Levodopa (L-Dopa), a commonly used clinical medication for treating Parkinson's disease, hepatic encephalopathy, and hyperprolactinemia. This study designed and synthesised a chiral nanocatalyst (Cu O@His) based on the structural characteristics of L-Dopa and inspired by the structure of polyphenol oxidase. First, through a series of characterisation techniques, the successful preparation of Cu O@His was confirmed from both its apparent morphology and chemical structure. The catalytic mechanism of the nanoenzyme was then thoroughly investigated, analysing the influence of Cu O@His structure and properties on catalytic activity. The study reveals that the activity and selectivity of the nanoenzyme can be optimised by adjusting the histidine (His) content. At a molar concentration of 3.0%, Cu O@His exhibits the highest chiral recognition efficiency for Dopa enantiomers, achieving an intensity ratio of peak current responses of 2.38 (IL/ID = 2.38). Subsequently, to enhance the electrochemical activity of the nanoenzyme, it was loaded onto the surface of reduced graphene oxide (rGO) nanosheets. The Cu O@His/rGO composite material was employed to construct an electrochemical sensor, and an analytical method for Dopa enantiomers was established using differential pulse voltammetry (DPV). This analytical method exhibits a low detection limit (LODL-Dopa = 0.56 mu M, LODD-Dopa = 1.03 mu M), high sensitivity, excellent stability, and strong resistance to interference. It demonstrates satisfactory recovery rates in tablet, human serum and urine samples. In summary, the Cu O@His chiral nanoenzyme proposed in this chapter offers a novel approach for the chiral recognition and quantitative analysis of L-Dopa.

In complex systems, a universal and effective method for accurately determining the dissociation constant (Kd) of drug-protein interactions (DPI) has not been identified yet. In this study, a novel biomimetic affinity capillary electrochromatography (ACEC) platform was developed. Polydopamine (PDA) was employed not only as a coating material but also as an immobilization agent for human serum albumin (HSA), resulting in the fabrication of the PDA/PDA/HSA@capillary. A series of characterization experiments on the PDA/PDA/HSA@capillary showed that PDA was successfully coated on the inner wall of the capillary, and HSA was also successfully immobilized on the capillary column. The optimal concentration of PDA for preparing the PDA/PDA/HSA@capillary was determined to be 0.8 mg mL-1, and the optimal concentration for immobilizing HSA was 0.25 mM, respectively. Moreover, the PDA/PDA/HSA@capillary showed good separation effects in the complex systems of different drugs. Furthermore, the electrophoretic performance of individual and mixed samples was compared across different capillary columns. Through interaction studies between proteins and compounds, the Kd value of rutin was 1.09 × 103 mol L-1 that of quercitrin was 2.78 × 103 mol L-1, and that of quercetin was 7.44 × 104 mol L- 1, aligning with results from other established methods. The method was applied to the Sophora japonica extract, and the Kd was consistent with the rutin in the mixed system. Reproducibility studies demonstrated that high separation efficiency was maintained even after 50 consecutive runs. By integrating biomimetic material science with chromatographic innovation, this work overcomes critical bottlenecks in traditional affinity capillary electrophoresis (ACE), providing a universal tool for high-throughput drug screening and structure-guided therapeutic design.

The widespread use of acetamiprid (ACE) poses increasing threats to food safety and human health due to its environmental persistence and potential toxicity. Herein, a fluorescent europium-based metal–organic framework (Eu-MOF) was synthesized via a facile room-temperature direct mixing strategy, which serves as a rapid and selective fluorescent probe for ACE detection. The dual-ligand Eu-MOF exhibited intrinsic multi-emission properties, with a dominant red fluorescence at 616 nm that is selectively quenched upon ACE exposure. Under optimized conditions, the sensor showed two linear response ranges (0.01–6 and 6–20 µg/mL) with a detection limit as low as 3.03 ng/mL. Mechanistic investigations reveal that the quenching is primarily governed by the inner filter effect (IFE), supported by spectral overlap and unaltered fluorescence lifetime. The probe demonstrates high specificity against common interfering substances and enables accurate quantification of ACE in complex matrices such as apples and oranges, with satisfactory recovery rates (94.35–100.6

