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Ethyl-linked anthocyanin-flavanol pigments are one of the most important condensation products formed during the red winemaking and ageing period. They have great contribution to the color characteristics and stability of aged red wines. In this study, the color characteristics and stability of ethyl-linked anthocyanin-flavanol pigments and their precursor anthocyanins were evaluated by combined spectrophotometry and 3D molecular simulations. In model wine solutions, the condensation reactions between three anthocyanins and (-)-epicatechin, mediated by acetaldehyde, were conducted to produce ethyl-linked anthocyanin-flavanol pigments. The color was assessed by the CIELab method, and the concentration changes were analyzed by HPLC-DAD. On the other hand, the stability of these pigmented compounds was also calculated by the three 3D molecular simulation methods, that is molecular mechanics, molecular dynamics, and quantum chemistry simulation. The results obtained from CIELab analysis indicated that the formation of ethyl-linked anthocyanin-flavanol pigments resulted in a decrease of L*, a*, b* and C* values, and conversely, a rising of h* value. The 3D molecular simulations revealed that the stability of anthocyanins was as follows: Mv-3-O-glu > Pn-3-O-glu > Cy-3-O-glu. The cis or trans ethyl-linked anthocyanin-flavanol pigments were much more stable than their precursor anthocyanins. Among the pigments, ethyl-linked malvidin-3-O-glucoside-flavanol was more stable than ethyl-linked cyanidin-3-O-glucoside-flavanol and ethyl-linked peonidin-3-O-glucoside-flavanol.

Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature and damage‐repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) ‐modified metal‐organic frameworks (MOF). After cellular, Mito‐Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+‐based Fenton‐like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu‐ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer. [ABSTRACT FROM AUTHOR]

Background: Evidence of osimertinib as neoadjuvant therapy for resectable non-small cell lung cancer (NSCLC) are currently lacking. This case series study aimed to assess the safety and feasibility of neoadjuvant osimertinib therapy followed by surgery for resectable NSCLC. Materials and methods: Patients with resectable NSCLC with epidermal growth factor receptor (EGFR) mutation who received osimertinib as neoadjuvant therapy followed by surgery at our center were included. Demographic features, radiologic and pathological assessment of response, surgery-related details and complications, toxicity profiles, and prognostic outcomes were extracted. Results: A total of 13 patients were included in this study. The median age at the time of surgical resection was 57 years (interquartile range: 52–64 years), and eight (61.5%) patients were female. The objective response rate (ORR) was 69.2% (9/13), and the complete resection rate was 100%. The rates of pathologic downstaging and lymph node downstaging were 100% (13/13) and 66.7% (6/9), respectively. There were no perioperative deaths and only three (23.1%) patients had postoperative complications. Seven (53.8%) and 13 (100%) patients experienced grade 1 treatment-related adverse reactions and laboratory abnormalities, respectively. No patients experienced drug withdrawal or surgical delays due to the adverse events. No patients showed grade 2 or worse toxicity profiles. One patient was lost to follow-up. The other 12 patients were alive and free of disease recurrence with a median follow-up time of 9.5 months. Conclusion: Neoadjuvant osimertinib therapy seemed to be safe and feasible for resectable EGFR-mutated NSCLC. Future large prospective studies are warranted to confirm whether osimertinib as neoadjuvant therapy outperforms standard tyrosine kinase inhibitors (TKIs) or chemotherapy for resectable EGFR-mutated NSCLC. [ABSTRACT FROM AUTHOR]

Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria-mediated cell death. However, the highly adaptive nature and damage-repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self-reinforced bimetallic Mito-Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO 2 ) into hyaluronic acid (HA) -modified metal-organic frameworks (MOF). After cellular, Mito-Jammer dissociates into CaO 2 and Cu 2+ in the tumor microenvironment. The exposed CaO 2 further yields hydrogen peroxide (H 2 O 2 ) and Ca 2+ in a weakly acidic environment to strengthen the Cu 2+ -based Fenton-like reaction. Furthermore, the combination of chemodynamic therapy and Ca 2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu-ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Tumor-associated macrophages (TAMs) are the most abundant infiltrating immune cells in the tumor microenvironment (TME) and play an important role in tumor progression. Clinically, the increase of TAMs infiltration is linked to poor prognosis of patients with various cancer types. Multiple studies have demonstrated that reducing or reprogramming TAMs can inhibit the occurrence or development of tumors. Therefore, TAMs have been identified as novel targets for the treatment of cancer therapy. In this review, the origin, polarization, roles, and targeting of TAMs in malignancies, are discussed., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)