Detection of Arsenic(V) by Fluorescence Sensing Based on Chlorin e6-Copper Ion.

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 µM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV-visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M-1 and 2.35 × 1012 M-2, respectively, using B-H (Benesi-Hildebrand) plots. Fluorescence lifetimes, B-H plots, FT-IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule.

Preparation of Alcohol Dehydrogenase-Zinc Phosphate Hybrid Nanoflowers through Biomimetic Mineralization and Its Application in the Inhibitor Screening.

A biomimetic mineralization method was used in the facile and rapid preparation of nanoflowers for immobilizing alcohol dehydrogenase (ADH). The method mainly uses ADH as an organic component and zinc phosphate as an inorganic component to prepare flower-like ADH/Zn3(PO4)2 organic-inorganic hybrid nanoflowers (HNFs) with the high specific surface area through a self-assembly process. The synthesis conditions of the ADH HNFs were optimized and its morphology was characterized. Under the optimum enzymatic reaction conditions, the Michaelis-Menten constant (Km) of ADH HNFs (ß-NAD+ as substrate) was measured to be 3.54 mM, and the half-maximal inhibitory concentration (IC50) of the positive control ranitidine (0.2-0.8 mM) was determined to be 0.49 mM. Subsequently, the inhibitory activity of natural medicine Penthorum chinense Pursh and nine small-molecule compounds on ADH was evaluated using ADH HNFs. The inhibition percentage of the aqueous extract of P. chinense is 57.9%. The vanillic acid, protocatechuic acid, gallic acid, and naringenin have obvious inhibitory effects on ADH, and their percentages of inhibition are 55.1%, 68.3%, 61.9%, and 75.5%, respectively. Moreover, molecular docking analysis was applied to explore the binding modes and sites of the four most active small-molecule compounds to ADH. The results of this study can broaden the application of immobilized enzymes through biomimetic mineralization, and provide a reference for the discovery of ADH inhibitors from natural products.

Prediction of radiosensitivity and radiocurability using a novel supervised artificial neural network.

BACKGROUND: Radiotherapy has been widely used to treat various cancers, but its efficacy depends on the individual involved. Traditional gene-based machine-learning models have been widely used to predict radiosensitivity. However, there is still a lack of emerging powerful models, artificial neural networks (ANN), in the practice of gene-based radiosensitivity prediction. In addition, ANN may overfit and learn biologically irrelevant features. METHODS: We developed a novel ANN with Selective Connection based on Gene Patterns (namely ANN-SCGP) to predict radiosensitivity and radiocurability. We creatively used gene patterns (gene similarity or gene interaction information) to control the "on-off" of the first layer of weights, enabling the low-dimensional features to learn the gene pattern information. ANN-SCGP was trained and tested in 82 cell lines and 1,101 patients from the 11 pan-cancer cohorts. RESULTS: For survival fraction at 2 Gy, the root mean squared errors (RMSE) of prediction in ANN-SCGP was the smallest among all algorithms (mean RMSE: 0.1587-0.1654). For radiocurability, ANN-SCGP achieved the first and second largest C-index in the 12/20 and 4/20 tests, respectively. The low dimensional output of ANN-SCGP reproduced the patterns of gene similarity. Moreover, the pan-cancer analysis indicated that immune signals and DNA damage responses were associated with radiocurability. CONCLUSIONS: As a model including gene pattern information, ANN-SCGP had superior prediction abilities than traditional models. Our work provided novel insights into radiosensitivity and radiocurability.

Comparative analysis of antibiotic susceptibility patterns and clinical features of mucoid and non-mucoid Pseudomonas aeruginosa infections: a retrospective study.

