Ischemic stroke is one of the leading causes of death, and even timely treatment can result in severe disabilities. Reperfusion of the ischemic stroke region and restoration of the blood supply often ...lead to a series of cellular and biochemical consequences, including generation of reactive oxygen species (ROS), expression of inflammatory cytokines, inflammation, and cerebral cell damage, which is collectively called cerebral ischemia-reperfusion (IR) injury. Since ROS and inflammatory cytokines are involved in cerebral IR injury, injury could involve cellular senescence. Thus, we investigated whether senolytic therapy that eliminates senescent cells could be an effective treatment for cerebral IR injury. To determine whether IR induces neural cell senescence in vitro, astrocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced astrocyte senescence and senescent cells in OGD/R-injured astrocytes were effectively eliminated in vitro by ABT263, a senolytic agent. IR in rats with intraluminal middle cerebral artery occlusion induced cellular senescence in the ischemic region. The senescent cells in IR-injured rats were effectively eliminated by intravenous injections of ABT263. Importantly, ABT263 treatment significantly reduced the infarct volume and improved neurological function in behavioral tests. This study demonstrated, for the first time, that senolytic therapy has therapeutic potential for cerebral IR injury.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aims
To determine the potential association between the use of either glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) or dipeptidyl peptidase‐4 (DPP‐4) inhibitors, and the risk of thyroid cancer ...in individuals with type 2 diabetes.
Materials and Methods
This population‐based cohort study used claims data from the Korean National Health Insurance Database, 2014‐2020. Two distinct cohorts were established to compare each incretin‐based drug with sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, chosen as active comparators because of their previous non‐association with thyroid cancer, and their common usage as add‐on therapy to metformin along with GLP‐1RAs and DPP‐4 inhibitors. The first cohort included 21 722 new users of GLP‐1RAs and 326 993 new users of SGLT2 inhibitors, whereas the second cohort included 904 300 DPP‐4 inhibitor new users and 112 017 SGLT2 inhibitor new users. The outcome was the time to incident thyroid cancer. Weighted Cox proportional models were used to estimate hazard ratios of thyroid cancer incidence associated with incretin‐based drugs of interest.
Results
The use of GLP‐1RAs was not associated with an increased risk of thyroid cancer (weighted hazard ratio 0.98, 95% confidence interval 0.62‐1.53) compared with that of SGLT2 inhibitors. Using DPP‐4 inhibitors was also not associated with an increased risk of thyroid cancer (0.95, 0.79‐1.14) compared with that of SGLT2 inhibitors. No significant effect modifications were observed across subgroup analyses. Sensitivity analyses, including alternative outcome definition analysis of medullary thyroid cancer, were consistent with the primary analysis results.
Conclusions
GLP‐1RAs and DPP‐4 inhibitors were not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include ...the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea.
...HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination.
A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 95.3%; BNT162b2, n = 277 4.7%) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (
< 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age.
In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.
NALP3 inflammasome, composed of the three proteins NALP3, ASC, and Caspase-1, is a macromolecular complex responsible for the innate immune response against infection with bacterial and viral ...pathogens. Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. The assembly of the NALP3 inflammasome depends on the protein-interacting domain known as the death domain superfamily. NALP3 inflammasome is assembled via a pyrin domain (PYD)/PYD interaction between ASC and NALP3 and a caspase recruitment domain/caspase recruitment domain interaction between ASC and Caspase-1. As a first step toward elucidating the molecular mechanisms of inflammatory caspase activation by formation of inflammasome, we report the crystal structure of the PYD from NALP3 at 1.7-Å resolution. Although NALP3 PYD has the canonical six-helical bundle structural fold similar to other PYDs, the high resolution structure reveals the possible biologically important homodimeric interface and the dynamic properties of the fold. Comparison with other PYD structures shows both similarities and differences that may be functionally relevant. Structural and sequence analyses further implicate conserved surface residues in NALP3 PYD for ASC interaction and inflammasome assembly. The most interesting aspect of the structure was the unexpected disulfide bond between Cys-8 and Cys-108, which might be important for regulation of the activity of NALP3 by redox potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study was to develop a robust algorithm to quantify pulse sharpness that can complement the limitations of radial augmentation index (rAIx) and explore the role of this quantitative ...sharpness index in reflecting vascular aging or arterial stiffness. The pulse sharpness index (PSI) was developed by combining the end point angle and virtual height, and 528 radial pulses were analyzed. The PSI could be uniformly applied to various waveform morphologies, even those with no or vague tidal waves, unlike the rAIx. Significant sex differences were identified in the rAIx and PSI (P < 0.01 for both), and significant age-dependent decreases in the PSI were observed (P < 0.01). In addition, the PSI and age were correlated (r = - 0.550) at least as strong as the rAIx and age (r = 0.532), and the PSI had a significant negative correlation with arterial stiffness (r = - 0.700). Furthermore, the multiple linear regression model for arterial stiffness using the PSI, age, sex and heart rate showed the excellent performance (cross-validated R
= 0.701), and the PSI was found to have the greatest influence on arterial stiffness. This study confirmed that the PSI could be a quantitative index of vascular aging and has potential for use in inferring arterial stiffness with an advantage over the rAIx.