Introduction: Insomnia is a common clinical sleep disorder, for which current medications only relieve symptoms symptomatically and highly specific therapeutic targets are limited. This study integrates multi-omics analysis and machine learning to screen and identify novel, safe, and efficient potential therapeutic targets for insomnia, thereby providing new insights for its targeted drug development and precision diagnosis and treatment. Methods: We intersected a druggable gene set with blood, brain, and plasma Quantitative Trait Loci (QTL) data, using insomnia and its comorbidities as Genome-Wide Association Study (GWAS) outcomes. Two-sample Mendelian randomization (MR) analysis was used to assess causality, followed by sensitivity testing. The Gene Expression Omnibus (GEO) dataset GSE208668 was used for differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Cross-validation and machine learning (LASSO regression and random forests) were employed to screen key hub genes and evaluate their diagnostic efficacy. Summary-data-based Mendelian Randomization (SMR), colocalization, and immune infiltration analyses were performed, and potential drugs were predicted via databases and molecular docking simulations. Results: Through multi-omics analyses including Mendelian randomization, transcriptome profiling and WGCNA, we identified 10 candidate genes, which were further refined by machine learning to five key hub genes: HLA-G, S1PR1, LGALS3, VIM, and PIK3CG. These genes were upregulated in insomnia patients and had high diagnostic AUC values. They showed extensive genetic associations with the risk of comorbidities such as depression, anxiety, hypertension, and diabetes. SMR and colocalization analyses provided convergent suggestive causal evidence for HLA-G, while the remaining four genes were supported as candidate targets rather than causal drivers. Immune infiltration analysis showed that key genes were associated with altered immune cell subsets. Drug prediction screened potential intervention compounds like decitabine and tamibarotene. Discussion: These findings provide robust evidence for novel druggable targets in insomnia, which exert regulatory effects via immune-inflammatory pathways and link insomnia to comorbidity risks. Their diagnostic potential and functional implications further underscore their translational value for clinical application and drug development, but all conclusions remain preliminary due to lack of independent validation. Conclusion: This study identified five core genes, among which HLA-G shows suggestive causal links to insomnia, while the others are supported as promising candidate targets. They show promising diagnostic and drug development value, providing insights into insomnia pathogenesis and a theoretical basis for novel biomarkers and targeted therapies.

Detecting abnormal lipid levels and timely intervention have great potential for diagnosis and treatment of non-alcoholic fatty liver disease (NAFLD). Herein, a novel molecular electron density engineering strategy for synergistically strengthened lipid droplets (LDs) fluorescence probes based on the chalcone skeleton is presented for simultaneous fluorescence diagnosis and drug evaluation of NAFLD. Specifically, a series of novel chalcone derivatives (C1-C7) with controlled intrinsic electron density distribution are rationally fabricated via introducing various push-pull electronic groups into triphenylamine-fused chalcones. Notably, the optical properties including polarity sensibility, Stokes shift, fluorescence emission, photostability, and aggregation-induced emission (AIE) characteristics are all synergistically boosted upon transforming from D-π-A-π-D to D-π-A-π-A architectures. C2 is identified as the optimal probe for LDs-targeted dynamic high-fidelity fluorescence monitoring in live cells, revealing a novel LDs motion pattern termed "Sequential Separation". Further, C2 permits multiscale fluorescence imaging diagnosis of NAFLD in vitro/vivo. Moreover, two LDs-based drug evaluation protocols utilizing C2 for NAFLD intervention are first established, and sesamol is identified as a potential NAFLD therapeutic agent through these assays. Overall, this work not only provides a rational design strategy and novel probe toolbox for the early diagnosis of NAFLD, but also develops pioneering drug screening methodologies for exploiting potential NAFLD therapeutic drugs.