Background: Pseudomonas aeruginosa (PA) is a prevalent opportunistic pathogen that has close associations with both acute and chronic infections. However, there exists an insufficiency of accurate and comprehensive data pertaining to the antimicrobial susceptibility patterns and clinical characteristics of both mucoid and non-mucoid strains of PA (mPA and non-mPA, respectively). Methods: From January 1, 2021 to December 31, 2022, a thorough retrospective study was carried out to examine and compare the antibiotic susceptibility test outcomes and clinical characteristics of hospitalized patients with mPA and non-mPA infections. Results: This study investigated a cohort of 111 patients who were diagnosed with mPA infections, as well as 792 patients diagnosed with non-mPA infections. Significant demographic disparities, including gender (p < 0.001), age (p < 0.001), length of hospital stay (p < 0.001), diabetes (p = 0.043), and hypertension (p < 0.001), are evident between the mPA and non-mPA groups. The mPA group commonly necessitates hospitalization for respiratory system diseases, whereas the non-mPA group is associated with concomitant cardiovascular and cerebrovascular diseases. The mPA group demonstrates lower utilization rates of medical devices, such as Foley catheter (p < 0.001), nasogastric tube (p < 0.001), mechanical ventilation (p < 0.001), tracheostomy (p < 0.001), arterial and venous catheterization (p < 0.001), and exhibits superior organ function status, including lower incidences of hypoalbuminemia (p < 0.001), septic shock (p < 0.001), liver dysfunction (p < 0.001), renal failure (p < 0.001), and respiratory failure (p < 0.001). The non-mPA group is more vulnerable to infection with two or more bacterial pathogens compared to the mPA group, with the non-mPA group frequently resulting in Enterobacteriaceae infections and the mPA group being associated with fungal infections. Variations in antibiotic sensitivity are noted for Amikacin (p < 0.001), Ciprofloxacin (p < 0.001), Cefepime (p = 0.003), and Levofloxacin (p < 0.001) in antibiotic susceptibility testing, with resistance patterns closely tied to specific antibiotic usage. Conclusion: There are significant demographic characteristics, clinical manifestations and antibiotic susceptibility between mPA and non-mPA infections. It is crucial to emphasize these characteristics due to their significant role in preventing and treating PA infections.

Selective fluorescence detection of acetylsalicylic acid, succinic acid and ascorbic acid based on a responsive lanthanide metal fluorescent coordination polymer.

A fluorescent sensor for highly selective and ultrasensitive detection of acetylsalicylic acid (ASA), succinic acid (SA), and ascorbic acid (AA) was reported. The water-soluble fluorescent ligand salicylic acid (Sal) was generated through catalyzing ASA by the hydrolase activity of zeolitic-imidazolate framework-8 (ZIF-8) or natural esterase (Est). The Sal can coordinate with 2-methylimidazole (2-MIm) and Ln(III) to form a fluorescent lanthanide coordination polymer (LCP), which has a fluorescence emission peak with the maximum wavelength at 412 nm (the excitation wavelength at 300 nm). Therefore, the detection of ASA can be achieved through the fluorescence intensity changes of LCPs in the system, which has comparable sensitivity and good selectivity (linear range of 0.031-1.00 mM and LODs of 11.72 and 3.22 µM) as compared to a direct reaction between Est/ZIF-8 and ASA for detecting ASA (linear range of 0.05-1.20 mM and limits of detection (LODs) of 4.43 and 4.58 µM). Furthermore, upon the addition of SA and AA, the fluorescence intensity of the reaction system can be enhanced and weakened through changing the energy resonance transfer pathways and affecting the enzymatic reaction process, respectively, realizing their sensitive and selective fluorescence detection. The established fluorescent sensors can work well in a wide linear range of SA concentrations from 0 to 2.50 mM (Est-based reaction system) and 0 to 1.50 mM (ZIF-8-based reaction system) with the LODs of 0.032 and 0.028 mM, respectively. The linear ranges of AA concentrations are from 0.0078 to 0.25 mM (Est-based reaction system) and 0.0078 to 0.13 mM (ZIF-8-based reaction system) with the LODs of 2.54 and 3.80 µM, respectively. The established sensors were successfully used in the detection of SA in rabbit plasma, with a recovery of 84.0%-98.7%. Additionally, the contents of ASA in Aspirin Enteric-Coated tablets and AA in vitamin C tablets were also determined by the developed methods.

Rapid and sensitive detection of alkaline phosphatase and glucose oxidase activity through fluorescence and colorimetric dual-mode analysis based on CuO NPs@ZIF-8 mediated enzyme-cascade reactions.

