The function of the chloride channel ClC-1 is crucial for the control of muscle excitability. Thus, reduction of ClC-1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not allow in vivo screening of potentially therapeutic drugs, as the zebrafish model does. In this work, we identified and characterized the two zebrafish orthologues (clc-1a and clc-1b) of the ClC-1 channel. Both channels are mostly expressed in the skeletal muscle as revealed by RT-PCR, western blot, and electrophysiological recordings of myotubes, and clc-1a is predominantly expressed in adult stages. Characterization in Xenopus oocytes shows that the zebrafish channels display similar anion selectivity and voltage dependence to their human counterparts. However, they show reduced sensitivity to the inhibitor 9-anthracenecarboxylic acid (9-AC), and acidic pH inverts the voltage dependence of activation. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement, which could be reverted by expression of human ClC-1 but not by some ClC-1 containing myotonia mutations. Treatment of clc-1-depleted zebrafish with mexiletine, a typical drug used in human myotonia, improves the motor behaviour. Our work extends the repertoire of ClC channels to evolutionary structure-function studies and proposes the zebrafish clcn1 crispant model as a simple tool to find novel therapies for myotonia. KEY POINTS: We have identified two orthologues of ClC-1 in zebrafish (clc-1a and clc-1b) which are mostly expressed in skeletal muscle at different developmental stages. Functional characterization of the activity of these channels reveals many similitudes with their mammalian counterparts, although they are less sensitive to 9-AC and acidic pH inverts their voltage dependence of gating. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement which could be reverted by expression of human ClC-1. Myotonia-like symptoms caused by clc-1a/b depletion can be reverted by mexiletine, suggesting that this model could be used to find novel therapies for myotonia.

To solve the problems existing in the clinical application of hypericin (Hyp) and tirapazamine (TPZ), a nano-drug delivery system with synergistic anti-tumor functions was constructed using mesoporous silica nanoparticles (MSN) and sodium alginate (SA). The system exhibited excellent stability, physiological compatibility and targeted drug release performance in tumor tissues. In the in vitro and in vivo experiments, Hyp released from MSN killed tumor cells through photodynamic therapy (PDT). The degree of hypoxia in the tumor tissue site was exacerbated, enabling TPZ to fully exert its anti-tumor activity. Our studies suggested that the synergistic effects between the components of the nano-drug delivery system significantly improve the anti-tumor properties of Hyp and TPZ.

Chemical and microlitter (ML) pollution in three Estonian coastal areas (Baltic Sea) was investigated using mussels (Mytilus trossulus). Polycyclic aromatic hydrocarbons (PAH) in mussel tissues were observed in moderate levels with high bioaccumulation factors for the more hydrophilic and low molecular weight PAH (LMW PAH), namely anthracene and fluorene. Tissue concentrations of polybrominated diphenyl ethers (PBDE) and cadmium within mussel populations exceeded the Good Environmental Status thresholds by more than 200% and 60%, respectively. Multiple contamination at the Muuga Harbour site by tributyltin, high molecular weight PAH, including the highly toxic benzo[c]fluorene and PBDE, coincided with the inhibition of acetylcholinesterase activity and a lower condition index of the mussels. The metabolization and removal of bioaccumulated LMW PAH, reflected in the dominance of oxy-PAH such as anthracene-9,10-dione, is likely associated with the increased activity of glutathione S-transferase in caged mussels. Only a few microplastic particles were observed among the ML in mussel tissues, with coloured cellulose-based microfibers being the most prevalent. The average concentration of ML in mussels was significantly higher at the harbour area than at other sites. The integrated biomarker response index values allowed for the differentiation of pollution levels across studied locations representing high, intermediate, and low pollution levels within the studied area.

