New Insights into the Discovery of Novel Drugs to Treat Human Pulmonary Adenocarcinoma

Lung cancer is one of the most prevalent cancers in the world. A cisplatin-based chemotherapy regimen is commonly used to major patients who have adenocarcinoma. Because of the limited remission rate, many patients need receive second-line treatment after receiving first-line chemotherapy. Drug screenings carried out currently are mainly from single phase. In consideration of systemic treatment, evaluation of a novel drug candidate from the point of view of first-line and second-line treatment is supposed to be important in the process of drug screening. In this review, we propose a flow of searching for new drugs, which is tailored to accommodate to first-line and second-line treatment in clinic.

MOF负载Weel抑制剂实现p53突变胆囊癌的合成致死靶向治疗

Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications.Herein,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are developed.The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment.Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality.The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity.Moreover,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.

Ultra-low threshold continuous-wave quantum dot mini-BIC lasers

Highly compact lasers with ultra-low threshold and single-mode continuous wave(CW)operation have been a long sought-after component for photonic integrated circuits(PICs).Photonic bound states in the continuum(BICs),due to their excellent ability of trapping light and enhancing light-matter interaction,have been investigated in lasing configurations combining various BIC cavities and optical gain materials.However,the realization of BIC laser with a highly compact size and an ultra-low CW threshold has remained elusive.We demonstrate room temperature CW BIC lasers in the 1310 nm O-band wavelength range,by fabricating a miniaturized BIC cavity in an InAs/GaAs epitaxial quantum dot(QD)gain membrane.By enabling effective trapping of both light and carriers in all three dimensions,ultra-low threshold of 12μW(0.052 kW cm^(-2))is achieved at room temperature.Single-mode lasing is also realized in cavities as small as only 5×5 unit cells(~2.5×2.5μm^(2) cavity size)with a mode volume of 1.16(λ/n)^(3).The maximum operation temperature reaches 70℃ with a characteristic temperature of T_(0)~93.9 K.With its advantages in terms of a small footprint,ultra-low power consumption,and adaptability for integration,the mini-BIC lasers offer a perspective light source for future PICs aimed at high-capacity optical communications,sensing and quantum information.

Influence of imidazole derivatives on the dielectric and energy storage performance of epoxy

Imidazoles are widely used as curing agents and accelerators for fabricating crosslinked epoxy materials applied in electrical and electronic fields.However,the intrinsic chemical structure of imidazole derivatives would greatly influence the polymerisation process,and further change the electrical properties,which was not emphasised.To achieve an in-depth understanding,commonly used imidazole only containing pyridine-type nitrogen and imidazole with both pyridine and pyrrole-type nitrogen were selected in this study.Electrical properties including dielectric properties,volume resistivity,breakdown strength,and especially energy storage performances were systematically investigated.We figured out that higher breakdown strength,glass transition temperature,and lower dielectric loss can be achieved with imidazole containing pyrrole-type nitrogen.Structure-induced curing mechanism diversity and the generated differences in polymer network were highlighted.With the capability to incorporate into the polymer network,the dielectric constant/loss of epoxy cured by imidazole containing pyrrole-type nitrogen is less sensitive with variation in concentration and a high breakdown strength of 577.9 MV/m was achieved.On the contrary,conspicuous decrease in the breakdown strength and increase in dielectric loss of the epoxy cured by imidazole only containing pyridine-type nitrogen were observed,especially at high concentration.Moreover,we also found that the epoxy can be fabricated into films with an attractive energy storage density/efficiency of 1.1 J/cm^(3)/97%@200 MV/m,which is twice of the commercial dielectric polypropylene film under the same electric field.