Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness ...the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC
values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.
Plant diseases pose a significant challenge for food production and safety. Therefore, it is indispensable to correctly identify plant diseases for timely intervention to protect crops from massive ...losses. The application of computer vision technology in phytopathology has increased exponentially due to automatic and accurate disease detection capability. However, a deep convolutional neural network (CNN) requires high computational resources, limiting its portability. In this study, a lightweight convolutional neural network was designed by incorporating different attention modules to improve the performance of the models. The models were trained, validated, and tested using tomato leaf disease datasets split into an 8:1:1 ratio. The efficacy of the various attention modules in plant disease classification was compared in terms of the performance and computational complexity of the models. The performance of the models was evaluated using the standard classification accuracy metrics (precision, recall, and F1 score). The results showed that CNN with attention mechanism improved the interclass precision and recall, thus increasing the overall accuracy (>1.1%). Moreover, the lightweight model significantly reduced network parameters (~16 times) and complexity (~23 times) compared to the standard ResNet50 model. However, amongst the proposed lightweight models, the model with attention mechanism nominally increased the network complexity and parameters compared to the model without attention modules, thereby producing better detection accuracy. Although all the attention modules enhanced the performance of CNN, the convolutional block attention module (CBAM) was the best (average accuracy 99.69%), followed by the self-attention (SA) mechanism (average accuracy 99.34%).
Three-dimensional (3D) printing is increasingly being utilized in the dental field. After fabricating a prosthesis using a 3D printed resin, a post-curing process is required to improve its ...mechanical properties, but there has been insufficient research on the optimal post-curing conditions. We used various 3D printed crown and bridge materials in this study, and evaluated the changes in their properties according to post-curing time by evaluating the flexural strength, Weibull modulus, Vickers hardness, color change, degree of conversion, and biocompatibility. The obtained results confirmed that the strength of the 3D printed resin increased when it was post-cured for 60–90 min. The Vickers hardness, the degree of conversion, and biocompatibility of the 3D printed resins increased significantly around the beginning of the post-curing time, and then increased more gradually as the post-curing time increased further. It was observed that the color tone also changed as the post-curing time increased, with some groups showing a ΔE00 value of ≥ 2.25, which can be recognized clinically. This study has confirmed that, after the printing process of a 3D printed resin was completed, a sufficient post-curing time of at least 60 min is required to improve the overall clinical performance of the produced material.
YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. ...However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.
Three-dimensional (3D) printing technology is highly regarded in the field of dentistry. Three-dimensional printed resin restorations must undergo a washing process to remove residual resin on the ...surface after they have been manufactured. However, the effect of the use of different washing solutions and washing times on the biocompatibility of the resulting resin restorations is unclear. Therefore, we prepared 3D-printed denture teeth and crown and bridge resin, and then washed them with two washing solutions (isopropyl alcohol and tripropylene glycol monomethyl ether) using different time points (3, 5, 10, 15, 30, 60, and 90 min). After this, the cell viability, cytotoxicity, and status of human gingival fibroblasts were evaluated using confocal laser scanning. We also analyzed the flexural strength, flexural modulus, and surface SEM imaging. Increasing the washing time increased the cell viability and decreased the cytotoxicity (
< 0.001). Confocal laser scanning showed distinct differences in the morphology and number of fibroblasts. Increasing the washing time did not significantly affect the flexural strength and surface, but the flexural modulus of the 90 min washing group was 1.01 ± 0.21 GPa (mean ± standard deviation), which was lower than that of all the other groups and decreased as the washing time increased. This study confirmed that the washing time affected the biocompatibility and mechanical properties of 3D printed dental resins.
Efficient techniques for developing latent fingerprints are invaluable resources to solve crimes. In this work, we developed a fluorescent molecular rotor probe that responds to hydrophobic and ...viscous environments and visualizes latent fingerprints with level 3 details. We believe that the simple and convenient features of LFP-1 will benefit forensic practice.
While cyberbullying shares characteristics with face-to-face bullying, there is a uniqueness of online interaction that makes it more pervasive and the impact longer-lasting. Cyberbullying should be ...understood within a broader context of online activities and how adolescents perceive of what is permissible in the online space. This study investigated the relationship between levels of online activities and cyberbullying behavior, while examining the moderating impact of netiquette. Communication with parents, age, gender and location were also considered. A face-to-face survey was conducted on a nationally representative sample of 12 to 15year-old adolescents (N=1200) in South Korea during April and May, 2013. The results show that frequent users of the Internet and SNS are more likely to engage in, become victims of and witness cyberbullying behavior. On the other hand, studying online, netiquette, and communication time with parents were negatively correlated to cyberbullying behavior. Knowing the mechanism of social interaction online and the awareness about the consequences of their behavior are important factors that shape young people's online behavior. This suggests that a more proactive approach to prevent and mitigate negative behavior online is needed. The results add to the knowledge that informs cyberbullying prevention methods.
