Progress in the Computer-Aided Analysis in Multiple Aspects of Nanocatalysis Research.

Making the utmost of the differences and advantages of multiple disciplines, interdisciplinary integration breaks the science boundaries and accelerates the progress in mutual quests. As an organic connection of material science, enzymology, and biomedicine, nanozyme-related research is further supported by computer technology, which injects in new vitality, and contributes to in-depth understanding, unprecedented insights, and broadened application possibilities. Utilizing computer-aided first-principles method, high-speed and high-throughput mathematic, physic, and chemic models are introduced to perform atomic-level kinetic analysis for nanocatalytic reaction process, and theoretically illustrate the underlying nanozymetic mechanism and structure-function relationship.

A deep learning based holistic diagnosis system for immunohistochemistry interpretation and molecular subtyping.

Background: Breast cancer in different molecular subtypes, which is determined by the overexpression rates of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), and Ki67, exhibit distinct symptom characteristics and sensitivity to different treatment. The immunohistochemical method, one of the most common detecting tools for tumour markers, is heavily relied on artificial judgment and in clinical practice, with an inherent limitation in interpreting stability and operating efficiency. Here, a holistic intelligent breast tumour diagnosis system has been developed for tumour-markeromic analysis, combining the automatic interpretation and clinical suggestion.

A pH-Mediated Highly Selective System Enabling Simultaneous Analysis of Circulating RNAs Carried by Extracellular Vesicles and Lipoproteins.

Extracellular vesicles (EVs) and lipoproteins (LPPs) serve as important carriers of circulating miRNAs in peripheral blood, offering immense potential for disease diagnosis and therapeutic interventions. Due to their shared physicochemical attributes, EVs and LPPs are frequently coisolated, potentially leading to misunderstandings regarding their distinct functional roles in physiological and pathological processes. Here, we report a highly selective magnetic system based on the pH-mediated affinity displayed by cibacron blue (CB) toward EVs and LPPs, enabling successful separation and collection of these two nanoparticles without cross-contamination for subsequent circulating RNA analysis.

Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis.

Background: Severe acute pancreatitis (SAP) is the most common gastrointestinal disease and is associated with unpredictable seizures and high mortality rates. Despite improvements in the treatment of acute pancreatitis, the timely and accurate diagnosis of SAP remains highly challenging. Previous research has shown that extracellular vesicles (EVs) in the plasma have significant potential for the diagnosis of SAP since the pancreas can release EVs that carry pathological information into the peripheral blood in the very early stages of the disease.

Artificial Intelligence-Aided Multiple Tumor Detection Method Based on Immunohistochemistry-Enhanced Dark-Field Imaging.

The immunohistochemical method serves as one of the most practical tools in clinical cancer detection and thus has great application value to overcome the existing limits of the conventional method and further improve the detecting efficiency and sensitivity. This study employed 3,3'-diaminobenzidine (DAB), a conventional color indicator for immunohistochemistry, as a novel high-sensitive scattering reagent to provide a multidimensional image signal varying with the overexpression rate of tumor markers. Based on the scattering properties of DAB aggregates, an efficient and robust artificial intelligence-aided immunohistochemical method based on dark-field imaging has been established, with improvement in both the imaging quality and interpretation efficiency in comparison with the conventional manual-operated immunohistochemical method.

Metabolomic analysis of exosomal-markers in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a worldwide malignancy with high mortality rates and poor prognosis due to the lack of effective biomarkers for early detection. Exosomes have been extensively explored as attractive biomarkers for cancer diagnosis and treatment. However, little is known about exosome metabolomics and their roles in ESCC.

Ultrafiltration combing with phospholipid affinity-based isolation for metabolomic profiling of urinary extracellular vesicles.

Recent years have seen the field of extracellular vesicle (EV) studies burgeoning. This is mainly because EV constituents including nucleic acid, proteins, lipids, and metabolites are promising sources towards disease biomarker discovery. However, EV study remains challenging due to the complexity of biofluids as well as technical limitations during sample preparation.

Exosome detection via the ultrafast-isolation system: EXODUS.

Exosomes have shown great potential in disease diagnostics and therapeutics. However, current isolation approaches are burdensome and suffer from low speed, yield and purity, limiting basic research and clinical applications. Here, we describe an efficient exosome detection method via the ultrafast-isolation system (EXODUS) that allows automated label-free purification of exosomes from varied biofluids.

Deep dive on the proteome of salivary extracellular vesicles: comparison between ultracentrifugation and polymer-based precipitation isolation.

