Deciphering the links: Fragmented polystyrene as a driver of skin inflammation.

Nano- and microplastics (NMPs), ubiquitous in the environment, pose significant health risks. We report for the first time a comprehensive study using in-vitro, in-vivo, and ex-vivo models to investigate the penetration and inflammatory effects of fragmented polystyrene (fPS) on human skin, including the analysis of both penetration depth and fPS amounts that penetrate the skin. Human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells exposed to fPS exhibited notable internalization and cytotoxicity. In a 3D human skin model, fPS particles penetrated the dermal layer within one hour, with an average maximum penetration of 4.7 µg for particles smaller than 2 µm. Similarly, mouse dorsal skin and human abdominal skin models confirmed fPS penetration. RNA sequencing revealed substantial upregulation of inflammatory genes, including IL-1α, IL-1ß, IL-18, IL-6, IL-8, ICAM-1, FOS, and JUN, following fPS exposure. These findings were validated at both the mRNA and protein levels, indicating a robust inflammatory response. Notably, the inflammatory response in both the 3D human skin and mouse models increased in a dose-dependent manner, underscoring the toxicological impact of fPS on skin health. This study provides crucial insights into the mechanisms through which NMPs affect human health and underscores the need for further research to develop effective mitigation strategies.

Neurotoxic effects of polystyrene nanoplastics on memory and microglial activation: Insights from in vivo and in vitro studies.

Nanoplastics, arising from the fragmentation of plastics into environmental pollutants and specialized commercial applications, such as cosmetics, have elicited concerns due to their potential toxicity. Evidence suggests that the oral ingestion of nanoplastics smaller than 100 nm may penetrate the brain and induce neurotoxicity. However, comprehensive research in this area has been hampered by technical challenges associated with the detection and synthesis of nanoplastics. This study aimed to bridge this research gap by successfully synthesizing fluorescent polystyrene nanoplastics (PSNPs, 30-50 nm) through the incorporation of IR-813 and validating them using various analytical techniques. We administered PSNPs orally (10 and 20 mg/kg/day) to mice and observed that they reached brain tissues and induced cognitive dysfunction, as measured by spatial and fear memory tests, while locomotor and social behaviors remained unaffected. In vitro studies (200 µg/mL) demonstrated a predominant uptake of PSNPs by microglia over astrocytes or neurons, leading to microglial activation, as evidenced by immunostaining of cellular markers and morphological analysis. Transcriptomic analysis indicated that PSNPs altered gene expression in microglia, highlighting neuroinflammatory responses that may contribute to cognitive deficits. To further explore the neurotoxic effects of PSNPs mediated by microglial activation, we measured endogenous neuronal activity using a multi-electrode array in cultured hippocampal neurons. The application of conditioned media from microglia exposed to PSNPs suppressed neuronal activity, which was reversed by inhibitors of microglial activation. Our findings offer detailed insights into the mechanisms by which nanoplastics damage the brain, particularly emphasizing the potential environmental risk factors that contribute to cognitive impairment in neurodegenerative diseases.

A colorimetric and fluorescent signaling probe for assaying Pd2+ in practical samples.

We developed an optical signaling probe to detect Pd2+ ions in Pd-containing catalyst and drug candidate. The Pd2+ signaling probe (Res-DT) was readily prepared by reacting the versatile fluorochrome resorufin with phenyl chlorodithioformate. In a phosphate-buffered saline solution (pH 7.4) containing sodium dodecyl sulfate (SDS) as a signal-boosting surfactant, Res-DT exhibited a pronounced colorimetric response with a chromogenic yellow to magenta shift, leading to a substantial increase in the fluorescence intensity. The Pd2+ signaling performance of Res-DT was attributed to the Pd2+-promoted hydrolysis of the dithioate moiety. The probe displayed high selectivity toward Pd2+ ions and remained unaffected by commonly encountered coexisting components. Moreover, the detection limit of Res-DT for Pd2+ ions was 10 nM, and the signaling was achieved within 7 min. Furthermore, to demonstrate the real-world applicability of Res-DT, a Pd2+ assay was performed in Pd-containing catalyst and drug candidate using an office scanner as an easily accessible measurement device. Our results highlight the prospects of Res-DT as a tool to detect Pd2+ ions in various practical samples, with potential applications in catalysis, medicine, and environmental science.

