Notes

E-cigarette esmoking fluids and the flavors substance cinnamaldehyde perturb bone fragments, cartilage material as well as vascular boost zebrafish embryos.
The present work reports the synthesis and investigation by semi-empirical Density Functional Theory (DFT), physical chemistry, and spectroscopic methods of two dithiocarbazates, 2-acetylpyridine-S-p-bromobenzyl-dithiocarbazate (HL1) and 2-acetylpyridine-S-p-nitrobenzyl-dithiocarbazate (HL2) and their Cu(II) complexes, [Cu(L1)Cl] (1), [Cu(L1)Br] (2), [Cu(L2)Cl] (3) and [Cu(L2)Br] (4). Single crystal X-ray analyzes showed distorted square planar geometry to the metal centers, which tridentate ligands coordinated by the NNS system and an additional halogen (Cl- or Br-) to complete the coordination sphere. Mass spectrometry data indicated the presence of [Cu(L1)(DMF)]+ and [Cu(L2)(DMF)]+, due to the exchanging of chloride/bromide ions and characteristic fragmentations of the compounds. The DFT composite method B97-3c was employed to optimize the geometries of ligands and complexes and IR spectra were calculated revealing good agreement with experimental data. Hydrogen bonds and π⋅⋅⋅π stacking interactions upon the molecular packing were investigated by Hirshfeld surface and fingerprint plots with the main interactions attributed to the H⋅⋅⋅H contacts. The biological activity of the dithiocarbazates and their Cu(II) complexes were evaluated in vitro against the human glioma U251 cells. Results revealed that the free dithiocarbazates present great in vitro antitumor activity that is increased after the complexation with copper. The measurement of cytotoxicity of the compounds showed biological activity in a low range of concentration, which indicates high efficiency as potential drugs.Modifying the foot progression angle during walking can reduce the knee adduction moment, a surrogate measure of medial knee loading. However, not all individuals reduce their knee adduction moment with the same modification. This study evaluates whether a personalized approach to prescribing foot progression angle modifications increases the proportion of individuals with medial knee osteoarthritis who reduce their knee adduction moment, compared to a non-personalized approach. Individuals with medial knee osteoarthritis (N=107) walked with biofeedback instructing them to toe-in and toe-out by 5° and 10° relative to their self-selected angle. We selected individuals' personalized foot progression angle as the modification that maximally reduced their larger knee adduction moment peak. Additionally, we used lasso regression to identify which secondary kinematic changes made a 10° toe-in gait modification more effective at reducing the first knee adduction moment peak. Seventy percent of individuals reduced their larger knee adduction moment peak by at least 5% with a personalized foot progression angle modification, which was more than (p≤0.002) the 23-57% of individuals who reduced it with a uniformly assigned 5° or 10° toe-in or toe-out modification. When toeing-in, greater reductions in the first knee adduction moment peak were related to an increased frontal-plane tibia angle (knee more medial than ankle), a more valgus knee abduction angle, reduced contralateral pelvic drop, and a more medialized center of pressure in the foot reference frame. In summary, personalization increases the proportion of individuals with medial knee osteoarthritis who may benefit from a foot progression angle modification.In this paper, the solution method for foot arch index (FAI) based on plantar force measurement was proposed. The entire pelma (EP) was divided into three partitions posterior heel (HP), lateral side of the sole (SL) and medial side of the sole (SM) according to the three-point support mechanics mechanism of the foot and ankle. A distributed force platform was established to obtain the mean positions of the center of pressure (CoP) trajectories on SL, SM, HP, and EP, which were defined as A, B, C, and O, respectively. Based on the principle that the arch height influences the distance from point O to the boundary of triangle ABC, the area ratio of triangle BOC to triangle ABC was defined as FAI. Arch height index (AHI) measurement of thirty participants by combined calipers was compared with FAI measurement of their right feet. The arches were classified based on AHI, and ANOVA was performed. The Pearson correlation coefficient between the FAI method and the AHI method is 0.79 (p＜0.0001). The Bland-Altman analysis showed good agreement. ANOVA indicated FAI was statistically significant (F = 18.81,p＜0.001), and there were statistical differences between groups. These results suggest that the proposed distributed force measurement method can provide support surface boundary (triangle ABC) information related to point O.Low back joint compression forces have been linked to the development of chronic back pain. Back-support exoskeletons controllers based on low back compression force estimates could potentially reduce the incidence of chronic pain. However, progress has been hampered by the lack of robust and accurate methods for compression force estimation. Electromyography (EMG)-driven musculoskeletal models have been proposed to estimate lumbar compression forces. Nonetheless, they commonly underrepresented trunk musculoskeletal geometries or activation-contraction dynamics, preventing validation across large sets of conditions. Here, we develop and validate a subject-specific large-scale (238 muscle-tendon units) EMG-driven musculoskeletal model for the estimation of lumbosacral moments and compression forces, under eight box-lifting conditions. Ten participants performed symmetric and asymmetric box liftings under 5 and 15 kg weight conditions. EMG-driven model-based estimates of L5/S1 flexion-extension