Foodborne residue of carbendazim (CBZ) poses a major threat to human health. Here, we rationally designed a smartphone-assisted fluorescent sensor based on bimetallic-organic framework (Eu/Tb-MOF) for ultrasensitive and visual monitoring of CBZ. The Eu/Tb-MOF nanorods fabricated using Eu3+/Tb3+ as metal nodes and homobenzoic tricarboxylic acid (H3BTC) as organic ligand exhibit superior optical properties. After adding CBZ, the strong orange fluorescence of Eu/Tb-MOF nanorods was suppressed by the inner filter effect (IFE). The linear ranges of the fluorescent sensor were 0.02-15 and 15-80 mu g/mL, with a detection limit as low as 7.09 ng/mL. The analyses of CBZ residue in tomato and orange samples showed satisfactory recoveries of 98.93 %-101.97 % and low relative standard deviations of 0.87 %-3.44 %, verifying the practicality of the probe for CBZ. Notably, a simple and portable smartphone-assisted sensing platform based on the Eu/Tb-MOF nanorods was successfully constructed for quick, visual, and real-time monitoring of CBZ residue. This work provides an efficient onsite analytical method for assessment and warning-early of CBZ to safeguard food quality.

Lotus leaves (LL), petals (LP), and seeds (LS) are believed to have properties that can potentially improve sleep. However, their efficacy in improving sleep has not yet been fully validated. This study aimed to investigate the multitarget mechanisms of extracts from these lotus parts for sleep improvement using chemical analysis, bioactivity assessment, meta-analysis, network pharmacology evaluation, and molecular docking studies. The chemical components in LL, LP, and LS were qualitatively detected using ultra-high-performance liquid chromatography-ultraviolet-quadrupole time-of-flight tandem mass spectrometry, their total flavonoid and phenolic contents were determined, and their 2,2-diphenyl-1-picrylhydrazyl scavenging activity was estimated. Subsequently, relevant literature was collected for meta-analysis. Finally, potential targets were predicted using network pharmacology, and the results were validated by molecular docking studies. A total of 48 compounds, including 16 flavonoids, 26 alkaloids, 2 amino acids, and 4 other compounds, were identified from the lotus extracts. LL had the highest total flavonoid content, while LS had the highest total phenolic content. Extracts from both parts exerted significant antioxidant effects. A meta-analysis identified the potential of lotus to improve sleep. Armepavine, asimilobine, nuciferin, and luteolin were identified as key components, and AKT1, EGFR, DRD2, and PIK3R1 were revealed as key targets. PI3K-Akt was identified as a key signaling pathway. This study provides an important reference for studying the role of the lotus in improving sleep quality.

The concentration of mitoxantrone in the blood of mice was determined by a high-performance liquid chromatography-ultraviolet method with aloe-emodin as the internal standard. The separation was performed on a Hypersil BDS2 column (4.6 × 250 mm, 5 μm) as the analytical column, the mobile Phase A was acetonitrile, and B was 20-mM potassium dihydrogen phosphate (adding 1% triethylamine and adjusting the pH to 2.8 with phosphoric acid) and 4.6-mM sodium octyl sulfonate. The flow rate was 1.0 mL·min-1, the detection wavelength was 243 nm, the column temperature is 25 ± 5°C and the injection amount was 20 μL. Finally, the linear range of mitoxantrone was 5-200 μg·mL-1, and the correlation coefficient was r = 0.9999. The recovery rate of the method was 91.93-105.5%, and the extraction recovery rate was 91.45-105.5%. The intraday precision and interday precision were <3.29% (limit of detection = 0.3 μg·mL-1). The HPLC method established in this paper was simple, rapid, sensitive and accurate, and can be used to determine the content of mitoxantrone in mouse plasma after tail vein injection.

