Tao Suo

Nitinol (NiTi) stents are widely used for biliary decompression, but their biofluid‐exposed metallic surfaces remain susceptible to mechanical irritation, bacterial colonization, sludge deposition, and inflammation‐associated restenosis. Inspired by the dynamic, low‐adhesion interfacial function of the native glycocalyx, we developed a self‐assembled slippery liquid‐infused porous surface (SASLIPS) for NiTi biliary stents. The modified surface formed a continuous liquid‐infused architecture, exhibited water sliding angles E. coli adhesion and biofilm formation, and attenuated inflammatory responses, while preserving macroscopic thermally induced shape recovery. Molecular dynamics simulations supported favorable interactions between perfluorooctyltrichlorosilane (PFOTS) and perfluorodecalin (PFD) and showed that the PFD‐rich interfacial region reduced water and cholesterol access to the modeled substrate. In a porcine study with independent 1‐ and 6‐month cohorts, SASLIPS‐coatedstents showed 89.92% lower sludge‐associated autofluorescence than bare NiTi stents at 1 month and no gross evidence of luminal obstruction at the 6‐month retrieval. This work established a liquid‐infused fluorinated surface strategy for engineering anti‐fouling, anti‐inflammatory, and mechanically compatible biliary stents, and offered a materials‐driven solution to persistent interfacial failure in biofluid‐rich implant environments.

Metal‐based immunotherapy represents a promising strategy for enhancing antitumor efficacy; however, its clinical application is limited by challenges such as inefficient drug delivery, low specificity, and suboptimal therapeutic outcomes. In this study, a therapeutic platform is constructed on a magnesium (Mg) surface utilizing self‐healing thiolated hyaluronic acid (HA‐SH) and cell membrane‐derived vesicle (CMV) drug system, which improves structural stability, enables spatiotemporal drug release, and facilitates immune‐hormone combination therapy for prostate cancer. CMV with phospholipid bilayers promotes HA‐SH disulfide bond interactions through weak hydrophobic interactions, mitigating corrosion and ensuring structural integrity. Additionally, HA‐SH exhibits glutathione (GSH)‐responsive drug release within the tumor microenvironment. CMV facilitates pH‐sensitive drug delivery and enables efficient cytoplasmic entry via membrane fusion mechanisms, ensuring precise spatiotemporal control. Through drug library screening, ginsenoside Rb1 is identified as a key therapeutic agent, competitively inhibiting androgen receptor signaling. Coupled with hydrogen release from Mg, it induces immunogenic cell death and promotes the formation of tertiary lymphoid structures (TLS) via inhibiting the PI3K‐AKT pathway, achieving synergistic androgen deprivation therapy and immune activation. This implantable drug delivery system effectively tackles mechanical stability, local drug delivery, and systemic immune activation concerns, demonstrating substantial translational promise for various malignancies to improve treatment effectiveness and reduce structural failure risks.

Gallbladder cancer (GBC) is a biliary tract cancer with a poor prognosis. Consistent evidence suggests that fasting has extensive antitumor effects in various cancers and influences levels of poly (rC)-binding protein 2 (PCBP2). However, whether fasting and PCBP2 are involved in GBC remains unknown. We assessed the expression of PCBP2 in GBC tumor tissues and cells. Knockdown and overexpression of PCBP2, combined with in vitro and in vivo assays using fasting mimic medium or diets, were conducted to provide functional significance. The effect of PCBP2 on glycolysis was assessed by glucose uptake, lactate production, oxygen consumption rate, and limiting glycolytic-associated enzymes (PDK1, PKM2, and HK-2). We found that fasting could inhibit glycolysis and cell migration/invasion in GBC cells and that fasting mimic diets could significantly inhibit GBC cell proliferation in a mouse xenograft model. PBCP2 was upregulated in GBC tumor tissues and cells. Moreover, PCBP2 is a key downstream target of fasting, and fasting decreases PCBP2 expression in GBC cells. PCBP2 knockdown inhibits GBC cell proliferation, migration/invasion, and glycolysis, whereas PCBP2 overexpression has the opposite effect. Through co-immunoprecipitation, we identified a physical connection between PCBP2 and the angiopoietin-like protein ANGPTL4. PCBP2 can negatively regulate the expression of ANGPTL4. Hence, fasting inhibits cell proliferation, migration/invasion, and glycolysis through PCBP2/ANGPTL4 signaling. We conclude that PCBP2 is a target of fasting and is involved in cell migration/invasion and glycolysis through the negative regulation of ANGPTL4 in GBC. PCBP2 represents a potential therapeutic target for GBC.

