Near-infrared imaging for visualizing the synergistic relationship between autophagy and NFS1 protein during multidrug resistance using an ICT-TICT integrated platform.

Drug resistance is a major challenge for cancer treatment, and its identification is crucial for medical research. However, since drug resistance is a multi-faceted phenomenon, it is important to simultaneously evaluate multiple target fluctuations. Recently developed fluorescence-based probes that can simultaneously respond to multiple targets offer many advantages for real-time and in situ monitoring of cellular metabolism, including ease of operation, rapid reporting, and their non-invasive nature. As such we developed a dual-response platform (Vis-H2S) with integrated ICT-TICT to image H2S and viscosity in mitochondria, which could simultaneously track fluctuations in cysteine desulfurase (NFS1 protein and H2S inducer) and autophagy during chemotherapy-induced multidrug resistance. This platform could monitor multiple endogenous metabolites and the synergistic relationship between autophagy and NFS1 protein during multidrug resistance induced by chemotherapy. The results indicated that chemotherapeutic drugs simultaneously up-regulate the levels of NFS1 protein and autophagy. It was also found that the NFS1 protein was linked with autophagy, which eventually led to multidrug resistance. As such, this platform could serve as an effective tool for the in-depth exploration of drug resistance mechanisms.

Excited-state dynamics of 4-hydroxyisoindoline-1,3-dione and its derivative as fluorescent probes.

Fluorescent probes have become promising tools for monitoring the concentration of peroxynitrite, which is linked to many diseases. However, despite focusing on developing numerous peroxynitrite based fluorescent probes, limited emphasis is placed on their sensing mechanism. Here, we investigated the sensing mechanism of a peroxynitrite fluorescent probe, named BHID-Bpin, with a focus on the relevant excited state dynamics. The photoexcited BHID-Bpin relaxes to its ground state via an efficient nonradiative process (∼300 ps) due to the presence of a minimum energy conical intersection between its first excited state and ground state. However, upon reacting with peroxynitrite, the Bpin moiety is cleaved from BHID-Bpin and BHID is formed. The formed BHID exhibits strong dual band fluorescence which is caused by an ultrafast excited-state intramolecular proton transfer process (∼1 ps).

Advancements in Cortisol Detection: From Conventional Methods to Next-Generation Technologies for Enhanced Hormone Monitoring.

The hormone cortisol, released as the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, has a well-characterized circadian rhythm that enables an allostatic response to external stressors. When the pattern of secretion is disrupted, cortisol levels are chronically elevated, contributing to diseases such as heart attacks, strokes, mental health disorders, and diabetes. The diagnosis of chronic stress and stress related disorders depends upon accurate measurement of cortisol levels; currently, it is quantified using mass spectroscopy or immunoassay, in specialized laboratories with trained personnel. However, these methods are time-consuming, expensive and are unable to capture the dynamic biorhythm of the hormone. This critical review traces the path of cortisol detection from traditional laboratory-based methods to decentralised cortisol monitoring biosensors. A complete picture of cortisol biology and pathophysiology is provided, and the importance of precision medicine style monitoring of cortisol is highlighted. Antibody-based immunoassays still dominate the pipeline of development of point-of-care biosensors; new capture molecules such as aptamers and molecularly imprinted polymers (MIPs) combined with technologies such as microfluidics, wearable electronics, and quantum dots offer improvements to limit of detection (LoD), specificity, and a shift toward rapid or continuous measurements. While a variety of different sensors and devices have been proposed, there still exists a need to produce quantitative tests for cortisol ─ using either rapid or continuous monitoring devices that can enable a personalized medicine approach to stress management. This can be addressed by synergistic combinations of technologies that can leverage low sample volumes, relevant limit of detection and rapid testing time, to better account for cortisol's shifting biorhythm. Trends in cortisol diagnostics toward rapid and continuous monitoring of hormones are highlighted, along with insights into choice of sample matrix.

Pyrene-Appended Boronic Acids on Graphene Foam Electrodes Provide Quantum Capacitance-Based Molecular Sensors for Lactate.

