Adaptive-modulated fast fluctuation super-resolution microscopy.

Fluorescence microscopy has significantly advanced biological imaging at the nanoscale, particularly with the advent of super-resolution microscopy (SRM), which transcends the Abbe diffraction limit. Most cutting-edge SR methods require high-precision optical setups, which constrain the widespread adoption of SRM. Fluorescence fluctuation-based SRM (FF-SRM) can break the diffraction limit without complex optical components, making it particularly well-suited for biological imaging.

Development of a carboxymethyl chitosan functionalized slide for small molecule detection using oblique-incidence reflectivity difference technology.

Label-free optical biosensors have become powerful tools in the study of biomolecular interactions without the need for labels. High throughput and low detection limit are desirable for rapid and accurate biomolecule detection. The oblique-incidence reflectivity difference (OI-RD) technique is capable of detecting thousands of biomolecular interactions in a high-throughput mode, specifically for biomolecules larger than 1000 Da.

Visualizing highly bright and uniform cellular ultrastructure by expansion-microscopy with tetrahedral DNA nanostructures.

Expansion Microscopy (ExM) is a widely used super-resolution technique that enables imaging of structures beyond the diffraction limit of light. However, ExM suffers from weak labeling signals and expansion distortions, limiting its applicability. Here, we present an innovative approach called Tetrahedral DNA nanostructure Expansion Microscopy (TDN-ExM), addressing these limitations by using tetrahedral DNA nanostructures (TDNs) for fluorescence labeling.

Non-invasive screening of bladder cancer using digital microfluidics and FLIM technology combined with deep learning.

Non-invasive screening for bladder cancer is crucial for treatment and postoperative follow-up. This study combines digital microfluidics (DMF) technology with fluorescence lifetime imaging microscopy (FLIM) for urine analysis and introduces a novel non-invasive bladder cancer screening technique. Initially, the DMF was utilized to perform preliminary screening and enrichment of urine exfoliated cells from 54 participants, followed by cell staining and FLIM analysis to assess the viscosity of the intracellular microenvironment.

P53 upregulation by USP7-engaging molecular glues.

Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation. Identifying molecular glues is challenging. There is a scarcity of target-specific upregulating molecular glues, which are highly anticipated for numerous targets, including P53.

Analysis of Fluid Replacement in Two Fluidic Chambers for Oblique-Incidence Reflectivity Difference (OI-RD) Biosensor.

Optical biosensors have a significant impact on various aspects of our lives. In many applications of optical biosensors, fluidic chambers play a crucial role in facilitating controlled fluid delivery. It is essential to achieve complete liquid replacement in order to obtain accurate and reliable results.

Enhancing the photodynamic effect of curcumin through modification with TiO nanoparticles and cationic polymers.

Curcumin (CUR), a natural compound extracted from turmeric, has shown potential as a photosensitizer in photodynamic therapy (PDT). The aim of this work was to enhance the efficacy of CUR by modifying it using titanium dioxide (TiO) nanoparticles and a cationic polymer called Sofast to create a nanocomposite TiO-CUR-Sofast (TCS). Compared to unmodified CUR, TCS exhibited a broadening toward longer wavelength in the absorption wavelength within the 400-550 nm range, leading to improved CUR absorption.

Closed, one-stop intelligent and accurate particle characterization based on micro-Raman spectroscopy and digital microfluidics.

Monoclonal antibodies are prone to form protein particles through aggregation, fragmentation, and oxidation under varying stress conditions during the manufacturing, shipping, and storage of parenteral drug products. According to pharmacopeia requirements, sub-visible particle levels need to be controlled throughout the shelf life of the product. Therefore, in addition to determining particle counts, it is crucial to accurately characterize particles in drug product to understand the stress condition of exposure and to implement appropriate mitigation actions for a specific formulation.

Detection speed optimization of the OI-RD microscope for ultra-high throughput screening.

The oblique-incidence reflectivity difference (OI-RD) microscope is a label-free detection system for microarrays that has many successful applications in high throughput drug screening. The increase and optimization of the detection speed of the OI-RD microscope will enable it to be a potential ultra-high throughput screening tool. This work presents a series of optimization methods that can significantly reduce the time to scan an OI-RD image.

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity.

Enhancing chemosensitivity is one of the largest unmet medical needs in cancer therapy. Cyclic GMP-AMP synthase (cGAS) connects genome instability caused by platinum-based chemotherapeutics to type I interferon (IFN) response. Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator.

Early Detection of Cervical Cancer by Fluorescence Lifetime Imaging Microscopy Combined with Unsupervised Machine Learning.

Cervical cancer has high morbidity and mortality rates, affecting hundreds of thousands of women worldwide and requiring more accurate screening for early intervention and follow-up treatment. Cytology is the current dominant clinical screening approach, and though it has been used for decades, it has unsatisfactory sensitivity and specificity. In this work, fluorescence lifetime imaging microscopy (FLIM) was used for the imaging of exfoliated cervical cells in which an endogenous coenzyme involved in metabolism, namely, reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H], was detected to evaluate the metabolic status of cells.

Emerging degrader technologies engaging lysosomal pathways.

