Investigation of the Uptake and Transport of Two Novel Camptothecin Derivatives in Caco-2 Cell Monolayers

Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118. The transport and uptake of FL118, FL77-28, and FL77-29 were investigated in Caco-2 cells for the preliminary prediction of intestinal absorption. The apparent permeability coefficient from apical to basolateral (P_{app AP-BL}) values of FL77-28 and FL77-29 were (2.32 ± 0.04) × 10⁻⁶ cm/s and (2.48 ± 0.18) × 10⁻⁶ cm/s, respectively, suggesting that the compounds had moderate absorption. Since the transport property of FL77-28 was passive diffusion and the efflux ratio (ER) was less than 2, two chemical inhibitors were added to further confirm the involvement of efflux proteins. The results showed that FL77-28 was not a substrate of P-gp or BCRP, but FL77-29 was mediated by P-gp. In conclusion, FL77-28 might be a promising candidate to overcome drug resistance induced by multiple efflux proteins.     

Dynamic Variation of Amino Acid Contents and Identification of Sterols in Xinyang Mao Jian Green Tea

As important biomolecules in Camellia sinensis L., amino acids (AAs) are considered to contribute to the overall green tea sensory quality and undergo dynamic changes during growth. However, limited by analytical capacity, detailed AAs composition in different growth stages remains unclear. To address this question, we analyzed the dynamic changes of 23 AAs during leaf growth in Xinyang Mao Jian (XYMJ) green tea. Using amino acid analyzer, we demonstrated that most AAs are abundant on Pure Brightness Day and Grain Rain Day. After Grain Rain, 23 AAs decreased significantly. Further analysis shows that theanine has a high level on the day before Spring Equinox and Grain Rain, accounting for 44–61% of the total free AAs content in tea leaves. Glu, Pro, and Asp are the second most abundant AAs. Additionally, spinasterol and 22,23-dihydrospinasterol are first purified and identified in ethanol extract of XYMJ by silica gel column chromatography method. This study reveals the relationship between plucking days and the dynamic changes of AAs during the growth stage and proves the rationality of the traditional plucking days of XYMJ green tea.     

An unexpected all-metal aromatic tetranuclear silver cluster in human copper chaperone Atox1

Metal clusters, such as iron–sulfur clusters, play key roles in sustaining life and are intimately involved in the functions of metalloproteins. Herein we report the formation and crystal structure of a planar square tetranuclear silver cluster when silver ions were mixed with human copper chaperone Atox1. Quantum chemical studies reveal that two Ag 5s¹ electrons in the tetranuclear silver cluster fully occupy the one bonding molecular orbital, with the assumption that this Ag₄ cluster is Ag₄²⁺, leading to extensive electron delocalization over the planar square and significant stabilization. This bonding pattern of the tetranuclear silver cluster represents an aromatic all-metal structure that follows a 4n + 2 electron counting rule (n = 0). This is the first time an all-metal aromatic silver cluster was observed in a protein.

Metal clusters, such as iron–sulfur clusters, play key roles in sustaining life and are intimately involved in the functions of metalloproteins.     

Alpha-Beta Hybrid Quantum Associative Memory Using Hamming Distance

This work presents a quantum associative memory (Alpha-Beta HQAM) that uses the Hamming distance for pattern recovery. The proposal combines the Alpha-Beta associative memory, which reduces the dimensionality of patterns, with a quantum subroutine to calculate the Hamming distance in the recovery phase. Furthermore, patterns are initially stored in the memory as a quantum superposition in order to take advantage of its properties. Experiments testing the memory’s viability and performance were implemented using IBM’s Qiskit library.     

Packed-Fiber Solid Phase-Extraction Coupled with HPLC-MS/MS for Rapid Determination of Lipid Oxidative Damage Biomarker 8-Iso-Prostaglandin F2α in Urine

The 8-iso-prostaglandin F_2α (8-iso-PGF_2α) biomarker is used as the gold standard for tracing lipid oxidative stress in vivo. The analysis of urinary 8-iso-PGF_2α is challenging when dealing with trace amounts of 8-iso-PGF_2α and the complexity of urine matrixes. A packed-fiber solid-phase extraction (PFSPE)–coupled with HPLC-MS/MS–method, based on polystyrene (PS)-electrospun nanofibers, was developed for the specific determination of 8-iso-PGF_2α in urine and compared with other newly developed LC-MS/MS methods. The method, which simultaneously processed 12 samples within 5 min on a self-made semi-automatic array solid-phase extraction processor, was the first to introduce PS-electrospun nanofibers as an adsorbent for the extraction of 8-iso-PGF_2α and was successfully applied to real urine samples. After optimizing the PFSPE conditions, good linearity in the range of 0.05–5 ng/mL with R² > 0.9996 and a satisfactory limit of detection of 0.015 ng/mL were obtained, with good intraday and interday precision (RSD < 10%) and recoveries of 95.3–103.8%. This feasible method is expected to be used for the batch quantitative analysis of urinary 8-iso-PGF_2α.     

