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In this paper, we firstly report the synthesis and structural characterization of a discrete coordination metallacycle complex, [CuI (bipy)] 2 (1). The x-ray diffraction structure, temperature-dependent electronic absorption, and photoluminescence spectra have been investigated. The solid-state fluorescence at variable temperatures shows that complex 1 exhibits an obvious thermochromic fluorescence. At low temperature, the dual fluorescence with peaks at 590 and 694 nm was observed. The emission color significantly changes from red at 77 K to yellow at 200 K and blue-green at 330 K. The thermochromic fluorescent molecular materials show great potential as temperature sensing., (© 2024 John Wiley & Sons Ltd.)

Pesticides are usually found as mixtures in surface water bodies, even though their regulation in aquatic ecosystems is usually approached individually. In this context, this work aimed to investigate the enzymatic- and transcriptional-level responses after the mixture exposure of phoxim (PHX) and prochloraz (PRC) in the livers of hook snout carp Opsariichthys bidens. These data exhibited that co-exposure to PHX and PRC induced an acute synergistic impact on O. bidens. The activities of catalase (CAT), superoxide dismutase (SOD), carboxylesterase (CarE), and caspase3 varied significantly in most of the individual and combined challenges relative to basal values, indicating the activation of oxidative stress, detoxification dysfunction, as well as cell apoptosis. Besides, the transcriptional levels of five genes (gst, erα, mn-sod, cxcl-c1c, and il-8) exhibited more pronounced changes when subjected to combined pesticide exposure in contrast to the corresponding individual compounds. The findings revealed the manifestation of endocrine dysfunction and immune disruption. These results underscored the potential biochemical and molecular toxicity posed by the combination of PHX and PRC to O. bidens, thereby contributing to a deeper comprehension of the ecological toxicity of pesticide mixtures on aquatic organisms. Importantly, the concurrent presence of PHX and PRC might exacerbate hepatocellular damage in hook snout carps, potentially attributable to their synergistic toxic interactions. This study underscored the toxicological potency inherent in the co-occurrence of PHX and PRC in influencing fish development, thereby offering valuable insights for the risk assessment of pesticide mixtures and the safeguarding of aquatic organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Crizotinib (CRZ), one of anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs), has emerged as a frontline treatment for ALK-positive (ALK+) lung adenocarcinoma. However, the overexpression of P-glycoprotein (P-gp, a mitochondrial adenosine triphosphate (ATP)-dependent protein) in lung adenocarcinoma lesions causes multidrug resistance (MDR) and limits the efficacy of CRZ treatment. Herein, a mitochondria-targeting nanosystem, zeolitic imidazolate framework-90@indocyanine green (ZIF-90@ICG), was fabricated to intervene in mitochondria and overcome drug resistance. Due to the zinc ion (Zn 2+ ) interference of ZIF-90 and the photodynamic therapy (PDT) of ICG, this nanosystem is well suited for damaging mitochondrial functions, thus downregulating the intracellular ATP level and inhibiting P-gp expression. In addition, systematic bioinformatics analysis revealed the upregulation of CD44 in CRZ-resistant cells. Therefore, hyaluronic acid (HA, a critical target ligand of CD44) was further modified on the surface of ZIF-90@ICG for active targeting. Overall, this ZIF-90@ICG nanosystem synergistically increased the intracellular accumulation of CRZ and reversed CRZ resistance to enhance its anticancer effect, which provides guidance for nanomedicine design to accurately target tumours and induce mitochondrial damage and represents a viable regimen for improving the prognosis of patients with ALK-TKIs resistance. STATEMENT OF SIGNIFICANCE: The original aim of our research was to combat multidrug resistance (MDR) in highly aggressive and lethal lymphoma kinase-positive (ALK+) lung adenocarcinoma. For this purpose, a cascade-targeted system was designed to overcome MDR, integrating lung adenocarcinoma-targeted hyaluronic acid (HA), mitochondrion-targeted zeolitic imidazolate framework-90 (ZIF-90), the clinically approved drug crizotinib (CRZ), and the fluorescence imaging agent/photosensitizer indocyanine green (ICG). Moreover, using a "two birds with one stone" strategy, ion interference and oxidative stress induced by ZIF-90 and photodynamic therapy (PDT), respectively, disrupt mitochondrial homeostasis, thus downregulating adenosine triphosphate (ATP) levels, inhibiting MDR-relevant P-glycoprotein (P-gp) expression and suppressing tumour metastasis. Overall, this research represents an attempt to implement the concept of MDR reversal and realize the trade-offs between MDR and therapeutic effectiveness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Empagliflozin (EMPA), a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been shown to reduce major adverse cardiovascular events in patients with heart failure of different etiologies, although the underlying mechanism still remains unclear. Ponatinib (PON) is a multi-tyrosine kinase inhibitor successfully used against myeloid leukemia and other human malignancies, but its cardiotoxicity remains worrisome. Cardiac connexins (Cxs) are both substrates and regulators of autophagy and responsible for proper heart function. Alteration in connexin expression and localization have been described in patients with heart failure., Aims: To assess whether EMPA can mitigate PON-induced cardiac dysfunction by restoring the connexin 43-autophagy pathway., Methods and Results: Male C57BL/6 mice, randomized into four treatment groups (CNTRL, PON, EMPA, PON+EMPA) for 28 days, showed increased autophagy, decreased Cx43 expression as well as Cx43 lateralization, and attenuated systo-diastolic cardiac dysfunction after treatment with EMPA and PON compared with PON alone. Compared with CNTRL (DMSO), cardiomyocyte-differentiated H9c2 (dH9c2) cells treated with PON showed significantly reduced cell viability to approximately 20 %, decreased autophagy, increased cell senescence and reduced DNA binding activity of serum response factor (SRF) to serum response elements (SRE), which were paralleled by reduction in cardiac actin expression. Moreover, PON induced a significant increase of Cx43 protein and its S368-phosphorylated form (pS368-Cx43), as well as their displacement from the plasma membrane to the perinuclear and nuclear cellular region. All these effects were reverted by EMPA., Conclusion: EMPA attenuates PON-induced cardiotoxicity by reducing senescence, enhancing the SRE-SRF binding and restoring the connexin 43-autophagy pathway. This effect may pave the way to use of SGLT2 inhibitors in attenuating tyrosine-kinase inhibitor cardiotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

