Search

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18 , exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC 50 values were 0.042 and 0.038 μM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC 50 = 0.446 μM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18 , which possesses significant potential for treating esophageal cancers. [Display omitted] • Compound K18 showed low nanomolar IC 50 values of 0.042 and 0.038 μM against Kyse30 and EC-109 cells. • Compound K18 inhibited tubulin polymerization (EC 50 = 0.445 μM). • Compound K18 induced YAP degradation. • Compound K18 induced the G2/M phase arrest and apoptosis in Kyse30 and EC-109 cells. [ABSTRACT FROM AUTHOR]

This study was developed based on the lateral inhibition effect and the Mach band effect. In the study, various human vision experiments involving blurred circular 3D images of different shapes were conducted under fixed brightness and contrast, and the results of those experiments are described in detail herein, with each type of display and each shape considered and discussed separately. The results show that although the maximum values of the contrast sensitivity function curves of the various displays were different, they showed minimal variations. With changes in spatial frequency, the degree of diminution of the different lines was also minimal. However, since the shape at the intersection of the contour was modified by the Mach band effect, a greater degree of variation was generated. In addition, as the Gaussian blur was increased at the intersection of the contour lines, its Mach band effect tended to decrease as the corresponding contrast sensitivity function curve changed. Summarizing the results of the various experiments on human visual characteristics, a new visual model was developed to match the model tested with the blurred circular 3D images. This model can be used as a reference for the development of artificial vision systems and technological applications in the future. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA‐135b (miR‐135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR‐135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR‐135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR‐135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR‐135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR‐135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR‐135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR‐135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR. [ABSTRACT FROM AUTHOR]

The aim of this study was to research the effects of microRNA‐10a (miR‐10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF‐TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR‐10a mimics, miR‐10a inhibitors, K252a, and miR‐10a inhibitors + K252a groups. Expressions of miR‐10a, p38, PSD95, BDNF, cAMP‐response element‐binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT‐qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit‐8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR‐10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR‐10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR‐10a mimics and K252a groups. Compared with the blank and NC group, the miR‐10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR‐10a inhibitors group presented an opposite trend to the miR‐10a mimics and K252a groups. The synapse was complete and abundant in the miR‐10a inhibitors group while disappeared in the miR‐10a mimics and K252a groups. The results indicated that miR‐10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF‐TrkB signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The anatomical basis of pituitary adenomas (PAs) with oculomotor cistern (OC) extension as a growth corridor is overlooked in the literature. In this paper, the authors use the technique of epoxy sheet plastination to study the membranous structure of the OC and validate the results by retrospective analysis of patients with OC extension. Methods: Eighteen specimens were used to study the membranous anatomy surrounding the OC using the epoxy sheet plastination technique. Thirty-four patients with OC extension were retrospectively reviewed. Results: The OC consisted of two thin membranous layers. The inner layer was extended by the arachnoid layer from the posterior fossa, and the lateral layer consisted of the dura mater sinking from the roof of the cavernous sinus. The oculomotor nerve is more likely to displace with a superolateral trajectory due to the weakness of the posterior dura and the relatively large space in the medial and posterior trajectories, which is consistent with the intraoperative observations. Among the anatomical factors that affect the PA by OC extension, we found that the relative position of the internal carotid artery (ICA) and posterior clinoid process may lead to the narrowing of the OC. Of 34 cases, 28 patients achieved total resection. Among 24 preoperative patients with oculomotor nerve palsy, 16 cases were relieved to varying degrees postoperatively. There was no ICA injury or severe intracranial infection found in any of the patients. Conclusions: Extension into the OC is influenced by two anatomical factors: a weak point in the dura in the posterior OC and a potential space beyond this region of the dura. Meticulous knowledge of the membranous anatomy in endoscopic endonasal surgery is required to safely and effectively resect PA with OC extension. [ABSTRACT FROM AUTHOR]

Abstract: In response to the rapid advancement of auto-refractor technology, most optometry shops provide refraction services. Despite their speed and convenience, the measurement values provided by auto-refractors include a significant degree of error due to psychological and physical factors. Therefore, there is a need for repetitive testing to obtain a smaller mean error value. However, even repetitive testing itself might not be sufficient to ensure accurate measurements. Therefore, research on a method of measurement that can complement auto-refractor measurements and provide confirmation of refraction results needs to be conducted. The customized optometry model described herein can satisfy the above requirements. From the existing optical technologies, using human eye measurement devices to obtain individual relevant optical feature parameters is no longer difficult. These parameters allow us to construct an optometry model for individual eyeballs. They also allow us to compute spot diagrams produced from the optometry model using the CODE V macro programming language before recognizing the geometrical spot diagram with the back-propagation neural network algorithm to obtain the accurate refractive diopter. Results show that the accuracy achieved was above 98% and that this application could significantly enhance the service quality of refraction. [Copyright &y& Elsevier]