The combined application of nanozymes and natural enzymes has received widespread attention in recent years. In this work, a simple and efficient method was used to synthesize a composite material of CuO nanoparticle-modified zeolitic imidazolate framework-8 (CuO NPs@ZIF-8) with multiple enzyme activities (glucose oxidase-like and hydrolase-like activities) to detect the activity of natural enzymes through fluorescence and colorimetric (UV-vis) dual-mode detection. The hydrolase- and oxidase-like activities of CuO NPs@ZIF-8 show an acceptable affinity with l-ascorbic acid 2-phosphate trisodium (AAP) and o-phenylenediamine (OPD). Using the developed sensor, highly sensitive detection of natural enzymes glucose oxidase (GOX) and alkaline phosphatase (ALP) was achieved through both fluorescent and colorimetric analyses with a wide linear range (fluorescence for GOX: 0.86-1.23 × 105 mU mL-1, UV-vis for GOX: 0.081-1.62 × 105 mU mL-1; fluorescence for ALP: 0.042-1.20 × 104 mU mL-1, UV-vis for ALP: 0.0046-1.23 × 104 mU mL-1) and low LOQs (fluorescence for GOX: 0.86 mU mL-1, UV-vis for GOX: 0.081 mU mL-1; fluorescence for ALP: 0.042 mU mL-1, UV-vis for ALP: 0.0046 mU mL-1). Compared to the other fluorescent and colorimetric sensors, this sensor has better catalytic activity due to the addition of GOX and ALP, which can amplify the detection signal and improve the sensitivity. This is the first time that composite material CuO NPs@ZIF-8 with "tandem enzyme" activity was synthesized and applied in the detection of enzyme activity. Additionally, the proposed fluorescent and UV-vis platforms exhibit the capability to detect GOX and ALP in serum samples with satisfactory recovery, indicating potential application prospects in biochemical analysis.

Biomineralized Manganese Oxide Nanoparticles Synergistically Relieve Tumor Hypoxia and Activate Immune Response with Radiotherapy in Non-Small Cell Lung Cancer.

Radiotherapy (RT) is currently considered as an essential treatment for non-small cell lung cancer (NSCLC); it can induce cell death directly and indirectly via promoting systemic immune responses. However, there still exist obstacles that affect the efficacy of RT such as tumor hypoxia and immunosuppressive tumor microenvironment (TME). Herein, we report that the biomineralized manganese oxide nanoparticles (Bio-MnO2 NPs) prepared by mild enzymatic reaction could be a promising candidate to synergistically enhance RT and RT-induced immune responses by relieving tumor hypoxia and activating cGAS-STING pathway. Bio-MnO2 NPs could convert endogenic H2O2 to O2 and catalyze the generation of reactive oxygen species so as to sensitize the radiosensitivity of NSCLC cells. Meanwhile, the release of Mn2+ into the TME significantly enhanced the cGAS-STING activity to activate radio-immune responses, boosting immunogenic cell death and increasing cytotoxic T cell infiltration. Collectively, this work presents the great promise of TME reversal with Bio-MnO2 NPs to collaborate RT-induced antitumor immune responses in NSCLC.

Dual tumor-targeted poly(lactic-co-glycolic acid)-polyethylene glycol-folic acid nanoparticles: a novel biodegradable nanocarrier for secure and efficient antitumor drug delivery.

Further specific target-ability development of biodegradable nanocarriers is extremely important to promote their security and efficiency in antitumor drug-delivery applications. In this study, a facilely prepared poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-folic acid (FA) copolymer was able to self-assemble into nanoparticles with favorable hydrodynamic diameters of around 100 nm and negative surface charge in aqueous solution, which was expected to enhance intracellular antitumor drug delivery by advanced dual tumor-target effects, ie, enhanced permeability and retention induced the passive target, and FA mediated the positive target. Fluorescence-activated cell-sorting and confocal laser-scanning microscopy results confirmed that doxorubicin (model drug) loaded into PLGA-PEG-FA nanoparticles was able to be delivered efficiently into tumor cells and accumulated at nuclei. In addition, all hemolysis, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, and zebrafish-development experiments demonstrated that PLGA-PEG-FA nanoparticles were biocompatible and secure for biomedical applications, even at high polymer concentration (0.1 mg/mL), both in vitro and in vivo. Therefore, PLGA-PEG-FA nanoparticles provide a feasible controlled-release platform for secure and efficient antitumor drug delivery.