4-methylimidazole (4-MI), a derivative of imidazole, is a widely used component in caramel-colored food products such as soy sauce, beer and other soft drinks. The present study is aimed to investigate the effects of 4-MI on the male reproduction. The results revealed that 8 weeks of 4-MI exposure did not significantly alter the body weight and testicular weight of male mice. However, testicular morphology and computer-assisted sperm analysis showed that exposed to 4-MI caused irregular arrangement of spermatogenic cells in the testes and weakened sperm motility. Consistently, we observed the decreased fertilization ability in vivo of 4-MI-treated male mice. We further demonstrated that 4-MI disrupted the blood-testis barrier (BTB) integrity by decreasing the protein expression of BTB-related junction with permeability assay and western blot. In addition, the apoptosis of Sertoli cells (TM4) occurred in 4-MI treated mice, which might be caused by the generation of oxidative stress. Collectively, our findings document that 4-MI exposure damages the sperm mobility via disruption of BTB integrity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

1-octyl-3-methylimidazolium bromide ([C 8 mim]Br), one of the ionic liquids (ILs), has been used in various fields as an alternative green solvent of conventional organic solvents. Increased application and stabilization of imidazole ring structure lead to its release into the aquatic environment and long-term retention. Structure-activity relationship consideration suggested that ILs may be acetylcholinesterase inhibitors; however, neurotoxicity in vivo, especially the underlying mechanisms is rarely studied. In this study, the zebrafish were exposed to 2.5-10 mg/L [C 8 mim]Br for 28 days to comprehensively evaluate the neurotoxicity of ILs on adult zebrafish from the behavioral profiles and neurotransmitter systems for the first time. The results indicate that zebrafish exhibit suppressed spatial working memory and anxious behaviors. To assess the potential neurotoxic mechanisms underlying the behavioral responses of zebrafish, we measured the levels of neurotransmitters and precursors, key enzyme activities, and expression levels of relevant genes. Nissl staining showed significant neural cell death in zebrafish after 28-day [C 8 mim]Br exposure, with corresponding decreases in the levels of neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptophan, gamma-aminobutyric acid, dopamine, and norepinephrine). Furthermore, these results were associated with mRNA expression levels of the disrupted neurotransmitter key genes (th, tph2, mao, slc6a3, ache, gad67). Overall, our study determined that [C 8 mim]Br caused potential mental disorders like anxiety and memory deterioration in zebrafish by impairing neurotransmitter systems, providing recommendations for the industrial production and application of [C 8 mim]Br., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A class of chemical with a potentially important perceived future contribution to the net zero carbon goal (as "green" solvents) is the methylimidazolium ionic liquids (MILs). These solvents are used in industrial processes such as biofuel production yet little is known about their environmental stability or toxicity in man although one MIL - 1-octyl-3-methylimidazolium (M8OI) - has been shown to activate the human estrogen receptor alpha (ERα). The stabilities of the chloride unsubstituted methylimidazolium (MI) and MILs possessing increasing alkyl chain lengths (2C, 1-ethyl-3-methylimidazolium (EMI); 4C, 1-butyl-3-methylimidazolium (BMI); 6C; 1-hexyl-3-methylimidazolium (HMI), 8C, M8OI; 10C, 1-decyl-3-methylimidazolium (DMI)) were examined in river water and a human liver model system. The MILs were also screened for their abilities to activate the human ERα in vitro and induce uterine growth in pre-pubertal rats in vivo. Short chain MILs (EMI, BMI and HMI) underwent negligible metabolism and mineralisation in river water; were not metabolised in a model of human liver metabolism; activated the human ERα in vitro and were estrogenic in vivo in rats. A structure-based computational approach predicted short chain MIL binding to both the estrogen binding site and an additional site on the human estrogen receptor alpha. Longer chain MILs (M8OI and DMI) were metabolised in river water and partially mineralised. Based on structure-activity considerations, some of these environmentally-derived metabolites may however, remain a hazard to the population. MILs therefore have the potential to become forever chemicals with adverse effects to both man, other animals and the environment in general., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Acquired drug resistance is the major cause for disease recurrence in cancer patients, and this is particularly true for patients with metastatic melanoma that carry a BRAF V600E mutation. To address this problem, we investigated cyclic membrane-active peptides as an alternative therapeutic modality to kill drug-tolerant and resistant melanoma cells to avoid acquired drug resistance. We selected two stable cyclic peptides (cTI and cGm), previously shown to have anti-melanoma properties, and compared them with dabrafenib, a drug used to treat cancer patients with the BRAF V600E mutation. The peptides act via a fast membrane-permeabilizing mechanism and kill metastatic melanoma cells that are sensitive, tolerant, or resistant to dabrafenib. Melanoma cells do not become resistant to long-term treatment with cTI, nor do they evolve their lipid membrane composition, as