Cyano-functionalized porous hyper-crosslinked cationic polymers for efficient preconcentration and detection of phenolic endocrine disruptors in fresh water and fish

Article

Author: Zhao, Guijiao ; Wang, Qianqian ; Wang, Chenhuan ; Wang, Chun ; Wu, Qiuhua ; Wang, Zhi

Sensitively analyzing phenolic endocrine-disrupting chemicals (EDCs) in environmental substrates and aquatic organisms provides a significant challenge. Here, we developed a novel porous hyper-crosslinked ionic polymer bearing cyano groups (CN-HIP) as adsorbent for the highly efficient solid phase extraction (SPE) of phenolic EDCs in water and fish. The CN-HIP gave an excellent adsorption capability for targeted EDCs over a wide pH range, and the adsorption capacity was superior to that of several common commercial SPE adsorbents. The coexistence of electrostatic forces, hydrogen bond, and π-π interactions was confirmed as the main adsorption mechanism. A sensitive quantitative method was established by coupling CN-HIP based SPE method with high-performance liquid chromatography for the simultaneously determining trace bisphenol A, bisphenol F, bisphenol B and 4-tert-butylphenol in fresh water and fish. The method afforded lower detection limits (S/N = 3) (at 0.03-0.10 ng mL^-1 for water and 0.8-4.0 ng g^-1 for fish), high accuracy (the recovery of spiked sample at 88.0%-112 %) and high precision (the relative standard deviation < 8.5 %). This work provides a feasible method for detecting phenolic EDCs, and also opens a new perspective in developing functionalized cationic adsorbent.

01 Jan 2025·Drug Resistance Updates

TMOD3 accelerated resistance to immunotherapy in KRAS-mutated pancreatic cancer through promoting autophagy-dependent degradation of ASCL4

Article

Author: Zeng, Zhirui ; Zheng, Dijie ; Li, Futang ; He, Zhiwei ; Yu, Chao ; Wu, Changhao ; Chen, Liwen

The high prevalence of KRAS mutations in pancreatic cancer (PC) is widely acknowledged and results in the resistance of targeted ferroptosis therapy and immunotherapy. Herein, via a CRISPR/Cas9 library screen, the effects of ferroptosis agonists were increased in KRAS-mutant PC cells upon knockout of tropomodulin 3 (TMOD3), while these effects were not observed in KRAS-wild-type cells. Increased levels of TMOD3 were found in PC tissues, particularly in those with KRAS mutations. The increase in TMOD3 expression was facilitated by KRAS via the ETS transcription factor ELK1. Liquid chromatography-mass spectrometry (LC/MS) showed that TMOD3 increased acyl-CoA synthetase long chain family member 4 (ACSL4) protein expression and fatty acid metabolism. Mechanistically, TMOD3 promoted F-actin polymerization, thereby facilitating the fusion of autophagosomes with lysosomes, increasing the degradation of the ACSL4 protein, and augmenting the ferroptosis-inducing effects of RSL3. These effects of TMOD3 were counteracted by the administration of cytochalasin, the removal of the α2 domain of TMOD3, or the introduction of a mutation at S71. Cangrelor, an FDA-approved drug, can target TMOD3. In a mouse model, the suppression of TMOD3 using cangrelor or gene silencing technology resulted in increased infiltration of CD8+ T cells into tumor tissues with KRAS mutations and exhibited a synergistic effect with the PD-1 antibody. In conclusion, TMOD3 was found to inhibit ferroptosis and induced the resistance to PD-1 antibody by facilitating the fusion of autophagosomes and lysosomes through the promotion of F-actin polymerization in KRAS-mutant PC. TMOD3 was identified as a novel target for PC therapy.

01 Jan 2025·Food Chemistry

Absorption and transport mechanism of colloidal nanoparticles (CNPs) in lamb soup based on Caco-2 cell

Article

Author: Fu, Jianing ; Xu, Meizhen ; Liu, Ling ; Li, Shaobo ; Chen, Li ; Zhang, Dequan

Soup is an important presence in diet, but its absorption and transport mechanism by the human body remains unclear. In this study, Caco-2 intact cell and monolayer cell models were constructed to simulate small intestine absorption on colloidal nanoparticles (CNPs) isolated from lamb soup. The intracellular localization of CNPs was viewed by laser confocal microscopy (LSCM). CNPs uptake and release pathways were explored by differences in CNPs concentrations in 5 endocytosis inhibitor models and 4 exocytosis inhibitor models. Results indicated that CNPs endocytosis by Caco-2 cells was restrained by Nystatin and Cytochalasin D, with exocytosis being inhibited by Nocodazole and Monensin. Therefore, the major absorption pathways for CNPs were caveolin-dependent endocytosis, macropinocytosis and phagocytosis. The major transport pathways were microtubule-vesicle-mediated protein transport to the membrane and transportation between the Golgi apparatus and membrane. This study may provide theoretical support for the transport mechanism of soup products in the small intestine.

100 Deals associated with Cytochalasin B

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Restenosis	Phase 1	-	Poniard Pharmaceuticals, Inc.	-
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