Colorimetric screening of elevated urinary mercury levels by a novel Hg2+-selective probe of resorufin phosphinothioate.

Urinary mercury levels are the most reliable indicators of mercury exposure but identifying them requires complex techniques and heavy instruments. In this research, we reported a simple and convenient urinary mercury analysis method using a readily available office scanner. Probe MP-1 synthesized by the reaction of resorufin and dimethylthiophosphinoyl chloride revealed Hg2+-selective chromogenic and fluorescent signaling behavior. Signaling was realized through Hg2+-induced deprotection of the phosphinothioate protecting group in the resorufin-based probe MP-1 to yield the parent fluorochrome. A pronounced colorimetric response of color change from light yellow to pink alongside a turn-on type fluorescence enhancement was perceived exclusively toward Hg2+ ions over other metal ions and anions. The colorimetry provided a more advantageous ratiometric approach than the simple fluorometric analysis exhibiting an off-on type response, with a detection limit of 12 nM (2.4 ppb). The Hg2+ signaling of the MP-1 probe was not disturbed by the presence of coexisting metal ions and anions. The sensitive and convenient diagnosis of clinically important neurological symptoms and fatal inorganic mercury levels in urine was successfully demonstrated using a standard office scanner.

A simple hypochlorous acid signaling probe based on resorufin carbonodithioate and its biological application.

A novel hypochlorous-acid-selective signaling probe based on the carbonodithioate derivative of resorufin (RT-1) was developed. Probe RT-1 showed prominent colorimetric and turn-on type fluorescence signaling behavior exclusively toward hypochlorous acid, induced by oxidative hydrolysis, to regenerate resorufin dye. Hypochlorous acid signaling was not affected by the presence of common metal ions and anions as background, except for the redox active bromide and iodide anions. The detection limit of RT-1 for hypochlorous acid was found to be 2.18 × 10-9 M (0.11 ppb), and the signaling was completed within 3 min. It was also confirmed that hypochlorous acid signaling by the carbonodithioate-based probe RT-1 was superior to that of the closely related carbonothioate derivative RT-2. This was rationalized by density functional theory calculations, which demonstrated that the C[double bond, length as m-dash]S sulfur atom of the former is more negatively charged than that of the latter. Finally, as a biological application of the probe, visualization of hypochlorous acid in RAW 264.7 murine macrophages and HeLa cells was successfully conducted to detect the cellular response to hypochlorous acid.

The first hydride-Meisenheimer adduct of electron-deficient 3-nitronaphthalimide: application to colorimetric borohydride determination.

The first hydride-Meisenheimer adduct of 3-nitronaphthalimide was used for the colorimetric borohydride assay. To explain the regioselectivity of the adduct, the reaction enthalpies of the two most plausible Meisenheimer adducts were obtained via computational calculation. Using the adduct formation, the assay of borohydride reagents was successfully conducted.

Reaction-based fluorometric analysis of N-bromosuccinimide by oxidative deprotection of dithiane.

In this study, a fluorescent probe is developed for the first time for N-bromosuccinimide (NBS), a synthetically and analytically important compound. Pyrene-dithiane-based probe 1 showed prominently selective and sensitive signaling behavior toward NBS owing to the oxidative cleavage of the dithiane protecting group of 1-pyrenecarboxaldehyde. The NBS-selective signaling of the probe was possible under competitive conditions in the presence of common metal ions and anions as a background. The detection limit of the probe for NBS was found to be 5.6 × 10-8 M (10.0 ppb). The signaling product was sufficiently stable under the oxidative stress of NBS in contrast to another tested compound, 6-methoxy-2-naphthaldehyde-based dithiane derivative 2, which showed a gradually decaying response because of the reaction of the signaling product with the residual NBS. In the practical application of the probe, a smartphone was used as a stand-alone device, and the fluorometric assays of the commercial NBS reagents could be conducted rapidly and in a convenient manner.