Molecular recognition and sensing can be coupled to interfacial capacitance changes on graphene foam surfaces linked to double layer effects and coupled to enhanced quantum capacitance. 3D graphene foam film electrodes (Gii-Sens; thickness approximately 40 µm; roughness factor approximately 100) immersed in aqueous buffer media exhibit an order of magnitude jump in electrochemical capacitance upon adsorption of a charged molecular receptor based on pyrene-appended boronic acids (here, 4-borono-1-(pyren-2-ylmethyl)pyridin-1-ium bromide, or abbreviated T1). This pyrene-appended pyridinium boronic acid receptor is employed here as a molecular receptor for lactate. In the presence of lactate and at pH 4.0 (after pH optimization), the electrochemical capacitance (determined by impedance spectroscopy) doubles again. Lactic acid binding is expressed with a Hillian binding constant (Klactate = 75 mol-1 dm3 and α = 0.8 in aqueous buffer, Klactate = 460 mol-1 dm3 and α = 0.8 in artificial sweat, and Klactate = 340 mol-1 dm3 and α = 0.65 in human serum). The result is a selective molecular probe response for lactic acid with LoD = 1.3, 1.4, and 1.8 mM in aqueous buffer media (pH 4.0), in artificial sweat (adjusted to pH 4.7), and in human serum (pH adjusted to 4.0), respectively. The role of the pyrene-appended boronic acid is discussed based on the double layer structure and quantum capacitance changes. In the future, this new type of molecular capacitance sensor could provide selective enzyme-free analysis without analyte consumption for a wider range of analytes and complex environments.

Visual monitoring of biocatalytic processes using small molecular fluorescent probes: strategies-mechanisms-applications.

Real-time monitoring of biocatalytic-based processes is significantly improved and simplified when they can be visualized. Visual monitoring can be achieved by integrating a fluorescent unit with the biocatalyst. Herein, we outline the design strategies of fluorescent probes for monitoring biocatalysis: (1) probes for monitoring biocatalytic transfer: γ-glutamine is linked to the fluorophore as both a recognition group and for intramolecular charge transfer (ICT) inhibition; the probe is initially in an off state and is activated via the transfer of the γ-glutamine group and the release of the free amino group, which results in restoration of the "Donor-π-Acceptor" (D-π-A) system and fluorescence recovery. (2) Probes for monitoring biocatalytic oxidation: a propylamine is connected to the fluorophore as a recognition group, which cages the hydroxyl group, leading to the inhibition of ICT; propylamine is oxidized and subsequently ß-elimination occurs, resulting in exposure of the hydroxyl group and fluorescence recovery. (3) Probes for monitoring biocatalytic reduction: a nitro group attached to a fluorophore as a fluorescence quenching group, this is converted to an amino group by catalytic reduction, resulting in fluorescence recovery. (4) Probes for monitoring biocatalytic hydrolysis: ß-D-galactopyranoside or phosphate acts as a recognition group attached to hydroxyl groups of the fluorophore; the subsequent biocatalytic hydrolysis reaction releases the hydroxyl group resulting in fluorescence recovery. Following these 4 mechanisms, fluorophores including cyanine, coumarin, rhodamine, and Nile-red, have been used to develop systems for monitoring biocatalytic reactions. We anticipate that these strategies will result in systems able to rapidly diagnose and facilitate the treatment of serious diseases.

Theranostic Fluorescent Probes.

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.

A Rationally Designed Prodrug for the Fluorogenic Labeling of Albumin and Theranostic Effects on Drug-Induced Liver Injury.

The development of small-molecular fluorogenic tools for the chemo-selective labeling of proteins in live cells is important for the evaluation of intracellular redox homeostasis. Dynamic imaging of human serum albumin (HSA), an antioxidant protein under oxidative stress with concomitant release of antioxidant drugs to maintain redox homeostasis, affords potential opportunities for disease diagnosis and treatment. In this work, we developed a nonfluorogenic prodrug named TPA-NAC, by introducing N-acetyl-l-cysteine (NAC) into a conjugated acceptor skeleton. Through combined thiol and amino addition, coupling with HSA results in fluorescence turn-on and drug release. It was reasoned that the restricted intramolecular motion of the probe under an HSA microenvironment after covalent bonding inhibited the nonradiative transitions. Furthermore, the biocompatibility and photochemical properties of TPA-NAC enabled it to image exogenous and endogenous HSA in living cells in a wash-free manner. Additionally, the released drug evoked upregulation of superoxide dismutase (SOD), which synergistically eliminated reactive oxygen species in a drug-induced liver injury model. This study provides insights into the design of new theranostic fluorescent prodrugs for chemo-selective protein labeling and disease treatments.

Photocured room temperature phosphorescent materials from lignosulfonate.

