Auxochrome Dimethyl-Dihydroacridine Improves Fluorophores for Prolonged Live-Cell Super-Resolution Imaging.

Superior photostability, minimal phototoxicity, red-shifted absorption/emission wavelengths, high brightness, and an enlarged Stokes shift are essential characteristics of top-tier organic fluorophores, particularly for long-lasting super-resolution imaging in live cells (e.g., via stimulated emission depletion (STED) nanoscopy). However, few existing fluorophores possess all of these properties. In this study, we demonstrate a general approach for simultaneously enhancing these parameters through the introduction of 9,9-dimethyl-9,10-dihydroacridine (DMA) as an electron-donating auxochrome. DMA not only induces red shifts in emission wavelengths but also suppresses photooxidative reactions and prevents the formation of triplet states in DMA-based fluorophores, greatly improving photostability and remarkably minimizing phototoxicity. Moreover, the DMA group enhances the fluorophores' brightness and enlarges the Stokes shift. Importantly, the "universal" benefits of attaching the DMA auxochrome have been exemplified in various fluorophores including rhodamines, difluoride-boron complexes, and coumarin derivatives. The resulting fluorophores successfully enabled the STED imaging of organelles and HaloTag-labeled membrane proteins.

Dimethyl Dihydrophenazine: A Highly Conjugated Auxochrome in Fluorophores to Improve Photostability, Red-Shift Wavelength, and Enlarge Stokes Shift.

5,10-Dimethyl-5,10-dihydrophenazine (MP) is utilized as an effective auxochrome, leveraging its highly conjugated structure to enhance the photophysical and photochemical properties of fluorophores. As illustrated in the difluoride-boron complex and coumarin fluorophores, the extensive conjugation of MP auxochrome substantially red-shifts the absorption/emission wavelengths and increases Stokes shift due to the intensified intramolecular charge transfer effect; notably, MP auxochrome effectively improves fluorophores' photostability by mitigating photooxidative reactions through enhanced electron density delocalization on nitrogen atoms and increased ionization potential. Importantly, MP-based fluorophores demonstrate applicability in stimulated emission depletion nanomicroscopy, showcasing their utility in lipid droplet labeling.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with limited treatment options and high drug resistance, presenting significant challenges in the pursuit of effective treatment strategies. Epigenetic modifications have emerged as promising diagnostic biomarkers and therapeutic targets for GBM. For instance, histone deacetylase 6 (HDAC6) has been identified as a potential pharmacological target for GBM. Furthermore, the overexpression of monoamine oxidase A (MAO A) in glioma has been linked to tumor progression, making it an attractive target for therapy. In this study, we successfully engineered HDAC-MB, an activatable multifunctional small-molecule probe with the goal of efficiently detecting and killing glioma cells. HDAC-MB can be selectively activated by HDAC6, leading to the "turn on" of near-infrared fluorescence and effective inhibition of MAO A, along with potent photodynamic therapy (PDT) effects. Consequently, HDAC-MB not only enables the imaging of HDAC6 in live glioma cells but also exhibits the synergistic effect of MAO A inhibition and PDT, effectively inhibiting glioma invasion and inducing cellular apoptosis. The distinctive combination of features displayed by HDAC-MB positions it as a versatile and highly effective tool for the accurate diagnosis and treatment of glioma cells. This opens up opportunities to enhance therapy outcomes and explore future applications in glioma theranostics.

Harnessing J-aggregation for dual-color cellular imaging with chromenoquinoline-benzimidazole dyes.

Fluorescence imaging has revolutionized the visualization of cellular structures and biomolecules due to its non-invasive nature and high sensitivity. Chromenoquinoline (CQ)-based dyes offer promising optical properties, yet their widespread application is hindered by aggregation-caused quenching (ACQ). In contrast, J-aggregates, characterized by distinctive photophysical properties, present a solution to ACQ. Here, we introduce a novel platform employing chromenoquinoline-benzimidazole (CQ-BI) dyes, capable of forming J-aggregates, for dual-color cellular imaging. The incorporation of a methyl group into the benzimidazole moiety enhances J-aggregate formation, leading to robust emission in both dilute solutions and aggregated states. Our study demonstrates that methyl moiety-modified CQ-BI derivatives enable simultaneous imaging of mitochondria and lipid droplets in living cells. This work underscores the potential of CQ-BI dyes for dual-channel fluorescence imaging, leveraging the unique properties of J-aggregation.

The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-induced constipation.