The northeastern Pacific (NEP) Ocean spans the coast of British Columbia (Canada) and is impacted by anthropogenic activities including oil pipeline developments, maritime fossil fuel tanker traffic, industrial chemical effluents, agricultural and urban emissions in tandem with stormwater and wastewater discharges, and forest wildfires. Such events may expose surrounding marine environments to toxic polycyclic aromatic hydrocarbons (PAHs) and impact critical habitats of threatened killer whales (Orcinus orca). We analyzed skeletal muscle and liver samples from stranded Bigg\'s killer whales and endangered Southern Resident killer whales (SRKWs) for PAH contamination using LRMS. C3-phenanthrenes/anthracenes (mean: 632 ng/g lw), C4-dibenzothiophenes (mean: 334 ng/g lw), and C4-phenanthrenes/anthracenes (mean: 248 ng/g lw) presented the highest concentrations across all tissue samples. Diagnostic ratios indicated petrogenic-sourced contamination for SRKWs and pyrogenic-sourced burdens for Bigg\'s killer whales; differences between ecotypes may be attributed to habitat range, prey selection, and metabolism. A mother-fetus skeletal muscle pair provided evidence of PAH maternal transfer; low molecular weight compounds C3-fluorenes, dibenzothiophene, and naphthalene showed efficient and preferential exposure to the fetus. This indicates in-utero exposure of PAH-contamination to the fetus. Our results show that hydrocarbon-related anthropogenic activities are negatively impacting these top predators; preliminary data found here can be used to improve oil spill and other PAH pollution management and regulation efforts, and inform policy to conserve killer whale habitats in the NEP.

A new anthracene-based probe (E)-N\'-(1-(anthracen-9-yl)ethylidene)-2-hydroxybenzohydrazide (AHB) has been efficiently synthesized and characterized by various spectroscopic methods. It exhibits extremely selective and sensitive fluorometric sensing of Al3+ ions with a large enhancement in the fluorescent intensity due to the restricted photoinduced electron transfer (PET) mechanism with a chelation-enhanced fluorescence (CHEF) effect. The AHB-Al3+ complex shows a remarkably low limit of detection at 0.498 nM. The binding mechanism has been proposed based on Job\'s plot, 1H NMR titration, Fourier transform infrared (FT-IR), high-resolution mass spectrometry (HRMS), and density functional theory (DFT) studies. The chemosensor is reusable and reversible in the presence of ctDNA. The practical usability of the fluorosensor has been established by a test strip kit. Further, the therapeutic potential of AHB against Al3+ ion-induced tau protein toxicity has been tested in the eye of Alzheimer\'s disease (AD) model of Drosophila via metal chelation therapy. AHB shows great therapeutic potential with 53.3% rescue in the eye phenotype. The in vivo interaction study of AHB with Al3+ in the gut tissue of Drosophila confirms its sensing efficiency in the biological environment. A detailed comparison table included evaluates the effectiveness of AHB.

Post-consumption waterpipe tobacco waste (PWTW) is an unrecognized type of hazardous waste that is produced and released in large quantities into the aquatic environment. It may contain high amounts of various pollutants including PAH, and to date, there has been no research on the potential for contamination by PAH from PWTW leaching into aquatic environments. In this study, the concentrations of PAH via PWTW of fruit-flavored and traditional tobacco leachate into three water types, including distilled water (DW), tap water (TW) and sea water (SW) at different contact times were evaluated. There were significantly higher concentration levels of ƩPAH in waters with leachates from fruit-flavored PWTW than traditional tobacco (P-value<0.05). The concentration levels of ƩPAH in DW, TW and SW at a total contact time of two months ranged from 0.13 to 3.51, 0.12 to 3.63 and 0.11-3.64 μg/L, respectively. Lower molecular weight PAH such as naphthalene (Naph), acenaphthylene (Acen) and fluorine (Flu) were detected in leachates immediately after a short contact time of 15 min. Higher molecular weight PAH including benzo [a]anthracene (BaA), benzo [b]fluoranthene (BbF), benzo [k]fluoranthene (BkF), chrysene (Chr), and benzo [a]pyrene (BaP) were detected after one month contact time, while indeno [1,2,3-cd] pyrene (Indp), benzo [ghi]perylene (BghiP) and dibenz [a,h]anthracene (DahA) were only observed at the contact time measurement of two months. By adding sodium azide as an antimicrobial agent and chemical preservative to SW samples, higher concentrations of PAH including IP, DahA and BghiP were observed. The concentration levels of PAH in water samples after two months contact time were higher than water quality standards provided by the World Health Organization (WHO) and other international organizations.