In this study, dual stimulus-response molecularly imprinted hydrogels (MIHs) with water-soluble doxorubicin (DOX) as the imprinted molecule were developed for improving the selective specific recognition capacity. By using N-isopropylacrylamide (NIPAM) as a temperature-sensitive monomer, and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) as a pH-responsive functional monomer, a series of MIHs with different concentration ratios of dual functional monomers and cross-linker were prepared to study the influencing factors of selective recognition. The results show the prepared MIHs have different rigidity and flexibility under different synthesis conditions. The MIH7 with good adsorption performance and specific recognition ability was selected with its molar ratio of NIPAM/DMAPMA/cross-linker (200/10/100). Its imprinting factor of DOX was as high as 2.26. Adsorption kinetic and adsorption thermodynamic studies showed that MIH7 and DOX had high affinity, and its affinity constant KD was as high as 9.11 × 10-6 mol/L. For selectivity adsorption, the MIH7 had excellent selectivity at pH 5, with a selectivity factor as high as 1.97 for epirubicin, which is extremely similar in structure, and selectivity factors as high as 6 and 7.68 for idarubicin and oxytetracycline, respectively. The prepared MIH7 was well separated with good specific recognition of DOX in the serum samples, which provided a potential strategy based on the dual stimulus-response and cross-linker for the efficient recognition of water-soluble molecules.

This study developed a high-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) method for the simultaneous determination of 19 amino acids in the cortex, hippocampus, and bone marrow samples of BALB/C-nu/nu and NOD/SCID mice. We measured the changes in the levels of 19 amino substances in the cortex, hippocampus, and bone marrow samples of mice in the blank model group, acute leukemia model group, chronic leukemia model group, and treatment group. The chromatographic column used was a COSMOSIL 5 C18-MS-II analytical column (150 mm × 4.6 mm, 5 μm), with the column temperature set at 35 °C. The mobile phase was a methanol-ammonium acetate buffer solution (30 mmol L-1 ammonium acetate solution, adjusted to pH 6.40 with acetic acid), at a flow rate of 0.9 mL min-1. The single analysis time was 46 minutes. By optimizing the analysis conditions, the newly established HPLC-FLD method exhibits high sensitivity, good accuracy, and good reproducibility. This method can be successfully applied to determine 19 amino substances in the cortex, hippocampus, and bone marrow of BALB/C-nu/nu and NOD/SCID mice. The differences in amino acid content between different groups can be used to further study the development process of leukemia, disease diagnostic markers, and personalized treatment plans.

Diethylstilbestrol (DES), a synthetic estrogen, is associated with severe endocrine disruption and carcinogenic risks, posing persistent biological and environmental hazards. Herein, a bimetallic Fe/Eu-based metal-organic framework (Fe/Eu-MOF) with distinct multi-emission properties was developed as a ratiometric fluorescent sensor for sensitive and intelligent visual detection of DES. The Fe/Eu-MOF exhibited stable red emission at 615 nm and DES-responsive blue emission at 410 nm, enabling self-referenced quantification. The sensor showed two linear ranges (0.005-2 and 2-30 μg/mL), a low detection limit (1.78 ng/mL), and excellent selectivity against potential interferents. Its practicality was validated in milk and shrimp, demonstrating excellent recovery and reproducibility. Additionally, a paper-based sensor integrated with smartphone RGB analysis enabled rapid, on-site, and instrument-free detection. Mechanism studies revealed that DES coordination with Fe centers suppressed non-radiative decay and enhanced fluorescence. This work provides a robust and intelligent platform for portable monitoring of DES residues, offering significant potential for real-time biohazard surveillance and visual diagnostics in resource-limited settings.

