A novel electrochemical biosensor was constructed to detect p53 gene based on MIL-101-NH 2 (Cr) by combining target-responsive releasing and self-catalysis strategy. MIL-101-NH 2 (Cr) with suitable pore structure was used to encapsulate methylene blue (MB) as signal probe. The hairpin DNA (HP) containing rich-G sequences was used as gatekeeper to seal up the pores and avoid MB leakage through covalent immobilization. The p53 gene could hybridize with the loop portion of HP for the formation of dsDNA, which had the specific nicking site of the nicking endonuclease (Nt.BstNBI). Then Nt.BstNBI recognized the specific recognition site and cleaved HP to open the pore for releasing of MB. Meanwhile, the cleavage of HP released the target DNA to trigger the target recycling for signal amplification. More importantly, the plentiful rich-G sequences were exposed to form Hemin/G-quadruplex DNAzymes, which could unite MIL-101-NH 2 (Cr) to catalyze redox reaction of MB released by itself for signal amplification. The biosensor for p53 had wide linear range from 1×10 -14 to 1×10 -7 M and a low detection limit of 1.4×10 -15 M. The combination of target-responsive releasing and self-catalysis strategy provided a promising way for constructing ultrasensitive and simple biosensor.
Functional MRI (fMRI) and single-cell transcriptomics are pivotal in Alzheimer's disease (AD) research, each providing unique insights into neural function and molecular mechanisms. However, integrating these complementary modalities remains largely unexplored. Here, we introduce scBIT, a novel method for enhancing AD prediction by combining fMRI with single-nucleus RNA (snRNA). scBIT leverages snRNA as an auxiliary modality, significantly improving fMRI-based prediction models and providing comprehensive interpretability. It employs a sampling strategy to segment snRNA data into cell-type-specific gene networks and utilizes a self-explainable graph neural network to extract critical subgraphs. Additionally, we use demographic and genetic similarities to pair snRNA and fMRI data across individuals, enabling robust cross-modal learning. Extensive experiments validate scBIT's effectiveness in revealing intricate brain region-gene associations and enhancing diagnostic prediction accuracy. By advancing brain imaging transcriptomics to the single-cell level, scBIT sheds new light on biomarker discovery in AD research. Experimental results show that incorporating snRNA data into the scBIT model significantly boosts accuracy, improving binary classification by 3.39% and five-class classification by 26.59%. The codes were implemented in Python and have been released on GitHub (https://github.com/77YQ77/scBIT) and Zenodo (https://zenodo.org/records/11599030) with detailed instructions.
Herein, an electrochemical sensing system based on porphyrin MOFs/MXenes composites has been constructed for in situ and real-time monitoring of H2O2 released by cells. The coordination bond connected porphyrin-MOFs/Mxenes composites were synthesized by introducing 4-mercaptopyridine and utilizing its binding interaction with titanium in Mxenes and iron in MOFs. This composite was then transferred to the surface of ITO to construct an electrochemical sensing system. The unique properties of Mxenes and porphyrin MOFs endowed the sensing system with excellent electrocatalytic activity, good electrical conductivity and desirable biocompatibility. The electrochemical detections of hydroquinone verified the superior electrochemical performances of the sensing system. The constructed system achieved sensitive electrochemical detection of H2O2 with a detection limit of 3.1 μM and a linear range of 10 μM to 3 mM. Furthermore, the excellent biocompatibility of the composites ensured HeLa cells growth and proliferation on its surface. Based on these favorable properties, the sensing system successfully achieved in-situ and real-time monitoring of H2O2 released by HeLa cells.
Prodigiosin is an important secondary metabolite produced by Serratia marcescens. It can help strains resist stresses from other microorganisms and environmental factors to achieve self-preservation. Prodigiosin is also a promising secondary metabolite due to its pharmacological characteristics. However, pigmentless S. marcescens mutants always emerge after prolonged starvation, which might be a way for the bacteria to adapt to starvation conditions, but it could be a major problem in the industrial application of S. marcescens. To identify the molecular mechanisms of loss of prodigiosin production, two mutants were isolated after 16 days of prolonged incubation of wild-type (WT) S. marcescens 1912768R; one mutant (named 1912768WR) exhibited reduced production of prodigiosin, and a second mutant (named 1912768W) was totally defective. Comparative genomic analysis revealed that the two mutants had either mutations or deletions in rpoS. Knockout of rpoS in S. marcescens 1912768R had pleiotropic effects. Complementation of rpoS in the ΔrpoS mutant further confirmed that RpoS was a positive regulator of prodigiosin production and that its regulatory role in prodigiosin biosynthesis was opposite that in Serratia sp. ATCC 39006, which had a different type of pig cluster; further, rpoS from Serratia sp. ATCC 39006 and other strains complemented the prodigiosin defect of the ΔrpoS mutant, suggesting that the pig promoters are more important than the genes in the regulation of prodigiosin production. Deletion of rpoS strongly impaired the resistance of S. marcescens to stresses but increased membrane permeability for nutritional competence; competition assays in rich and minimum media showed that the ΔrpoS mutant outcompeted its isogenic WT strain. All these data support the idea that RpoS is pleiotropic and that the loss of prodigiosin biosynthesis in S. marcescens 1912768R during prolonged incubation is due to a mutation in rpoS, which appears to be a self-preservation and nutritional competence (SPANC) trade-off.
Herein, the coordination bond connected porphyrin-MOFs/MXenes composites has been prepared to construct an electrochemical sensing system for in situ and real-time monitoring of H2O2 released by cells. The composites were synthesized by introducing 4-mercaptopyridine and utilizing its binding interaction with titanium in Mxenes and iron in MOFs. This composite was then transferred to the surface of ITO to construct an electrochemical sensing system. The unique properties of Mxenes and porphyrin MOFs endowed the sensing system with excellent electrocatalytic activity, good electrical conductivity and desirable biocompatibility. The electrochemical detections of hydroquinone verified the superior electrochemical performances of the sensing system. The constructed system achieved sensitive electrochemical detection of H2O2 with a detection limit of 3.1 µM and a linear range of 10 µM to 3 mM. Furthermore, the excellent biocompatibility of the composites ensured HeLa cells growth and proliferation on its surface. Based on these favorable properties, the sensing system successfully achieved in-situ and real-time monitoring of H2O2 released by HeLa cells.
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