Novel Hg2+-Selective Signaling Probe Based on Resorufin Thionocarbonate and its µPAD Application.

In this study, a novel resorufin thionocarbonate-based Hg2+-selective signaling probe (RT) for microfluidic paper-based analytical device (µPAD) applications is reported. The designed probe, RT, was readily synthesized by the one-step reaction of resorufin with phenyl thionochloroformate. The RT probe displayed a prominent color change from yellow to pink and a marked turn-on fluorescence signaling behavior exclusively toward the Hg2+ ion. The signaling of RT was due to Hg2+-induced hydrolysis of the phenyl thionocarbonate moiety to form the parent resorufin dye, which restored its spectroscopic properties. In addition, RT exhibited the Hg2+-selective signaling behavior without interference by coexisting environmentally relevant metal ions. The detection limit for Hg2+ in simulated wastewater samples was estimated to be 5.8 × 10-8 M. In particular, an RT-equipped µPAD prepared using a wax printing technique enabled simple and convenient determination of Hg2+ ions in simulated wastewater samples, with a detection limit of 5.9 × 10-6 M.

Visible-light-induced regioselective synthesis of polyheteroaromatic compounds.

A method for visible-light-induced synthesis of polyheteroaromatics from 2-heteroaryl-substituted anilines and heteroarylalkynes was developed. The process, which uses fac-Ir(ppy)3 as the photocatalyst and (t)BuONO as the diazotization reagent, is highly regioselective.

Modulation of quinone PCET reaction by Ca2+ ion captured by calix[4]quinone in water.

Calix[4]arene-triacid-monoquinone (CTAQ), a quinone-containing water-soluble ionophore, was utilized to investigate how proton-coupled electron transfer (PCET) reactions of quinones were influenced by redox-inactive metal ions in aqueous environment. This ionophoric quinone derivative captured a Ca(2+) ion that drastically altered the voltammetric behavior of quinone, showing a characteristic response to pH and unique redox wave separation. Spectroelectrochemistry verified significant stabilization of the semiquinone, and electrocatalytic currents were observed in the presence of Ca(2+)-free CTAQ. Using digital simulation of cyclic voltammograms to clarify how the thermodynamic properties of quinones were altered, a simple scheme was proposed that successfully accounted for all the observations. The change induced by Ca(2+) complexation was explained on the basis of the combined effects of the electrostatic influence of the captured metal ion and hydrogen bonding of water molecules with the support of DFT calculation.

Reaction-based dual signaling of fluoride ions by resorufin sulfonates.

We developed new reaction-based probes for the dual signaling of fluoride ions. Selective fluoride-assisted deprotection of resorufin nosylate to generate resorufin fluorochrome was used for signaling. Resorufin nosylate exhibited selective colorimetric and fluorogenic signaling of fluoride ions in acetonitrile. The response from sulfide ions was effectively masked by using the TPEN-Cu(2+) complex as a source of Cu(2+) ions for masking sulfide. Selective optical signaling of fluoride was possible in the presence of commonly encountered anions with a detection limit of 1.9 × 10(-6) M.

Dual signaling of hydrazine by selective deprotection of dichlorofluorescein and resorufin acetates.

The highly selective chemosignaling behaviors for hydrazine by a reaction-based probe of dichlorofluorescein and resorufin acetates were investigated. Hydrazinolysis of latent dichlorofluorescein and resorufin acetate fluorochromes caused prominent chromogenic and fluorescent turn-on type signals. The probes selectively detected hydrazine in the presence of commonly encountered metal ions and anions as background. Dichlorofluorescein and resorufin acetates selectively detected hydrazine with detection limits of 9.0 × 10(-8) M and 8.2 × 10(-7) M, respectively. Furthermore, hydrazine was selectively detected over other closely related compounds, such as hydroxylamine, ethylenediamine, and ammonia. As a possible application of the acetate probes, hydrazine signaling in tap water was tested.

Colorimetric and fluorescent signaling of Au3+ by desulfurization of thiocoumarin.