Photocured room temperature phosphorescent (RTP) materials hold great potential for practical applications but are scarcely reported. Here, we develop photocured RTP materials (P-Lig) using a combination of lignosulfonate, acrylamide, and ionic liquid (1-ethyl-3-methylimidazolium bromide). With this design, lignosulfonate simultaneously serves as RTP chromophore and photoinitiator. Specifically, lignosulfonate in the ionic liquid generates radicals to polymerize the acrylamide upon UV irradiation. The resulting lignosulfonate is automatically confined in an as-formed crosslinked matrix to provide RTP. As such RTP with an emission lifetime of ~110 ms is observed from the confined lignosulfonate in P-Lig. Additionally, energy transfer occur between P-Lig and Rhodamine B (RhB), triggering red afterglow emission when P-Lig is in situ loaded with RhB (P-Lig/RhB). As a demonstration of potential applications, the P-Lig and P-Lig/RhB are used as photocured RTP coatings and RTP inks for fabricating 3D materials and for information encryption.

Selective FRET nano probe based on carbon dots and naphthalimide-isatin for the ratiometric detection of peroxynitrite in drug-induced liver injury.

Drug-induced liver injury (DILI) is the most common cause for acute liver failure in the USA and Europe. However, most of DILI cases can recover or be prevented if treatment by the offending drug is discontinued. Recent research indicates that peroxynitrite (ONOO-) can be a potential indicator to diagnose DILI at an early stage. Therefore, the establishment of an assay to detect and track ONOO- in DILI cases is urgently needed. Here, a FRET-based ratiometric nano fluorescent probe CD-N-I was developed to detect ONOO- with high selectivity and excellent sensitivity. This probe consists of carbon dots and a naphthalimide-isatin peroxynitrite sensing system assembled based on electrostatic interactions. Using CD-N-I we were able to detect exogenous ONOO- in live cells and endogenous ONOO- in APAP-induced liver injury of HepG2 cells.

De Novo Green Fluorescent Protein Chromophore-Based Probes for Capturing Latent Fingerprints Using a Portable System.

Rapid visualization of latent fingerprints, preferably at their point of origin, is essential for effective crime scene evaluation. Here, we present a new class of green fluorescent protein chromophore-based fluorescent dyes (LFP-Yellow and LFP-Red) that can be used for real-time visualization of LFPs within 10 s. Compared with traditional chemical reagents for LFPs, these fluorescent dyes are completely water-soluble, exhibit low cytotoxicity, and are harmless to users. Level 1-3 details of the LFPs could be clearly revealed through "off-on" fluorescence signal readout. Additionally, the fluorescent dyes were constructed based on an imidazolinone core and so do not contain pyridine groups or metal ions, which ensures that the DNA is not contaminated during extraction and identification after the LFPs are treated with the dyes. Combined with our as-developed portable system for capturing LFPs, LFP-Yellow and LFP-Red enabled the rapid capture of LFPs. Therefore, these green fluorescent protein chromophore-based probes provide an approach for the rapid identification of individuals who were present at a crime scene.

BINOL as a Chiral Solvating Agent for Sulfiniminoboronic Acids.

1H NMR spectroscopic studies using BINOL as a chiral solvating agent (CSA) for a scalemic sulfiniminoboronic acid (SIBA) have revealed concentration- and enantiopurity-dependent variations in the chemical shifts of diagnostic imine protons used to determine enantiopurity levels. 11B/15N NMR spectroscopic studies and X-ray structural investigations revealed that unlike other iminoboronate species, BINOL-SIBA assemblies do not contain N-B coordination bonds, with 1H NMR NOESY experiments indicating that intermolecular H-bonding networks between BINOL and the SIBA analyte are responsible for these variations. These effects can lead to diastereomeric signal overlap at certain er values that could potentially lead to enantiopurity/configuration misassignments. Consequently, it is recommended that hydrogen-bonding-CSA-based 1H NMR protocols should be repeated using both CSA enantiomers to ensure that any concentration- and/or er-dependent variations in diagnostic chemical shifts are accounted for when determining the enantiopurity of a scalemic analyte.

Fluorescent naphthalimide boronates as theranostics: structural investigations, confocal fluorescence and multiphoton fluorescence lifetime imaging microscopy in living cells.

