Investigation of Drug-Induced Hepatotoxicity and Its Remediation Pathway with Reaction-Based Fluorescent Probes

Drug-induced liver injury (DILI) is considered a serious problem related to public health, due to its unpredictability and acute response. The level of peroxynitrite (ONOO^–) generated in liver has long been regarded as a biomarker for the prediction and measurement of DILI. Herein we present two reaction-based fluorescent probes (Naph-ONOO^– and Rhod-ONOO^–) for ONOO^– through a novel and universally applicable mechanism: ONOO^–-mediated deprotection of α-keto caged fluorophores. Among them, Rhod-ONOO^– can selectively accumulate and react in mitochondria, one of the main sources of ONOO^–, with a substantial lower nanomolar sensitivity of 43 nM. The superior selectivity and sensitivity of two probes enable real-time imaging of peroxynitrite generation in lipopolysaccharide-stimulated live cells, with a remarkable difference from cells doped with other interfering reactive oxygen species, in either one- or two-photon imaging modes. More importantly, we elucidated the drug-induced hepatotoxicity pathway with Rhod-ONOO^– and revealed that CYP450/CYP2E1-mediated enzymatic metabolism of acetaminophen leads to ONOO^– generation in liver cells. This is the first time to showcase the drug-induced hepatotoxicity pathways by use of a small-molecule fluorescent probe. We hence conclude that fluorescent probes can engender a deeper understanding of reactive species and their pathological revelations. The reaction-based fluorescent probes will be a potentially useful chemical tool to assay drug-induced hepatotoxicity

One-Stop Integrated Nanoagent for Bacterial Biofilm Eradication and Wound Disinfection

To meet the requirements of biomedical applications in the antibacterial realm, it is of great importance to explore nano-antibiotics for wound disinfection that can prevent the development of drug resistance and possess outstanding biocompatibility. Therefore, we attempted to synthesize an atomically dispersed ion (Fe) on phenolic carbon quantum dots (CQDs) combined with an organic photothermal agent (PTA) (Fe@SAC CQDs/PTA) via a hydrothermal/ultrasound method. Fe@SAC CQDs adequately exerted peroxidase-like activity while the PTA presented excellent photothermal conversion capability, which provided enormous potential in antibacterial applications. Based on our work, Fe@SAC CQDs/PTA exhibited excellent eradication of Escherichia coli (>99% inactivation efficiency) and Staphylococcus aureus (>99% inactivation efficiency) based on synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT). Moreover, in vitro experiments demonstrated that Fe@SAC CQDs/PTA could inhibit microbial growth and promote bacterial biofilm destruction. In vivo experiments suggested that Fe@SAC CQDs/PTA-mediated synergistic CDT and PTT exhibited great promotion to wound disinfection and recovery effects. This work indicated that Fe@SAC CQDs/PTA could serve as a broad-spectrum antimicrobial nano-antibiotic, which was simultaneously beneficial for bacterial biofilm eradication, wound disinfection, and wound healing

Diversity of Prokaryotic Communities Indigenous to Acid Mine Drainage and Related Rocks from Baiyin Open-Pit Copper Mine Stope, China

<p>Metagenomic approach permits us to obtain the latent resources from culturable and unculturable microorganisms in ecosystem. In this study, high-throughput sequencing was practiced to comprehensively probe prokaryotic community within extreme acidic environment of Baiyin open-pit mine stope, which varied in pH and other physicochemical parameters. Bioinformatics analysis was further accomplished to process millions of Illumina reads and analyzed alpha and beta diversities, and prokaryotic community profile in different samples obtained from the acidic mine stope. Diversity indices such as ACE, Chao, Shannon, and Simpson were varied among samples. Both taxon richness and evenness were significantly higher in the solid samples than that of the water samples. Taxonomic diversity was unexpectedly higher within confined pit ecosystem. Most of the sequences were assigned to phyla <i>Proteobacteria, Firmicutes</i>, and <i>Acidobacteria</i>. In archaea, <i>Euryarchaeota</i> and <i>Thaumarchaeota</i> were major phyla reported, however, archaea occupied very little share in the metagenome. At class level, variation in community structure was higher within samples. Among iron- and sulfur-related acidophiles, 30.8% of the sequences were unidentified at genera level, while the remaining were dominated by sulfur and/or iron oxidizing <i>Acidithiobacillus</i> and heterotrophic <i>Acidiphilum</i> related groups. The community profile of solid and water groups was different and metagenomic biomarkers were higher in solid, while acidophiles and archaea were reported only in water group by using LEfSe. Among samples, community structure and abundance was varied in terms of OTUs abundance, which clearly indicates spatial variation and proposed the influence of physicochemical and geochemical properties on phylogenetic diversity. This study offers numerous treasured datasets for better understanding the community composition under the influence of geochemical and physicochemical factors and possible novelty in terms of taxonomic/phylogenetic diversity in acidic ecosystem.</p