measured by lipidomic and proteomic studies. In vivo studies in mice demonstrated that the combination treatment of cTI and dabrafenib resulted in fewer metastases and improved overall survival. Such cyclic membrane-active peptides are thus well suited as templates to design new anticancer therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Advanced glycation end products (AGEs) are important contributors to the progression of chronic kidney diseases (CKD), including renal fibrosis. Although the relationship between AGEs and renal fibrosis has been well studied, the mechanisms of individual AGE-induced renal injury remain poorly understood. This study investigated the adverse effect of methylglyoxal-derived hydroimidazolone-1 (MG-H1), a methylglyoxal (MG)-derived AGE generated by the glycation of MG and arginine residues, on kidney damage. We aimed to elucidate the molecular mechanisms of MG-H1-mediated renal injury and fibrosis, focusing on the receptor for AGEs (RAGE) signaling and its effects on the Wnt/β-catenin pathway, MAPK pathway, and inflammatory responses. Our results suggest that the MG-H1/RAGE axis plays a significant role in the pathogenesis of CKD and its downstream events involving MAPK kinase-related factors and inflammatory factors. MG-H1 treatment modulated the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and MAPK proteins (ERK1/2, JNK, and p38)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kwang-Won Lee reports a relationship with Korea University that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dynamic self-assembly has significant implications in the regulation of the enzyme activities. In this study, we present a histidine-based enzyme-mimicking catalyst, formed by the self-assembly of carefully-engineered FH-based short peptides with hemin, showcasing switchable catalytic activity of hemin due to externally induced reversible inclusion of a cucurbit[7]uril-peptide hybrid. 1H NMR, ITC and theoretical simulation are employed to examine the binding affinity between the guest and host components, and UV-vis spectra are used to investigate changes in the hemin coordination environment. The histidine segment of the short peptide can be partially shielded by the cucurbituril and released following addition of the azo compound, leading to a decrease and subsequent restoration of the histidine-hemin coordination affinity and hemin activity. The photoisomeriziable nature of the azo compound enabled the activation of FHH/hemin activity to be switched on and off by exposure to different wavelengths of light. During the operation, the Phe residue remained within the cucurbituril, allowing reversible inclusion and exposure of the histidine residues. The hemin stayed connected to FHH/cucurbit[7]uril hybrid, preventing the severe aggregation of hemin and irreversible deactivation. This work may provide insights into engineering the dynamic behaviors of the cofactor-dependent catalytic assemblies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to analyze the expression pattern of Toll receptor 7/8 (TLR7/8) in canine sperm, and explore the feasibility of using TLR7/8 ligand resiquimod(R848)to separate canine X and Y sperm. In this study, cellular immunofluorescence was used to analyze the expression of TLR7/8 in canine sperm, real-time fluorescence quantitative PCR was used to calculate the proportion of X sperm in the lower layer of the incubation solution with R848 to evaluate the sorting effect of R848 on canine X/Y sperm, and sperm quality detection system was used to analyze the effect of R848 on the motility of canine sperm. The mechanism of effect of R848 on canine sperm motility was analyzed by Western blot. The results showed that TLR8 was not expressed in all canine sperm, while TLR7 was expressed in all canine sperm and was localized in the head and tail of sperm. When 0.4 μM R848 was incubated with canine sperm for 1 h, the total motility, average path velocity (VAP), average straight-line velocity (VSL), and average curved-line velocity (VCL) of canine sperm were significantly decreased(P < 0.05). There was no significant difference between the lower and upper layers of the R848 treatment group and the control group(P > 0.05), and the proportion of X sperm was nearly half. The levels of NF-κB and GSK3α/β phosphorylation of sperm in R848 treatment group were significantly increased compared with control group(P < 0.05). The above results showed that TLR7/8 was not differentially expressed in canine X and Y sperm. R848 could decrease the motility of canine spermatozoa and inhibit sperm motility by the GSK3α/β-hexokinase pathway through the phosphorylation of NFκB and GSK3α/β, while could not separate X and Y spermatozoa. The method of sorting X/Y sperm based on TLR7/8 is not feasible for dogs., Competing Interests: Declaration of competing interest In the preparation of this paper, we hereby declare that we have no conflicts of interest that could potentially bias our research or its outcomes. We have conducted this study independently, without any undue influence from external parties. To ensure the objectivity and integrity of our research, I have adhered to strict ethical guidelines and have cited all sources appropriately. The data collected and analyzed in this paper are based on reliable and publicly available sources, and we have made every effort to ensure their accuracy and reproducibility. We also confirm that none of the content in this paper has been previously published or is currently under consideration for publication in any other journal. Finally, we understand that failure to disclose any potential conflicts of interest could jeopardize the credibility and reputation of both ourselves and the journal. We therefore undertake to inform the editor of any relevant changes in our interest status that may arise during the review or publication process. We hereby submit this Declaration of Interest Statement as a testament to my commitment to ethical and responsible research practices., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anthraimidazoledione based amphiphilic dye is synthesized that exhibits pH‐responsive chromogenic response in aqueous environment. This entices us to investigate its anion‐responsive behavior. In pure water, the compound shows no optical response towards anions (poor sensitivity), whereas interaction with multiple anions is witnessed in acetonitrile medium (poor selectivity). Interestingly, changes in solution color from yellow to orange is observed explicitly upon addition of acetate anion, accompanied by fluorescence turn‐off response. Further, it is revealed that the acetate engaged in hydrogen bonding interaction with both imidazole −NH group and hydroxyl unit. The high basicity of acetate anion along with 'Y‐shaped' structure might be responsible for such unique selectivity. The present system has been involved in analyzing residual acetate in natural water samples. Low‐cost, reusable paper strips have been designed for equipment free, rapid on‐location detection of acetate. [ABSTRACT FROM AUTHOR]

