Discovery and biological evaluation of 6-aryl-4-(3,4,5-trimethoxyphenyl)quinoline derivatives with promising antitumor activities as novel colchicine-binding site inhibitors.

Tubulin, as the fundamental unit of microtubules, is a crucial target in the investigation of anticarcinogens. The synthesis and assessment of small-molecule tubulin polymerization inhibitors remains a promising avenue for the development of novel cancer therapeutics. Through an analysis of reported colchicine-binding site inhibitors (CBSIs) and tubulin binding models, a set of 6-aryl-4-(3,4,5-trimethoxyphenyl)quinoline derivatives were meticulously crafted as potential CBSIs. Notably, compound 14u exhibited potent anti-proliferative efficacy, displaying IC50 values ranging from 0.03 to 0.18 µM against three human cancer cell lines (Huh7, MCF-7, and SGC-7901). Mechanistic investigations revealed that compound 14u could disrupt tubulin polymerization, dismantle the microtubule architecture, arrest the cell cycle at G2/M phase, and induce apoptosis in cancer cells. Furthermore, compound 14u demonstrated significant inhibition of tumor proliferation in vivo with no discernible toxicity in the Huh7 orthotopic tumor model mice. Additionally, physicochemical property predictions indicated that compound 14u adhered well to Lipinski's rule of five. These findings collectively suggest that compound 14u holds promise as an antitumor agent targeting the colchicine-binding site on tubulin and warrants further investigation.

Strategies for the development of stimuli-responsive small molecule prodrugs for cancer treatment.

Approved anticancer drugs typically face challenges due to their narrow therapeutic window, primarily because of high systemic toxicity and limited selectivity for tumors. Prodrugs are initially inactive drug molecules designed to undergo specific chemical modifications. These modifications render the drugs inactive until they encounter specific conditions or biomarkers in vivo, at which point they are converted into active drug molecules. This thoughtful design significantly improves the efficacy of anticancer drug delivery by enhancing tumor specificity and minimizing off-target effects. Recent advancements in prodrug design have focused on integrating these strategies with delivery systems like liposomes, micelles, and polymerosomes to further improve targeting and reduce side effects. This review outlines strategies for designing stimuli-responsive small molecule prodrugs focused on cancer treatment, emphasizing their chemical structures and the mechanisms controlling drug release. By providing a comprehensive overview, we aim to highlight the potential of these innovative approaches to revolutionize cancer therapy.

Integrated influence of sulfide modification on the reactivity of nanoscale zero-valent iron towards decabromodiphenyl ether under an electromagnetic field.

Individual application of sulfide modification and electromagnetic field (EMF) can enhance the reactivity of nanoscale zero-valent iron (nZVI), yet the potential of both in combination is not clear. This work found that the reactivity of nZVI towards decabromodiphenyl ether was significantly enhanced by the combined effect of sulfidation and EMF. The specific reaction rate constant of nZVI increased by 7 to 10 times. A series of characterization results revealed that the sulfidation level not only affects the inherent reactivity but also the magnetic-induced heating (MIH) and corrosion (MIC) of nZVI. These collectively influence the degradation efficiency of nZVI under EMF. Sulfidation generally diminished the MIH effect. The low degree of sulfidation (S/Fe = 0.1) slightly reduced the MIC effect by 21.4%. However, the high degree of sulfidation (S/Fe = 0.4) led to significantly enhanced MIC effect by 107.1%. For S/Fe = 0.1 and 0.4, the overall enhancement in the reactivity resulting from EMF was alternately dominated by the contributions of MIH and MIC. This work provides valuable insights into the MIH and MIC effects about the sulfidation level of nZVI, which is needed for further exploration and optimization of this combined technology.

Trends and predictions in the physical shape of Chinese preschool children from 2000 to 2020.

Objective: To explore physical shape changes in preschool children from 2000 to 2020, and forecast development trends over the next 10 years. Method: The grey GM (1,1) prediction model was used to fit the physical shape indicators of preschool children in China from 2000 to 2020, and then the longitudinal change trend of physical shape was compared and analyzed. Finally, the development trend of physical shape in China in 2025 and 2030 was predicted. Results: (1) During the period from 2000 to 2020, the height, weight and chest circumference of Chinese preschool children all increased rapidly. Specifically, the weight of male and female children increased by 1.8 kg and 1.6 kg, their chest circumference increased by 1.6 cm and 1.5 cm, respectively, and both their heights increased by 3.6 cm. Among these indicators, the older the age, the greater the growth rate. It is expected that all the indicators will continue to grow rapidly over the next 10 years, but the growth rate will slow. (2) From 2000 to 2020, the growth rate of weight was higher than that of height, and BMI showed an increasing trend. The obesity detection rates in boys and girls increased by 5.6 and 2.8%, respectively. Over the next 10 years, the incidence of obesity is expected to increase by 3.8% in boys and 2.8% in girls. (3) Improvement in the growth and development of preschool children in China has a certain correlation with the rapid growth of China's economy,less physical activity, education and other factors. Conclusion: Over the past 20 years, the growth and nutritional status of Chinese preschoolers have improved dramatically, but overweight and obesity remain. Overweight and obesity rates are expected to continue to increase rapidly over the next 10 years, particularly among boys, and effective measures should be taken to control the obesity epidemic.

The Establishment of the Cut-off Value of Weight-for-Height for Preschool Children in China and an Empirical Study on the Influence of Overweight and Obesity on Physical Performance.

Background: We aimed to establish the cut-off value of weight-for-height for preschool children in China, and to explore the influence of overweight and obesity on the physical performance of preschool children. Methods: Data from 31 provinces in China monitored in 2010 and 2014, the standard deviation unit curves of WFH were established by using GAMLSS (generalized additive model for location, scale, and shape) method preschool children in China, and then the cut-off values of normal weight, overweight and obesity were divided. The research group tested 5 physical performance indicators of 5154 preschool children from April 2018 to June 2019 in Beijing and Zhejiang in China. We then compared physical performance differences between the normal-weight group and the overweight-obesity group. Results: A smooth and effective standard deviation unit curve of WFH was established. The overweight and obesity of Chinese preschool children were at a high level. Being overweight and obese reduced preschool children's relative strength, speed, sensitivity, coordination, and balance ability, but did not reduce preschool children's flexibility. In general, the physical performance of preschool children in the normal weight group was better than that in the overweight and obesity group. Conclusion: It is suggested to use the WFH criteria in this study to evaluate overweight and obesity in Chinese preschool children, and strengthen physical activity and take in energy substances properly of preschool children, to control the spread of overweight and obesity, to improve physical performance level.