We investigated the chemosignaling of Au(3+) by the selective desulfurization of thiocoumarin. In the presence of a heavy metal ion chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine, thiocoumarin was selectively converted to its oxo analogue by reaction with Au(3+), resulting in a pronounced chromogenic and fluorescent signaling. Selective signaling of Au(3+) was possible in the presence of common alkali, alkaline earth, and transition metal ions, as well as Au(+) in a mixed aqueous environment. The colorimetric determination of Au(3+) was possible by the color change from pink to yellowish green of the designed probe. The detection limit for the determination of Au(3+) in 50% aqueous acetonitrile was 1.1 × 10(-7) M.

Fluorescence signaling of Zr4+ by hydrogen peroxide assisted selective desulfurization of thioamide.

Thioamide derivative with a pyrene fluorophore was smoothly transformed to its corresponding amide by Zr(4+) ions in the presence of hydrogen peroxide. The transformation was evidenced by (1)H NMR spectroscopy and the signaling was completed within 10 min after sample preparation. Interference from Ag(+) and Hg(2+) ions in Zr(4+)-selective fluorescence signaling was readily suppressed with the use of Sn(2+) as a reducing additive. Discrimination of Zr(4+) from closely related hafnium, which is a frequent contaminant in commercial zirconium, was not possible. Prominent Zr(4+)-selective turn-on type fluorescence signaling was possible with a detection limit of 4.6 × 10(-6) M in an aqueous 99% ethanol solution.

Hydrazine-selective chromogenic and fluorogenic probe based on levulinated coumarin.

Chemosignaling of hydrazine by selective deprotection of levulinated coumarin was investigated. In the presence of hydrazine, levulinated coumarin was selectively deprotected, resulting in chromogenic and fluorescent turn-on type signaling. The selective naked-eye detectable signaling of hydrazine was possible in the presence of representative metal ions and common anions in an aqueous environment.

Signaling of hypochlorous acid by selective deprotection of dithiane. [corrected].

The selective signaling of hypochlorous acid by dithiane-protected [corrected] pyrene-aldehyde was investigated. Dithiolane derivative of pyrene-aldehyde was efficiently deprotected by hypochlorous acid to its corresponding aldehyde, which resulted in a prominent UV-vis and turn-on type fluorescence signaling. The signaling was not affected by the presence of other common alkali, alkaline earth metal ions, and anions. Interference from Hg(2+) ions could be successfully circumvented by using Chelex-100 resin. Dithiane [corrected] also provided selectivity toward hypochlorous acid over other commonly used oxidant of hydrogen peroxide.

Fluorescent signaling of oxone by desulfurization of thioamide.

The chemosignaling of the oxidant Oxone by selective desulfurization of a thioamide was investigated. Pyrene-thioamide was efficiently converted to its amide analogue by reaction with Oxone, resulting in a pronounced fluorescent turn-on type signaling. Selective signaling of Oxone in aqueous solution was possible in the presence of representative alkali and alkaline earth metal ions, as well as common anions.

Chromogenic and fluorogenic signaling of sulfite by selective deprotection of resorufin levulinate.

A new sulfite-selective probe system based on resorufin was investigated. Levulinate of resorufin exhibited a prominent chromogenic and turn-on type fluorogenic signaling toward sulfite ions in aqueous media based on the selective deprotection of the levulinate group. The sulfite-selective signaling was possible in the presence of commonly encountered anions.

Selective perborate signaling by deprotection of fluorescein and resorufin acetates.

The acetate derivatives of fluorescein and resorufin exhibited a prominent turn-on type signaling behavior toward BO(3)(-) ions over other common anions. Signaling is based on the selective deprotection of acetate groups by perborate, which resulted in significant chromogenic and fluorogenic signaling. Compound 1 also exhibited a pronounced perborate selectivity over other commonly used oxidants in 90% aqueous acetonitrile solution.

Sulfide-selective chemosignaling by a Cu2+ complex of dipicolylamine appended fluorescein.

A new sulfide-selective chemosignaling system was devised based on a Cu(2+) complex of fluorescein derivative having a dipicolylamine (DPA) binding site; the fluorescein-DPA conjugate 1, in the presence of Cu(2+) ions, revealed a selective turn-on type signaling behavior toward sulfide ions with a detection limit of 420 nM in 100% aqueous solution.