Background: Computer vision syndrome is common and affects performance of visual tasks. Background illumination, light source, light compensation, position of the display, contrast and glare are environmental factors associated with computer vision syndrome. The aim of this study is to investigate the effects of reflected glare and visual field lighting on computer vision syndrome.Methods: In a reflected glare experiment, participants performed a two-hour visual task using a glossy, matte, or glare-free surface display in two visual environments (normal, glare). In a visual field lighting experiment, participants performed the visual task in dim lighting, uneven supplementary lighting, or uniform supplementary lighting. Visual function parameters, including critical fusion frequency, heterophoria, amplitude of accommodation and accommodative facility were evaluated by the investigators and a visual fatigue questionnaire was completed before and after the visual task. Visual performance was also recorded. In addition, the variation of pupil size under different lighting conditions was analysed.Results: Critical fusion frequency was the only visual function parameter which decreased significantly after the visual task. The questionnaire score was significantly higher in a glare environment and was lower when the task was performed using a glare-free display. Visual performance was significantly worse in the glossy display group. The increment in the questionnaire score was smaller in the uniform supplementary lighting group. Visual performance was significantly worse in the dim lighting or uneven supplementary lighting group, but not in the uniform supplementary lighting group. Variation in pupil size was significantly greater in the dim lighting condition than in the supplementary lighting condition.Conclusion: Critical fusion frequency is an effective indicator of computer vision syndrome. Glare-free displays could alleviate visual fatigue and preserve visual performance. Uniform supplementary lighting could decrease variation in pupil size and prevent eye strain. [ABSTRACT FROM AUTHOR]

Abstract Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antiproliferative activity results with IC50 values from 0.13 μM to 1.74 μM than anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote apoptosis by regulating DR5 and Bcl-2 family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site. Graphical abstract Image 1 Highlights • Molecular diversity of trimethoxyphenyl-1,2,3-triazoles was explored. • 19c inhibited colony formation against MGC803 cells at 30 nM. • 19c arrested cell cycle at G2/M phase and induced apoptosis. • 19c was a novel colchicine site tubulin polymerization inhibitor. [ABSTRACT FROM AUTHOR]

Abstract: Following the development of a digitalized image optics system, chromatic aberration has become increasingly important especially in lateral color aberration. For rear projection television L-type lens, chromatic aberration plays the significant role because it is easily seen when facing bright screen. Basically, the elimination of axial chromatic and lateral color aberration for an optical lens depends on the choice of optical glass. DLS (damped least squares), a Ray-tracing-based method, is limited, owing to its inability to identify an enhanced optical system configuration. Genetic algorithms were applied to so-called global optimization but unfortunately so far the results show little success. Additionally, L-type optics with aspherical surface might complicate optimization due to being nonlinear response during optimization. As an alternative, this research proposes a new feasible chromatic aberration optimization process by using algorithms involving theories of geometric optics in a lens, real encoding, multiple dynamic crossover and random gene mutation techniques. In this research, rear projection television lens with aspherical surface and L-type lens are mainly discussed. Results and conclusions show that attempts to eliminate difficult axial and lateral color aberration are successful. [Copyright &y& Elsevier]

On the basis and continuation of our previous studies on anti-tubulin and anti-gastric cancer agents, novel tertiary amide derivatives incorporating benzothiazole moiety were synthesized and the antiproliferative activity was studied in vitro. Preliminary structure activity relationships (SARs) were explored according to the in vitro antiproliferative activity results. Some of compounds could significantly inhibit the proliferation of three cancer cells (HCT-116, MGC-803 and PC-3 cells) and compound F10 exhibited excellent antiproliferative activity against HCT-116 cells (IC 50 = 0.182 μM), MGC-803 cells (IC 50 = 0.035 μM), PC-3 cells(IC 50 = 2.11 μM) and SGC-7901 cells (IC 50 = 0.049 μM). Compound F10 effectively inhibited tubulin polymerization (IC 50 = 1.9 μM) and bound to colchicine binding site of tubulin. Molecular docking results suggested compound F10 could bind tightly into the colchicine binding site of β-tubulin. Moreover, compound F10 could regulate the Hippo/YAP signaling pathway. Compound F10 activated Hippo signaling pathway from its very beginning MST1/2, as the result of Hippo cascade activation YAP were inhibited. And then it led to a decrease of c-Myc and Bcl-2 expression. Further molecular experiments showed that compound F10 arrested at G2/M phase, inhibited cell colony formatting and induced extrinsic and intrinsic apoptosis in MGC-803 and SGC-7901 cells. Collectively, compound F10 was the first to be reported as a new anticancer agent in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway. Image 1 • Novel tertiary amide derivatives containing benzothiazole moiety were designed and prepared. • Compound F10 displayed excellent antiproliferative activity against gastric cancer cell lines. • Compound F10 acted as a novel colchicine site tubulin polymerization inhibitor with an IC 50 value of 1.9 μM. • Compound F10 activated Hippo signaling pathway. [ABSTRACT FROM AUTHOR]

