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Background Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs. Methods Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems. Results sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs. Conclusions We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.

Backgrounds Allergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. Methods Induced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4 + T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4 + T cells. Results Stable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4 + T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4 + T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4 + T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role. Conclusion IL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.

The protection of industrial cultural heritage is related to sustainable urban development. Cultural and creative parks (CCPs) are a way for many cities to protect their industrial cultural heritage. In the context of CCPs, this study examines the relationships among the antecedents of exhibition experiential value, CCP experiential value, and behavioral intentions. Surveying 428 visitors in two well-known CCPs in Taipei, this study found that the four antecedents (attractiveness, existential authenticity, self-congruence, and exhibition–park image congruence) have a positive impact on exhibition experiential value. Exhibition experiential value has a positive impact on CCP experiential value, which in turn, affects behavioral intentions toward the CCP. In addition, this study finds that exhibition experiential value has a mediating effect between the four antecedents and CCP experiential value. Moreover, CCP experiential value has a mediating effect between exhibition experiential value and behavioral intentions. The findings of this study provide a direction for CCPs to achieve sustainable development through exhibitions that can attract more tourists.

In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

This study systematically investigates the evolution of vacancy-type defects and heterogeneous Cu nanoprecipitates in an Fe60Cr12Mn8Cu15Mo3V2 (at%) multi-principal element alloy during thermal processing, utilizing Positron annihilation lifetime spectroscopy (PAS), coincidence Doppler broadening (CDB) spectroscopy, and transmission electron microscopy (TEM). The results show that the alloy exhibited a dual-phase coexistence structure of Body-Centered Cubic (BCC) and Face-Centered Cubic (FCC). The CDB results show that the density of heterogeneous Cu precipitates gradually increases with annealing temperature. Compared to the as-cast alloy, the precipitates annealed at 773 K exhibit a significantly reduced size (approximately 33 nm) with higher density. The PAS results demonstrate that gradual migration and aggregation of monovacancies at 573 K form vacancy clusters, while contraction and dissociation of these clusters dominate at 673 K. Within the temperature range of 773–973 K, the dynamic equilibrium between the aggregation and decomposition of vacancy clusters maintains stable annihilation characteristics with minimal lifetime changes.

Transcranial magnetic stimulation (TMS) is a non-invasive brain neurostimulation technique that can be used as one of the adjunctive treatment techniques for neurological recovery after stroke. Animal studies have shown that TMS treatment of rats with middle cerebral artery occlusion (MCAO) model reduced cerebral infarct volume and improved neurological dysfunction in model rats. In addition, clinical case reports have also shown that TMS treatment has positive neuroprotective effects in stroke patients, improving a variety of post-stroke neurological deficits such as motor function, swallowing, cognitive function, speech function, central post-stroke pain, spasticity, and other post-stroke sequelae. However, even though numerous studies have shown a neuroprotective effect of TMS in stroke patients, its possible neuroprotective mechanism is not clear. Therefore, in this review, we describe the potential mechanisms of TMS to improve neurological function in terms of neurogenesis, angiogenesis, anti-inflammation, antioxidant, and anti-apoptosis, and provide insight into the current clinical application of TMS in multiple neurological dysfunctions in stroke. Finally, some of the current challenges faced by TMS are summarized and some suggestions for its future research directions are made.

Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation.

Background/Objectives: Antimicrobial peptides (AMPs) are promising therapeutic agents due to their broad-spectrum activity against bacteria, viruses, and fungi. Unlike traditional antibiotics, AMPs target microbial membranes directly and are less likely to induce resistance. They also possess immunomodulatory and wound-healing properties. However, clinical application remains limited by factors such as salt sensitivity, low bioavailability, and poor stability. To address these challenges, researchers have turned to structural optimization strategies. Recently, artificial intelligence (AI) has facilitated peptide drug design by rapidly screening large peptide libraries. Still, AI struggles to predict how subtle sequence changes affect peptide structure and function. Traditional sequence permutation offers a complementary approach by analyzing structural and functional effects without altering amino acid composition. Methods: In this study, we applied a clockwise sequence permutation strategy to the AMP W5K/A9W, generating derivative peptides with identical molecular weight, net charge, and hydrophobicity. We aimed to investigate how lysine and tryptophan distribution affects antimicrobial activity, membrane permeability, and selectivity. We assessed the secondary structures using circular dichroism (CD) spectroscopy and evaluated in vitro antimicrobial activity, salt resistance, membrane-permeabilizing ability, hemolysis, and wound healing effects. Results: The results revealed that the sequence arrangement of key residues significantly impacts peptide bioactivity and therapeutic index. Conclusions: This study highlights the importance of sequence order in determining AMP function. It also supports integrating permutation strategies with AI-based design to enhance AMP discovery. Together, these approaches offer new opportunities to combat drug-resistant pathogens and advance next-generation anti-infective therapies.

Background: Multimorbidity and polypharmacy increase the risk of hospitalization in older adults receiving potentially inappropriate medication (PIM). The current study compared the ability of PIM-Taiwan, PRISCUS, and Beers criteria to predict 90-day rehospitalization in older patients with and without PIM. Methods: The retrospective cohort study used Taiwan’s Longitudinal Health Insurance Database to retrieve quarterly information about prescribed medication for adults aged ≥65 years hospitalized between 2001 and 2018. We analyzed the association of PIM with 90-day rehospitalization using logistic regression. Results: The study cohort included 206,058 older adults (mean age: 72.5 years). In the analysis, 133,201 (64.6%), 97,790 (47.5%), and 147,450 (71.6%), were identified as having PIM exposure in PIM-Taiwan, PRICUS, and Beers criteria, respectively. PIM-Taiwan criteria found exposure to PIM affecting the cardiovascular (adjusted OR [aOR] 1.37, 95% confidence interval [CI] = 1.32–1.41), gastrointestinal (aOR 1.26, 95% CI = 1.23–1.30), central nervous (aOR 1.11, 95% CI = 1.08–1.14), and respiratory (aOR 1.16, 95% CI = 1.12–1.20) systems significantly increased the risk of 90-day rehospitalization, after adjustment for covariates. In PRISCUS criteria, exposure to PIM affecting the respiratory (aOR 1.48, 95% CI = 1.41–1.56), central nervous (aOR 1.12, 95% CI = 1.09–1.15), and cardiovascular (aOR 1.20, 95% CI = 1.16–1.24) systems significantly increased the risk. In Beers criteria, exposure to PIM affecting the cardiovascular (aOR 1.37, 95% CI = 1.32–1.41), gastrointestinal (aOR 1.38, 95% CI = 1.35–1.42), central nervous (aOR 1.18, 95% CI = 1.15–1.21), endocrine (aOR 1.10, 95% CI = 1.06–1.15), and respiratory (aOR 1.09, 95% CI = 1.04–1.13) systems significantly increased the risk. Patients with 90-day rehospitalization had higher rates of the potentially harmful drug-drug interaction (DDI) pairs of serotonin syndrome (n = 19; 48.8%), QT prolongation (n = 4; 30.8%), extrapyramidal symptoms (EPS) (n = 102; 24.5%), and hypokalemia (n = 275; 20.1%). Conclusion: Beers criteria was more efficient in predicting 90-day rehospitalization among older adults experiencing PIM in Taiwan than either PIM-Taiwan or PRISCUS. The risk of 90-day rehospitalization was associated with the potentially harmful DDI classes of serotonin syndrome, QT prolongation, EPS, and hypokalemia.