For conjugated macrocycles, conformational disorder plays a key role in determining whether the unique form of excitons that are fully delocalized over the cyclic framework (cyclic excitons) is ...formed by photoexcitation. We have investigated the ring size dependence of conformations and photophysical properties of macrocyclic thiophenes of varying ring sizes (C-5 N T N V ) by using single-molecule fluorescence spectroscopy. We measured modulation depth, M, values and fluorescence intensities. As the ring size increases, the correlation plots of the two parameters show bimodal distributions, revealing that larger macrocycles exhibit extremely congested linear structures. The size dependence of structural changes in macrocyclic thiophenes have been clearly confirmed by molecular dynamics simulation. The number of torsional defects from simulated structures, in conjunction with survival times from fluorescence intensity trajectories and photon coincidence measurements, demonstrated the existence of multiple acyclic chromophores in the larger macrocycles from the ground state due to complete deformation of circular structures.
Imaging-guided diagnosis and treatment of cancer hold potential to significantly improve therapeutic accuracies and efficacies. Central to this theragnostic approach has been the use of ...multicomponent-based multimodal nanoparticles (NPs). Apart from this conventional approach, here we propose a design strategy for the simple and straightforward formulation of NPs based on boron dipyrromethene (BODIPY) derivatives, LaB-
X
(
X
= H, Et, and Br). Specifically, the conjugation of lactose to the inherently hydrophobic BODIPY promoted the formation of LaB-
X
NPs in water. Furthermore, the BODIPY backbone was subjected to distyrylation, dibromination, and diethylation to tailor the optical window and the balance between fluorescence and singlet oxygen generation capabilities. We demonstrate that while the photoinduced anticancer activities of LaB-H and LaB-Et NPs were trivial, LaB-Br NPs effectively induced the apoptotic death of hepatocellular carcinoma cells under red light irradiation while allowing fluorescence cell imaging in the phototherapeutic window. This dual fluorescence photosensitizing activity of LaB-Br NPs could be switched off and on, so that both fluorescence and singlet oxygen generation were paused during NP formation in an aqueous solution, while both processes resumed after cellular uptake, likely due to NP disassembly.
Imaging-guided diagnosis and treatment of cancer hold potential to significantly improve therapeutic accuracies and efficacies.
The socioecological approach emphasises that health promotion should focus on a variety of factors that surround individuals simultaneously, yet there is little evidence on how these factors ...relatively affect physical activity (PA). The main objective was to identify relevant determinants of PA by examining the associations between factors within multilayered socioecological categories and PA. A prospective analysis was conducted with 84,052 participants participating in the accelerometer measurement from the UK Biobank. Time spent in moderate-to-vigorous PA (MVPA) was calculated from participants who wore a wrist-worn accelerometer for seven days; a questionnaire-based self-reported leisure-time physical activity was also assessed. A categorical principal component analysis was conducted to reduce the dimensions of 184 variables. The associations between principal components (PCs) and PA were evaluated using general linear models. A network of PCs was constructed to assess the comprehensive association with PA. PCs related to body composition and chronic diseases were suggested as key determinants of objectively measured MVPA and found to be clustered in the network. PCs related to body composition and socio-economic status were proposed as the key regulatory hubs in the network because they exhibited the highest level of indirect linkages with other components. In the environmental category, PCs related to greenness and air pollution were revealed to be key factors in the self-reported walking for pleasure. Using a socioecological approach, it was discovered that obesity and disease-related factors were the most important determinants, and they had an integrative influence with other factors in different categories.
•Body composition, chronic diseases, and overall health rating were proposed as the key determinants of MVPA.•Major determinants having significant effects on physical activity were clustered in the network of socioecological model.•Body composition and socioeconomic factors operated as main regulatory hubs in the network of socioecological model.•Walking for pleasure was found to be influenced by environmental factors such as greenery and air pollution.
Abstract Background Traditional open surgery for bone tumours sometimes has as a consequence an excessive removal of healthy bone tissue because of the limitations of rigid surgical instruments, ...increasing infection risk and recovery time. Methods We propose a remote robot with a 4.5‐mm diameter bendable end‐effector, offering four degrees of freedom for accessing the inside of the bone and performing tumour debridement. The preclinical studies evaluated the effectiveness, clinical scenario, and usability across 12 total surgeries–six phantom surgeries and six bovine bone surgeries. Evaluation criteria included skin incision size, bone window size, surgical time, removal rate, and conversion to open surgery. Results Preclinical studies demonstrated that the robotic approach requires significantly smaller incision size and procedure times than traditional open curettage. Conclusion This study validated the performance of the proposed system by assessing its preclinical effectiveness and optimising surgical methods using human phantom and bovine bone tumour models.