Transition metal oxides have recently been demonstrated as highly attractive anodes for high-capacity lithium ion batteries, whose electrochemical properties could be further improved through rational architecture design and incorporating reliable conductive network. Herein, mesoporous γ-Fe2O3 spheres/graphene aerogel composites were synthesized via a solvothermal pathway followed by suitable annealing. Experimental results reveal the uniform mesoporous structure and well-dispersed γ-Fe2O3 spheres with the size of 300−400 nm embedded in the mesopores of the graphene aerogel network. Compared with α-Fe2O3/graphene aerogel and pure γ-Fe2O3, the as-synthesized composite delivers, at the first cycle, a high discharging capacity of 1080 mAh g−1 at current density of 200 mA g−1. Even at much higher current density of 8000 mA g−1, satisfactory discharging capacities of 421.5 mAh g−1 can still be achieved. Upon 100 charging-discharging cycles, the specific capacity of as high as 890.5 mAh g−1 at 200 mA g−1 is maintained. The enhanced electrochemical properties could be attributed to their favorable three-dimensional graphene aerogel network, which accounts for the improved structural stability and electronic conductivity of γ-Fe2O3 during the lithiation/delithiation process. [ABSTRACT FROM AUTHOR]

• 1,2,4-Triazine scaffold was screened out from in-house structurally diverse molecular library. • Novel 1,2,4-triazine derivatives as neddylation inhibitors were discovered. • Compound V11 could block the neddylation in MGC-803 cells and inhibited NAE activity. • Among them, compound V11 exerted the most excellent anti-proliferative activities against MGC-803 cells. • Compound V11 caused cell cycle arrest at G2/M phase and induced cell apoptosis. Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our in-house library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC 50 value of 3.56 µM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed. Molecular docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC 50 value of 8.22 μM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity. [ABSTRACT FROM AUTHOR]

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC 50 = 1.02 μM), HGC-27 cells (IC 50 = 1.61 μM), SGC-7901 (IC 50 = 2.30 μM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p- c -Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents. Image 1 • Novel sulfonamide derivatives containing benzimidazole moiety were designed and prepared. • Compound 13g displayed excellent anti-proliferative activity and lower toxicity against the non-cancer cells. • Structure-activity relationship of sulfonamide derivatives was depicted. • Compound 13g caused cell cycle arrest at G2/M phase and induced cell apoptosis. • Compound 13g could down-regulate the p-Akt and p- c -Raf expression. [ABSTRACT FROM AUTHOR]

NEDDylation pathway regulates multiple physiological process, unlike inhibitors, NEDDylation activators are rarely studied. Novel amide derivatives were synthesized and evaluated for antiproliferative activity against MGC803, MCF-7 and PC-3 cells. Among them, Ⅶ-31 displayed the most potent activity with an IC 50 value of 94 nmol/L against MGC803 cells. Cellular mechanisms elucidated that Ⅶ-31 inhibited the cell viability, arrested cell cycle at G2/M phase and induced apoptosis via intrinsic and extrinsic pathways against MGC803 cells. In addition, Ⅶ-31 activated NAE1-Ubc12-Cullin1 NEDDylation via interacting with NAE1 directly. Furthermore, the activation of NEDDylation resulted in the degradation of inhibitor of apoptosis proteins (IAPs). Importantly, Ⅶ-31 inhibited tumor growth in xenograft models in vivo without the apparent toxicity. In summary, it is the first time to reveal that Ⅶ-31 deserves consideration for cancer therapy as a NEDDylation activator. Image 1 • Tertiary amides were synthesized and evaluated for their anticancer activity. • It is the first time to report a NEDDylation activator. • The NEDDylation activator inhibit gastric cancer MGC803 cells. [ABSTRACT FROM AUTHOR]