It features high mutational burden and intense lymphocytic infiltration, supporting the use of immunotherapies, especially inhibitors of the programmed cell death protein 1 (PD-1) checkpoint. Despite advances with anti-PD-1 therapies, such as nivolumab and pembrolizumab, many patients still experience resistance. This result highlights additional immunosuppressive mechanisms within the tumor microenvironment (TME) that limit T-lymphocyte-mediated responses. Objectives: The aim was to discuss the immunologic and metabolic bases of PD-1- and CD73-mediated pathways and evidence that CD73 inhibition can boost PD-1 inhibitor efficacy by acting on convergent immunosuppressive pathways. Methods: We conducted a narrative literature review focusing on tumor immunosuppression, purinergic signaling and checkpoint inhibitor-based immunotherapy. Results: The purinergic pathway, mediated by the ectonucleotidase CD73, is a critical regulator of tumor immunosuppression. CD73 converts extracellular adenosine monophosphate (AMP) into adenosine. This adenosine accumulates in the hypoxic and inflamed TME, exerting immunosuppressive effects. Adenosine acts as a “metabolic brake,” inhibiting proliferation, cytokine production, and cytotoxic activity of CD8⁺ T lymphocytes and natural killer (NK) cells. It also promotes the expansion of regulatory T cells (Tregs) and tumor progression. This axis may limit responses to PD-1 blockade, suggesting that complementary pathways are active. Conclusions: Integration of PD-1 and CD73 pathways suggests that CD73 inhibition may enhance PD-1 blockade by targeting convergent immunosuppressive mechanisms. This supports the exploration of combination strategies to broaden the benefits of immunotherapy in CM. Full article

African swine fever (ASF) is a highly lethal viral disease of pigs caused by the African swine fever virus (ASFV). The mortality rate is nearly 100%. Currently, it is known that the ASFV has a complex structure, and its genome encodes various immune escape proteins. However, the pathogenic mechanism of ASFV remains to be studied. This study found that ASFV pD345L significantly inhibits the activation of the ISRE promoter triggered by interferon (IFN) β and the production of downstream IFN-stimulated genes (ISG). We further reveal that pD345L may degrade STAT1 via the autophagy pathway and impede its nuclear translocation; this inhibitory effect is closely associated with its exonuclease activity. Our research results have clarified the impact of ASFV pD345L on the JAK/STAT signaling pathway, expanding our understanding of the inhibitory effect of ASFV-encoded proteins on the host’s innate immunity, and to some extent, contributing to the development of an African swine fever vaccine. Full article

The pathophysiological basis of Parkinson’s disease (PD) remains incompletely understood. However, the influence of environmental factors, such as continuous cadmium exposure, requires further investigation. Notably, common comorbidities such as iron deficiency anemia (IDA), chronic obstructive pulmonary disease (COPD), and zinc deficiency are linked with increased cadmium bioavailability, and elevated blood cadmium levels have been reported in individuals with PD. Cd (II) deposits in the midbrain, causing the accumulation of inflammatory lipids, which promote neuronal destruction. Cd-treated animals develop Parkinson-like syndromes, and cadmium exposure is associated with neuronal loss and disruption of dopaminergic receptor expression. Neurofilament light chain (NfL), a biomarker of neurodegeneration, has been found to be elevated in patients with Parkinson’s disease and correlates with Cd blood concentrations. Iron deficiency promotes the secretion of FGF-23, which depletes vitamin D levels, further increasing the risk of PD. Moreover, COPD and IDA are two well-known examples of systemic hypoxia, which attracts metals bound to transferrin, such as cadmium and iron, leading to increased metal accumulation in various tissues, including the brain. Lead levels are also elevated in individuals with IDA, contributing to the risk of PD. Additionally, Cd exposure is associated with a reduced abundance of Lachnospiraceae in stool and decreased levels of butyrate, both of which are characteristic features of patients with Parkinson’s disease. Therefore, this review aims to explore how COPD, IDA, and zinc deficiency—known risk factors for Parkinson’s disease—lead to an increased cadmium burden and contribute to the onset and progression of the disease. Full article