Hepatic sinusoid, the smallest vessel in the liver, plays important roles in hepatic microcirculation. Although the structure of the hepatic sinusoids affects diverse functions of the liver, little ...is known about morphological alterations in the sinusoids under pathological conditions. In this study, we show that the structure of hepatic sinusoids can be identified three-dimensionally in normal and carbon tetrachloride-injured mouse liver, using the absorption mode of synchrotron radiation micro-computed tomography. We observed that the hepatic sinusoidal structure on tomographic slice images was similar to that on histological images of normal and acutely injured mice. Moreover, centrilobular necrosis and structural alterations of the sinusoids in the necrotic region were detectable on tomographic slice and volume-rendered images of the acutely injured mice. Furthermore, quantitative analyses on 3D volume-rendered images of the injured sinusoid revealed decrease in the volume of the sinusoid and connectivity of the sinusoidal network. Our results suggest that the use of synchrotron radiation micro-computed tomography may improve our understanding of the pathogenesis of hepatic diseases by detecting the hepatic sinusoids and their alterations in three-dimensional structures of the damaged liver.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Owing to their autonomous nature, computer‐aided pronunciation training systems are regarded as a useful tool for pronunciation training for beginner‐level students, particularly those who ...feel uncomfortable having their pronunciation corrected in front of other students or who have difficulty with face‐to‐face training for other reasons. In this study, we propose a computer‐assisted pronunciation training system targeting unacceptable pronunciation due to confusion among contextual allophones, a problem that often emerges from phoneme‐based feedback provided during pronunciation training. To consider the different pronunciation of phonemes according to position, the proposed system is implemented to recommend a set of words focusing on phoneme pairs. Experimental results show that the proposed system results in the improvement of pronunciation skills through training sessions that use recommended words containing phoneme pairs that were initially pronounced incorrectly.
Abstract
The Pd‐catalyzed γ‐position
sp
3
−C−H arylation of primary amines bearing an aliphatic chain or cycloalkyl substituent and related mechanistic studies are disclosed. ...3‐Bromo‐2‐hydroxybenzaldehyde plays a key role in γ‐position
sp
3
−C−H arylation as a transient directing group (TDG) to assist the regio‐ and stereoselective C−H activation of a Pd catalyst, and the development of a tandem reaction to transform 1°‐amines into γ‐aryl‐substituted ketones demonstrates synthetic utility. Density functional theory (DFT)‐based calculations revealed the detailed reaction mechanism and the origins of the high selectivity (γ‐position and
cis
‐only). The X‐ray crystal structure of the isolated endo‐palladacycle intermediate supported the DFT results, and a kinetic isotope experiment confirmed the results of DFT calculations indicating that the C−H activation step via simultaneous palladation and deprotonation is rate‐determining.
The effects of EGCG on the selective death of cancer cells by modulating antioxidant pathways through autophagy were explored in various normal and cancer cells. EGCG positively regulated the ...p62-KEAP1-NRF2-HO-1 pathway in normal cells, while negatively regulating it in cancer cells, leading to selective apoptotic death of cancer cells. In EGCG-treated MRC5 cells (EGCG-MRC5), autophagic flux was blocked, which was accompanied by the formation of p62-positive aggregates. However, EGCG-treated HeLa cells (EGCG-HeLa) showed incomplete autophagic flux and no aggregate formation. The levels of P-ULK1 S556 and S758 increased in EGCG-MRC5 through AMPK-mTOR cooperative interaction. In contrast, EGCG treatment in HeLa cells led to AMPK-induced mTOR inactivation, resulting in abrogation of P-ULK1 S556 and S758 levels. AMPK knockout in EGCG-HeLa restored positive regulation of the p62-mediated pathway, which was accompanied by increased P-mTOR S2448 and P-ULK1 S758 levels. Knockdown of 67LR in EGCG-HeLa abolished AMPK activity but did not restore the p62-mediated pathway. Surprisingly, both AMPK knockout and 67LR knockdown in EGCG-HeLa markedly increased cell viability, despite differential regulation of the antioxidant enzyme HO-1. In conclusion, EGCG induces the selective death of cancer cells through the modulation of at least two autophagy-dependent and independent regulatory pathways: negative regulation involves the mTOR-ULK1 (S556 and S758)-p62-KEAP1-NRF2-HO-1 axis via AMPK activation, whereas positive regulation occurs through the 67LR-AMPK axis.
Display omitted
•EGCG-induced selective death of cancer cells is achieved by regulation of the p62-KEAP1-NRF2-HO-1 antioxidant pathway.•The p62-mediated antioxidant pathway is regulated along with the formation of p62-positive aggregates.•The blockade or activation of autophagy is involved in the differential activation of ULK1 via regulation of mTOR and AMPK.•EGCG-induced apoptotic cell death can also be induced by the 67LR via AMPK activation, independently of the p62 pathway.
PDF
