Multiplex Profiling of miR-122 for Preclinical and Clinical Evaluation of Drug-Induced Liver Injury by a Full-Scale Platform.

Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence in situ hybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.

Strand displacement-triggered FRET nanoprobe tracking TK1 mRNA in living cells for ratiometric fluorimetry of nucleic acid biomarker.

A precisely designed dual-color biosensor has realized a visual assessment of thymidine kinase 1 (TK1) mRNA in both living cells and cell lysates. The oligonucleotide probe is constructed by hybridizing the antisense strand of the target and two recognition sequences, in which FAM serves as the donor and TAMRA as the acceptor. Once interacting with the target, two recognition strands are replaced, and then the antisense complementary sequence forms a more stable double-stranded structure. Due to the increasing spatial distance between two dyes, the FRET is attenuated, leading to a rapid recovery of FAM fluorescence and a reduction of TAMRA fluorescence. A discernible color response from orange to green could be observed by the naked eye, with a limit of detection (LOD) of 0.38 nM and 5.22 nM for spectrometer- and smartphone-based assays, respectively. The proposed ratiometric method transcends previous reports in its capacities in visualizing TK1 expression toward reliable nucleic acid biomarker analysis, which might establish a general strategy for ratiometric biosensing via strand displacement.

Prenatal PM2.5 exposure increases the risk of adverse pregnancy outcomes: evidence from meta-analysis of cohort studies.

Adverse pregnancy outcomes (APOs) are a significant cause of fetal death. A wide range of maternal psychological, social, and environmental factors may contribute to these outcomes. Mounting epidemiological studies have indicated that PM2.5 may result in these unfavorable consequences. Previously published meta-analyses have been updated and extended. Cohort studies were searched from three databases (up to July 24, 2023), and their quality was assessed by Newcastle-Ottawa Scale (NOS). Publication bias was examined by Egger's test and funnel plot. Despite a large number of studies showing similar results, the inconsistencies between these findings require careful generalization before concluding. This meta-analysis included 67 cohort studies from 20 countries, and the findings revealed that maternal PM2.5 exposure and five APOs were correlated significantly throughout pregnancy: preterm birth (PTB) (RR = 1.05; 95% CI: 1.03, 1.07); low birth weight (LBW) (RR = 1.02; 95% CI: 1.01, 1.04); small for gestational age (SGA) (RR = 1.03; 95% CI: 1.01, 1.04); stillbirth (RR = 1.24; 95% CI: 1.06, 1.45); and change in birthweight (weight change = -6.82 g; 95% CI: -11.39, -2.25). A positive association was found between APOs and PM2.5 exposure in this meta-analysis, and the degree of increased risk of APOs varied due to different gestation periods. Therefore, it is necessary to protect pregnant women at specific times.

Two birds with one stone: Ratiometric sensing platform overcoming cross-interference for multiple-scenario detection and accurate discrimination of tetracycline analogs.

Environmental pollution caused by tetracycline antibiotics (TCs) is a major concern for public health worldwide. Trace detection and reliable discrimination of tetracycline and its analogs are consequently essential to determine the distribution characteristics of various tetracycline family members. Here, a dual-response sensor was constructed by integrating the fluorescence emission of fluorescein isothiocyanate (FITC) doped SiO2 and Eu3+. A portable Lab-on-Paper device is further fabricated through probe immobilization, which allows convenient visual detection of tetracycline using a smartphone. In addition, for the coexistence of multiple tetracycline analogs, dimensionality reduction via principal component analysis is applied to the spectra, realizing accurate differentiation of the four most widely used tetracycline analogs (tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline (DOX)). The dual-response nanoplatform enabled a wide-gamut color variation crossing from green to red, with limit of detection (LOD) of 2.9 nM and 89.8 nM for spectrometer- and paper-based sensors, respectively. Analytical performance was examined in multiple real samples, including food, environmental, and biological settings, confirming robust environmental adaptability and resistance. Compared to previous TC sensors, this method has several notable improvements, including improved ecological safety, accessibility, reproducibility, practicality, and anti-cross-interference capacity. These results highlight the potential of the proposed "two birds with one stone" strategy, providing an integrated methodology for synchronous quantitative detection and derivative identification toward environmental contaminants.

Pyroptosis in neurodegenerative diseases: from bench to bedside.