A novel CB[6]-based supramolecular assembly [K(ANS)(CB[6]) 2 (DMF) 2 (H 2 O) 0.5 ] (1) (CB[6] = cucurbit[6]uril, ANS - = 8-amino-1-naphthalene sulfonic acid ion) was successfully synthesized under solvothermal condition. Performance studies have shown that 1 exhibited excellent chemical stability and recycling performance. Meanwhile, 1 exhibited remarkable potential as a fluorescence sensor for the detection of 2,4,6-trinitrophenol (TNP), 4-nitrophenol (4-NP), and rifampicin (RFP) in both aqueous environments and practical samples. This sensing capability is achieved through fluorescence quenching, which offers fast response times and exceptional sensitivity, with detection limits of 0.19 μM for both TNP and 4-NP, and 0.21 μM for RFP. Even more remarkably, an anti-counterfeiting ink based on 1 and a portable test hydrogel were devised for encrypting information and visually detecting using a smartphone application. This work has the potential to expand the utilization of CB[6]-based materials in optical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ponatinib is approved for use in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. Given that ponatinib can induce significant cardiotoxicity when taken, and that most Chinese medicines have cardioprotective effects, it is possible to administer them in combination in clinic to alleviate adverse effects. The quantitative determination of ponatinib and its metabolite N-desmethyl ponatinib was optimized and fully verified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). And the drug-drug interactions (DDI) of ponatinib with lycopene and shikonin, both in vivo and in vitro, were studied. The results of bioanalytical methodology showed that ponatinib and N-desmethyl ponatinib had good linearity in plasma samples, and their selectivity, accuracy, precision, stability, matrix effect and recovery were all satisfied with the need of quantitative analysis of samples. In animal experiments, compared with the control group, lycopene and shikonin significantly changed the pharmacokinetic parameters of ponatinib, including AUC (0-t) , AUC (0-∞) and CL z/F , while having no effect on the pharmacokinetic parameters of N-desmethyl ponatinib. In vitro interaction studies indicated that lycopene showed mixed inhibition mechanism on ponatinib metabolism in both rat liver microsomes (RLM) and human liver microsomes (HLM). And, shikonin displayed mixed inhibition mechanism in RLM and competitive inhibition mechanism in HLM, respectively. In summary, the UPLC-MS/MS method can accurately and sensitively quantify ponatinib and N-desmethyl ponatinib, and provide further reference for clinical drug combination between ponatinib and lycopene or shikonin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Open wounds are susceptible to bacterial infections, and antibiotics are commonly used to treat these infections. However, widespread use of antibiotics will easily induce bacterial resistance. Green antibacterial agents serve as excellent alternative for antibiotics in infection therapy. In this work, polydopamine (PDA) was used to modify the surface of ZIF-8, which not only enhances the water stability of Zeolitic imidazolate framework-8(ZIF-8) but also improves its photocatalytic and photothermal capabilities. ZIF-8@PDA was incorporated into carboxylated chitosan (CCS) films as an antibacterial agent, the resulting ZIF-8@PDA-CCS films exhibit excellent ionic/photocatalytic/photothermal antibacterial performance. The film exhibited an impressive 99% in vitro bacterial inhibition rate. After treatment with ZIF-8@PDA-CCS, the bacteria in infected wounds can be completely suppressed. These findings suggest that ZIF-8@PDA-CCS could serve as a potentional antibacterial dressing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dabrafenib is a BRAF inhibitor that has been demonstrated to be efficacious in the treatment of melanoma and non-small-cell lung cancer patients with BRAF V600E mutations. The objective of this study was to investigate the effects of 51 traditional Chinese medicines on the metabolism of dabrafenib and to further investigate the inhibitory effect of imperatorin. The quantification of dabrafenib and its metabolite hydroxy-dabrafenib was carried out using a sensitive, rapid, and accurate assay method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results of in vitro experiments showed that 20 drugs inhibited the metabolism of dabrafenib by more than 80 %. In a further study of imperatorin on dabrafenib, the half-maximal inhibitory concentration (IC 50 ) values of imperatorin on dabrafenib were 0.22 μM and 3.68 μM in rat liver microsomes (RLM) and human liver microsomes (HLM), respectively, while the inhibition mechanisms were non-competitive and mixed type inhibition, respectively. The results of in vivo experiments demonstrated that in the presence of imperatorin, the AUC (0-t) , AUC (0-∞) , C max , and T max of dabrafenib were increased by 2.38-, 2.26-, 1.05-, and 6.10-fold, respectively, while CL z/F was decreased by 67.9 %. In addition, T max of hydroxy-dabrafenib was increased by 1.4-fold. The results of the research showed that imperatorin had a consistent inhibitory effect on dabrafenib in vitro and in vivo. When the concurrent use of dabrafenib and imperatorin is unavoidable, clinicians should closely monitor for potential adverse events and make timely adjustments to the administered dosage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel zeolitic imidazolate framework-encapsulated zinc porphyrin (ZnTCPP@ZIF-90) photoresponsive nanozyme is proposed for the colorimetric/fluorescent dual-mode visual sensing of glyphosate (Gly). ZnTCPP@ZIF-90 exhibits photoresponsive oxidase-like activity and fluorescence quenching behavior. Meanwhile, the outer ZIF-90 layer can be selectively destroyed by Gly, causing the release of free ZnTCPP, resulting in the enhanced enzyme-like activity as well as fluorescence emission. The constructed ZnTCPP@ZIF-90 was successfully used for the colorimetric/fluorescent dual-mode detection of Gly. Additionally, the colorimetric and fluorescent images information captured by the smartphone were converted to color intensity (HSV/RGB values), with limits of detection of 0.27 μg/mL and 0.19 μg/mL, respectively. The proposed dual-mode sensor exhibits excellent selectivity and reliability for detecting Gly, and can be successfully applied to the analysis of real samples such as tap water, lake water, and fruit washing water. The current research efforts are expected to provide new perspectives for designing highly active photoresponsive nanozymes and their stimuli-responsive sensing systems, paving the way for their applications in portable dual-mode chemical sensing and environmental monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alkyl imidazolium ionic liquids (Cn[MIM]), initially heralded as eco-friendly green solvents for diverse industrial applications, have increasingly been recognized fortheir biodegradability challenges and multiple biotoxicity. Despite potential health risks, research into the effects of Cn[MIM] on human health remains scarce, particularly regarding their detection in biological serum samples. This study validated a matrix-matched calibration quantitative method that utilizes solid-phase extraction (SPE) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was used to analyze the presence of 10 ionic liquids (ILs) with varying alkyl carbon chain lengths (C 2 -C 12 ) across 300 human serum samples. Efficient separation was achieved using optimized SPE conditions and a BEH C18 column with an appropriate mobile phase. Results demonstrated a strong linear relationship (0.05-100 ng/mL; R 2  = 0.995-0.999), with detection and quantification limits with detection and quantification limits ranging from 0.001 to 0.107 ng/mL and 0.003-0.355 ng/mL, respectively. Intraday and inter-day precisions were 0.85-6.99 % and 1.50-7.46 %, with recoveries between 82 and 113 %. The validated method detected C 6 MIM in 19 % of samples and C 8 MIM in 8.3 % of samples, with concentrations ranging from 0.02 to 111.70 μg/L and 0.09-16.99 μg/L, respectively, suggesting a potential risk of human exposure. This underscores the importance of robust detection methods in monitoring environmental and human health impacts of alkyl imidazolium compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Peptide-bound histidines and imidazoles are important constituents of dissolved organic matter in water, and understanding the formation of halogenated disinfection byproduct (DBP) formation from these compounds during disinfection is important for ensuring a safe drinking water supply. Previous studies suggested that histidine has low reactivity with chlorine only; this study indicates that iodide substantially enhances histidine reactivity with the disinfectant at a time scale from days to hours. Mono- and di-iodinated histidines were identified as dominant transformation products with cumulative molar yields of 3.3 % at 6 h and they were stable in water over 7 days. These products were formed via electrophilic substitution of iodine to imidazole ring when hypoiodous acid reacted with histidine sidechain. Bromide minimally influenced the formation yields of these iodinated products, and higher pH increased yields up to 12 % for pH in the range 5-9. The cumulative concentration of low-molecular-weight DBPs, such as trihalomethanes and haloacetic acids, was less than 0.3 % under the same conditions. Similar iodinated imidazole analogs were also identified from other imidazoles (i.e., imidazole-carboxylic and phenyl-imidazole-carboxylic acids). This study demonstrated that peptide-bound histidine and imidazoles can serve as important precursors to iodinated aromatic DBPs, facilitating the identification of less-known iodinated DBPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals. However, fully effective treatments are unavailable for medical and veterinary uses. There is a need to explore new drug targets for potential development of new therapeutics. Because C. parvum relies on anaerobic metabolism to produce ATP, fermentative enzymes in this parasite are attractive targets for exploration. In this study, we investigated the ethanol-fermentation in the parasite and characterized the basic biochemical features of a bacterial-type bifunctional aldehyde/alcohol dehydrogenase, namely CpAdhE. We also screened 3892 chemical entries from three libraries and identified 14 compounds showing >50% inhibition on the enzyme activity of CpAdhE. Intriguingly, antifungal imidazoles and unsaturated fatty acids are the two major chemical groups among the top hits. We further characterized the inhibitory kinetics of selected imidazoles and unsaturated fatty acids on CpAdhE. These compounds displayed lower micromolar activities on CpAdhE (i.e., IC 50 values ranging from 0.88 to 11.02 μM for imidazoles and 8.93 to 35.33 μM for unsaturated fatty acids). Finally, we evaluated the in vitro anti-cryptosporidial efficacies and cytotoxicity of three imidazoles (i.e., tioconazole, miconazole and isoconazole). The three antifungal imidazoles exhibited lower micromolar efficacies against the growth of C. parvum in vitro (EC 50 values ranging from 4.85 to 10.41 μM and selectivity indices ranging from 5.19 to 10.95). The results provide a proof-of-concept data to support that imidazoles are worth being further investigated for potential development of anti-cryptosporidial therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The rapid developments in the field of zeolitic imidazolate frameworks (ZIFs) in recent years have created unparalleled opportunities for the development of unique bioactive ZIFs for a range of biosensor applications. Integrating bioactive molecules such as DNA, aptamers, and antibodies into ZIFs to create bioactive