Since launching the Saudi Vision 2030, it has witnessed a reflective sustainability action (SA) transformation. However, robust theoretical models investigating the multifaceted catalysts and consequences of SA in this less-developed country are still lacking in investigation. This lag prompted us to advance and validate a composite framework integrating multiple theories (e.g., institutional theory, the resource-based view (RBV), stakeholder theory, dynamic capabilities theory, and contingency theory) elucidating how policy direction (PD), market incentives (MIs), and knowledge collaboration (KC) stimulate SA adoption encompassing its environmental practices (EPs), social practices (SPs), and circular economy practices (CEPs). The investigation also probes how SA thereafter drives sustainable performance outcomes. A machine-learning approach using the PLS-SEM facility was applied based on 400 questionnaires targeted at managerial positions working in the tourism and hospitality segment based in Saudi Arabia. The findings reveal that all the proposed relationships were supported, providing strong empirical support for the proposed sustainability framework in the Saudi tourism and hospitality context. Institutional pressure and the governance/regulatory environment also showed a significant impact on environmental practices, sustainable performance, and circular economy practices, whereas cost efficiency, competitive advantage, customer demand for sustainability, and knowledge collaboration also demonstrated a positive impact on sustainability actions and outcomes. Furthermore, robust analysis shows that larger firms respond more strongly to MI in terms of cost efficiency, competitive advantage, and customer demand, while CEP produces a modest improvement in hotels compared with restaurants. Our model develops a theoretical synthesis beyond fragmented views. It also provides tangible guidance for industry leaders and regulators in driving strategic alignment with the SDGs and in developing a resilient, situational model that promotes regenerative tourism in high-growth, vulnerable destinations. Full article

Catalytic oxidation has become a crucial technology for removing CO from industrial flue gas. However, the complex composition of flue gas (including NH₃, NO, SO₂, H₂O, etc.) poses significant challenges to the catalytic activity and stability of catalysts. In this work, we propose a new strategy for constructing highly efficient catalysts by loading a Pd component onto TiO₂ nanosheets (NSs) with predominantly exposed {001} facets. It has been revealed that the well-connected channels, abundant oxygen vacancies and Ti³⁺ species on the TiO₂(NS) support facilitate the formation of highly dispersed and electron-rich Pd nanoparticles. The weak adsorption of impurities such as NH₃, SO₂, NO and H₂O on these active sites promotes the adsorption and activation of the target reactants (CO and O₂), thereby enhancing catalytic activity. Furthermore, such reduced adsorption inhibits the aggregation of Pd nanoparticles and synergizes with the intrinsically weak NH₃ adsorption of TiO₂(NS) to suppress ammonium sulfate species deposition, thereby enhancing long-term catalytic stability. This work advances TiO₂ facet engineering in catalysis and offers new design concepts for efficient CO oxidation catalysts in complex atmospheres. Full article

Polycomb repressive complex 2 (PRC2) regulates the expression of pluripotency genes in embryonic stem cells (ESCs) and suppresses multiple genes associated with development, cell fate determination, and differentiation. Mouse embryonic stem cells (mESCs) derived from protein kinase C inhibition (PKCi) exhibit self-renewal and pluripotency comparable to those ESCs captured by the classical 2iL (CHIR99021, PD0325901, and leukemia inhibitory factor) system. However, the dynamic expression pattern of PRC2 in PKCi-mESCs and its role in regulating pluripotency remain unclear. This study demonstrated that the expression level of the enhancer of zeste 2 gene (Ezh2), of which protein is the catalytic subunit of PRC2 responsible for the trimethylation of lysine 27 on nucleosome histone H3 subunit (H3K27me3), is significantly higher in PKCi-mESCs than in 2iL-mESCs. EZH2 knockdown enhances the self-renewal capacity of PKCi-mESCs, as evidenced by a significant increase in the number of undifferentiated mESCs colonies. The effect of an EZH2 reduced expression is accompanied by the upregulation of specific core pluripotency gene Nanog, along with the general downregulation of differentiational genes representing the three germ layers. Conversely, EZH2 overexpression promotes a significant differentiation of PKCi-mESCs, resulting in the downregulation of pluripotency genes, including core pluripotency genes Nanog and Sox2, as well as naïve pluripotency genes Klf4, Fgf4, and Esrrb, while with a wide upregulation of three germ layer associated genes. Importantly, Cleavage Under Targets and Tagmentation (CUT&Tag) demonstrates that EZH2 directly controls H3K27me3 enrichment at the Nanog promoter near the transcription start site. Thus, EZH2, a core subunit of PRC2, exhibits the distinct regulatory functions orchestrating mESCs at a poised state between self-renewal and differentiation under PKC inhibition. EZH2 exerts histone H3 methyltransferase activity to regulate Nanog expression as one of its key targets, thereby modulating the transcriptional regulatory network that maintains pluripotency and lineage specification in mESCs. Full article