•A survey on 12-15 year-olds’ cyberbullying behavior was conducted in Korea.•Frequent internet use is correlated to online bullying, victimization and witnessing.•Information activities on the internet increases cyberbullying behavior.•Netiquette, studying online, parent-interaction reduce cyberbullying behavior.•Knowledge of online interaction mechanism shapes adolescents’ online misbehavior.
Recent advances in three-dimensional (3D) printing have introduced new materials that can be utilized for dental restorations. Nonetheless, there are limited studies on the color stability of ...restorations using 3D-printed crowns and bridge resins. Herein, the color stability of conventional computer-aided design/computer-aided manufacturing (CAD/CAM) blocks and 3D-printing resins was evaluated and assessed for their degrees of discoloration based on material type, colorant types (grape juice, coffee, curry, and distilled water (control group)), and storage duration (2, 7, and 30 days) in the colorants. Water sorption, solubility, and scanning electron microscope (SEM) analyses were conducted. A three-way ANOVA analysis showed that all three factors significantly affected the color change of the materials. Notably, the discoloration (ΔE00) was significantly higher in all 3D printing resins (4.74–22.85 over the 30 days) than in CAD/CAM blocks (0.64–4.12 over the 30 days) following immersion in all colorants. 3D-printing resins showed color differences above the clinical limit (2.25) following storage for 7 days or longer in all experimental groups. Curry was the most prominent colorant, and discoloration increased in almost all groups as the storage duration increased. This study suggests that discoloration must be considered when using 3D printing resins for restorations.
This study aimed to isolate the proteolytic fraction from the silkworm thorn fruit (
) through ethanol precipitation at different ratios, and to determine its proteolytic activity and optimal ...activity conditions. Furthermore, the hydrolysis characteristics and antioxidant activity of soy protein isolate (SPI) and whey protein concentrate (WPC) hydrolyzates obtained through the enzymatic hydrolysis of freeze-dried silkworm thorn fruit powder (SF) were evaluated. For isolation and partial purification of proteolytic fraction, the water-solubilized fraction of the silkworm thorn fruit was purified through ethanol precipitation at four different ratios of 1:1, 1:2, 1:4, and 1:6 (
). The protein recovery rate, caseinolytic activity, protein pattern, and optimal activity (pH, temperature, and inhibitors) of fractional ethanol precipitate obtained from the silkworm thorn fruit (ESF) were evaluated. The proteolytic fraction obtained from silkworm thorn fruit exhibited a major protein band around 65-70 kDa and showed the highest proteolytic activity at a 1:4 ratio of ethanol precipitation (
< 0.05). The optimal activity of the measured enzyme fraction was determined to be at pH 9.0 and 50 °C, and the proteolytic activity of ESF was almost inhibited by phenyl methyl sulphonyl fluoride (PMSF, 2 mM), a serine protease inhibitor. Compared to Alcalase and papain, extensively used as commercial enzymes, the silkworm thorn fruit powder was less effective in hydrolyzing SPI and WPC. Nevertheless, SPI and WPC hydrolyzates mediated with silkworm thorn fruit powder showed even better antioxidant activities than those mediated with Alcalase and papain. Thus, our results show the potential application of silkworm thorn fruit as a novel source of plant protease for producing human-grade protein hydrolyzates.
This study analyzed the surface roughness and waviness, Vickers hardness (VHN), and color changes of six types of 3D printed resins and computer-aided design/computer-aided manufacturing (CAD/CAM) ...materials after artificial toothbrushing. The average surface roughness height (Ra) change of Formlabs denture teeth A2 resin (FMLB) was not significant between after artificial toothbrushing (0.17 ± 0.02 μm and 0.17 ± 0.05 μm, respectively; mean ± standard deviation). However, the Ra value increased significantly in all remaining groups. Regarding waviness, polymethylmethacrylate (PMMA) had the largest increases in average waviness height (Wa) and maximum surface waviness height (Wz) between, before (0.43 ± 0.23 μm and 0.08 ± 0.02 μm), and after (8.67 ± 4.03 μm, 1.30 ± 0.58 μm) toothbrushing. There were no significant changes in Wa for Formlabs denture teeth A2 resin (FMLB) and NextDent C&B (NXT). After artificial toothbrushing, the dispersed-filler composite (DFC) group had the largest color difference (ΔE, of 2.4 ± 0.9), and the remaining materials had smaller changes than the clinical acceptance threshold of ΔE = 2.25. The VHN of FMLB and NXT were 9.1 ± 0.4 and 15.5 ± 0.4, respectively, and were not affected by artificial toothbrushing. The flexural strengths of the 3D printed materials were 139.4 ± 40.5 MPa and 163.9 ± 14.0 MPa for FMLB and NXT, respectively, which were similar to those of the polycarbonate and PMMA groups (155.2 ± 23.6 MPa and 108.0 ± 8.1 MPa, respectively). This study found that the evaluated 3D printed materials had mechanical and optical properties comparable to those of CAD/CAM materials and were stable even after artificial toothbrushing and hydrothermal aging.
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