MicroRNAs (miRNAs) are critical regulators in cancer biology, yet their low abundance and high sequence similarity pose significant challenges for accurate intracellular detection. Herein, we present a metal-organic frameworks (MOFs) with self-confined catalytic DNA circuit (designated as MSCDC) integrated within a pH-responsive MIL-53(Fe) framework for on-site, nonenzymatic amplified imaging of miRNA-9 in hepatocellular carcinoma (HCC) cells. The MSCDC was synthesized by anchoring double-stemmed DNA hairpin probes onto MIL-53(Fe) through π-π stacking and electrostatic interactions, achieving high probe density and nuclease resistance. The pH-triggered degradation of MIL-53(Fe) facilitated efficient intracellular release of DNA probes, while the self-confined catalytic DNA circuit enabled autonomous, enzyme-free amplification, converting weak miRNA-9 inputs into strong fluorescence outputs. Compared with conventional carriers, the MSCDC exhibited superior probe loading capacity, enhanced serum stability, excellent biocompatibility, and a femtomolar detection limit (0.32 fM). Importantly, the nanoplatform enabled reliable, real-time visualization of oncogenic miRNA-9 in diverse HCC cell lines, yielding results that were highly consistent with qRT-PCR. This work highlights a generalizable self-confined, nonenzymatic nucleic acid amplification strategy for precise intracellular biosensing, thereby opening avenues for early cancer diagnosis and molecular imaging.

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARβ antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARβ. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.

A novel smartphone-assisted fluorescent sensor based on europium/zirconium metal-organic framework (Eu 0.5 / Zr 0.5-MOF) was developed for the fast and sensitive determination of doxycycline (DOX) and L-arginine (Arg). After the addition of DOX, the fluorescence of Eu 0.5 /Zr 0.5-MOF was quenched owing to the inner filter effect (IFE). When Arg was introduced into the Eu 0.5 /Zr 0.5-MOF@DOX complex system, the fluorescence was recovered because the interaction between Arg and Eu 0.5 /Zr 0.5-MOF@DOX weakened the IFE. Moreover, the Eu 0.5 /Zr 0.5- MOF produced continuous fluorescence color changes for the visual measurement of DOX and Arg. The fluorescent probe for DOX and Arg offered broad linear ranges of 0.05 -80 and 0.1 -60 mu g/mL, respectively, with detection limits as low as 2.07 and 67.5 ng/mL. The proposed method was successfully applied to monitor DOX in eggs and Arg in human serum. This work provides a powerful platform for the real-time and visual analysis of DOX and Arg in food and biological samples.

Dimetridazole (DMZ) is commonly used as a veterinary drug, resulting in high emissions and environmental pollution and DMZ residues are carcinogenic, genotoxic, and mutagenic to humans. Therefore, it is essential to construct a fast, sensitive and simple sensor to monitor DMZ. In this study, samarium molybdate nanosheets modified multi-walled carbon nanotube composites (SmM/MWCNT) were synthesized to modify GCE for detecting DMZ. The SmM/MWCNT material was also characterized by various analytical and spectroscopic techniques, such as FE-SEM, HRTEM, FT-IR, Raman spectroscopy, XRD, elemental mapping and XPS, to demonstrate the successful synthesis of the composite. Besides, the electrochemical behavior of SmM/MWCNT/GCE for DMZ was also investigated using CV and DPV, and the modified electrode showed good electrochemical sensing performance for DMZ with a low detection limit (0.08 μM), a wide linear range (0.1∼1000 μM), and excellent selectivity. Finally, the SmM/MWCNT/GCE was successfully applied to detect DMZ in environmental and biological samples, and satisfactory recoveries (95%∼105%) were obtained. To the best of our knowledge, the synthesis of SmM/MWCNT and its application in electrochemical sensors are reported for the first time, which demonstrates that it can provide a new route for real-time monitoring of environmental pollutants.

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Recently, the endocrine interference of endocrine disruptors on the environment and aquatic organisms has been a hot topic. Ethinyl estradiol (EE2) is an estrogen endocrine disruptor and one of the most widely used in-gredients in oral contraceptives, resulting in high emissions and environmental pollution. Therefore, it is urgent to construct a non-enzymic, simple and low-cost sensor to detect EE2 in environmental and biological samples. We successfully prepared cobalt ferric oxide with anti-spinel structure and reduced graphene oxide composite (CoFe2O4/RGO) using hydrothermal synthesis, which decorated on the glass carbon electrode (GCE) to detect EE2. The morphological structure of CoFe2O4/RGO composites was studied by FESEM, HRTEM, EDX, FT-IR, XRD, and XPS techniques. Additionally, the experimental conditions were optimized and the oxidation mecha-nism of EE2 was explained theoretically and EE2 was detected by CV, EIS, and SWV, which displayed a fantastic current response of EE2. The electrochemical results illustrated that the prepared sensor has good selectivity, high sensitivity, a wide linear range of 0.05-100 mu M, and a lower detection limit of 42 nM. Finally, the prac-ticability of the sensor to detect EE2 in real samples was also studied and obtained a satisfactory recovery.