Background: Zinc homeostasis regulated by ZIP transporters is critical for tumor glycolytic reprogramming and progression, yet the role of specific ZIP family members in lung adenocarcinoma (LUAD) remains unclear. This study aimed to identify the key ZIP transporter in LUAD and elucidate its molecular mechanisms and therapeutic value. Methods: siRNA-based functional screening of the ZIP family was performed in A549 and PC9 cells. A combination of in vitro cellular assays, in vivo animal models, clinical sample analysis and bioinformatics was used to validate the function of ZIP7 and explore its regulatory mechanisms. Results: ZIP7 (SLC39A7) was identified as a critical driver of glycolysis and proliferation in LUAD. It was significantly upregulated in LUAD tissues and cell lines. Mechanistically, ZIP7 increased inhibitory phosphorylation of GSK3β at Ser9 to stabilize NRF2, maintained low intracellular ROS levels, and sustained mTOR signaling to promote glycolytic flux. ZIP7-induced lactate secretion also drove M2-like macrophage polarization and PD-L1 upregulation to establish an immunosuppressive microenvironment. Notably, genetic or pharmacological inhibition of ZIP7 markedly enhanced the antitumor efficacy of anti-PD-1 therapy in vivo. Conclusions: ZIP7 is a pivotal oncogenic zinc transporter in LUAD that drives tumor progression via metabolic reprogramming and immune remodeling. Targeting ZIP7 represents a promising strategy to improve the efficacy of anti-PD-1 immunotherapy for LUAD. Full article

The safe and stable operation of air-insulated switchgear (AIS) in high-altitude and low-pressure environments is significantly affected by partial discharge (PD), which accelerates insulation aging and may threaten power system reliability. Therefore, effective online monitoring and fault diagnosis methods are of considerable engineering importance. This paper proposes a PD-type recognition method based on the concentration ratio of two characteristic decomposition gases, CO and NO₂. First, a hybrid numerical model coupling fluid dynamics and plasma chemistry was established to simulate the microscopic decomposition mechanism of air discharge. The simulation results indicate that CO and NO₂ are relatively stable and detectable among the considered air-discharge products and that their generation is promoted by increased average electron energy under low-pressure conditions. Subsequently, an experimental platform was developed to simulate three typical insulation defects, namely point discharge, air-gap discharge, and surface discharge, under different simulated altitudes. Quantitative analysis using Fourier-transform infrared spectroscopy and gas chromatography revealed clear correlations between defect type and gas concentration characteristics. Based on these results, a diagnostic criterion was established under the tested conditions: a CO/NO₂ concentration ratio less than 1 indicates the epoxy-resin-based surface discharge model, whereas a ratio greater than 1 indicates point discharge or air-gap discharge. The latter two types can be further distinguished according to the time-dependent increasing trend of the ratio for air-gap discharge. Finally, based on the observed diffusion characteristics of these gases in the laboratory switchgear model, a low-cost online detection prototype using semiconductor gas sensors was developed. Laboratory validation using three typical single-defect models showed that the proposed method achieved 100% recognition accuracy when sufficient time-series data were available. However, further field validation is required before large-scale industrial application. The proposed CO/NO₂ ratio method provides a potential low-cost auxiliary diagnostic approach for AIS insulation monitoring, particularly under high-altitude and low-pressure conditions. Full article

The transport and distribution of Scomber japonicus larvae significantly affect their habitat and population dynamics. Understanding these processes is crucial for developing effective fishing and conservation strategies. However, the interannual variability of the Kuroshio path introduces both complexity and uncertainty. This study implemented a coupled ocean–biophysical model to simulate and analyze the transport of S. japonicus larvae in the Pacific Ocean south of Japan across three Kuroshio path modes, including the offshore non-large-meander (ONLM), nearshore non-large-meander (NNLM), and typical large-meander (TLM) paths. Two transport scenarios, passive drift (PD) and active swimming (AS), were considered in the simulations. The simulated results presented a comprehensive analysis of the distribution, connectivity, and transport distances of S. japonicus larvae. These findings highlighted the significant influence of biological behavior on larval transport, notably reducing transport distances and shifting the distributions northward. This allowed larvae to actively migrate to areas with higher zooplankton aggregation. Larvae released from the western and nearshore spawning grounds around Southern Kyushu–Shikoku were mainly transported to the central nursery region between 132.5° E and 140° E, whereas larvae released from the eastern spawning grounds were mainly distributed in the eastern nursery region east of 140° E near the Kuroshio Extension. These patterns suggest that nursery areas 2 and 3 may warrant further attention in future spatial management assessments, particularly when considering larval transport under different Kuroshio path modes. This study provides valuable insights into the transport and distribution mechanisms of S. japonicus larvae, offering critical guidance for the conservation of fishery resources and the promotion of sustainable fishery management. Full article

