Selumetinib overcomes gefitinib primary and acquired resistance by regulating MIG6/STAT3 in NSCLC

Xiaoping Song,Lina Wang,Wei Tang,Luyao Yuan,Qingchao Liu,Jing Li,Daidi Fan 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.12

Gefitinib, as the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has achieved great advances in the treatment of non-small cell lung cancer (NSCLC), but drug resistance will inevitably occur. Therefore, exploring the resistance mechanism of gefitinib and developing new combination treatment strategies are of great importance. In our study, the results showed that selumetinib (AZD6244) synergistically inhibited the proliferation of NSCLC with gefitinib. Selumetinib also enhanced gefitinib-induced apoptosis and migration inhibition ability in gefitinib-resistant lung cancer cell lines. Subsequently, the negative regulation between MIG6 and STAT3 was observed and verified through the STRING database and western blotting assays. Sustained activation of STAT3 was significantly downregulated when co-treatment with selumetinib in gefitinib-resistant cells. However, the downregulation of p-STAT3, resulting from the combination of selumetinib and gefitinib was counteracted by the deletion of MIG6, suggesting that selumetinib enhanced gefitinib sensitivity by regulating MIG6/STAT3 in NSCLC. In contrast, p-STAT3 was further inhibited after treatment with gefitinib and selumetinib when MIG6 was overexpressed. Furthermore, the combined administration of selumetinib and gefitinib effectively promoted the sensitivity of lung cancer xenografts to gefitinib in vivo, and the tumor inhibition rate reached 81.49%, while the tumor inhibition rate of the gefitinib monotherapy group was only 31.95%. Overall, MIG6/STAT3 negative regulation plays an important role in the sustained activation of STAT3 and the resistance to EGFR-TKIs. Our study also suggests that EGFR-TKIs combined with MEK1/2 inhibitors, such as selumetinib, may be beneficial to those NSCLC patients who develop a primary or acquired resistance to EGFR-TKIs, providing theoretical support for combining TKIs and selumetinib in clinical cancer treatment.

Stress analysis model for un-bonded umbilical cables

Chen, Xiqia,Fu, Shixiao,Song, Leijian,Zhong, Qian,Huang, Xiaoping Techno-Press 2013 Ocean systems engineering Vol.3 No.2

For the optimization design and strength evaluation of the umbilical cable, the calculation of cross section stress is of great importance and very time consuming. To calculate the cross section stress under combined tension and bending loads, a new integrated analytical model of umbilical cable is presented in this paper. Based on the Hook's law, the axial strain of helical components serves as the tensile stress. Considering the effects of friction between helical components, the bending stress is divided into elastic bending stress and friction stress. For the former, the elastic bending stress, the curvature of helical components is deduced; and for the latter, the shear stress before and after the slipping of helical components is determined. This new analytical model is validated by the experimental results of an umbilical cable. Further, this model is applied to estimate the extreme strength and fatigue life of the umbilical cable used in South China Sea.

Compound heterozygous mutations of NDUFV1 identified in a child with mitochondrial complex I deficiency

Tang Xiaojun,Xu Wuhen,Song Xiaozhen,Ye Haiyun,Ren Xiang,Yang Yongchen,Zhang Hong,Wu Shengnan,Lan Xiaoping 한국유전학회 2022 Genes & Genomics Vol.44 No.6

Background: Mitochondrial complex I deficiency (MCID) is the most common biochemical defect identified in childhood with mitochondrial diseases, mainly including Leigh syndrome, encephalopathy, macrocephaly with progressive leukodystrophy, hypertrophic cardiomyopathy and myopathy. Objective: To identify genetic cause in a patient with early onset autosomal recessive MCID. Methods: Trio whole-exome sequencing was performed and phenotype-related data analyses were conducted. All candidate mutations were confirmed by Sanger sequencing. Results: Here we report a child of Leigh syndrome presented with global developmental delay, progressive muscular hypotonia and myocardial damage. A missense mutation c.118C > T (p.Arg40Trp) and a previously reported mutation c.1157G > A (p.Arg386His) in NDUFV1 have been identified as compound heterozygous in the patient. The mutation p.Arg386His is closely associated with the impairment of 4Fe-4S domain and this mutation has been reported pathogenic. The c.118C > T mutation has not been reported in ClinVar and HGMD database. In silico protein analyses showed that p.Arg40 is highly conserved in a wide range of species, and the amino acid substitution p.Trp40 largely decreases the stability of NDUFV1. In addition, the mutation has not been detected in the Asian populations and it was predicted to be deleterious by numerous prediction tools. Conclusion: This research expands the mutation spectrum of NDUFV1 and substantially provides an early and accurate diagnosis basis of MCID, which would benefit subsequently effective genetic counseling and prenatal diagnosis for future reproduction of the family.

