Stress-induced adaptations in nucleus accumbens dopamine D1 receptor-expressing cells correspond to social avoidance behavior in male mice.

Licochalcone A (LA) (CAS no. 58749-22-7), molecular formula CHO, is a pharmacologically significant flavonoid primarily isolated from . LA is historically regarded as a by-product during glycyrrhizic acid extraction, but LA has witnessed substantial pharmacological advancements in recent years. It exhibits potent inhibitory effects on the proliferation of carcinoma (e.g., hepatocellular carcinoma, breast, and colon cancer). Although extensive data indicate that the bioactivity of LA is mediated through diverse signaling pathways (e.g., PI3K/Akt/mTOR, MDM2, P53, p38, caspase-3-dependent apoptosis, and MAPK), its precise mechanism of action remains elusive. Additionally, like other flavonoids/flavones, LA possesses suboptimal pharmacokinetic properties, including poor aqueous solubility, low bioavailability, limited permeability, and instability, despite favorable organic solubility. These inherent weaknesses significantly restrict its widespread clinical implementation, underscoring an urgent need for sophisticated delivery strategies to harness its therapeutic potential while circumventing these limitations. Malignant obstructive jaundice predominantly affects elderly patients and is commonly caused by primary liver cancer, cholangiocarcinoma, metastatic carcinoma, or pancreatic carcinoma compressing or invading the biliary tract. Notably, colorectal cancer liver metastases (CRCLMs) represent another major cause of malignant biliary obstruction. The liver is the predominant site of hematogenous metastasis in colorectal cancer, with 15%–25% of patients presenting with synchronous liver metastases at diagnosis and an additional 15%–25% developing metachronous metastases after curative resection of the primary tumor. Critically, hilar or perihilar metastatic lesions can directly compress the common bile duct or hepatic ducts, leading to obstructive jaundice that is clinically indistinguishable from that caused by primary biliary malignancies and frequently necessitates biliary stenting. This leads to biliary stenosis/obstruction, cholestasis, and markedly elevated serum bilirubin levels, resulting in severe hepatic dysfunction and related symptoms. With rising incidence of biliary malignancies, the disease significantly impairs patients’ physical and mental well-being and activities of daily living. Clinically, biodegradable biliary stents have been increasingly used for the treatment of both malignant and benign biliary obstructions, and these stents can be further functionalized by loading therapeutic agents to enhance treatment efficacy. Research demonstrates that percutaneous transhepatic biliary drainage (PTBD) combined with stent implantation effectively reduces total serum bilirubin, improves liver function, prolongs survival, minimizes perioperative tissue damage, and accelerates postoperative recovery, leading to its widespread international adoption. While biliary stents offer advantages such as low reintervention rates and cost-effectiveness, their clinical utility is limited by complications including biliary sludge deposition, biofilm formation, and tumor ingrowth, which cause lumen obstruction, stent dysfunction, and reduced patency duration. Addressing these limitations requires strategies to alleviate obstruction and extend stent patency. Various synthetic coatings—encompassing organic, metallic, and inorganic formulations—have been engineered to prevent stent obstruction. Nevertheless, these monolithic coatings demonstrate limited efficacy in satisfying the multifarious demands imposed by the harsh luminal microenvironment. For instance, while the polyvinyl benzyl chloride-D-glucaro-1,4-lactonate polymer (PVBC-DGL) coating effectively impedes biliary sludge deposition, it lacks additional bifunctionality. Furthermore, our prior research developed a poly (trimethylene carbonate) (PTMC) blended with covalent organic frameworks (COFs) coating demonstrating antifouling properties; however, its deficiency in antitumor efficacy constrained clinical applicability. Therefore, extending the functional longevity of these implants while concurrently enhancing their bioactivity presents a formidable challenge pivotal to advancing clinical translation.