Gastric cancer (GC) is a common form of malignant cancer in worldwide which has a poor prognosis. Despite recent improvements in the treatment of GC, the prognosis is not yet satisfactory for GC ...patients. CYT997, a novel microtubule-targeting agent, recently has been identified to be a promising anticancer candidate for the treatment of cancers; however, the effects of CYT997 in GC remain largely unknown.
Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry. The mitochondrial ROS were detected by confocal microscope and flow cytometry. Gastric cancer patient-derived xenograft (PDX) model was used to evaluate its antitumor activity of CYT997 in vivo.
CYT997 inhibited gastric cancer cell proliferation and induced cell apoptosis and triggered autophagy. CYT997 induced apoptosis through triggering intracellular mitochondrial ROS generation in GC cells. ROS scavengers N-acetylcysteine (NAC) and Mitoquinone (MitoQ) distinctly weakened CYT997-induced cell cycle G2/M arrest and apoptosis in GC cells. Pretreatment with autophagy inhibitor 3-MA promoted the effect of CYT997 on cells apoptosis. Mechanistically, CYT997 performed its function through regulation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in GC cells. In addition, CYT997 inhibited growth of gastric cancer patient-derived xenograft (PDX) tumors.
CYT997 induces autophagy and apoptosis in gastric cancer by triggering mitochondrial ROS accumulation to silence JAK2/STAT3 pathway. CYT997 might be a potential antitumor drug candidate to treat GC.
Thermal barrier coatings (TBCs) can effectively protect the alloy substrate of hot components in aeroengines or land-based gas turbines by the thermal insulation and corrosion/erosion resistance of ...the ceramic top coat. However, the continuous pursuit of a higher operating temperature leads to degradation, delamination, and premature failure of the top coat. Both new ceramic materials and new coating structures must be developed to meet the demand for future advanced TBC systems. In this paper, the latest progress of some new ceramic materials is first reviewed. Then, a comprehensive spalling mechanism of the ceramic top coat is summarized to understand the dependence of lifetime on various factors such as oxidation scale growth, ceramic sintering, erosion, and calcium-magnesium-aluminium-silicate (CMAS) molten salt corrosion. Finally, new structural design methods for high-performance TBCs are discussed from the perspectives of lamellar, columnar, and nanostructure inclusions. The latest developments of ceramic top coat will be presented in terms of material selection, structural design, and failure mechanism, and the comprehensive guidance will be provided for the development of next-generation advanced TBCs with higher temperature resistance, better thermal insulation, and longer lifetime.
O6‐Corona3arene3tetraazines, a new class of macrocyclic compounds, were synthesized efficiently in a one‐pot reaction from the nucleophilic aromatic substitution reaction between 1,4‐dihydroxybenzene ...derivatives and 3,6‐dichlorotetrazine in warm acetonitrile. In the crystalline structure, the resulting macrocycles adopt highly symmetric structures of a regular hexagonal cavity with all bridging oxygen atoms and tetrazine rings located on the same plane with phenylene units orthogonally orientated. The constitutional aromatic rings are able to rotate around the macrocyclic annulus, depending on the steric effect of the substituents and temperature, in solution. The electron‐deficient nature revealed by cyclic voltammetry, differential pulse voltammetry, and characteristic absorbances at a visible region show the O6‐corona3arene3tetrazines to be suitable macrocyclic receptors for electron‐rich guests.
To crown it all: A novel class of functionalized macrocycles consisting of oxygen‐bridged 1,4‐arylene and 3,6‐tetrazinylene units was synthesized efficiently in a one‐pot reaction, and they adopted unique corona‐like structures with large hexagonal cavities. The macrocycles have tunable electronic properties and provide powerful molecular hosts which could find many applications in supramolecular chemistry.
Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations ...in a large Chinese general population to inform future Chinese ESCC screening guidelines.
We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models.
We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women.
This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.
: Integrin β3 is one of the main integrin heterodimer receptors on the surface of cardiac myocytes. Our previous studies showed that hypoxia induces apoptosis and increases integrin β3 expression in ...cardiomyocytes. However, the exact mechanism by which integrin β3 protects against apoptosis remains unclear. Hence, the present investigation aimed to explore the mechanism of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis.
: Stable cells and
acute and chronic heart failure rat models were generated to reveal the essential role of integrin β3 in cardiomyocyte proliferation and apoptosis. Western blotting and immunohistochemistry were employed to detect the expression of integrin β3 in the stable cells and rat cardiac tissue. Flow cytometer was used to investigate the role of integrin β3 in hypoxia-induced cardiomyocyte apoptosis. Confocal microscopy was used to detect the localization of integrin β3 and integrin αv in cardiomyocytes.