The Formation of Magnetite Nanoparticle in Ordered System of the Soybean Lecithin

Li, Tiefu,Deng, Yingjie,Song, Xiaoping,Jin, Zhixiong,Zhang, Ying Korean Chemical Society 2003 Bulletin of the Korean Chemical Society Vol.24 No.7

A method of preparation of magnetite nanoparticles in ordered systems, as in vesicle and microemulsion, consisting of soybean lecithin and water has been introduced. The size of magnetite grain was controlled by the content of soybean lecithin and size of liposomes in the systems. It was found by experiment that magnetite nanoparticles were formed inside the double layer vesicles. The magnetite nanoparticles were separated by magnetic separation and centrifugation and the dispersion of the magnetite nanoparticles prepared at 10% (w/w) soybean lecithin was particularly stable. The formation of pure magnetite nanoparticles was confirmed by analyses of XRD and electron diffraction pattern.

Excessive Daytime Sleepiness and Insomnia Symptoms in Adolescents With Major Depressive Disorder: Prevalence, Clinical Correlates, and the Relationship With Psychiatric Medications Use

Yudong Shi,Wei Li,Changhao Chen,Xiaoping Yuan,Yingying Yang,Song Wang,Zhiwei Liu,Feng Geng,Jiawei Wang,Xiangfen Luo,Xiangwang Wen,Lei Xia,Huanzhong Liu 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.11

Objective Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD.Methods The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12–18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma’anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity.Results The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027–1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028–1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199–3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052–3.633), suicide attempts (OR=1.765, 95% CI=1.037–3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523–2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196–0.952).Conclusion EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.

School Consolidation: Whither China’s Rural Education?

Hong Mei,Quanbao Jiang,Yuanyuan Xiang,Xiaoping Song 한국사회복지학회 2015 Asian Social Work and Policy Review Vol.9 No.2

The School Consolidation Policy in the 1990s significantly impacted Chinese rural compulsory education and Chinese rural communities. Although this policy has been involved in many negative news reports, there is a lack of scientific research on it. To address the research gap, this paper first delineates the evolution of this policy, which was formed to balance the disparity between urban and rural education, accelerated by rural financial reformation and aborted due to various emerging problems. It then discusses the educational problems caused by the policy including misallocated resources, poor quality, rising costs, student safety issues, high dropout rate, and lost rural culture heritage. Through the analyses, this paper provides a clear picture of the development of Chinese rural education, and offers implications for improving educational policy, promoting educational quality, and securing educational rights of students in rural China.

Improved cycling performance of polypyrrole coated potassium trivanadate as an anode for aqueous rechargeable lithium batteries

Najeeb ur Rehman Lashari,Mingshu Zhao,Jun Wang,XINHAI HE,Irfan Ahmed,Miao Miao Liang,Songpon Tangsee,Xiaoping Song 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.108 No.-

The energy storage properties of layered metal vanadate, especially alkali metal vanadates have beenextensively studied. Metal vanadates have a more robust electrochemical output in contrast with pristinevanadium oxides. However, the detailed processes underlying the efficiency contrast of vanadates andvanadium oxides have rarely been studied. Herein a facile hydrothermal and low-temperature polymerizationmethod was introduced to synthesize KV3O8 and KV3O8@PPy nanowire bundles as anode materialfor an aqueous rechargeable Lithium batteries. The nanowires are composed of KV3O8·0.59H2O calculatedusing thermal gravimetric analysis (TGA). Successfully synthesized layered vanadium based KV3O80.59H2O (KVO) and KV3O8 0.59H2O@PPy (KVO@PPy) nanowires and investigated the source of theimproved electrochemical efficiency of PPy coated potassium vanadates compared to pristine KVO usingcrystal structure analysis and electrochemical tests. We demonstrated increase in electrochemical stabilityfor KVO@PPy caused by synergistic effect of K+ in vanadate nanowires and PPy coating. In KVO theoxygen atoms have close contact with the K ions, and the stable K+ serve as ‘‘pillars” between interlayersto shield the layered structures from collapse during the charge/discharge phase, while the PPy reducescharge transfer resistance. This research adds helps us design better electrode materials to be used as ananode material for ARLB using alkali metal vanadate.