Luminescent Carbon Dot Mimics Assembled on DNA

Nanometer-sized fragments of carbon in the form of multilayer graphene (“carbon dots”) have been under highly active study for applications in imaging. While offering advantages of low toxicity and photostability, such nanomaterials are inhomogeneous and have limited wavelengths of emission. Here we address these issues by assembling luminescent aromatic C16–C38 hydrocarbons together on a DNA scaffold in homogeneous, soluble molecular compounds. Monomer deoxyribosides of five different aromatic hydrocarbons were synthesized and assembled into a library of 1296 different tetramer compounds on PEG-polystyrene beads. These were screened for photostability and a range of emission colors using 365 nm excitation, observing visible light (>400 nm) emission. We identified a set of six oligomers (DNA-carbon assemblies, DNA-CAs) with exceptional photostability that emit from 400 to 680 nm in water, with Stokes shifts of up to 110 nm, quantum yields ranging from 0.01 to 0.29, and fluorescence lifetimes from 3 to 42 ns. In addition, several of these DNA-CAs exhibited white emission in aqueous solution. The molecules were used in multispectral cell imaging experiments and were taken up into cells passively. The results expand the range of emission properties that can be achieved in water with all-hydrocarbon chromophores and establish the use of the DNA scaffold to arrange carbon layers in homogeneous, rapidly synthesized assemblies

Rational Engineering of Bioinspired Anthocyanidin Fluorophores with Excellent Two-Photon Properties for Sensing and Imaging

Fluorescent materials are widely employed in biological analysis owing to their biorthogonal chemistries for imaging and sensing purposes. However, it is always a challenge to design fluorophores with desired photophysical and biological properties, due to their complicated molecular and optical nature. Inspired by anthocyanidin, a class of flower pigments, we designed a new fluorescent molecular framework, AC-Fluor. The new fluorescent materials can be rationally engineered to produce a broad range of fluorescent scaffolds with flexibly tunable emission spectra covering the whole visible light range, from 467 to 707 nm. Furthermore, they exhibit unprecedented environment-insensitive two-photon properties with a substantial cross section as large as 1100 GM in aqueous solution. AC-Fluors demonstrate their biological values through two-photon deep tissue imaging, with penetration depths as much as 300 μm, while exhibiting minimal cytotoxicity. These features engender a rational engineering strategy for the design and optimization of new fluorescent materials for biological imaging

Additional file 1 of Anti-aging effect of β-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process

Additional file 1. Primer sequence

A General Method To Increase Stokes Shift by Introducing Alternating Vibronic Structures

Fluorescent dyes have enabled much progress in the broad range of biomedical fields. However, many commercially available dyes suffer from small Stokes shifts, resulting in poor signal-to-noise ratio and self-quenching on current microscope configurations. In this work, we have developed a general method to significantly increase the Stokes shifts of common fluorophores. By simply appending a 1,4-diethyl-decahydro-quinoxaline (DQ) moiety onto the conjugated structure, we introduced a vibronic backbone that could facilely expand the Stokes shifts, emission wavelength, and photostability of 11 different fluorophores by more than 3-fold. This generalizable method could significantly improve the imaging efficiency of commercial fluorophores. As a demonstration, we showed that the DQ derivative of hemicyanine generated 5-fold signal in mouse models over indocyanine green. Furthermore, the DQ-modified fluorophores could pair with their parent molecules to conduct one-excitation, multiple emission imaging, allowing us to study the cell behavior more robustly. This approach shows promise in generating dyes suitable for super-resolution microscopy and second window near-infrared imaging

