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Aurora kinase A (AURKA) carries out an essential role in proliferation and involves in cisplatin resistance in various cancer cells. Overexpression of AURKA is associated with the poor prognosis of cancer patients. Thus, AURKA has been considered as a target for cancer therapy. Developing AURKA inhibitors became an important issue in cancer therapy. A natural compound emodin mainly extracted from rhubarbs possesses anti‐cancer properties. However, the effect of emodin on AURKA has never been investigated. In the present study, molecular docking analysis indicated that emodin interacts with AURKA protein active site. We also found nine emodin analogues from Key Organic database by using ChemBioFinder software. Among that, one analogue 8L‐902 showed a similar anti‐cancer effect as emodin. The bindings of emodin and 8L‐902 on AURKA protein were confirmed by cellular thermal shift assay. Furthermore, emodin inhibited the AURKA kinase activity in vitro and enhanced the cisplatin‐DNA adduct level in a resistant ovarian cancer cell line. It seems that emodin may have the potential to inhibit cancer cell growth and enhance cisplatin therapy in cancer with resistance. Collectively, our finding reveals a novel AURKA inhibitor, emodin, which may be vulnerable to ovarian cancer therapy in the future. [ABSTRACT FROM AUTHOR]

In this study, the microwave dielectric properties of La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramics prepared by the conventional solid-state method had been investigated for application in mobile communication. B2O3 was selected as a liquid sintering aid to reduce the sintering temperature of La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramics. It was found that with 0.25 wt% B2O3 additive, the X-ray diffraction patterns of the La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramics exhibited no significant phase difference at different sintering temperatures from 1350 to 1500°C. The maximum values of the dielectric constant and the quality factor (Q × f) could be obtained when the La2.98/3Sr0.01(Mg0.5Sn0.5)O3 with 0.25 wt% B2O3 additive were sintered at 1450°C for 4h. The temperature coefficient of resonant frequency τf (-77.0 ppm/°C) was measured of La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramics with 0.25 wt% B2O3 sintered at 1450°C for 4 h. [ABSTRACT FROM AUTHOR]

Abstract: The microwave dielectric properties of La2.98/3Ba0.01(Mg0.5Sn0.5)O3 ceramics prepared by the conventional solid-state method were investigated for application in mobile communication. A 100°C reduction of the sintering temperature was obtained by using CuO as a sintering aid. A dielectric constant of 20.0, a quality factor (Q × f) of 50,100GHz and a temperature coefficient of resonant frequency τ f of −78.3ppm/°C were obtained when La2.98/3Ba0.01(Mg0.5Sn0.5)O3 ceramics with 0.25wt.% CuO were sintered at 1500°C for 4h. [ABSTRACT FROM AUTHOR]

Abstract: The microwave dielectric properties of La(1−2x/3)Sr x (Mg0.5Sn0.5)O3 ceramics were examined with a view to their exploitation for mobile communication. The La(1−2x/3)Sr x (Mg0.5Sn0.5)O3 ceramics were prepared by the conventional solid-state method with various sintering temperatures. The X-ray diffraction peaks of the La(1−2x/3)Sr x (Mg0.5Sn0.5)O3 ceramics shifted to lower angles as x increased from 0 to 0.05. The X-ray diffraction patterns of the La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramics revealed no significant variation of phase with sintering temperatures. A maximum density of 6.56g/cm3 was obtained for La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramic, sintered at 1550°C for 4h. A dielectric constant (ɛ r ) of 20.0 and a product of quality factor and resonant frequency (Q × f) of 57,100GHz and a temperature coefficient of resonant frequency (τ f ) of −77ppm/°C were obtained for La2.98/3Sr0.01(Mg0.5Sn0.5)O3 ceramics that were sintered at 1550°C for 4h. [ABSTRACT FROM AUTHOR]

Bladder cancer poses a significant challenge to chemotherapy due to its resistance to cisplatin, especially at advanced stages. Understanding the mechanisms behind cisplatin resistance is crucial for improving cancer therapy. The enzyme glutathione S‐transferase omega class 1 (GSTO1) is known to be involved in cisplatin resistance in colon cancer. This study focused on its role in cisplatin resistance in bladder cancer. Our analysis of protein expression in bladder cancer cells stimulated by secretions from tumor‐associated macrophages (TAMs) showed a significant increase in GSTO1. This prompted further investigation into the role of GSTO1 in bladder cancer. We found a strong correlation between GSTO1 expression and cisplatin resistance. Mechanistically, GSTO1 triggered the release of large extracellular vesicles (EVs) that promoted cisplatin efflux, thereby reducing cisplatin–DNA adduct formation and enhancing cisplatin resistance. Inhibition of EV release effectively counteracted the cisplatin resistance associated with GSTO1. In conclusion, GSTO1‐mediated EV release may contribute to cisplatin resistance caused by TAMs in bladder cancer. Strategies to target GSTO1 could potentially improve the efficacy of cisplatin in treating bladder cancer. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo . Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.

DNA damage responses contribute to cisplatin resistance; however, therapeutic strategies to overcome cisplatin resistance have not yet been established. Here, we demonstrate that inhibition of ATR-Chk1 pathway with the potent inhibitor WYC0209 sensitizes bladder cancer cells to cisplatin. In the clinical microarray profile, high ATR expression is associated with poor prognosis in bladder cancer patients who receive chemotherapy. We show that pharmacological and genetic suppressing of ATR sensitized cells to cisplatin. Treatment with WYC0209 or siATR increased levels of cisplatin-DNA adducts, concomitant with decreased levels of p-glycoprotein expression. Additionally, Combinations of cisplatin and WYC0209 show synergistic activity against bladder cancer. Ultimately, WYC0209 enhanced the anti-tumor effects of cisplatin and suppressed p-glycoprotein expression in bladder cancer xenografts. These results indicate that inhibiting ATR-Chk1 activation with WYC0209 suppresses p-glycoprotein expression and increases cisplatin activity in bladder cancer. Our findings collectively suggest that ATR-Chk1 is a target for improving the efficacy of cisplatin in bladder cancer.