ZIF composites has attracted great interest. Bioactive ZIF composites have been developed that combine the multiple functions of bioactive molecules with the superior chemical and physical properties of ZIFs. This review thoroughly summarizes the ZIFs as well as the novel strategies for incorporating bioactive molecules into ZIFs. They are used in many different applications, especially in biosensors. Finally, biosensor applications of bioactive ZIFs were investigated in optical (fluorescence and colorimetric) and electrochemical (amperometric, conductometric, and impedance) fields. The surface of ZIFs makes it easier to immobilize bioactive molecules like DNA, enzymes, or antibodies, which in turn enables the construction of cutting-edge, futuristic biosensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Among antifungal agents used in pharmaceuticals and personal care products, the synthetic azole climbazole (CBZ; 1-(4-Chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one) acts on the fungus Malassezia. Despite concerns surrounding its effects on health, based on alterations to reproduction and steroidogenesis found in fish, little is known about its mechanism of action as an endocrine disrupting chemical (EDC) in mammalian cells. In this study, using OECD test guidelines, we investigated the effects of CBZ (i) in H295R cells, on the production of estradiol and testosterone, as well as intermediate metabolites in steroidogenesis pathway, and (ii) in HeLa9903 and AR-EcoScreen cell lines, on the transactivation of estrogen and androgen receptors. Our results are the first evidence in H295R cells, that CBZ treatment (from 0.3 μM) decreased secreted levels of testosterone and estradiol. This was associated with reduced 17α-hydroxypregnenolone and 17α-hydroxyprogesterone levels. The altered levels of these metabolites were associated with a decrease in cytochrome P450 17α-hydroxylase/17,20-lyase (Cyp17A1) activity without any effect on its protein level. CBZ was also found to exert antagonistic effects toward androgen and estrogen α receptors. These results give insights into the toxicological mechanism of action of CBZ. Many azoles share structural similarities; therefore, caution should be adopted due to their potential toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Considerable attention has been devoted to the exploration of organometallic iridium(III) (Ir III ) complexes for their potential as metallic anticancer drugs. In this study, twelve half-sandwich Ir III imidazole-phenanthroline/phenanthrene complexes were prepared and characterized. Complexes exhibited promising in-vitro anti-proliferative activity, and some are obviously superior to cisplatin towards A549 cells. These complexes possessed suitable fluorescence, and a non-energy-dependent uptake pathway was identified, subsequently leading to their accumulation in the lysosome and the lysosomal damage. Additionally, complexes could inhibit the cell cycle (G1-phase) and catalyze intracellular NADH oxidation, thus substantiating the elevation of intracellular reactive oxygen species (ROS) level, which confirming the oxidative mechanism. Western blotting further confirmed that complexes could induce A549 cell apoptosis through the lysosomal-mitochondrial anticancer pathway, which was inconsistent with cisplatin. In summary, these complexes offer fresh concepts for the development of organometallic non‑platinum anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We report the use of trimethylsilyl azide and Selectfluor to implement a standard protocol targeted at the prenylated nucleic acid known as i 6 A-RNA. After optimizing the conditions, we applied this method to regulate a wide range of i 6 A-RNA species using synthetic imidazole-based probes (I-IV). We observed that prenylated nucleic acid plays a crucial role in the cell hemostasis in A549 cell lines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Imidazole is a five-membered heterocyclic ring containing three carbon atoms, two nitrogen atoms, and two double bonds. Among two nitrogen atoms, one of which carries with a hydrogen atom is a pyrrole-type nitrogen atom, another is a pyridine type nitrogen atom. Hence, the imidazole ring belongs to the π electron-rich aromatic ring and can accept strong suction to the electronic group. Moreover, the nitrogen atom of the imidazole ring is coordinated with metal ions to form metal-organic frameworks. In recent years, because of imidazole compounds' unique optical properties, their applications have attracted more and more attention in optical analysis. Thus, this review has summarized the synthesis, characterization, and application with emphasis on the research progress of imidazole compounds in optical analysis, including fluorescence probe, colorimetric probe, electrochemiluminescence sensor, fiber optical sensor, surface plasmon resonance, etc. This paper will suggest the direction for the development of imidazole-containing sensors with high sensitivity and selectivity.

Tumor-associated macrophages (TAMs) constitute 50-80% of stromal cells in most solid tumors with high mortality and poor prognosis. Tumor-infiltrating dendritic cells (TIDCs) and TAMs are key components mediating immune responses within the tumor microenvironment (TME). Considering their refractory properties, simultaneous remodeling of TAMs and TIDCs is a potential strategy of boosting tumor immunity and restoring immunosurveillance. In this study, mannose-decorated poly(lactic-co-glycolic acid) nanoparticles loading with R848 (Man-pD-PLGA-NP@R848) were prepared to dually target TAMs and TIDCs for efficient tumor immunotherapy. The three-dimensional (3D) cell culture model can simulate tumor growth as influenced by the TME and its 3D structural arrangement. Consequently, cancer spheroids enriched with tumor-associated macrophages (TAMs) were fabricated to assess the therapeutic effectiveness of Man-pD-PLGA-NP@R848. In the TME, Man-pD-PLGA-NP@R848 targeted both TAMs and TIDCs in a mannose receptor-mediated manner. Subsequently, Man-pD-PLGA-NP@R848 released R848 to activate Toll-like receptors 7 and 8, following dual-reprograming of TIDCs and TAMs. Man-pD-PLGA-NP@R848 could uniquely reprogram TAMs into antitumoral phenotypes, decrease angiogenesis, reprogram the immunosuppressive