New design and synthetic strategies were developed to generate functional phenyl boronic acid (BA)-based fluorescent probes incorporating the 1,8-naphthalimide (NI) tag. This fluorescent core was anchored onto the BA unit through small organic linkers consisting of nitrogen groups which can arrest, and internally stabilise the phenyl-boronate units. The newly synthesised fluorophores were characterised spectroscopically by NMR spectroscopy and mass spectrometry and evaluated for their ability to bind to a naturally occurring polysaccharide, ß-d-glucan in DMSO and simultaneously as act as in vitro cell imaging reagents. The uptake of these new NI-boronic acid derivatives was studied living cancer cells (HeLa, PC-3) in the presence, and absence, of ß-d-glucan. Time-correlated single-photon counting (TCSPC) of DMSO solutions and two-photon fluorescence-lifetime imaging microscopy (FLIM) techniques allowed an insight into the probes' interaction with their environment. Their cellular uptake and distributions were imaged using laser scanning confocal fluorescence microscopy under single- and two-photon excitation regimes (λmax 910 nm). FLIM facilitated the estimation of the impact of the probe's cellular surroundings using the fluorophore lifetime. The extent to which this was mediated by the ß-d-glucan was visualised by 2-photon FLIM in living cells. The fluorescence lifetime observed under a range of temperatures varied appreciably, indicating that changes in the environment can be sensed by these probes. In all cases, the cellular membrane penetration of these new probes was remarkable even under variable temperature conditions and localisation was widely concentrated in the cellular cytoplasm, without specific organelle trapping: we conclude that these new probes show promise for cellular imaging in living cancer cells.

Unveiling the Crucial Roles of O2•- and ATP in Hepatic Ischemia-Reperfusion Injury Using Dual-Color/Reversible Fluorescence Imaging.

Hepatic ischemia-reperfusion injury (HIRI) is mainly responsible for morbidity or death due to graft rejection after liver transplantation. During HIRI, superoxide anion (O2•-) and adenosine-5'-triphosphate (ATP) have been identified as pivotal biomarkers associated with oxidative stress and energy metabolism, respectively. However, how the temporal and spatial fluctuations of O2•- and ATP coordinate changes in HIRI and particularly how they synergistically regulate each other in the pathological mechanism of HIRI remains unclear. Herein, we rationally designed and successfully synthesized a dual-color and dual-reversible molecular fluorescent probe (UDP) for dynamic and simultaneous visualization of O2•- and ATP in real-time, and uncovered their interrelationship and synergy in HIRI. UDP featured excellent sensitivity, selectivity, and reversibility in response to O2•- and ATP, which rendered UDP suitable for detecting O2•- and ATP and generating independent responses in the blue and red fluorescence channels without spectral crosstalk. Notably, in situ imaging with UDP revealed for the first time synchronous O2•- bursts and ATP depletion in hepatocytes and mouse livers during the process of HIRI. Surprisingly, a slight increase in ATP was observed during reperfusion. More importantly, intracellular O2•-─succinate dehydrogenase (SDH)─mitochondrial (Mito) reduced nicotinamide adenine dinucleotide (NADH)─Mito ATP─intracellular ATP cascade signaling pathway in the HIRI process was unveiled which illustrated the correlation between O2•- and ATP for the first time. This research confirms the potential of UDP for the dynamic monitoring of HIRI and provides a clear illustration of HIRI pathogenesis.

Room-temperature phosphorescent materials derived from natural resources.

Room-temperature phosphorescent (RTP) materials have enormous potential in many different areas. Additionally, the conversion of natural resources to RTP materials has attracted considerable attention. Owing to their inherent luminescent properties, natural materials can be efficiently converted into sustainable RTP materials. However, to date, only a few reviews have focused on this area of endeavour. Motivated by this lack of coverage, in this Review, we address this shortcoming and introduce the types of natural resource available for the preparation of RTP materials. We mainly focus on the inherent advantages of natural resources for RTP materials, strategies for activating and enhancing the RTP properties of the natural resources as well as the potential applications of these RTP materials. In addition, we discuss future challenges and opportunities in this area of research.

Near-Infrared Fluorescent Probe for the In Situ Visualization of Oxidative Stress in the Brains of Neuroinflammatory and Schizophrenic Mice.

Schizophrenia is a common mental disorder with unclear mechanisms. Oxidative stress and neuroinflammation play important roles in the pathological process of schizophrenia. Superoxide anion (O2•-) is an important oxidative stress biomarker in vivo. However, due to the existence of the blood-brain barrier (BBB), few near-infrared (NIR) fluorescent probes have been used for the sensing and detection of O2•- in the brain. With this research, we developed the first near-infrared fluorescent probe (named CT-CF3) for noninvasive detection of endogenous O2•- in the brain of mice. Enabling fluorescence monitoring of the dynamic changes in O2•- flux due to the prolonged activation of microglia in neuroinflamed and schizophrenic (SZ) mice brains, thereby providing direct evidence for the relationship between oxidative stress, neuroinflammation, and schizophrenia. Furthermore, we confirmed the O2•- burst in the brains of first-episode schizophrenic mice and assessed the effect of two atypical antipsychotic drugs (risperidone and olanzapine) on redox homeostasis.

Current trends in the detection and removal of heavy metal ions using functional materials.

