Bioreaction-Compatible Bivariate Lanthanide MOF Sensor Enables Stimulus-Multiresponsive Platform for ctDNA On-Site Detection.

Detection of circulating tumor DNA (ctDNA) in liquid biopsy is of great importance for tumor diagnosis but difficult due to its low amount in bodily fluids. Herein, a novel ctDNA detection platform is established by quantifying DNA amplification by-product pyrophosphate (PPi) using a newly designed bivariable lanthanide metal-organic framework (Ln-MOF), namely, Ce/Eu-DPA MOF (CE-24, DPA = pyridine-2,6-dicarboxylic acid). CE-24 MOF exhibits ultrafast dual-response (fluorescence enhancement and enzyme-activity inhibition) to PPi stimuli by virtue of host-guest interaction. The platform is applied to detecting colon carcinoma-related ctDNA (KARS G12D mutation) combined with the isothermal nucleic acid exponential amplification reaction (EXPAR). ctDNA triggers the generation of a large amount of PPi, and the ctDNA quantification is achieved through the ratio fluorescence/colorimetric dual-mode assay of PPi. The combination of the EXPAR and the dual-mode PPi sensing allows the ctDNA assay method to be low-cost, convenient, bioreaction-compatible (freedom from the interference of bioreaction systems), sensitive (limit of detection down to 101 fM), and suitable for on-site detection. To the best of our knowledge, this work is the first application of Ln-MOF for ctDNA detection, and it provides a novel universal strategy for the rapid detection of nucleic acid biomarkers in point-of-care scenarios.

Enhancing Kinase Activity Detection with a Programmable Lanthanide Metal-Organic Framework via ATP-to-ADP Conversion.

Precise modulation of host-guest interactions between programmable Ln-MOFs (lanthanide metal-organic frameworks) and phosphate analytes holds immense promise for enabling novel functionalities in biosensing. However, the intricate relationship between these functionalities and structures remains largely elusive. Understanding this correlation is crucial for advancing the rational design of fluorescent biosensor technology. Presently, there exists a large research gap concerning the utilization of Ln-MOFsto monitor the conversion of ATP to ADP, which poses a limitation for kinase detection. In this work, we delve into the potential of Ln-MOFs to amplify the fluorescence response during the kinase-mediated ATP-to-ADP conversion. Six Eu-MOFs were synthesized and Eu-TPTC ([1,1':4',1″]-terphenyl-3,3'',5,5''-tetracarboxylic acid) was selected as a ratiometric fluorescent probe, which is most suitable for high-precision detection of creatine kinase activity through the differential response from ATP to ADP. The molecular -level mechanism was confirmed by density functional theory. Furthermore, a simple paper chip-based platform was constructed to realize the fast (20 min) and sensitive (limit of detection is 0.34 U/L) creatine kinase activity detection in biological samples. Ln-MOF-phosphate interactions offer promising avenues for kinase activity assays and hold the potential for precise customization of analytical chemistry.

Bioinspired Heterocoordination in Adaptable Cobalt Metal-Organic Framework for DNA Epigenetic Modification Detection.

Metal-organic frameworks (MOFs) show unique advantages in simulating the dynamics and fidelity of natural coordination. Inspired by zinc finger protein, a second linker was introduced to affect the homogeneous MOF system and thus facilitate the emergence of diverse functionalities. Under the systematic identification of 12 MOF species (i.e., metal ions, linkers) and 6 second linkers (trigger), a dissipative system consisting of Co-BDC-NO2 and o-phenylenediamine (oPD) was screened out, which can rapidly and in situ generate a high photothermal complex (η = 36.9%). Meanwhile, both the carboxylation of epigenetic modifications and metal ion (Fe3+, Ni2+, Cu2+, Zn2+, Co2+ and Mn2+) screening were utilized to improve the local coordination environment so that the adaptable Co-MOF growth on the DNA strand was realized. Thus, epigenetic modification information on DNA was converted to an amplified metal ion signal, and then oPD was further introduced to generate bimodal dissipative signals by which a simple, high-sensitivity detection strategy of 5-hydroxymethylcytosine (LOD = 0.02%) and 5-formylcytosine (LOD = 0.025‰) was developed. The strategy provides one low-cost method (< 0.01 $/sample) for quantifying global epigenetic modifications, which greatly promotes epigenetic modification-based early disease diagnosis. This work also proposes a general heterocoordination design concept for molecular recognition and signal transduction, opening a new MOF-based sensing paradigm.

Effects of Hydrogen Inhalation on Neurological Function Indicators, Oxidative Stress Markers, and E-Cadherin Levels in Patients with Brain Glioma.

Objective: This study aims to evaluate the effects of hydrogen therapy on nerve function and tumor progression markers in glioma patients, focusing on the modulation of oxidative stress and cadherin expression to establish its potential as a complementary treatment. Methods: 100 glioma patients were enrolled and divided into two groups using the random number table: routine treatment (50) and hydrogen inhalation plus routine treatment (50). After 2 weeks of treatment, clinical curative effect, levels of nerve function indexes [national institute of health stroke scale (NIHSS), central nervous specific protein (S100ß), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP)], oxidative stress indexes [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)] and E-cadherin before and after treatment, and occurrence of adverse reactions during treatment were compared between the two groups. Results: After treatment, the overall effect of the hydrogen inhalation group (90.00%) was significantly better than that of the conventional group (72.00%), which was statistically significant (P = .022). In terms of specific biomarkers, post-treatment levels of E-cadherin were elevated to 0.84±0.05 ng/mL in the hydrogen group compared to 0.72±0.06 ng/mL in the routine group. SOD and CAT levels rose to 63.21±5.36 U/L and 8.01±0.54 U/mL, respectively, versus 52.31±5.24 U/L and 5.25±0.59 U/mL in the routine group (P < .05 for both). Conversely, the NIHSS scores decreased significantly to 12.19±2.08 in the hydrogen group, compared to 16.92±2.23 in the routine group. Similarly, S100ß, NSE, GFAP, and MDA levels were found to be lower in the hydrogen group (0.41±0.09 µg/L, 8.24±1.64 ng/mL, 0.71±0.23 pg/mL, and 6.05±1.08 mmol/L respectively) than in the routine group (0.66±0.12 µg/L, 10.67±1.83 ng/mL, 0.93±0.29 pg/mL, and 7.21±1.12 mmol/L respectively) with P < .05 for all comparisons. The total incidence of adverse reactions was slightly lower in the hydrogen group (64.00%) compared to the routine group (68.00%), but this difference was not statistically significant (χ2=0.178, P = .673). Conclusion: Hydrogen inhalation therapy significantly enhances nerve function, reduces local oxidative stress levels, and increases E-cadherin levels in patients with brain glioma, suggesting its potential as an adjunct treatment. The findings underscore the therapy's role in enhancing patient recovery and guiding future research and treatment strategies.