Targeted therapy of RET fusion-positive non-small cell lung cancer

Lung cancer has very high morbidity and mortality worldwide, and the prognosis is not optimistic. Previous treatments for non-small cell lung cancer (NSCLC) have limited efficacy, and targeted drugs for some gene mutations have been used in NSCLC with considerable efficacy. The RET proto-oncogene is located on the long arm of chromosome 10 with a length of 60,000 bp, and the expression of RET gene affects cell survival, proliferation, growth and differentiation. This review will describe the basic characteristics and common fusion methods of RET genes; analyze the advantages and disadvantages of different RET fusion detection methods; summarize and discuss the recent application of non-selective and selective RET fusion-positive inhibitors, such as Vandetanib, Selpercatinib, Pralsetinib and Alectinib; discuss the mechanism and coping strategies of resistance to RET fusion-positive inhibitors

Full 360° Terahertz Dynamic Phase Modulation Based on Doubly Resonant Graphene–Metal Hybrid Metasurfaces

Dynamic phase modulation is vital for tuneable focusing, beaming, polarisation conversion and holography. However, it remains challenging to achieve full 360° dynamic phase modulation while maintaining high reflectance or transmittance based on metamaterials or metasurfaces in the terahertz regime. Here, we propose a doubly resonant graphene–metal hybrid metasurface to address this challenge. Simulation results show that by varying the graphene Fermi energy, the proposed metasurface with two shifting resonances is capable of providing dynamic phase modulation covering a range of 361° while maintaining relatively high reflectance above 20% at 1.05 THz. Based on the phase profile design, dynamically tuneable beam steering and focusing were numerically demonstrated. We expect that this work will advance the engineering of graphene metasurfaces for the dynamic manipulation of terahertz waves

Identification of key phenolic compounds responsible for antioxidant activities of free and bound fractions of blackberry varieties' extracts by boosted regression trees

Free fractions of different blackberry varieties extracts are high in phenolic compounds with antioxidant activities. However, the phenolic profiles and antioxidant activities against peroxyl radicals of bound fractions of different blackberry varieties extracts have not been previously reported. In addition, what are the key antioxidant phenolic compounds in free and bound fractions of blackberry extracts remain unknown. The present study aimed to investigate the phenolic profiles and antioxidant activities of free and bound fractions of eight blackberry varieties extracts and reveal the key antioxidant phenolic compounds by boosted regression trees.Results: Fifteen phenolics (three anthocyanins, four flavonols, three phenolic acids, two proanthocyanidins, and three ellagitannins) were identified in blackberry by UPLC-Q-TOF-MS. Ferulic acid, ellagic acid, procyanidin C1, kaempferol-O-hexoside, ellagitannins hex, and gallic acid were major bound phenolics. Bound fractions of eight blackberry varieties extracts were high in phenolics and showed great antioxidant activity. Boosted regression trees analysis showed that cyanidin-3-O-glucoside and chlorogenic acid were the most significant compounds, contributing 48.4 % and 15.9 % to the antioxidant activity of free fraction, respectively. Ferulic acid was the mostsignificant antioxidant compound in bound fraction with a contribution of 61.5%. Principal component analysis showed that Kiowa was the best among the eight varieties due to its phenolic profile and antioxidant activity.Conclusion: It was concluded that blackberry varieties contained high amounts of bound phenolics, which confer health benefits through reducing oxidative stress. Ferulic acid was key compound to explain the antioxidant activities of bound fractions.Fil: Gong, Er Sheng. Gannan Medical University; ChinaFil: Li, Bin. Shenyang Agricultural University; ChinaFil: Li, Binxu. Shenyang Agricultural University; ChinaFil: Podio, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Chen, Hongyu. Shanghai Academy Of Agricultural Science; ChinaFil: Li, Tong. Cornell University; Estados UnidosFil: Sun, Xiyun. Shenyang Agricultural University; ChinaFil: Gao, Ningxuan. Shenyang Agricultural University; ChinaFil: Wu, Wenlong. Jiangsu Province And Chinese Academy Of Sciences; ChinaFil: Yang, Tianran. South China University Of Technology; ChinaFil: Xin, Guang. Shenyang Agricultural University; ChinaFil: Tian, Jinlong. Shenyang Agricultural University; ChinaFil: Si, Xu. Shenyang Agricultural University; ChinaFil: Liu, Changjiang. Shenyang Agricultural University; ChinaFil: Zhang, Jiyue. Shenyang Agricultural University; ChinaFil: Liu, Rui Hai. Cornell University. Department of Food Science & Technology; Estados Unido

The Association between Leukocyte and Its Subtypes and Benign Breast Disease: The TCLSIH Cohort Study

Inflammation plays a crucial role in the formation of benign breast disease. Given the limited study to explore the association between leukocyte as an indicator of immune system and benign breast disease, we used data from a large cross-sectional study to investigate association between leukocyte and its subtypes and benign breast disease among women in the general population. The data were derived from baseline data of the Tianjin chronic low-grade systemic inflammation and health (TCLSIH) cohort study during 2014 and 2016. Breast thickness and nodules status were assessed by using ultrasonography. Leukocyte and its subtype counts were carried out using the automated hematology analyzer. Multiple logistic regression analysis was used to examine the association between leukocyte and its subtypes and prevalence of benign breast disease. In the present study, the prevalence of benign breast disease was 20.9%. After adjustments for potentially confounding factors, the odds ratios (95% confidence interval) for benign breast disease across lymphocyte quintiles were as follows: 1.00 (reference), 0.99 (0.82, 1.2), 0.85 (0.69, 1.04), 0.84 (0.68, 1.02), and 0.75 (0.61, 0.92) (P for trend = 0.002). An inverse association between lymphocyte counts and benign breast disease was found, but leukocyte and other subtypes have nothing to do with benign breast disease. Further prospective studies are needed to determine the findings