Improving Sensitivity and Reproducibility of Surface-Enhanced Raman Scattering Biochips Utilizing Magnetoplasmonic Nanoparticles and Statistical Methods.

Surface-enhanced Raman scattering (SERS) technology has been widely recognized for its remarkable sensitivity in biochip development. This study presents a novel sandwich immunoassay that synergizes SERS with magnetoplasmonic nanoparticles (MPNs) to improve sensitivity. By taking advantage of the unique magnetism of these nanoparticles, we further enhance the detection sensitivity of SERS biochips through the applied magnetic field. Despite the high sensitivity, practical applications of SERS biochips are often limited by the issues of stability and reproducibility. In this study, we introduced a straightforward statistical method known as "Gaussian binning", which involves initially binning the two-dimensional Raman mapping data and subsequently applying Gaussian fitting. This approach enables a more consistent and reliable interpretation of data by reducing the variability inherent in Raman signal measurements. Based on our method, the biochip, targeting for C-reactive protein (CRP), achieves an impressive detection limit of 5.96 fg/mL, and with the application of a 3700 G magnetic field, it further enhances the detection limit by 5.7 times, reaching 1.05 fg/mL. Furthermore, this highly sensitive and magnetically tunable SERS biochip is easily designed for versatile adaptability, enabling the detection of other proteins. We believe that this innovation holds promise in enhancing the clinical applicability of SERS biochips.

Antiviral therapy reduces hepatocellular carcinoma through suppressing hepatitis B virus replication may improve ER stress, mitochondrial and metabolic dysfunctions and decrease p62 in hybridized mice with single HBV transgene and miR-122.

Hepatitis B virus (HBV) hijacks autophagy for its replication. Nucleos(t)ide analogs (NUCs) treatment suppressed HBV replication and reduced hepatocellular carcinoma (HCC) incidence. However, the use of NUCs in chronic hepatitis B (CHB) patients with normal or minimally elevated serum alanine aminotransferase (ALT) levels is still debated. Animal models are crucial for studying the unanswered issue and evaluating new therapies. MicroRNA-122 (miR-122), which regulates fatty acid and cholesterol metabolism, is downregulated during hepatitis and HCC progression. The reciprocal inhibition of miR-122 with HBV highlights its role in HCC development as a tumor suppressor. By crossbreeding HBV-transgenic mice with miR-122 knockout mice, we generated a hybrid mouse model with a high incidence of HCC up to 89% and normal ALT levels before HCC. The model exhibited early-onset hepatic steatosis, progressive liver fibrosis, and impaired late-phase autophagy. Metabolomics and microarray analysis identified metabolic signatures, including dysregulation of lipid metabolism, inflammation, genomic instability, the Warburg effect, reduced TCA cycle flux, energy deficiency, and impaired free radical scavenging. Antiviral treatment reduced HCC incidence in hybrid mice by approximately 30-35% compared to untreated mice. This effect was linked to the activation of ER stress-responsive transcription factor ATF4, clearance of autophagosome cargo p62, and suppression of the CHOP-mediated apoptosis pathway. In summary, this study suggests that despite minimal ALT elevation, HBV replication can lead to liver injury. Endoplasmic reticulum stress, reduced miR-122 levels, mitochondrial and metabolic dysfunctions, blocking protective autophagy resulting in p62 accumulation, apoptosis, fibrosis, and HCC. Antiviral may improve the above-mentioned pathogenesis through HBV suppression.