: A cobaltous chloride-induced hypoxic microenvironment stimulated cardiomyocyte apoptosis and increased integrin β3 expression in H9C2 cells, AC16 cells, and cardiac tissue from acute and chronic heart failure rats. The overexpression of integrin β3 promoted cardiomyocyte proliferation, whereas silencing integrin β3 expression resulted in decreased cell proliferation
. Furthermore, knocking down integrin β3 expression using shRNA or the integrin β3 inhibitor cilengitide exacerbated cobaltous chloride-induced cardiomyocyte apoptosis, whereas overexpression of integrin β3 weakened cobaltous chloride-induced cardiomyocytes apoptosis. We found that integrin β3 promoted cardiomyocytes proliferation through the regulation of the PTEN/Akt/mTOR and ERK1/2 signaling pathways. In addition, we found that knockdown of integrin αv or integrin β1 weakened the effect of integrin β3 in cardiomyocyte proliferation.
: Our findings revealed the molecular mechanism of the role of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis, providing new insights into the mechanisms underlying myocardial protection.
Macrophages, associated with their heterogenous and dynamic polarization status, actively shape the development of renal fibrosis (RF). In this study, we revealed the significance of a signalling ...axis, circular RNA ACTR2 (circACTR2)/miR‐200c/Yes‐associated protein (YAP), in regulating macrophage polarization and the development of RF. A unilateral urethral obstruction (UUO)‐induced RF model was established in vivo. In vitro, interferon‐γ (IFNγ) and interleukin (IL)‐4 were applied to induce M1 and M2 polarization, respectively. The abundance of M1 and M2 macrophages were examined by immunofluorescence (IF) or flow cytrometry on markers specific for each subtype. Expressions of circACTR2, miR‐200c and YAP were measured by quantitative real‐time‐polymerase chain reaction and/or Western blotting. Interactions between circACTR2, miR‐200c and YAP were examined by combining luciferase assay, RNA immunoprecipitation and IF. Impact of targeting circACTR2 on RF and macrophage polarization was also examined in vivo. UUO‐induced RF was associated with increased M1 and M2 macrophages, up‐regulations of circACTR2 and YAP and the down‐regulation of miR‐200c in the obstructed kidney. circACTR2 was essential for IL‐4‐induced M2 polarization, but not IFNγ‐induced M1 polarization. This activity of circACTR2 was mediated by sponging miR‐200c and activating the downstream YAP signalling. In vivo, knocking down circACTR2 boosted miR‐200c expression, reduced YAP level, lowered M2 macrophages in obstructed kidney and ameliorated UUO‐induced RF. circACTR2, by targeting and sponging miR‐200c, activates YAP signalling, stimulates M2 macrophage polarization and promotes the development of RF. Therefore, targeting circACTR2 may benefit the treatment of RF.
circACTR2 is up‐regulated renal fibrosis, and circACTR2 promotes the development of renal fibrosis by increasing M2 macrophage polarization. Mechanistically, circACTR2 promotes YAP into the nucleus and activates YAP signaling by targeting and sponging miR‐200c, thereby increasing the expression of M2 biomarkers including CD206, Arg‐1, Fizz‐1, and IL‐10.
Background
Subtle cognitive decline (SCD) is considered the early stage of Alzheimer's disease (AD) and is of great clinical significance for the prevention and treatment of AD. The ankle‐brachial ...index (ABI) has been reported to be associated with cognitive impairment; however, there are few studies on the relationship between ABI and SCD.
Methods
From August 2019 to April 2021, subjects were recruited to participate in a cognitive function test at the Shanghai Sixth People's Hospital. Based on the test results, 217 patients with SCD were selected as the experimental group and 259 patients with normal cognitive function were selected as the control group. The data of the two groups were compared, and the correlation between the ABI and cognitive decline was analyzed.
Results
There were significant differences in age, sex, smoking status, hypertension, diabetes, triglycerides, serum creatinine, and ABI (p < .05)between the two groups. Logistic regression analysis showed that age, hypertension, diabetes, and ABI influenced cognitive decline(p < .05). After correcting for other factors, ABI was independently related to cognitive decline. Pearson's correlation analysis showed that a low ABI (<0.9) had a significant effect on memory and visual space of the cognitive domain (p < . 05).
Conclusions
ABI is significantly associated with SCD and may be a critical tool to predict early cognitive decline.
A total of 217 cases with subtle cognitive decline were selected as the experimental group and 259 cases with normal cognitive test as the control group. The data of the two groups were compared, and the correlation between ABI and cognitive decline was analyzed. The results indicate ABI is associated with subtle cognitive decline and may be used to predict early cognitive decline.