Cancer is a complex and evolutionary disease, with the development of different types of cancers leading to various different defective gene mutations. Synthetic lethality is a genetic-level precision medical strategy. Currently, treating BRCA (BReast CAncer)-mutated breast or ovarian cancer cells with a chemical inhibitor (Poly(ADP-ribose) polymerase, PARPi) is a typical synthetic lethal application in clinical practice. However, PARPi therapy has been found to cause off-target effects and therapy-induced immune escape driven by PD-L1 upregulation, allowing for cancer cells to escape attack from the immune response. To overcome these challenges, we developed a core–shell structure comprising a hydrophobic core of quercetin (Q)-mediated PARP inhibition and iron oxide nanoparticles (IONPs), enveloped by a hydrophilic fucoidan (Fu) shell to encapsulate short hairpin RNA targeting Programmed Death Ligand 1 (shPD-L1) for efficient gene transfection (shPD-L1@QIO@Fu). Structurally, the incorporation of quercetin into the intermediate hydrophobic layer enables modulate of the PARP effect, while the inner aqueous core with shPD-L1 gene silencing can inhibit the expression of PD-L1 protein. In this study, we proved that shPD-L1@QIO@Fu demonstrated a dual therapeutic mechanism against BRCA-mutant cancer cells by inducing extensive DNA double-strand breaks and promoting apoptosis. Furthermore, the combined action of quercetin-mediated DNA damage and shPD-L1-driven PD-L1 suppression led to a significant reduction in PD-L1 mRNA to approximately 5% at 72 h and decreased surface PD-L1 below baseline by 96 h. This effectively suppresses PARPi-induced PD-L1 upregulation and enhances antitumor immunity. These findings demonstrate the therapeutic efficacy of shPD-L1@QIO@Fu nanomedicine, providing a promising foundation for advanced co-delivery strategies to synergize PARP inhibition mediated synthetic lethality with immune checkpoint blockade in next-generation precision medicine. Full article

Background/Objectives: This study aimed to develop a novel tumor-associated macrophage (TAM)-targeting nanoplatform to improve the solubility and bioavailability of camptothecin (CPT) and achieve active targeted drug delivery for enhanced anti-tumor immunotherapy. Methods: We constructed a sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowire system. Sialic acid was used as a targeting ligand to specifically recognize the overexpressed Siglec-E receptor on TAMs. Upon cellular internalization, the disulfide bond was designed to respond to intracellular glutathione (GSH), enabling controlled drug release. Results: The SA-SS-CPT nanowires significantly improved CPT solubility and enabled targeted delivery to TAMs. Following GSH-responsive cleavage and CPT release, the nanowires induced DNA damage in TAMs, activating the cGAS-STING signaling pathway. This promoted TAM polarization toward the M1 phenotype, enhanced pro-inflammatory and anti-tumor immune responses, and inhibited tumor immune escape. Furthermore, SA-SS-CPT synergistically improved the efficacy of PD-L1 blockade immunotherapy, remodeling the tumor immune microenvironment. Conclusions: The SA-SS-CPT nanoplatform effectively targets TAMs, repolarizes them to an anti-tumor M1 phenotype, and activates the cGAS-STING pathway. It shows strong potential for overcoming tumor immune escape and synergizing with PD-L1 checkpoint blockade to achieve significant tumor clearance. Full article

Breast cancer is a type of cancer with the highest incidence and mortality rates among women. PD-L1 suppresses the proliferation and activation of T cells, thereby enabling cancer cells to evade immune surveillance and facilitating tumor progression. Micheliolide (MCL) is a guaianolide-type sesquiterpene lactone with broad biological activities. Our results revealed that radiation upregulates PD-L1 expression in breast cancer cells, while MCL pretreatment can inhibit this effect. Bioinformatics analysis combined with shRNA interference experiments confirmed that radiation upregulates PD-L1 by activating the IRF1-STAT1 signaling pathway, while MCL represses PD-L1 transcription by suppressing this pathway. In addition, MCL also downregulates PD-L1 protein level through accelerating proteasomal degradation of PD-L1. In vivo experiments demonstrated that MCL combined with radiotherapy significantly inhibits the growth of syngeneic tumors and increases intratumoral CD8⁺ T cell infiltration and the frequencies of granzyme B-positive cells. Taken together, our results indicate that MCL enhances T-cell-mediated antitumor immunity and improves radiotherapy efficacy through inhibiting IRF1-STAT1 signaling pathway-driven PD-L1 transcription and promoting PD-L1 protein degradation. This study provides a theoretical basis for the clinical application of MCL as an immunomodulator and radiosensitizer. Full article