Construction of Metal Organic Framework-Derived Fe-N-C Oxidase Nanozyme for Rapid and Sensitive Detection of Alkaline Phosphatase.

Alkaline phosphatase (ALP) is a phosphomonoester hydrolase and serves as a biomarker in various diseases. However, current detection methods for ALP rely on bulky instruments, extended time, and complex operations, which are particularly challenging in resource-limited regions. Herein, we synthesized a MOF-derived Fe-N-C nanozyme to create biosensors for the coulometric and visual detection of ALP. Specifically, we found the Fe-N-C nanozyme can efficiently oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to generate blue-colored tetramethyl benzidine (TMBox) without the need for H2O2. To construct the biosensor, we incorporated the ALP enzymatic catalytic reaction to inhibit the oxidation of TMB by Fe-N-C oxidase nanozyme. This biosensor showed rapid and highly sensitive detection of ALP in both buffer and clinical samples. The limit of detection (LOD) of our approach could be achieved at 3.38 U L-1, and the linear range was from 5 to 60 U L-1. Moreover, we also developed a visual detection for ALP by using a smartphone-based assay and facilitated practical and accessible point-and-care testing (POCT) in resource-limited areas. The visual detection method also achieved a similar LOD of 2.12 U L-1 and a linear range of 5-60 U L-1. Our approach presents potential applications for other biomarker detections by using ALP-based ELISA methods.

Analysis of inter-individual variability of antitussive effect of Farfarae Flos and its fecal metabolites based on gut microbiota.

In this study, the inter-individual variability of antitussive effect of Farfarae Flos was observed, and then the Farfarae Flos treated mice were divided into the mice with good or poor antitussive effect. Then a UHPLC-Q TOF-MS method was developed and validated to quantify 13 fecal metabolites of Farfarae Flos, and the results showed concentrated differences between the two subgroups. The results of 16 S rRNA gene sequencing analysis showed that mice with good or poor antitussive effects were also different at the structure of gut microbiota in phylum and genus, as well as the related 6 pathways. In addition, the differential fecal metabolites of Farfarae Flos between the two subgroups were probably related with 5 bacterial that participating in the CQAs and flavonoids metabolism. This study explained the inter-individual variability of the antitussive effect of Farfarae Flos from the perspective of gut microbiota. However, the specific bacterial that participate in the metabolism of Farfarae Flos as well as the antitussive effects of Farfarae Flos need to be further validated.

Altered Fecal Metabolomics and Potential Biomarkers of Psoriatic Arthritis Differing From Rheumatoid Arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/ß-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.

Enhanced photodynamic therapy of TiO2/N-succinyl-chitosan composite for killing cancer cells

Abstract The aim of this study was to investigate the effect of TiO2/N-succinyl-chitosan composite (TiO2/ NSCS) photodynamic therapy (PDT), while considering the effects of various light sources on the activation of photosensitizer. The methyl thiazolyl tetrazolium assay was used to examine the cell survival rate of the cells. The results showed that glioma cell strain (U251) was the most sensitive cancer cell strain to TiO2/NSCS. When the concentration of TiO2/NSCS was between 0 and 800 μg·mL-1, there was no obvious cytotoxicity to normal liver cells (HL-7702) and U251 cells. During the PDT process, the photokilling effect of TiO2/NSCS on U251 cells under ultraviolet-A (UVA) light irradiation was stronger than that of pure TiO2, and its killing effects were positively correlated with concentration and irradiation time. In addition, both UVA and visible light could excite TiO2/ NSCS, which had significant killing effect on U251 cells. The results of acridine orange/ethidium bromide fluorescent double staining and Annexin V/propidium iodide double staining indicated that TiO2/NSCS under UVA and visible light irradiation could kill U251 cells by inducing apoptosis, and the apoptosis rate of TiO2/NSCS treatment groups was higher than that of TiO2 treatment groups. Therefore, TiO2/NSCS might be used as a potential photosensitizer in PDT.

Comparison of nutritional compositions of foxtail millet from the different cultivation regions by UPLC-Q-Orbitrap HRMS based metabolomics approach.

Foxtail millet (Setaria italica (L.) P. Beauv) is cultivated throughout most parts of Shanxi province. Although quite a number of reports have been conducted on the bioactivities of foxtail millet, little information was available on the metabolite differences of the foxtail millet seeds from different cultivation regions. In this study, a systematic study on the metabolite composition of the foxtail millet seed from Shanxi province was conducted by ultra-high performance liquid chromatography combined with electrospray ionization quadrupole/orbitrap high-resolution mass spectrometry, and 158 compounds were characterized through analysis of mass fragmentation patterns and comparison with the data in the databases and literatures. Then the metabolomic analysis, in combination with heatmap and hierarchical clustering analysis revealed the significant differences between the foxtail millet from northern and southern Shanxi province, which was ascribed to 20 differential metabolites. Then metabolic pathway analysis was performed based on these differential metabolites, and three metabolic pathways were selected as the key contributors. The results showed that foxtail millet from different cultivation regions showed obvious metabolite differences, which was probably related to environmental factors. In addition, the findings also provide an important reference for further research on the functional food development from foxtail millet. PRACTICAL APPLICATIONS: Foxtail millet (Setaria italica (L.) P. Beauv) as a staple food among the majority of people, is rich in bioactive nutrients, including free fatty acids, triglycerides, cellulose, protein, vitamins, and polyphenol, et al. The metabolite composition of the foxtail millet seed was investigated systematically and the results showed that the climate conditions can directly affect the metabolite composition of foxtail millets, and provided important reference for the further research on the resource utilization and functional food development from foxtail millet.

Identification of the constituents and the cancer-related targets of the fruit of Solanum nigrum based on molecular docking and network pharmacology.

The fruit of Solanum nigrum (FSN) exhibited a variety of biological activities. However, the chemical composition of the fruit, as well as the steroidal alkaloids responsible for the bioactivity and the mechanism of action need to be further studied. The ultrahigh performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q Orbitrap HRMS) and nuclear magnetic resonance (NMR) were applied to investigate the chemical composition of FSN, which led to the identification of 170 compounds, including 12 amino acids, 4 caffeoylquinic acids, 2 flavonols, 114 steroid alkaloids, 5 steroid saponins and 33 other structure compounds. The network pharmacology showed that the anticancer effect of 14 steroid alkaloids was probably acting through 99 biological targets. Among them, 11 alkaloids and 11 targets probably played the important role based on the results of molecular docking. This study enriched our knowledge about the chemical composition of FSN, as well as the anticancer mechanism of steroidal alkaloids in FSN.