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167 result(s) for "Cho, Jaewon"
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High‐performance piezoelectric yarns for artificial intelligence‐enabled wearable sensing and classification
Piezoelectric polymer fibers offer a fundamental element in intelligent fabrics with their shape adaptability and energy‐conversion capability for wearable activity and health monitoring applications. Nonetheless, realizing high‐performance smart polymer fibers faces a technical challenge due to the relatively low piezoelectric performance. Here, we demonstrate high‐performance piezoelectric yarns simultaneously equipped with structural robustness and mechanical flexibility. The key to substantially enhanced piezoelectric performance is promoting the electroactive β‐phase formation during electrospinning via adding an adequate amount of barium titanate (BaTiO3) nanoparticles into the poly(vinylidene fluoride‐trifluoroethylene) (P(VDF‐TrFE)). When transformed into a yarn structure by twisting the electrospun mats, the BaTiO3‐doped P(VDF‐TrFE) fibers become mechanically strengthened with significantly improved elastic modulus and ductility. Owing to the tailored convolution neural network algorithms architected for classification, the as‐developed BaTiO3‐doped piezo‐yarn device woven into a cotton fabric exhibits monitoring and identifying capabilities for body signals during seven human motion activities with a high accuracy of 99.6%. Piezoelectric polymer fibers are available for intelligent fabrics with shape‐adaptability and energy conversion capability. Herein, an artificial intelligence‐integrated motion classification system was developed using a high‐performance BTO‐doped P(VDF‐TrFE) piezo‐yarn by twisting an electrospun mat to simultaneously enhance the piezoelectric and mechanical properties. Our piezo‐yarn device can provide human‐textile interfaces for monitoring and classifying signals captured from various human motions.
Discovery and functional characterization of canine PD-L1-targeted antibodies for evaluating antitumor efficacy in a canine osteosarcoma xenograft model
Targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is promising in treating cancer in humans and offers potential for veterinary applications. However, no PD-L1 antibodies have been approved specifically for treating canine cancer. We aimed to develop PD-L1-specific antibodies using phage display technology for treating canine cancer. A synthetic antibody library was screened, and 18 high-affinity single-chain variable fragment clones were subsequently converted to the IgG format for enhancing binding affinity and functional stability. The clone #15 exhibited the highest binding affinity and most pronounced antitumor effects. The PD-1/PD-L1 interaction was inhibited by antibody #15. The binding and thermal stabilities of the antibodies were validated by flow cytometry and thermal stability assays, respectively. In NOG mice xenografted with canine osteosarcoma cells and treated with canine peripheral blood mononuclear cells and antibody #15, the tumor size and weight were reduced. Antibody #15 significantly increased apoptosis of tumor cells and lymphocyte populations. Therefore, anti-PD-L1 antibodies, particularly antibody #15, have substantial potential as novel immunotherapeutic agents against canine osteosarcoma. This study represents a significant advancement in veterinary oncology, with the potential of improving treatment outcomes for canine cancers and providing insights into similar strategies in human cancer therapy.
ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions
Endoplasmic reticulum stress is closely associated with the onset and progression of inflammatory bowel disease. ERdj5 is an endoplasmic reticulum-resident protein disulfide reductase that mediates the cleavage and degradation of misfolded proteins. Although ERdj5 expression is significantly higher in the colonic tissues of patients with inflammatory bowel disease than in healthy controls, its role in inflammatory bowel disease has not yet been reported. In the current study, we used ERdj5 -knockout mice to investigate the potential roles of ERdj5 in inflammatory bowel disease. ERdj5 deficiency causes severe inflammation in mouse colitis models and weakens gut barrier function by increasing NF-κB-mediated inflammation. ERdj5 may not be indispensable for goblet cell function under steady-state conditions, but its deficiency induces goblet cell apoptosis under inflammatory conditions. Treatment of ERdj5 -knockout mice with the chemical chaperone ursodeoxycholic acid ameliorated severe colitis by reducing endoplasmic reticulum stress. These findings highlight the important role of ERdj5 in preserving goblet cell viability and function by resolving endoplasmic reticulum stress. Inflammatory bowel disease: A protective enzyme in intestinal goblet cells Studies of inflammatory bowel disease (IBD) in mice reveal the role of an enzyme that assists the degradation of mis-folded proteins in the ‘goblet’ cells involved in producing the mucus barrier that lines and protects the interior of the gut. The most common forms of IBD are ulcerative colitis and Crohn’s disease. Researchers in South Korea led by Hyun-Jeong Ko at Kangwon National University, Chuncheon, and Sun-Young Chang at Ajou University, Suwon, compared goblet cell biology in normal mice with mice in which the gene encoding the protein-degrading enzyme ERdj5 had been disabled. This showed that ERdj5 protects goblet cells from a form of stress-mediated cell death that occurs during gut inflammation. The results suggest that drugs modifying the molecular mechanisms underlying ERdj5’s actions could open new avenues towards preventing and treating IBD.
Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A/Puerto Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death and the replication of A/PR/8 at concentrations up to 2 μM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A/PR/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in the early stages of infection.
Multi‐Objective Bayesian Optimization for Laminate‐Inspired Mechanically Reinforced Piezoelectric Self‐Powered Sensing Yarns
Piezoelectric fiber yarns produced by electrospinning offer a versatile platform for intelligent devices, demonstrating mechanical durability and the ability to convert mechanical strain into electric signals. While conventional methods involve twisting a single poly(vinylidene fluoride‐co‐trifluoroethylene)(P(VDF‐TrFE)) fiber mat to create yarns, by limiting control over the mechanical properties, an approach inspired by composite laminate design principles is proposed for strengthening. By stacking multiple electrospun mats in various sequences and twisting them into yarns, the mechanical properties of P(VDF‐TrFE) yarn structures are efficiently optimized. By leveraging a multi‐objective Bayesian optimization‐based machine learning algorithm without imposing specific stacking restrictions, an optimal stacking sequence is determined that simultaneously enhances the ultimate tensile strength (UTS) and failure strain by considering the orientation angles of each aligned fiber mat as discrete design variables. The conditions on the Pareto front that achieve a balanced improvement in both the UTS and failure strain are identified. Additionally, applying corona poling induces extra dipole polarization in the yarn state, successfully fabricating mechanically robust and high‐performance piezoelectric P(VDF‐TrFE) yarns. Ultimately, the mechanically strengthened piezoelectric yarns demonstrate superior capabilities in self‐powered sensing applications, particularly in challenging environments and sports scenarios, substantiating their potential for real‐time signal detection. Inspired by composite laminates, electrospun fiber mats are strategically stacked to create highly strengthened P(VDF‐TrFE) yarns, preserving their high piezoelectric performance. A multi‐objective Bayesian optimization‐based machine learning algorithm is developed to optimize the stacking sequence, ultimately yielding mechanically robust piezoelectric polymer yarn with simultaneously improved ultimate tensile strength and failure strain for real‐time self‐powered sensing applications in diverse environmental conditions.
Enhanced Bifunctional Electrocatalysis for Zinc‐Air Battery Using Porous Conductive Substrate with Abundant Anchoring Sites
Efficient and robust bifunctional electrocatalysts for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are critical for high‐performance zinc‐air batteries (ZABs). However, balancing OER and ORR activity in a single catalyst remains challenging due to the different mechanisms during charging and discharging. Here, a scalable strategy is presented for enhancing both reactions by integrating two‐dimensional OER‐ and ORR‐active components onto a carbon‐based conductive substrate with abundant anchoring sites, via high‐shear exfoliation. The heterostructure catalyst demonstrates exceptional bifunctionality, achieving an extremely low overpotential difference of 0.63 V. First‐principles calculations confirm a strong chemical compatibility between the active components and substrate. In scaled‐up ZAB applications, the catalyst delivers a high peak power density of 1569 mW cm−2, and an outstanding cycling stability over 300 h (1800 cycles). This work highlights a versatile approach for designing multifunctional electrocatalysts, advancing scalable energy conversion and storage technologies. A scalable nanocomposite synthesis is reported for a high‐performance bifunctional electrocatalyst by combining exfoliated layered materials—each active for OER and ORR—with a porous conductive substrate via high‐shear exfoliation. The electrocatalyst exhibits the lowest potential gap among reported transition metal‐based bifunctional catalysts. In a scaled‐up zinc‐air battery, the system demonstrates outstanding stability over 300 h.