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Acne is a common skin condition caused by the growth of certain bacteria. Many plant extracts have been investigated for their potential to combat acne-inducing microbes, and one such plant extract ...is microwave-assisted
extract (MA-OHE). The MA-OHE was loaded onto zinc-aminoclay (ZnAC) and encapsulated in a Pickering emulsion system (MA-OHE/ZnAC PE) to evaluate its therapeutic potential against acne-inducing microbes. Dynamic light scattering and scanning electron microscopy were used to characterize MA-OHE/ZnAC PE with a mean particle diameter of 353.97 nm and a PDI of 0.629. The antimicrobial effect of MA-OHE/ZnAC was evaluated against
(
) and
(
), which contribute to acne inflammation. The antibacterial activity of MA-OHE/ZnAC was 0.1 and 0.025 mg/mL to
and
, respectively, which were close to naturally derived antibiotics. Additionally, the cytotoxicity of MA-OHE, ZnAC, and MA-OHE/ZnAC was tested, and the results showed that they had no cytotoxic effects on cultured human keratinocytes in a range of 10-100 μg/mL. Thus, MA-OHE/ZnAC is suggested to be a promising antimicrobial agent for treating acne-inducing microbes, while MA-OHE/ZnAC PE is a potentially advantageous dermal delivery system.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Over the past few decades, concentrically braced frames (CBFs) have become a commonly used load-resistant bearing system in steel structures. CBF systems have high lateral stiffness and lateral ...strength; however, they have low ductility and a low seismic energy dissipating capacity. Under seismic loading, the diagonal elements of a CBF system are susceptible to buckling, causing hysteresis in the compression zone and severely reducing energy absorption. Although steel dampers improve the hysteretic behaviour of the braces, they impose additional costs on structures. Therefore, in this study, an I-shaped steel damper with a shear yield mechanism was introduced; this is an economical solution, has a simple construction, and can be easily replaced after an earthquake. The proposed damper was evaluated numerically and parametrically. Results indicate that the proposed damper acts as a ductile fuse that prevents buckling of the diagonal element of a CBF system. It was found that both the web and flange plates contribute to the shear resistance, with the flange carrying approximately 15% of the shear force, as expressed in the presented equations. Additionally, overstrength obtained for the damper was greater than 1.5 (proposed by AISC). Necessary relations are represented to predict and design the damper and the elements outside it.
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•An innovative I-shaped link as a damper with shear mechanism is proposed.•The damper acts as a ductile fuse that prevents the nonlinear behavior of the CBF system.•Relations to design of the damper and elements outside the damper are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The development of unmanned aerial vehicles (UAVs) is expected to become one of the most commercialized research areas in the world over the next decade. Globally, unmanned aircraft have been ...increasingly used for safety surveillance in the construction industry and civil engineering fields. This paper presents an aerial image-based approach using UAVs to inspect cracks and deformations in buildings. A state-of-the-art safety evaluation method termed SMART SKY EYE (Smart building safety assessment system using UAV) is introduced; this system utilizes an unmanned airplane equipped with a thermal camera and programmed with various surveying efficiency improvement methods, such as thermography, machine-learning algorithms, and 3D point cloud modeling. Using this method, crack maps, crack depths, and the deformations of structures can be obtained. Error rates are compared between the proposed and conventional methods.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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