The central nervous system regulates all aspects of physiology to some extent. Neurodegenerative diseases (NDDs) lead to the progressive loss and dysfunction of neurons, which are particularly evident in Alzheimer's disease, Parkinson's disease, and many other conditions. NDDs are multifactorial diseases with complex pathogeneses, and there has been a rapid increase in the prevalence of NDDs. However, none of these diseases can be cured, making the development of novel treatment strategies an urgent necessity. Numerous studies have indicated how pyroptosis induces inflammation and affects many aspects of NDD. Therefore, components related to pyroptosis are potential therapeutic candidates and are attracting increasing attention. Here, we review the role of pyroptosis in the pathogenesis of NDDs and potential treatment options. Additionally, several of the current drugs and relevant inhibitors are discussed. Through this article, we provide theoretical support for exploring new therapeutic targets and updating clinical treatment strategies for NDDs. Notably, pyroptosis, a recently widely studied mode of cell death, is still under-researched compared to other traditional forms of cell death. Moreover, the focus of research has been on the onset and progression of NDDs, and the lack of organ-specific target discovery and drug development is a common problem for many basic studies. This urgent problem requires scientists and companies worldwide to collaborate in order to develop more effective drugs against NDDs.

DNA-enabled fluorescent-based nanosensors monitoring tumor-related RNA toward advanced cancer diagnosis: A review.

As a burgeoning non-invasive indicator for reproducible cancer diagnosis, tumor-related biomarkers have a wide range of applications in early cancer screening, efficacy monitoring, and prognosis predicting. Accurate and efficient biomarker determination, therefore, is of great importance to prevent cancer progression at an early stage, thus reducing the disease burden on the entire population, and facilitating advanced therapies for cancer. During the last few years, various DNA structure-based fluorescent probes have established a versatile platform for biological measurements, due to their inherent biocompatibility, excellent capacity to recognize nucleic and non-nucleic acid targets, obvious accessibility to synthesis as well as chemical modification, and the ease of interfacing with signal amplification protocols. After decades of research, DNA fluorescent probe technology for detecting tumor-related mRNAs has gradually grown to maturity, especially the advent of fluorescent nanoprobes has taken the process to a new level. Here, a systematic introduction to recent trends and advances focusing on various nanomaterials-related DNA fluorescent probes and the physicochemical properties of various involved nanomaterials (such as AuNP, GO, MnO2, SiO2, AuNR, etc.) are also presented in detail. Further, the strengths and weaknesses of existing probes were described and their progress in the detection of tumor-related mRNAs was illustrated. Also, the salient challenges were discussed later, with a few potential solutions.

A smartphone-based platform for ratiometric visualization of SARS-CoV-2 via an oligonucleotide probe.

COVID-19 necessitates the development of reliable and convenient diagnostic tools. In this work, a facile 3D-printed smartphone platform was constructed that achieved reliable visual detection of SARS-CoV-2 by eliminating the effect of ambient light and fixing the camera position relative to the sample. The oligonucleotide probe is modified with orange-red-emitting TAMRA working as an internal standard and green-emitting FAM serving as a sensitive sensing agent. Under 365-nm UV excitation, the emission wavelengths of TAMRA and FAM are 580 nm and 518 nm, respectively. When the probes interact with the targets, the green fluorescence gradually restores while the orange-red fluorescence remains stable. Thus, a striking color transition from orange-red to green could be observed by the naked eye. The detection limit of SARS-CoV-2 nucleic acid is 0.23 nM, and the entire process of color change could be completed in 25 min. Furthermore, the RGB value analysis of the sample solution was conducted using a smartphone for reliable and reproducible discrimination of SARS-CoV-2. The proposed smartphone platform might establish a general method for visual detection of SARS-CoV-2 nucleic acid as well as other virus-related diseases.

A simplified model for nonlinear cross-phase modulation in hybrid optical coherent system.

Cross-phase modulation (XPM) has been considered as one of the ultimate obstacles for optical coherent dense wavelength division multiplexing (DWDM) systems. In order to facilitate the XPM analysis, a simplified model was proposed. The model reduced the distributed XPM phenomena to a lumped phase modulation. The XPM phase noise was generated by a linear system which was determined by the DWDM system parameters and whose inputs were undistorted pump channel intensity waveforms. The model limitations induced by the lumped phase modulation and undistorted pumps approximations were intensively discussed and verified. The simplified model showed a good agreement with simulations and experiments for a typical hybrid optical coherent system. Various XPM phenomena were explained by the proposed model.