This study was designed to explore the expression changes of P2Y1 receptors in the distal colonic myenteric layer of rats. An opioid induced constipation(OIC) rat model was generated by intraperitoneal (i.p) injection of loperamide. At 7 days post-treatment, the model rats were assessed by calculating the fecal water content and the gastrointestinal transit ratio. The immunofluorescence (IF)-based histochemical study was used to observe the distribution of P2Y1 receptors in the distal colonic myenteric plexus. Western blotting (WB) was performed to evaluate the expression changes of P2Y1 proteins in the myenteric layer, and the electrophysiological approaches were carried out to determine the regulatory roles of P2Y1 receptors on distal colonic motor function. IF showed that P2Y1 receptors are co-expressed MOR in the enteric nerve cells of the distal colonic myenteric plexus. Moreover, the WB revealed that the protein levels of P2Y1 were significantly decreased in the distal colonic myenteric layer of OIC rats. In vitro tension experiments exhibited that the P2Y1 receptor antagonist MRS2500 enhanced the spontaneous contraction amplitude, adding EM2 and ß-FNA did not have any effect on MRS2500. Therefore, P2Y1 receptor expression could be associated with the occurrence of OIC in this rat model and the regulation of colonic motility by MOR may be related to the release of purine neurotransmitters such as ATP in the colonic nervous system.

Research hotspots and trends of complementary and alternative therapy for neuropathic pain: A bibliometric analysis.

BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.

Effect of aggregation configuration of molecular fluorophore CZA on photoluminescence properties of carbon dots.

The effect of aggregation configuration of molecular fluorophore citrazinic acid (CZA) on the photoluminescence (PL) properties of carbon dots (CDs) has been investigated using first-principles method. The structural stability of all aggregates has been analyzed, and the results show that the most stable structures are J-type CZA aggregates with head-to-tail configurations and the CZA/CD aggregates are bonded by replacing H atoms on the CD edges with de-OH from the pyridine ring of CZA. The luminescent properties of CZA/CD aggregates are mainly affected by the binding modes and binding sites. When the sites belong to electron-donating groups, electron-withdrawing groups or sp2 domain, the PL spectra of CDs are shifted and the luminescent intensities are significantly enhanced. The results suggest that covalently bonded CZA/CD aggregates are responsible for the high fluorescence quantum yield of CD. Moreover, the distance between the centers of the two pyridine rings in H-type CZA dimers less than 3.5 Å is prone to π-π stacking, leading to fluorescence quenching of aggregates. The present work is helpful in understanding the effect of molecular fluorophores on the PL properties of CDs and provides theoretical guidance for the controllable synthesis of CDs.

In-Doped ZnO Electron Transport Layer for High-Efficiency Ultrathin Flexible Organic Solar Cells.

Sol-gel processed zinc oxide (ZnO) is one of the most widely used electron transport layers (ETLs) in inverted organic solar cells (OSCs). The high annealing temperature (≈200 °C) required for sintering to ensure a high electron mobility however results in severe damage to flexible substrates. Thus, flexible organic solar cells based on sol-gel processed ZnO exhibit significantly lower efficiency than rigid devices. In this paper, an indium-doping approach is developed to improve the optoelectronic properties of ZnO layers and reduce the required annealing temperature. Inverted OSCs based on In-doped ZnO (IZO) exhibit a higher efficiency than those based on ZnO for a range of different active layer systems. For the PM6:L8-BO system, the efficiency increases from 17.0% for the pristine ZnO-based device to 17.8% for the IZO-based device. The IZO-based device with an active layer of PM6:L8-BO:BTP-eC9 exhibits an even higher efficiency of up to 18.1%. In addition, a 1.2-micrometer-thick inverted ultrathin flexible organic solar cell is fabricated based on the IZO ETL that achieves an efficiency of 17.0% with a power-per-weight ratio of 40.4 W g-1, which is one of the highest efficiency for ultrathin (less than 10 micrometers) flexible organic solar cells.

Mechanism of enhanced microalgal biomass and lipid accumulation through symbiosis between a highly succinic acid-producing strain of Escherichia coli SUC and Aurantiochytrium sp. SW1.

Microalgae, known for rapid growth and lipid richness, hold potential in biofuels and high-value biomolecules. The symbiotic link with bacteria is crucial in large-scale open cultures. This study explores algal-bacterial interactions using a symbiotic model, evaluating acid-resistant Lactic acid bacteria (LAB), stress-resilient Bacillus subtilis and Bacillus licheniformis, and various Escherichia coli strains in the Aurantiochytrium sp. SW1 system. It was observed that E. coli SUC significantly enhanced the growth and lipid production of Aurantiochytrium sp. SW1 by increasing enzyme activity (NAD-IDH, NAD-ME, G6PDH) while maintaining sustained succinic acid release. Optimal co-culture conditions included temperature 28 °C, a 1:10 algae-to-bacteria ratio, and pH 8. Under these conditions, Aurantiochytrium sp. SW1 biomass increased 3.17-fold to 27.83 g/L, and total lipid content increased 2.63-fold to 4.87 g/L. These findings have implications for more efficient microalgal lipid production and large-scale cultivation.

Reactivity-Tunable Fluorescent Platform for Selective and Biocompatible Modification of Cysteine or Lysine.

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine-selective warheads face challenges due to cross-reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro- or phenoxy-substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy-NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH-overexpressed cancer cells. Conversely, alkoxy-NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti-interfering ability against thiols. Leveraging a proximity-driven approach, alkoxy-NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.