As the main precursor of cardiovascular diseases, atherosclerosis is a complex inflammatory disorder that preferentially occurs in stenotic, curved, and branched arterial regions. Although various in ...vitro models are established to understand its pathology, reconstructing the native atherosclerotic environment that involves both co‐cultured cells and local turbulent flow singling remains challenging. This study develops an arterial construct via in‐bath coaxial cell printing that not only facilitates the direct fabrication of three‐layered conduits with tunable geometry and dimensions but also maintains structural stability. Functional vascular tissues, which respond to various stimulations that induce endothelial dysfunction, are rapidly generated in the constructed models. The presence of multiple vascular tissues under stenotic and tortuous turbulent flows allows the recapitulation of hallmark events in early atherosclerosis under physiological conditions. Furthermore, the fabricated models are utilized to investigate the individual and synergistic functions of cell co‐culture and local turbulent flows in regulating atherosclerotic initiation, as well as the dose‐dependent therapeutic effect of atorvastatin. These outcomes suggest that the constructed atherosclerotic model via a novel fabrication strategy is a promising platform to elucidate the pathophysiology of atherosclerosis and seek effective drugs and therapies.
An advanced in vitro atherosclerosis model that enables the co‐culture of multiple vascular cells under local turbulent flows is developed from geometry‐tunable arterial constructs engineered by a novel in‐bath coaxial cell printing strategy. This platform recapitulates the hallmark events in early atherosclerosis and shows great potential for understanding the atherosclerotic pathophysiology and evaluating drug efficacy.
The ability to efficiently and selectively process mixed polymer waste is important to address the growing plastic waste problem. Herein, we report that the combination of ZnCl2 and an additive ...amount of poly(ethylene glycol) under vacuum can readily and selectively depolymerize polyesters and polycarbonates with high ceiling temperatures (Tc>200 °C) back to their constitute monomers. Mechanistic experiments implicate a random chain scission mechanism and a catalyst structure containing one equivalent of ZnCl2 per ethylene glycol repeat unit in the poly(ethylene glycol). In addition to being general for a wide variety of polyesters and polycarbonates, the catalyst system could selectively depolymerize a polyester in the presence of other commodity plastics, demonstrating how reactive distillation using the ZnCl2/PEG600 catalyst system can be used to separate mixed plastic waste.
Polyesters and polycarbonates are depolymerized using the combination of zinc dichloride and polyethylene glycol as a catalyst under reactive distillation conditions carried out at temperatures significantly below the ceiling temperature of the polymers evaluated. Selective polyester depolymerization occurred in the presence of other polymer classes, thereby demonstrating the promise for using the chemistry for the chemical recycling of plastics.
Zinc is an essential micronutrient with crucial roles in multiple facets of biological processes. Dysregulated zinc homeostasis impairs overall immune function and resultantly increases ...susceptibility to infection. Clinically, zinc supplementation is practiced for treatment of several infectious diseases, such as diarrhea and malaria. Recent focus on zinc as a beneficial element for immune system support has resulted in investigation of the immunomodulatory roles of zinc in a variety of immune cells. Besides its classical role as a cofactor that regulates the structural function of thousands of proteins, accumulating evidence suggests that zinc also acts, in a manner similar to calcium, as an ionic regulator of immune responses via participation as an intracellular messenger in signaling pathways. In this review, we focus on the role of zinc as a signaling molecule in major pathways such as those downstream of Toll-like receptors-, T cell receptor-, and cytokine-mediated signal transduction that regulate the activity and function of monocytes/macrophages and T cells, principal players in the innate and adaptive immune systems.
The association between proton pump inhibitor (PPI) use and gastric cancer related to
eradication has not been fully investigated in geographical regions with high risk of gastric cancer. We aimed to ...evaluate the association between PPIs and gastric cancer in Korea.
This study analysed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. We compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. We also analysed the incidence of gastric cancer among PPI users after
eradication.
The analysis included 11 741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI≥30 days vs non-PPI; 118/51 813 person-years vs 40/49 729 person-years; HR 2.37, 95% CI 1.56 to 3.68, p=0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In
-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI≥180 days vs non-PPI; 30/12 470 person-years vs 9/7814 person-years; HR 2.22, 95% CI 1.05 to 4.67, p=0.036).
PPI use was associated with gastric cancer, regardless of
eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.
To reconstruct an ideal full-thickness skin model, basal keratinocytes must be distributed as a confluent monolayer on the dermis. However, the currently available extrusion bioprinting method for ...the skin is limited when producing an air-exposed cellular monolayer because the cells are encapsulated within a bioink. This is the first study to use sacrificial gelatin-assisted extrusion bioprinting to reproduce a uniform and stratified epidermal layer. Experimental analyses of the rheological properties, printability, cell viability, and initial keratinocyte adhesion shows that the optimal gelatin bioink concentration is 4 wt.%. The appropriate thickness of the bioprinted gelatin structure for achieving a confluent keratinocyte layer is determined to be 400 µm. The suggested strategy generates a uniform keratinocyte monolayer with tight junctions throughout the central and peripheral regions, whereas manual seeding generates non-uniform cellular aggregates and vacancies. These results influence gene expression, exhibiting a propensity for epidermal differentiation. Finally, the gelatin-assisted keratinocytes are bioprinted onto a dermis composed of gelatin methacryloyl and dermis-derived decellularized extracellular matrix to establish a full-thickness skin model. Thus, this strategy leads to significant improvements in epidermal differentiation/stratification. The findings demonstrate that the gelatin-assisted approach is advantageous for recreating reliable full-thickness skin models with significant consistency for mass production.
Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction ...in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how uremic toxins affect cellular immunity and the mechanisms underlying pathogenesis of atherosclerosis in ESRD patients. Here, we investigated the characteristics of monocytes and CD4
T cells in ESRD patients and the immune responses induced by indoxyl sulfate (IS), a key uremic toxin, in order to explore the pathogenic effects of these cells on vascular endothelial cells. In ESRD patients, monocytes respond to IS through the aryl hydrocarbon receptor (AhR) and consequently produce increased levels of TNF-α. Upon stimulation with TNF-α, human vascular endothelial cells produce copious amounts of CX3CL1, a chemokine ligand of CX3CR1 that is highly expressed on CD4
CD28
T cells, the predominantly expanded cell type in ESRD patients. A migration assay showed that CD4
CD28
T cells were preferentially recruited by CX3CL1. Moreover, activated CD4
CD28
T cells exhibited cytotoxic capability allowing for the induction of apoptosis in HUVECs. Our findings suggest that in ESRD, IS-mediated immune dysfunction may cause vascular endothelial cell damage and thus, this toxin plays a pivotal role in the pathogenesis of CVD.
Two new Y6 derivatives of symmetrical YBO‐2O and asymmetrical YBO‐FO nonfullerene acceptors (NFAs) are prepared with a simplified synthetic procedure by incorporating octyl and fluorine substituents ...onto the terminal 2‐(3‐oxo‐2,3‐dihydro‐1H‐inden‐1‐ylidene)malononitrile (INCN) moiety. By moving the alkyl substituents on the Y6 core to the terminal INCN moiety, the lowest unoccupied molecular orbital of the YBO NFAs increases without decreasing solubility, resulting in high open‐circuit voltages of the devices. Molecular dynamics simulation shows that YBO‐2O/‐FO preferentially form core–core and terminal–terminal dimeric interactions, demonstrating their tighter packing structure and higher electron mobility than Y6, which is consistent with 2D grazing incidence X‐ray scattering and space charge limited current measurements. In blend films, the hole transfer (HT) from YBO‐2O/‐FO to the polymer donor PM6 is studied in detail by transient absorption spectroscopy, demonstrating efficient HT from YBO‐FO to PM6 with their suitable energy level alignment. Despite the simplified synthesis, YBO‐FO demonstrates photovoltaic performance similar to that of Y6, exhibiting a power conversion efficiency of 15.01%. Overall, this design strategy not only simplifies the synthetic procedures but also adjusts the electrical properties by modifying the intermolecular packing and energy level alignment, suggesting a novel simplified molecular design of Y6 derivatives.
Two acceptor–donor–acceptor‐type nonfullerene acceptors (NFAs) are prepared by moving the alkyl substituents on the Y6 core to the terminal A moiety. This design strategy significantly simplifies the synthetic process, increases the lowest unoccupied molecular orbital, and improves dimeric interactions of nonfullerene acceptor (NFA) molecules. The photoelectrical, molecular dynamics simulation, molecular packing, and charge dynamics are discussed in detail.
Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant ...E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.
Background and Aim
Association between protonpump inhibitors (PPIs) and osteoporosis, hip fractures has not been fully elucidated. We aimed to evaluate the relationship between PPIs use and the risk ...of osteoporosis and hip fractures in the databases converted to a common data model (CDM) and to compare the results across the databases.
Methods
This was a population‐based, propensity‐matched, retrospective cohort study that included patients aged ≥ 50 years who were prescribed with PPIs for over 180 days. We compared the incidence of osteoporosis and hip fractures between new PPI user and new user of other drugs using the Cox proportional hazards model and performed meta‐analysis in the electronic health record (EHR) databases.
Results
In the Korean National Health Insurance Service (NHIS)–CDM database, long‐term PPI users had greater risk of osteoporosis PPIs vs non‐PPIs groups, 28.42/1000 person‐years vs 19.29/1000 person‐years; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.22–2.15; P = 0.001. The meta‐analytic results of six EHR databases also showed similar result (pooled HR, 1.57; 95% CI, 1.28–1.92). In the analysis of hip fracture, PPI use was not significantly associated with a hip fracture in the NHIS–CDM database (PPI vs non‐PPI groups, 3.09/1000 person‐years vs 2.26/1000 person‐years; HR, 1.45; 95% CI, 0.74–2.80; P = 0.27). However, in the meta‐analysis of four EHR databases, the risk of hip fractures was higher in PPI users (pooled HR, 1.82; 95% CI, 1.04–3.19).
Conclusions
Long‐term PPI was significantly associated with osteoporosis; however, the results of hip fractures were inconsistent. Further study based on better data quality may be needed.
A novel quasi-Yagi antenna is proposed for millimeter-wave (mmWave) 5G cellular handsets operating in the 28 GHz band. The proposed antenna is designed to be compact through modification of the ...planar folded dipole topology so that it can be mounted inside a compact mobile terminal. A vertically stacked structure utilizing a multilayer printed circuit board (PCB) and via holes is applied to the antenna topology to minimize the antenna lateral width while maintaining the characteristics of the planar folded dipole antenna. A single antenna yields a <inline-formula><tex-math notation="LaTeX">-</tex-math></inline-formula>10 dB bandwidth for a return loss of 12.3% (26.3 to 29.75 GHz) and a gain of 5.51 dBi at 28 GHz. The change in beam patterns due to the chassis effect when four-element linear arrays are inserted into the upper and side edge inside the terminal is analyzed.
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