ABSTRACT
Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained ß cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory ß cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy.
ABSTRACT
The application of porphyrin metal-organic frameworks (MOFs) as a ratiometric electrochemical sensing platform is still unexplored. In this paper, we report a ratiometric electrochemical sensor by the integration of multiple redox centers into porphyrin MOFs for the detection of dissolved oxygen (DO). Specifically, the ferrocene (Fc) group was integrated into the nanosized PCN-222(Fe) (PCN = porous coordination networks) via acid-base reaction to synthesize the Fc@PCN-222(Fe) composite with two redox centers of the Fc group and Fe-porphyrin. The Fc group that is insensitive to DO serves as an internal reference, and the Fe-porphyrin in PCN-222(Fe) is a DO indicator. The ratios of the cathodic currents for the two redox centers exhibit a linear relationship with DO concentrations from 2.8 to 28.9 mg mL-1 and a limit of detection of 0.3 mg mL-1. In addition, the ratiometric electrochemical sensor has high selectivity and stability for DO sensing results from the Fc@PCN-222(Fe) composite. Because there are numerous redox centers, such as methylene blue and thionine, which can be integrated into MOFs, many MOF-based ratiometric electrochemical sensors can be simply developed for high-performance biosensing.
ABSTRACT
Herein, we have constructed a target-triggered and DNA walker-mediated biosensor with triple signal (BTS) outputs mode for sensitive and reliable detection of pathogenic bacteria. Vibrio parahaemolyticus (VP) being the detection target model, the aptamer conformational changes induced by VP have been designed to activate the DNA walk on the modifiable and conductive surface of Fe3O4 nanoparticles to generate triple signal outputs, including electrochemiluminescence (ECL), fast scan cyclic voltammetry (FSCV) and fluorescent pixel counting (FLPC). Limits of quantification (LOQ) of VP were as low as 1 CFUâ mL-1 by ECL with a linear range of 1-106 CFUâ mL-1, 1 CFUâ mL-1 by FSCV with a linear range of 1-106 CFUâ mL-1, and 10 CFUâ mL-1 by FLPC with a linear range of 10-107 CFUâ mL-1 respectively, all squared correlation coefficients R2 being > 0.99. In addition, optical and electrochemical results, signal-on and signal-off results, electrode phase and solution phase results could be mutually verified by integrating of multiple detection techniques in one biosensor, greatly improving the accuracy and reliability. Therefore, the designed BTS has provided a powerful strategy for pathogenic bacteria detection considering its high detection sensitivity and accuracy, exhibiting great potential in food safety, water quality and biological contamination.