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Mer and c-Met kinases, which are commonly overexpressed in various tumors, are ideal targets for the development of antitumor drugs. This study focuses on the design, synthesis, and evaluation of several 2-substituted aniline pyrimidine derivatives as highly potent dual inhibitors of Mer and c-Met kinases for effective tumor treatment. Compound 18c emerged as a standout candidate, demonstrating robust inhibitory activity against Mer and c-Met kinases, with IC50 values of 18.5 ± 2.3 nM and 33.6 ± 4.3 nM, respectively. Additionally, compound 18c displayed good antiproliferative activities on HepG2, MDA-MB-231, and HCT116 cancer cells, along with favorable safety profiles in hERG testing. Notably, it exhibited exceptional liver microsomal stability in vitro, with a half-life of 53.1 min in human liver microsome. Compound 18c also exhibited dose-dependent cytotoxicity and hindered migration of HCT116 cancer cells, as demonstrated in apoptosis and migration assays. These findings collectively suggest that compound 18c holds promise as a dual Mer/c-Met agent for cancer treatment. [ABSTRACT FROM AUTHOR]

Intensive aquaculture combatting the decline of large yellow croaker populations can trigger bacterial outbreaks, resulting in extensive antibiotic use. In this study, we screened 5 aquaculture sites in the coastal areas of Zhejiang and identified 17 antibiotics in large yellow croakers using UPLC-MS/MS. The distribution and occurrence of antibiotic pollutants were different in the different tissues of large yellow croakers, being primarily dominated by quinolones. Relatively higher average residue levels of enrofloxacin and ciprofloxacin were detected in the inedible parts, specifically the gills (37.29 μg/kg). Meanwhile, relatively high average residue levels of enrofloxacin and ciprofloxacin were also found in the edible parts, particularly in the muscle (23.18 μg/kg). We observed that the residue levels detected in the swim bladder exceeded the prescribed limit for fish muscle, but there is currently no specific regulatory limit established for this particular tissue. Despite the HI values of enrofloxacin and ciprofloxacin being below 0.01, the health risks should not be disregarded. The findings of this research provide significant practical implications for assessing antibiotic contamination and enhancing the risk management of coastal regions. [ABSTRACT FROM AUTHOR]

Detecting and controlling illegal websites (gambling and pornography sites) through illegal domain names has been an unsolved problem. Therefore, how to mine and discover potential illegal domain names in advance has become a current research hotspot. This paper studies a method of generating illegal domain names based on the character similarity of domain name structure. Firstly, the K-means algorithm classified illegal domain names with similar structures. Then, put the classified clusters into the adversarial generative network for training. Finally, through a specific result verification method, the experiment shows that the average concentration of the generation algorithm is 23.82%, the effective concentration is 63.54%, and the expansion rate is 7.5. By comparing the results with the enumeration algorithm, the generation algorithm has greatly improved in terms of generation efficiency and accuracy. [ABSTRACT FROM AUTHOR]

A large number of domains are abused every day for cybercrime. At the same time, the fight against abusive domains is not the fight of one person or organization but a battle that requires the cooperation of the entire community. However, very little research has been done to quantify the positive benefits of this strategy for dealing with abusive domains. As a result, using pornography and gambling domain names as examples, we present the first empirical study evaluating the usability and effectiveness of all Internet entities (e.g., registrars and hosting providers) in the DNS ecosystem for receiving and handling abusive domain reports. First, the paper thoroughly demonstrates the mechanisms for receiving and handling abusive domain reports at various Internet entities in China. Second, we select and report the appropriate 2433 abusive domains to 43 service providers across six categories of Internet entities. Finally, we discover the methods and response time used by each Internet entity to handle abuse reports based on the changes in reported domains. Based on the above data, we analyze and evaluate the effectiveness of Internet entities in dealing with abusive domains. Moreover, we indicate the scope of protection and disadvantages of each method, i.e., whether the abusive domain can escape handling. The paper aims to provide a more detailed overview and reference for the security communities, service providers, and Internet entities concerned with dealing with abusive domains. [ABSTRACT FROM AUTHOR]