The shortage of freshwater resources caused by heavy metal pollution is an acute global issue, which has a great impact on environmental protection and human health. Therefore, the exploitation of new strategies for designing and synthesizing green, efficient, and economical materials for the detection and removal of heavy metal ions is crucial. Among the various methods for the detection and removal of heavy ions, advanced functional systems including nanomaterials, polymers, porous materials, and biomaterials have attracted considerable attention over the past several years due to their capabilities of real-time detection, excellent removal efficiency, anti-interference, quick response, high selectivity, and low limit of detection. In this tutorial review, we review the general design principles underlying the aforementioned functional materials, and in particular highlight the fundamental mechanisms and specific examples of detecting and removing heavy metal ions. Additionally, the methods which enhance water purification quality using these functional materials have been reviewed, also current challenges and opportunities in this exciting field have been highlighted, including the fabrication, subsequent treatment, and potential future applications of such functional materials. We envision that this tutorial review will provide invaluable guidance for the design of functional materials tailored towards the detection and removal of heavy metals, thereby expediting the development of high-performance materials and fostering the development of more efficient approaches to water pollution remediation.

Aggregation-Induced Emission (AIE), Life and Health.

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Near-Infrared Bodipy-Based Molecular Rotors for ß-Amyloid Imaging In Vivo.

ß-amyloid (Aß) is one of the important biomarkers for diagnosing Alzheimer's disease (AD). Many near-infrared probes based on the donor-π-acceptor structure have been developed to detect Aß. Most reported Aß probes are based on the N,N-dimethylamino group as the ideal donor, which is a widely accepted binding unit. As such, the development of fluorescent probes with improved binding units to detect Aß is urgently required. Therefore, with this research three anchoring molecular rotor electron donors consisting of cyclic amines of different ring sizes are developed, namely five-membered ring (TPyr), six-membered ring (TPip), and seven-membered ring (THAI). These new anchored molecular rotors are connected to a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) and named TPyrBDP, TPipBDP, and THAIBDP. These probes exhibit high affinities (from 28 to 54 nm) for Aß1-42 aggregates. The six-membered ring dye TPipBDP exhibits the highest signal-to-noise (75.5-fold) and higher affinity (28.30 ± 5.94 nm). TPipBDP can cross the blood-brain barrier and exhibits higher fluorescence enhancement with APP/PS1 (AD) double transgenic (Tg) mice than with wild-type (WT) mice.

Development of a hydroxyflavone-labelled 4554W peptide probe for monitoring αS aggregation.

Parkinson's is the second most common neurodegenerative disease, with the number of individuals susceptible due to increase as a result of increasing life expectancy and a growing worldwide population. However, despite the number of individuals affected, all current treatments for PD are symptomatic-they alleviate symptoms, but do not slow disease progression. A major reason for the lack of disease-modifying treatments is that there are currently no methods to diagnose individuals during the earliest stages of the disease, nor are there any methods to monitor disease progression at a biochemical level. Herein, we have designed and evaluated a peptide-based probe to monitor αS aggregation, with a particular focus on the earliest stages of the aggregation process and the formation of oligomers. We have identified the peptide-probe K1 as being suitable for further development to be applied to number of applications including: inhibition of αS aggregation; as a probe to monitor αS aggregation, particularly at the earliest stages before Thioflavin-T is active; and a method to detect early-oligomers. With further development and in vivo validation, we anticipate this probe could be used for the early diagnosis of PD, a method to evaluate the effectiveness of potential therapeutics, and as a tool to help in the understanding of the onset and development of PD.

Chemoselective Fluorogenic Bioconjugation of Vicinal Dithiol-Containing Proteins for Live Cellular Imaging via Small Molecular Conjugate Acceptors.

To develop small molecular fluorogenic tools for the chemoselective labeling of vicinal dithiol-containing proteins (VDPs) in live cells is important for studying intracellular redox homeostasis. With this research, we developed small molecule-based fluorescent probes, achieving selective labeling of VDPs through thiol-thiol substitutions on bisvinylogous thioester conjugated acceptors (IDAs). Initially, IDAs demonstrated its ability to bridge vicinal cysteine-sulfhydryls on a peptide as a mimic. Then, the peptide complex could be decoupled to recover the original peptide-SH in the presence of dithiothreitol. Furthermore, fluorometric signal amplification of the fluorescent probes occurred with high sensitivity, low limit of detection, and selectivity toward vicinal dithiols on reduced bovine serum albumin, as an example of real world VDPs. More importantly, the probes were utilized successfully for labeling of endogenous VDPs at different redox states in live cells. Thus, the bisvinylogous thioester-based receptor as a functional probe represents a new platform for uncovering the function of VDPs in live cells.