Enantiomeric analysis is a crucial aspect of the investigation of the properties of chiral substances, and it plays a pivotal role in the development and application of chiral substances. Therefore, the objective of this study was to develop a highly sensitive and user-friendly tyrosine (Tyr) enantiomer detector based on chiral helical polyaniline (PANI). In this study, the helical PANI was generated in an alcohol-water system and doped with Camphorsulfonic acid (CSA) to enhance its electrochemical properties. The chiral helical PANI was then obtained by eluting the CSA under alkaline conditions. The electrochemical sensors developed using this material enable selective recognition of Tyr enantiomers. The mechanism of enantioselective recognition was also explored from a molecular perspective with the help of modeling software. The chiral recognition ability and properties of the sensor were investigated using DPV, EIS, and CV. The surface characteristics of doped and de-doped chiral sensor were analyzed using FE-SEM, HR-TEM, AFM, CD, XPS, and FT-IR. Finally, an electrochemical analysis method for Tyr enantiomers was established using DPV, offering high sensitivity, superior anti-interference ability, quick analysis speed, and good long-term stability. The constructed chiral electrochemical sensor can be used for the detection of human serum and urine samples, which provides a new idea for the selective recognition of Tyr enantiomers in clinical sample.

Gefitinib, a highly significant antitumor drug, is now commonly employed in clinical settings as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer, colon cancer, and breast cancer. Herein, a convenient, rapid, and accurate fluorescence method based on nitrogen-doped carbon dots (NCDs) was designed for ultrasensitive detection of gefitinib. The NCDs were easily synthesized through one-pot hydrothermal process using p-phenylenediamine and D-glutamic acid as the precursors. The sensing strategy relied on the fluorescence of NCDs at 345 nm, which was selectively reduced by gefitinib based on the inner filter effect (IFE). With a broad linear range of 0.025-30 μg/mL and a low limit of detection of 5.5 ng/mL, the probe was successfully applied to the detection of gefitinib in human serum samples, demonstrating strong practicality, affordability, and high accuracy. The proposed sensor is simple in design, fast in detection and cost-effective, and exhibits promising application in drug real-time analysis.

The study was aimed to validate and optimize high performance liquid chromatographic (HPLC) method for the determination of coumarin-3-carboxylic acid (C3A) in the heart and liver issue of Sprague-Dawley (SD) rats after intragastric administration of extractive of leaves of Ficus virens var sublanceolata. And simple ADME and target prediction analyses were performed for C3A. Ethyl acetate was employed to precipitate protein with appropriate sensitivity and acceptable matrix effects. The satisfactory separation was developed on an ODS2 column (4.6 mm 3 250 mm, 5 mu m) by gradient elution with a methanol-acetic acid solution (pH 5 3.0) as the mobile phase. The flow rate was 1.0 mL min-1, the column temperature was maintained at 30 +/- 2 8C, the injection volume was 20 mu L, and the detection wavelength was set as 309 nm. The method was fully validated in terms of selectivity, linearity, accuracy, precision, extraction recovery and stability. The results of the ADME analysis found that C3A has excellent characteristics of drug-likeness, consistent with good bio-absorption. And the predicted 12 target protein belongs to the amine oxidoreductase and carbonic anhydrase target class. This method is simple, rapid, sensitive, and accurate for the determination of coumarin-3-carboxylic acid in the heart and liver tissue of SD rats.