Recombinant attenuated Salmonella vaccine promotes CD8+ T cell-dependent antitumor immunity via IFN-γ-induced IRF-1-mediated upregulation of IL-7
Background Cancer is a leading cause of mortality worldwide, necessitating the development of novel therapeutic targets and strategies to prevent recurrence and metastasis. In this study, we aimed to evaluate whether a recombinant attenuated Salmonella vaccine (RASV) can stimulate antitumor immunity and prevent cancer progression in vivo. Methods We established a mouse model by transplanting cancer cells subcutaneously 4 weeks after oral RASV inoculation and analyzed bone marrow (BM) cells and tumor-infiltrated immune cells by flow cytometry. Further, we established a 4 T-1-induced metastatic cancer model to evaluate the RASV-mediated prevention of tumor metastasis. Results Adjuvant RASV significantly reduced tumor growth by enhancing CD8 + T cell activity and inducing changes in BM progenitor cells, which contributed combinatorically to the antitumor effects of RASV by increasing the number of common lymphoid progenitor cells. The antitumor effects mediated by RASV were inhibited upon interleukin (IL)-7 receptor blockage. Moreover, interferon-γ-stimulated genes, including Irf1 , were upregulated in the BM of RASV-treated mice, thus mediating IL-7 expression. Furthermore, RASV inoculation prevented lung metastasis in mice with breast cancer. Conclusions RASV inoculation can promote marked alterations in the BM microenvironment, thus reshaping the anticancer immune response in vivo. This strategy holds therapeutic potential for preventing cancer recurrence and metastasis. Graphical abstract
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38
The effector function of tumor-infiltrated CD4+ T cells is readily suppressed by many types of immune regulators in the tumor microenvironment, which is one of the major mechanisms of immune tolerance against cancer. Cathelicidin-related antimicrobial peptide (CRAMP), the mouse analog of LL-37 peptide in humans, is a cationic antimicrobial peptide belonging to the cathelicidin family; however, its secretion by cancer cells and role in the tumor microenvironment (TME) remain unclear. In this study, we explored the possibility of an interaction between effector CD4+ T cells and CRAMP using in vitro-generated mouse Th17 cells. We found that CRAMP stimulates Th17 cells to express the ectonucleotidase CD73, while simultaneously inducing cell death. This finding suggested that CD73-expressing Th17 cells may function as immune suppressor cells instead of effector cells. In addition, treatment of pharmacological inhibitors of the transforming growth factor-beta (TGF-β) signaling pathway showed that induction of CD73 expression is mediated by the p38 signaling pathway. Overall, our findings suggest that tumor-derived LL-37 likely functions as an immune suppressor that induces immune tolerance against tumors through shaping effector Th17 cells into suppressor Th17 cells, suggesting a new intervention target to improve cancer immunotherapy.
The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells
Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.
Recombinant attenuated Salmonella vaccine promotes CD8+ T cell-dependent antitumor immunity via IFN-gamma-induced IRF-1-mediated upregulation of IL-7
Cancer is a leading cause of mortality worldwide, necessitating the development of novel therapeutic targets and strategies to prevent recurrence and metastasis. In this study, we aimed to evaluate whether a recombinant attenuated Salmonella vaccine (RASV) can stimulate antitumor immunity and prevent cancer progression in vivo. We established a mouse model by transplanting cancer cells subcutaneously 4 weeks after oral RASV inoculation and analyzed bone marrow (BM) cells and tumor-infiltrated immune cells by flow cytometry. Further, we established a 4 T-1-induced metastatic cancer model to evaluate the RASV-mediated prevention of tumor metastasis. Adjuvant RASV significantly reduced tumor growth by enhancing CD8.sup.+ T cell activity and inducing changes in BM progenitor cells, which contributed combinatorically to the antitumor effects of RASV by increasing the number of common lymphoid progenitor cells. The antitumor effects mediated by RASV were inhibited upon interleukin (IL)-7 receptor blockage. Moreover, interferon-[gamma]-stimulated genes, including Irf1, were upregulated in the BM of RASV-treated mice, thus mediating IL-7 expression. Furthermore, RASV inoculation prevented lung metastasis in mice with breast cancer. RASV inoculation can promote marked alterations in the BM microenvironment, thus reshaping the anticancer immune response in vivo. This strategy holds therapeutic potential for preventing cancer recurrence and metastasis.