Salivary extracellular vesicles (EVs), as novel functional carriers and potential biomarkers, are usually obtained by ultracentrifugation (UC) and polyethylene glycol (PEG)-based precipitation methods. However, salivary EVs obtained by these two methods have not been systematically compared. Here, we perform an in-depth analysis on EVs isolated by these two methods using proteomics.

An integrative microfluidic device for isolation and ultrasensitive detection of lung cancer-specific exosomes from patient urine.

Exosomes, derived from various biofluids, may serve as potential biomarkers for cancer early detection. Nevertheless, exosome clinical translation remains challenging due to the lack of reliable isolation and detection methods. Herein, we present a novel integrated microfluidic device specifically designed for isolation and in-situ detection of lung cancer-specific exosomes collected from patient's urine.

High-Efficiency Separation of Extracellular Vesicles from Lipoproteins in Plasma by Agarose Gel Electrophoresis.

Isolation and purification of extracellular vesicles (EVs) from plasma is essential to understand the EV circulation mechanism and discover biomarkers for the early detection of diseases. However, the size range of lipoprotein particles such as high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) overlap that of EVs, making it difficult to remove lipoproteins from EVs. Here, we propose a method for the high efficiency separation of EVs in plasma using agarose gel electrophoresis based on their differences in size and zeta potential properties.

Antibody-Oriented Strategy and Mechanism for the Preparation of Fluorescent Nanoprobes for Fast and Sensitive Immunodetection.

Nanoprobes have been widely used in biomedical engineering. However, antibodies are generally conjugated onto nanoparticles disorderly, which reduces their antigen recognition ability. The existing antibody orientation approaches are usually complex.

A Rapid Test Strip for Diagnosing Glycosylated Hemoglobin (HbA1c) Based on Fluorescent Affinity Immunochromatography.

In this research, we developed a rapid and easy-to-operate point-of-care testing (POCT) strip based on fluorescent affinity immunochromatography to quantitatively determine HbA1c concentrations in whole blood. This assay, based on a sandwich method performed on test strips, effectively utilized the principle of an affinity chromatography column, which was commonly used in the detection of HbA1c, and the technology of traditional fluorescence immunochromatographic test strips (FICTS) were combined. In our test strips, the test line of traditional FICTS was transformed into the region of affinity chromatography, while improving the linearity and reducing the interference of the precursor of HbA1c and hemoglobin variants.

Fluorescent Nanoprobes with Oriented Modified Antibodies to Improve Lateral Flow Immunoassay of Cardiac Troponin I.

Performance of nanoprobes can often determine the detection level of Lateral immunochromatography. Traditional probes were limited by the quantity and orientation of antibodies, immune activity of the Fab region or binding strength between protein and substrate. This study developed a new efficient and robust technology to construct fluorescent nanoprobes with oriented modified antibodies, based on specific binding of the Fc region of antibody with streptococcal protein G (SPG) on the surface of polystyrene microspheres (MS) and subsequent covalent cross-linking at binding sites to firm them.

Peroxidase-Like Activity of Gold Nanoparticles and Their Gold Staining Enhanced ELISA Application.

We found that the peroxidase-like activity of gold nanoparticles (GNPs) followed the Michaelis-Menten kinetic model and was dependent on environmental pH and temperature, which was very similar to natural Horseradish Peroxidase (HRP). However, unlike HRP, which needs a lower H2O2 concentration with a very narrow range to reach a maximum reaction rate and avoid enzyme poisoning, GNPs have very high activity, even at an H2O2 concentration two orders of magnitude higher than HRP. It was demonstrated that H2O2 treatment could enhance the peroxidase-like activity of GNPs, resulting thus in the activity increase in a circular catalytic reaction by the reduplicative use of GNPs.

Enzyme catalysis enhanced dark-field imaging as a novel immunohistochemical method.

Conventional immunohistochemistry is limited to subjective judgment based on human experience and thus it is clinically required to develop a quantitative immunohistochemical detection. 3,3'-Diaminobenzidin (DAB) aggregates, a type of staining product formed by conventional immunohistochemistry, were found to have a special optical property of dark-field imaging for the first time, and the mechanism was explored. On this basis, a novel immunohistochemical method based on dark-field imaging for detecting HER2 overexpressed in breast cancer was established, and the quantitative analysis standard and relevant software for measuring the scattering intensity was developed.

Rituximab-Au nanoprobes for simultaneous dark-field imaging and DAB staining of CD20 over-expressed on Raji cells.

A novel dual-modal cell immunodetection method based on both dark-field imaging and catalysis functions of gold nanoparticles has been established, where the Rituximab-Au conjugates were used as nanoprobes to label and image specifically the CD20 overexpressed on the surface of malignant lymphoma cells of Raji with high affinity.