Facile Fabrication of 1-Methylimidazole/Cu Nanozyme with Enhanced Laccase Activity for Fast Degradation and Sensitive Detection of Phenol Compounds

Facile construction of functional nanomaterials with laccase-like activity is important in sustainable chemistry since laccase is featured as an efficient and promising catalyst especially for phenolic degradation but still has the challenges of high cost, low activity, poor stability and unsatisfied recyclability. In this paper, we report a simple method to synthesize nanozymes with enhanced laccase-like activity by the self-assembly of copper ions with various imidazole derivatives. In the case of 1-methylimidazole as the ligand, the as-synthesized nanozyme (denoted as Cu-MIM) has the highest yield and best activity among the nanozymes prepared. Compared to laccase, the K_m of Cu-MIM nanozyme to phenol is much lower, and the v_max is 6.8 times higher. In addition, Cu-MIM maintains excellent stability in a variety of harsh environments, such as high pH, high temperature, high salt concentration, organic solvents and long-term storage. Based on the Cu-MIM nanozyme, we established a method for quantitatively detecting phenol concentration through a smartphone, which is believed to have important applications in environmental protection, pollutant detection and other fields.     

Genetically engineered materials: Proteins and beyond

Information-rich molecules provide opportunities for evolution. Genetically engineered materials are superior in that their properties are coded within genetic sequences and could be fine-tuned. In this review, we elaborate the concept of genetically engineered materials(GEMs) using examples ranging from engineered protein materials to engineered living materials. Proteinbased materials are the materials of choice by nature. Recent progress in protein engineering has led to opportunities to tune...     

Discriminant Analysis of the Nutritional Components between Organic Eggs and Conventional Eggs: A 1H NMR-Based Metabolomics Study

The difference of nutrient composition between organic eggs and conventional eggs has always been a concern of people. In this study, ¹H nuclear magnetic resonance (NMR) technique combined with multivariate statistical analyses was conducted to identify the metabolite different in egg yolk and egg white in order to reveal the nutritional components information between organic and conventional eggs. The results showed that the nutrient content and composition characteristics were different between organic and conventional eggs, among which the content of glucose, putrescine, amino acids and their derivatives were found higher in the organic eggs yolk, while phospholipids were demonstrated higher in conventional eggs yolk. Organic acid, alcohol, amine, choline and amino acids were higher in conventional eggs white, but glucose and lactate in organic egg were higher. Our study demonstrated that there are more nutritive components and higher nutritional value in organic eggs than conventional eggs, especially for the growth and development of infants and young children, and conventional eggs have more advantages in promoting lipid metabolism, preventing fatty liver, and reducing serum cholesterol. Eggs have important nutritional value to human body, and these two kinds of eggs can be selected according to the actual nutrient needs.     

Impact of the Acetaldehyde-Mediated Condensation on the Phenolic Composition and Antioxidant Activity of Vitis vinifera L. Cv. Merlot Wine

Acetaldehyde is a critical reactant on modifying the phenolic profile during red wine aging, suggesting that the acetaldehyde-mediated condensation can be responsible for the variation of antioxidant activity during the aging of this beverage. The present study employs exogenous acetaldehyde at six levels of treatment (7.86 ± 0.10–259.02 ± 4.95 mg/L) before the bottle aging of Merlot wines to encourage phenolic modification. Acetaldehyde and antioxidant activity of wine were evaluated at 0, 15, 30, 45, 60 and 75 days of storage, while monomeric and polymeric phenolics were analyzed at 0, 30 and 75 days of storage. The loss of acetaldehyde was fitted to a first-order reaction model, the rate constant (k) demonstrated that different chemical reaction happened in wines containing a different initial acetaldehyde. The disappearance of monomeric phenolics and the formation of polymeric phenolics induced by acetaldehyde could be divided into two phases, the antioxidant activity of wine did not alter significantly in the first phase, although most monomeric phenolics vanished, but the second phase would dramatically reduce the antioxidant activity of wine. Furthermore, a higher level of acetaldehyde could shorten the reaction time of the first phase. These results indicate that careful vinification handling aiming at controlling the acetaldehyde allows one to maintain prolonged biological activity during wine aging.