Studies have shown that the expression of CD133, leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5), and ATP binding cassette (ABC)G2 proteins is associated with malignancy and poor ...prognosis in colon cancer. However, molecular regulation mechanism of the three proteins has not been elucidated. Here, we report that microRNA-142-3p (miR-142-3p) inhibits the expression of CD133, Lgr5, and ABCG2 in colon cancer cells by binding to both the 3′-untranslated region and the coding sequences of the three genes. The miR-142-3p was markedly decreased in colon cancer specimens, in which it was negatively correlated with the expression of CD133, Lgr5, and ABCG2. Reduction of miR-142-3p corresponds to poor differentiation and bigger tumor size in colon cancers. Moreover, miR-142-3p levels were reduced in cells that formed spheres compared to cells that were cultured in regular media. Transfection of miR-142-3p mimics in colon cancer cells downregulated cyclin D1 expression, induced G
1
phase cell cycle arrest, and elevated the sensitivity of the cells to 5-fluorouracil. Furthermore, OCT4 suppressed miR-142-3p, and hypomethylation of the
OCT4
promoter was associated with a reduction in miR-142-3p. Finally, the miR-142-3p inhibited the growth of colon cancer cells in vivo, which was accompanied by the downregulation of CD133, Lgr5, and ABCG2 in tumor tissues. Our results elucidate a novel regulation pathway in colon cancer cells and suggest a potential therapeutic approach for colon cancer therapy.
•We fabricate a metal–insulator–metal capacitive humidity sensor.•The functional sensing polymer comprises TiO2 nanoparticles.•The polymer is subjected to inductive plasma and reactive-ion ...etching.•This increases the sensor sensitivity, stability, and performance.•Our sensor is useful for temperature-independent applications.
We propose a high-performance porous metal–insulator–metal-type capacitive humidity sensor based on a functional polymer mixed with TiO2 microparticles subjected to inductively coupled plasma (ICP) and reactive-ion etching (RIE) treatments. The humidity sensor is composed of a porous top electrode, a TiO2-containing functional polymer humidity-sensitive layer subjected to two types of oxygen plasma treatment, a bottom electrode, and a glass substrate. The initial O2 ICP dry-etching utilizes higher intensity plasma for deep etching in the inlet holes on the top electrode to increase the contact area and shorten the vapor absorption path, thereby yielding high sensitivity and low hysteresis. Further, the RIE treatment leads to roughening of the polymer etching surface and further improving the performance of the humidity sensor. The functional polymer mixed with TiO2 microparticles exhibits excellent hysteresis over a wide humidity sensing range. The fabricated sensors are tested at various relative humidity (RH) values, achieving an ultra-low hysteresis of 0.64% RH at 60% RH, a high sensitivity of 1.24pF/% RH, a fast response time of less than 25s, good temperature dependence, and a stable capacitance value with a maximum error rate of 0.15% over 120h of continuous testing.
Renal fibrosis is the characteristic of all kinds of chronic kidney diseases (CKDs). Fascin-1 plays an important role in tumor development, but the roles of fascin-1 in renal fibrosis have not been ...studied. Here, we explored the role of fascin-1 in renal fibrosis and the potential mechanisms.
Kidney unilateral ureteral obstruction (UUO) mouse model was used as an in vivo model, and proximal tubule epithelial cell lines treated with TGF-β1 were used as in vitro model of renal fibrosis. Cell transfection was performed to manipulate the expression of miR-200b/c, fascin-1 and CD44. Western blotting, qRT-PCR, immunohistochemistry or immunofluorescence assays were used to measure levels of miR-200b/c, fascin-1, CD44, and fibrosis and EMT-related markers. H&E and Masson stainings were used to examine the degree of injury and fibrosis in kidneys. Dual luciferase assay was used to examine the interaction between miR-200b/c family and fascin-1.
Fascin-1 and CD44 levels were both significantly up-regulated while miR-200b/c family was reduced in models of renal fibrosis. Furthermore, overexpression of miR-200b/c family and inhibition of fascin-1 or CD44 ameliorated renal fibrosis through suppressing EMT process. Mechanistically, miR-200b/c family directly and negatively regulated the expression of fascin-1. Overexpression of fascin-1 could reverse the effects of miR-200b/c family on renal fibrosis, and fascin-1 regulated renal fibrosis by activating CD44.
Our study is the first to show that fascin-1 plays a critical role in renal fibrosis. MiR-200b/c family could inhibit renal fibrosis through modulating EMT process by directly targeting fascin-1/CD44 axis.
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