moments displayed high correlation, R2 (mean range 0.88-0.94), and root mean squared errors between 0.21 and 0.38 Nm/kg, with respect to reference inverse dynamics moments. Model-derived muscle forces were utilized to compute lumbosacral compression forces, which reached eight times participants body weight in 15 kg liftings. For conditions involving stooped postures, model-based analyses revealed a predominant decrease in peak lumbar EMG amplitude during the lowering phase of liftings, which did not translate into a decrease in muscle-tendon forces. During eccentric contraction (box-lowering), our model employed the muscle force-velocity relationship to preserve muscle force despite significant EMG reduction. Our modeling methodology can inherently account for EMG-to-force non-linearities across subjects and lifting conditions, a crucial requirement for robust real-time control of back-support exoskeletons.Alzheimer's disease (AD) is characterized by progressive cognitive impairment and mental behavior. The combination inhibition of two essential AD targets, acetylcholinesterase (AChE) and glycogen synthase kinase-3β (GSK-3β), might be a breakthrough in the discovery of therapeutic success. Herein, 17 β-carboline-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their AChE and GSK-3β inhibitory potential. The results indicated that compound 21 has the most potent inhibition against eeAChE (IC50 = 0.20 ± 0.02 μM), hAChE (IC50 = 0.34 ± 0.01 μM) and GSK-3β (IC50 = 1.14 ± 0.05 μM) among these compounds. In addition, it inhibited hAChE in a mixed type manner and could occupy the binding pocket forming diverse interactions with the target of AChE and GSK-3β. Moreover, compound 21 showed low cytotoxicity against SH-SY5Y and HepG2 cell lines and good BBB permeability. Compound 21 also attenuated the tau hyperphosphorylation in the Tau (P301L) 293T cell model. The ADME projection exhibited that compound 21 has acceptable physicochemical characteristics. This study provides new leads for the assessment of AChE and GSK-3β dual inhibition as a promising strategy for AD treatment.Three series of novel 1-aryl-3-(4-methylsulfonylphenyl) pyrazole derivatives were synthesized, characterized by several spectroscopic techniques, and investigated as potential anti-inflammatory and anticancer agents. The biological evaluation showed that almost all the synthesized compounds have significant potency and selectivity for the COX-2 enzyme over COX-1 with noticeable anti-inflammatory activity compared to celecoxib and indomethacin. Accordingly, compounds 8a, 8b, 8e, 8j, 8l, 9a, 9b, 9c, and 10b showed the best COX-2 inhibition (IC50 ranged from 0.059 to 0.079 µM) with good anti-inflammatory activity (% of edema inhibition ranged from 87.9 to 67.5). Moreover, compound 8b possessed the highest selectivity index regarding COX-2 isozyme (SI = 211) in comparison to celecoxib (SI = 312) with good in vivo anti-inflammatory activity (% edema inhibition = 77.70 after 5 h). Also, compounds 8a, 8b, 8j, 8l, and 9a showed ulcerogenic liability and histopathological changes close to celecoxib. Molecular docking ry activity and good anti-inflammatory activity with minimal ulcerogenic effect as well as potent anticancer activity.From the anti-inflammatory screening of Formosan Lauraceous plants, the methanolic extract of the root of Machilus zuihoensis var. mushaensis stood out for its potent inhibitory activity toward superoxide anion and elastase release in human neutrophils. Bioassay-guided fractionation of the root of M. zuihoensis var. mushaensis led to eight new compounds, including two butanolides (1-2), five lignanoids (3-7), and one sesquiterpenoid (8), along with 50 known compounds (9-58). Structures of these compounds were elucidated by NMR, UV, IR, CD, and MS analyses. Thirty-two isolates were evaluated for their anti-inflammatory activity. Among them, 9, 20, 27, 28, 30, 31, 35, and 40 exhibited significant superoxide anion generation inhibition selectively (IC50 value less then 7.4 μM), 15 and 19 showed selective inhibition toward elastase release (IC50 value less then 8.0 μM). Moreover, 3, 16, 21, and 22 simultaneously displayed superoxide anion generation and elastase release inhibition. It is worth mentioning that 21 and 22 showed more potent inhibitory activities (IC50 less then 1.0 μM) on superoxide anion than the positive control, LY294002. Further quantitative HPLC analysis indicated the content of 21 and 22 were 0.90 and 3.04 mg/g (w/w) in the ethyl-acetate layer of the root of M. zuihoensis var. mushaensis, respectively. Altogether, M. zuihoensis var. mushaensis revealed a potential for developing the botanical new drug against inflammation-related disease.A series of novel nitric oxide (NO)-releasing 5,8-quinolinedione/furoxan hybrids (8a-h and 9a-h) were designed and synthesized through coupling different alkanolamine substituted phenylsulfonyl furoxan with 5,8-quinolinedione. Most compounds displayed high cytotoxic activity against drug-sensitive/-resistant cancer cells. Metabolism inhibitor In particular, the IC50 of 9a (0.42 µM) was about 9-fold lower than that of β-lap (3.69 µM) and 12-fold lower than that of SAHA (5.24 µM) in drug-resistant cancer cells. Also, 9a was demonstrated to selectively inhibit the growth of Bel7402/5-FU cancer cells. Mechanistic studies demonstrated that 9a could serve as an NO donor and nicotinamide quinone oxidoreductase 1 (NQO1) inhibitor (IC50 = 0.8 µM), which could induce the highest level of NO and reactive oxygen species (ROS) in Bel-7402/5-FU cancer cells. Furthermore, 9a could promote tumor cell apoptosis and autophagy via regulation of apoptosis-related protein (Bax, Bcl-2, and Caspase 3) and autophagy-associated proteins (LC3 and p62) in Bel-7402/5-FU cells.
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