Targeted protein degradation (TPD) provides unprecedented opportunities for drug discovery. While the proteolysis-targeting chimera (PROTAC) technology has already entered clinical trials and changed the landscape of small-molecule drugs, new degrader technologies harnessing alternative degradation machineries, especially lysosomal pathways, have emerged and broadened the spectrum of degradable targets. We have recently proposed the concept of autophagy-tethering compounds (ATTECs) that hijack the autophagy protein microtubule-associated protein 1A/1B light chain 3 (LC3) for targeted degradation.

Visible Particle Identification Using Raman Spectroscopy and Machine Learning.

Visible particle identification is a crucial prerequisite step for process improvement and control during the manufacturing of injectable biotherapeutic drug products. Raman spectroscopy is a technology with several advantages for particle identification including high chemical sensitivity, minimal sample manipulation, and applicability to aqueous solutions. However, considerable effort and experience are required to extract and interpret Raman spectral data.

Application of Dual-Enhanced Surface-Enhanced Raman Scattering Probe Technology in the Diagnosis of Tumor Cells in Vitro.

With the development of precision medicine, antigen/antibody-targeted therapy has brought great hope to tumor patients; however, the migration of tumor cells, especially a small number of cells flowing into blood or other tissues, remains a clinical challenge. In particular, it is difficult to use functional gold nanomaterials for targeted clinical tumor diagnosis while simultaneously obtaining stable and highly sensitive Raman signals. Therefore, we developed a detection method for functional Au Nanostars (AuNSs) with dual signal enhancement that can specifically track location and obtain high-intensity surface-enhanced Raman scattering (SERS) signals.

CDK inhibitor Palbociclib targets STING to alleviate autoinflammation.

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators.

Tunable optofluidic microbubble lens.

Optofluidic microlenses are one of the crucial components in many miniature lab-on-chip systems. However, many optofluidic microlenses are fabricated through complex micromachining and tuned by high-precision actuators. We propose a kind of tunable optofluidic microbubble lens that is made by the fuse-and-blow method with a fiber fusion splicer.

Suppression of toxicity of the mutant huntingtin protein by its interacting compound, desonide.

Identifying inhibitors of pathogenic proteins is the major strategy of targeted drug discoveries. This strategy meets challenges in targeting neurodegenerative disorders such as Huntington’s disease (HD), which is mainly caused by the mutant huntingtin protein (mHTT), an “undruggable” pathogenic protein with unknown functions. We hypothesized that some of the chemical binders of mHTT may change its conformation and/or stability to suppress its downstream toxicity, functioning similarly to an “inhibitor” under a broader definition.

Single cell sorting of young yeast based on label-free fluorescence lifetime imaging microscopy.

Saccharomyces cerevisiae is an attractive organism used in the fermentation industry and is an important model organism for virus research. The ability to sort yeast cells is important for diverse applications. Replicative aging of Saccharomyces Cerevisiae is accompanied by metabolic changes that are related to an essential coenzyme, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H).

Dynamic Structure of Yeast Septin by Fast Fluctuation-Enhanced Structured Illumination Microscopy.

When divides, a structure composed of different septin proteins arranged according to a certain rule is formed at the cell division site. The structure undergoes multiple remodeling stages during the cell cycle, thus guiding the yeast cells to complete the entire division process. Although the higher-order structure of septins can be determined using electron microscopy, the septin's dynamic processes are poorly understood because of limitations in living cell super-resolution imaging technology.

Metabolic Changes in Maternal and Cord Blood in One Case of Pregnancy-Associated Breast Cancer Seen by Fluorescence Lifetime Imaging Microscopy.

Pregnancy-associated breast cancer (PABC) is a rare disease, which is frequently diagnosed at an advanced stage due to limitations in current diagnostic methods. In this study, fluorescence lifetime imaging microscopy (FLIM) was used to study the metabolic changes by measuring maternal blood and umbilical cord blood via the autofluorescence of coenzymes, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), and flavin adenine dinucleotide (FAD). The NAD(P)H data showed that a PABC case had significant differences compared with normal cases, which may indicate increased glycolysis.

High Performance of a Metal Layer-Assisted Guided-Mode Resonance Biosensor Modulated by Double-Grating.

Guided-mode resonance (GMR) sensors are widely used as biosensors with the advantages of simple structure, easy detection schemes, high efficiency, and narrow linewidth. However, their applications are limited by their relatively low sensitivity (<200 nm/RIU) and in turn low figure of merit (FOM, <100 1/RIU). Many efforts have been made to enhance the sensitivity or FOM, separately.

Application of SNAP-Tag in Expansion Super-Resolution Microscopy Using DNA Oligostrands.

Expansion super-resolution technology is a new technology developed in recent years. It anchors the dye on the hydrogel and the dye expands with the expansion of the hydrogel so that a super-resolution map can be obtained under an ordinary microscope. However, by labeling the target protein with a first antibody and secondary antibody, the distance between the fluorescent group and the actual target protein is greatly increased.

Label-free and noninvasive method for assessing the metabolic status in type 2 diabetic rats with myocardium diastolic dysfunction.

This study assesses the metabolic status of rat diabetic cardiomyopathy (DCM) models. Echocardiography is used to detect the diastolic dysfunction in type 2 diabetic rats, and a lower threshold for inducible atrial fibrillation is found in type 2 diabetic rats with diastolic dysfunction compared to the control. Metabolic abnormalities are detected by status changes of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), which is an essential coenzyme in cells or tissues.