Datasheet1_Prediction of acute kidney injury after cardiac surgery with fibrinogen-to-albumin ratio: a prospective observational study.docx

BackgroundThe occurrence of acute kidney injury (AKI) following cardiac surgery is common and linked to unfavorable consequences while identifying it in its early stages remains a challenge. The aim of this research was to examine whether the fibrinogen-to-albumin ratio (FAR), an innovative inflammation-related risk indicator, has the ability to predict the development of AKI in individuals after cardiac surgery.MethodsPatients who underwent cardiac surgery from February 2023 to March 2023 and were admitted to the Cardiac Surgery Intensive Care Unit of a tertiary teaching hospital were included in this prospective observational study. AKI was defined according to the KDIGO criteria. To assess the diagnostic value of the FAR in predicting AKI, calculations were performed for the area under the receiver operating characteristic curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ResultsOf the 260 enrolled patients, 85 developed AKI with an incidence of 32.7%. Based on the multivariate logistic analyses, FAR at admission [odds ratio (OR), 1.197; 95% confidence interval (CI), 1.064–1.347, p = 0.003] was an independent risk factor for AKI. The receiver operating characteristic (ROC) curve indicated that FAR on admission was a significant predictor of AKI [AUC, 0.685, 95% CI: 0.616–0.754]. Although the AUC-ROC of the prediction model was not substantially improved by adding FAR, continuous NRI and IDI were significantly improved.ConclusionsFAR is independently associated with the occurrence of AKI after cardiac surgery and can significantly improve AKI prediction over the clinical prediction model.</p

High-Efficiency in Vitro and in Vivo Detection of Zn²⁺ by Dye-Assembled Upconversion Nanoparticles

Development of highly sensitive and selective sensing systems of divalent zinc ion (Zn²⁺) in organisms has been a growing interest in the past decades owing to its pivotal role in cellular metabolism, apoptosis, and neurotransmission. Herein, we report the rational design and synthesis of a Zn²⁺ fluorescent-based probe by assembling lanthanide-doped upconversion nanoparticles (UCNPs) with chromophores. Specifically, upconversion luminescence (UCL) can be effectively quenched by the chromophores on the surface of nanoparticles via a fluorescence resonant energy transfer (FRET) process and subsequently recovered upon the addition of Zn²⁺, thus allowing for quantitative monitoring of Zn²⁺. Importantly, the sensing system enables detection of Zn²⁺ in real biological samples. We demonstrate that this chromophore–UCNP nanosystem is capable of implementing an efficient in vitro and in vivo detection of Zn²⁺ in mouse brain slice with Alzheimer’s disease and zebrafish, respectively

An Artificial Tongue Fluorescent Sensor Array for Identification and Quantitation of Various Heavy Metal Ions

Herein, a small-molecule fluorescent sensor array for rapid identification of seven heavy metal ions was designed and synthesized, with its sensing mechanism mimicking that of a tongue. The photoinduced electron transfer and intramolecular charge transfer mechanism result in combinatorial interactions between sensor array and heavy metal ions, which lead to diversified fluorescence wavelength shifts and emission intensity changes. Upon principle component analysis (PCA), this result renders clear identification of each heavy metal ion on a 3D spatial dispersion graph. Further exploration provides a concentration-dependent pattern, allowing both qualitative and quantitative measurements of heavy metal ions. On the basis of this information, a “safe-zone” concept was proposed, which provides rapid exclusion of versatile hazardous species from clean water samples based on toxicity characteristic leaching procedure standards. This type of small-molecule fluorescent sensor array could open a new avenue for multiple heavy metal ion detection and simplified water quality analysis