The human body comprises various tubular structures that have essential functions in different bodily systems. These structures are responsible for transporting food, liquids, waste, and other substances throughout the body. However, factors such as inflammation, tumors, stones, infections, or the accumulation of substances can lead to the narrowing or blockage of these tubular structures, which can impair the normal function of the corresponding organs or tissues. To address luminal obstructions, stenting is a commonly used treatment. However, to minimize complications associated with the long-term implantation of permanent stents, there is an increasing demand for biodegradable stents (BDS). Magnesium (Mg) metal is an exceptional choice for creating BDS due to its degradability, good mechanical properties, and biocompatibility. Currently, the Magmaris^® coronary stents and UNITY-B^TM biliary stent have obtained Conformité Européene (CE) certification. Moreover, there are several other types of stents undergoing research and development as well as clinical trials. In this review, we discuss the required degradation cycle and the specific properties (anti-inflammatory effect, antibacterial effect, etc.) of BDS in different lumen areas based on the biocompatibility and degradability of currently available magnesium-based scaffolds. We also offer potential insights into the future development of BDS.

Accumulating evidence indicates that the lysosomal Ragulator complex is essential for the full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in cancer and glycolytic metabolism associated with drug resistance. Fasting is known to upregulate the ring finger protein 152 (RNF152) and mediate the metabolic status of cells. Here we report that RNF152 regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator, and attenuates gemcitabine resistance in gallbladder cancer (GBC). The effects of RNF152 expression on molecular behavior were analyzed. RNF152 and p18 levels were detected in tissues, and detailed mechanistic studies were undertaken by using activators, inhibitors, and lentivirus transfections. RNF152 levels were significantly lower in GBC than in adjacent non-cancer tissues. Fasting impairs glycolysis, induces gemcitabine sensitivity, and upregulates the expression of RNF152. RNF152 overexpression increases the sensitivity of GBC cells to the chemotherapeutic drug gemcitabine, whereas silencing RNF152 exhibited the opposite effect. Our study verified that fasting-induced RNF152 ubiquitinates p18, resulting in proteasomal degradation. RNF152 deficiency induces the increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity, to promote glycolysis and decrease gemcitabine sensitivity in GBC. Our research suggests that RNF152 is a fasting sensor and an important regulator of the mTORC1 signal. RNF152 functions as a tumor suppressor that can suppress the activity of mTORC1 to inhibit glycolysis and enhance the sensitivity of gemcitabine in GBC. RNF152 may have potential in the therapeutic management of GBC.

Background: The genomic feature of biliary tract carcinoma (BTC) has been characterized, but limited studies focus on the potential therapeutic target for cholangiocarcinoma patients. Methods: 43 BTC patients were enrolled in this retrospective study. Genomic characteristics including genomic alterations and mutational signatures were detected and analyzed. Then, the correlation between the genomic characteristics and clinicopathologic features was investigated. Next, the prognostic significance of these altered genes was evaluated. Besides, personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: Among 43 patients, the genomic mutation was detected in 38 patients. Among these mutations, KRAS (44.2%), TP53(37.2%), ARID1A (18.6%), SMAD4(18.6%), BRCA2, CDKN2A (11.6%), and VEGFA (11.6%) are the most frequently altered cancer-related genes. Besides, germline mutations mainly occurred in ERBB, PI3K/AKT, MAPK, and RAS signaling. Among detected mutations, we found that TP53, STK11, MYC, and ERBB3 are gene alternations with significant prognostic values. In terms of potentially actionable target (PAT) analysis, 19 genes were proposed to be PATs in BTCs. and we found out that 79.1% of patients have Tier II somatic mutation in our cohort. Conclusions: The molecular feature is closely related to clinical characteristics in cholangiocarcinoma patients. In this study, we identified several commonly altered genes in cholangiocarcinoma patients and determined potential prognostic biomarkers and therapeutic targets for cholangiocarcinoma patients.