The US Environmental Protection Agency (US-EPA) published a priority list of 16 polycyclic aromatic hydrocarbons (PAHs), which are compounds that are studied in a variety of matrices due to their wide range of risks. Environmental compartments can be contaminated with PAHs from different sources, such as wastewater from industries and petroleum spills. For the case of Cameroon, there are no recorded data concerning the sources, distributions, and toxicity levels of PAHs in water and sediment from Cameroon beaches which are found in South-West, Littoral, and South Regions. In this work, only three beaches from South-West Region were studied regarding the sources, distributions, and toxicity levels of PAHs in water and sediment. The analyzed samples came from Bobende coastal beach, Down-beach, and Cape-Limboh beach. To achieve the analyses, liquid-liquid extraction and gas chromatography enabled the identification and quantification of PAH compounds from sediments and marine water. Out of the 16 PAHs listed by US-EPA, twelve were identified and quantified among which four of them were light molecular weight PAHs (acenaphthylene, fluorene, phenanthrene, and anthracene). Anthracene in the Cape-Limboh sample presented the highest concentration (477.57 ng/kg weight of dry sediment) of LMW-PAHs. Eight identified and quantified PAHs of high molecular weight as a whole, three absent PAHs (benzo[a]anthracene, dibenzo[a,h]anthracene, and benzo[g,h,i]perylene) in the Cape-Limboh sample, while only one is absent in the Bobende samples (dibenzo[a,h]anthracene) and Down Beach (benzo[g,h,i]perylene). According to the ratios used for the determination of the sources of PAHs, it came out that the source of PAHs from all beaches is pyrolytic. In all samples, BaA is the only high molecular weight PAH presenting serious toxicity and ecological risk.

In this article, we used the numerical self-consistent field method of Scheutjens-Fleer to study the micellization of hybrid molecules consisting of one polylysine dendron with charged end groups and several linear hydrophobic tails attached to its root. The main attention was paid to spherical micelles and the determination of the range of parameters at which they can appear. A relationship has been established between the size and internal structure of the resulting spherical micelles and the length and number of hydrophobic tails, as well as the number of dendron generations. It is shown that the splitting of the same number of hydrophobic monomers from one long tail into several short tails leads to a decrease in the aggregation number and, accordingly, the number of terminal charges in micelles. At the same time, it was shown that the surface area per dendron does not depend on the number of hydrophobic monomers or tails in the hybrid molecule. The relationship between the structure of hybrid molecules and the electrostatic properties of the resulting micelles has also been studied. It is found that the charge distribution in the corona depends on the number of dendron generations G in the hybrid molecule. For a small number of generations (up to G=3), a standard double electric layer is observed. For a larger number of generations (G=4), the charges of dendrons in the corona are divided into two populations: in the first population, the charges are in the spherical layer near the boundary between the micelle core and shell, and in the second population, the charges are near the periphery of the spherical shell. As a result, a part of the counterions is localized in the wide region between them. These results are of potential interest for the use of spherical dendromicelles as nanocontainers for drug delivery.

1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.

Semiconducting minerals (such as iron sulfides) are highly abundant in surface water, but their influences on the natural photochemical process of contaminants are still unknown. By simulating the natural water environment under solar irradiation, this work comprehensively investigated the photochemical processes of anthracene (a typical Polycyclic Aromatic Hydrocarbons) in both freshwater and seawater. The results show that the natural pyrite (NP) significantly promotes the degradation of anthracene under solar illumination via 1) NP induced photocatalytic degradation of anthracene, and 2) Fenton reaction due to the NP induced photocatalytic generation of H2O2. The material characterization and theoretical calculation reveal that the natural impurity in NP enlarges its band gap, which limits the utilization of solar spectra to shorter wavelength. The contribution of generated reactive intermediates on anthracene degradation follows the order of 1O2 >OH > O2- in freshwater and O2- >1O2 >OH in seawater. The photochemically generated H2O2 is a vital source for OH generation (from Fenton reaction). The steady-state concentration of OH, 1O2 and O2- in freshwater were monitored as 3.0 × 10-15 M, 1.1 × 10-13 M, and 4.5 × 10-14 M, respectively. However, the OH concentration in seawater can be negligible due to the quenching effects by halides, and the 1O2 and O2- concentrations are higher than that in freshwater. An anthracene degradation kinetic model was built based on the experimentally determined reactive intermediates concentration and its second order rate constant with anthracene. Moreover, the anthracene degradation pathway was proposed based on intermediates analysis and DFT calculation, and its toxicity evolution during the photochemical process was assessed by quantitative structure-activity relationship (QSAR) based prediction. This finding suggests that the natural semiconducting minerals can affect the fate and environmental risks of contaminants in natural water.