TME from "cold tumor" into "hot tumor", with high CD4+ and CD8+ T cell infiltration, and consequently hinder tumor development in B16F10 tumor-bearing mice. Therefore, dual-reprograming of TIDCs and TAMs with the Man-pD-PLGA-NP@R848 is a promising cancer immunotherapy strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Peanut web blotch (PWB) caused by Phoma arachidicola, is one of the most serious foliar diseases of peanut. Although prochloraz is an active fungicide with broad anti-fungal spectrum, it has not been registered for the control of PWB in China. The activity of prochloraz against P. arachidicola and the risk of resistance to prochloraz in P. arachidicola are still unclear. In current study, the inhibitory activity of prochloraz against 96 P. arachidicola strains was determined with the average EC 50 value of 1.2700 ± 0.7786 μg/mL. Prochloraz exhibited excellent protective and curative effect on detached peanut leaves, and the effect was obviously better than that of carbendazim and difenoconazole at the same concentration. After prochloraz treatment, the mycelium of P. arachidicola contorted, shrunk and ruptured, with shrinking of cell wall and membrane, enhanced cell membrane permeability, and reduced ergosterol content. Totally 80 prochloraz-resistant mutants were obtained by fungicide adaptation with the frequency of 6.7 × 10 -3 . All the selected 12 prochloraz-resistant mutants lost their resistance to prochloraz after 10 transfers on PDA plates. And these mutants exhibited decreased biological fitness in mycelial growth and pathogenicity. Moreover, there was positive cross-resistance between prochloraz and other demethylation inhibitor (DMI) fungicides, such as tebuconazole, triflumizole and difenoconazole, but no cross-resistance was found between prochloraz and other classes of fungicides, such as carbendazim, pydiflumetofen or fludioxonil. Overexpression of PaCYP51 and PaAtrB genes were detected in the resistant mutants. All the above results demonstrated that prochloraz has a great potential in management of PWB. The risk of P. arachidicola developing resistance to prochloraz is relatively low-to-medium. Overexpressing of PaCYP51 and PaAtrB might be linked to prochloraz resistance in P. arachidicola., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The development of new effective drugs to treat breast cancer remains a huge challenge. ABT-737 can inhibit Bcl-2 proteins to promote apoptosis. Resiquimod (R848) is a TLR7/8 agonist that is effective in modulating the immunosuppressive microenvironment. In this study, a codelivery system (TPGS/ABT+R848 NPs) based on D-α-tocopheryl poly (ethylene glycol) 1000 succinate as a potential drug delivery vector to codelivery ABT-737 and R848 was investigated. The size of TPGS/ABT+R848 NPs was 102.5 nm, the drug loading of ABT-737 and R848 was 30.6 % and 12.5 %, and the entrapment efficiency was 84.2 % and 23.7 %, respectively. The nanoparticles showed no significant change in particle size over 14 days. R848 and ABT-737 were released in co-loaded nanoparticles in sequential order. In vitro anti-tumor experiments, the IC 50 value of TPGS/ABT+R848 NPs was 0.30 μg·mL -1 , 34 times lower than that of free ABT-737. Animal experiments also verified that TPGS/ABT+R848 NPs could enhance the anti-tumor activity, and the tumor weight inhibition rate was 75.3 %. This study demonstrated that TPGS NPs loaded with ABT-737 and R848 have superior combination tumor therapeutic effects, and the co-loaded preparation is conducive to anti-tumor efficacy. The TPGS/ABT+R848 NPs could be a promising platform against breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Applying various drug design strategies including ring variation, substituents variation, and ring fusion, two series of 2-(alkylthio)-5-(arylidene/heteroarylidene)imidazolones and imidazo[1,2-a]thieno[2,3-d]pyrimidines were designed and prepared as dual potential Chk1 and Chk2 inhibitors. The newly synthesized hybrids were screened in NCI 60 cell line panel where the most active derivatives 4b, d-f, and 6a were further estimated for their five dose antiproliferative activity against the most sensitive tumor cells including breast MCF-7 and MDA-MB-468 and non-small cell lung cancer EKVX as well as normal WI-38 cell. Noticeably, increasing the carbon chain attached to thiol moiety at C-2 of imidazolone scaffold elevated the cytotoxic activity. Hence, compounds 4e and 4f, containing S-butyl fragment, exhibited the most antiproliferative activity against the tested cells where 4f showed extremely potent selectivity toward them. As well, compound 6a, containing imidazothienopyrimidine core, exerted significant cytotoxic activity and selectivity toward the examined cells. The mechanistic investigation of the most active cytotoxic analogs was achieved through the evaluation of their inhibitory activity against Chk1 and Chk2. Results revealed that 4f displayed potent dual inhibition of both Chk1 and Chk2 with IC 50 equal 0.137 and 0.25 μM, respectively. It also promoted its antiproliferative and Chk suppression activity via EKVX cell cycle arrest at S phase through stimulating the apoptotic approach. The apoptosis induction was also emphasized by elevating the expression of Caspase-3 and Bax, that are accompanied by Bcl-2 diminution. The in silico molecular docking and ADMET profiles of the most active analogs have been carried out to evaluate their potential as significant anticancer drug candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats. Thirty-two rats were divided into four groups including control, IMI (5mg/kg), IMI (5mg/kg) + MAL (10mg/kg) and MAL (10mg/kg) alone treated group. The recommended dosages were administrated through oral gavage for 4 weeks. It was revealed that IMI intoxication disrupted the PI3K/AKT and Nrf-2/Keap-1 pathway. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (OH-1) and glutathione reductase (GSR) were reduced while upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels after IMI treatment. Moreover, IMI poisoning increased the levels of ALT (Alanine aminotransferase), AST (Aspartate transaminase), and ALP (Alkaline phosphatase) while reducing the levels of total proteins and albumin in hepatic tissues of rats. Besides, IMI administration escalated the expressions of Bcl-2-associated protein x (Bax) and cysteine-aspartic acid protease-3 (Caspase-3) while downregulating the expressions of B-cell lymphoma 2 (Bcl-2). Similarly, IMI intoxication, increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, IMI disrupted the normal architecture of hepatic tissues. However, MAL treatment remarkably protected the liver tissues via regulating abovementioned disruptions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A sensitive, reproducible, robust, high-throughput ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of fexofenadine and olmesartan in human serum. Samples (50 µL) undergo protein precipitation prior to UPLC-MS/MS analysis. The analytes were separated using an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 µm) at a flow rate of 0.5 mL/min using a gradient elution with a total run time of 4 min. The analytes were detected in positive ion mode and selected reaction monitoring (SRM) was used for quantitation. The standard curve concentration range was 1.0-500.0 ng/mL for both analytes and each analyte showed excellent linearity with correlation coefficients (R 2 > 0.99). The intra- and inter-day accuracy and precision were ±15% for each analyte, and excellent recovery was demonstrated (93-98%) for both analytes. The method is well suited for high-throughput quantitative determination of fexofenadine and olmesartan simultaneously and was successfully applied to an in vivo pharmacokinetic and transporter phenotyping study in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrocolloids synthesized by gallic acid (GA) and ferulic acid (FA) grafting onto chitosan (CS) were characterized, and their effects on PhIP formation in pan-fried golden pompano were investigated. Spectrograms including nuclear magnetic resonance, Fourier transform infrared spectroscopy and ultraviolet-visible confirmed that GA and FA were successfully grafted onto CS via covalent bonds, with grafting degree of 97.06 ± 2.56 mg GA/g and 93.56 ± 2.76 mg FA/g, respectively. The CS-g-GA and CS-g-FA exerted better solubility and antioxidant activities than CS. For the 8-min pan-fried golden pompano fillets, CS-g-GA and CS-g-FA (0.5 %, m/v) significantly reduced the PhIP formation by 61.71 % and 81.64 %, respectively. Chemical models revealed that CS-g-GA and CS-g-FA inhibited PhIP formation mainly by decreasing the phenylacetaldehyde contents from Maillard reaction and competing with creatinine to react with phenylacetaldehyde. Therefore, it was suggested that CS-g-phenolic acids emerge as novel coating for aquatic products during processing and inhibit heterocyclic amines generation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Piroxicam (PX) is a nonsteroidal anti-inflammatory drug (NSAID) commonly associated with gastrointestinal (GI) injuries, including dyspepsia, heartburn, inflammation, bleeding, ulceration, and life-threatening perforation. The β-cyclodextrin (β-CD)-based PX formulation (PX@CD) has been shown to reduce gastric side effects by improving PX's solubility and dissolution rates. However, the solubility of PX can only be increased to a limited extent by β-CD, due to the low binding constant between PX and β-CD (∼100 M -1 ). As a result, adverse reactions such as epigastric pain and pyrosis are still commonly reported. Cucurbit[7]uril (CB[7]) is a synthetic macrocyclic host compound that binds strongly to various drugs. In this study, we demonstrated that CB[7] forms complexes with PX in the gastric acid environment with a binding constant approximately 70 times higher than that between β-CD and PX. The PX@CB[7] inclusion complexes exhibited rapid dissolution rates in the gastric environment. In addition, PX@CB[7] showed significantly higher oral bioavailability and maximum concentration (C max ) compared to PX and PX@CD (1:2.5), resulting in improved anti-inflammatory effects in both mouse and rat models. Moreover, PX@CB[7] (1:2.5) had the least adhesion to the gastric mucosa and caused the mildest gastric side effects in rat models when compared to PX, PX@CD (1:2.5), and PX@CB[7] (1:1). Lastly, CB[7] demonstrated good oral biocompatibility in a subacute toxicity evaluation study. These findings indicate that CB[7] could be used as an excipient to improve treatment effectiveness and decrease adverse reactions in orally administered formulations with a favorable safety profile., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiangjun Zhang reports financial support was provided by Natural Science Foundation Project of Chongqing. Xiangjun Zhang reports financial support was provided by Chongqing Municipal Education Commission Foundation. Yan Wang, Chao Yu and Xiangjun Zhang has patent pending to National Intellectual Property Administration，PRC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although marine environments represent huge reservoirs of the potent greenhouse gas methane, they currently contribute little to global net methane emissions. Most of the methane is oxidized by methanotrophs, minimizing escape to the atmosphere. Aerobic methanotrophs oxidize methane mostly via the copper (Cu)-bearing enzyme particulate methane monooxygenase (pMMO). Therefore, aerobic methane oxidation depends on sufficient Cu acquisition by methanotrophs. Because they require both oxygen and methane, aerobic methanotrophs reside at oxic-anoxic interfaces, often close to sulphidic zones where Cu bioavailability can be limited by poorly soluble Cu sulphide mineral phases. Under Cu-limiting conditions, certain aerobic methanotrophs exude Cu-binding ligands termed chalkophores, such as methanobactin (mb) exuded by Methylosinus trichosporium OB3b. Our main objective was to establish whether chalkophores can mobilise Cu from Cu sulphide-bearing marine sediments to enhance Cu bioavailability. Through a series of kinetic batch experiments, we investigated Cu mobilisation by mb from a set of well-characterized sulphidic marine sediments differing in sediment properties, including Cu content and phase distribution. Characterization of solid-phase Cu speciation included X-ray absorption spectroscopy and a targeted sequential extraction. Furthermore, in batch experiments, we investigated to what extent adsorption of metal-free mb and Cu-mb complexes to marine sediments constrains Cu mobilisation. Our results are the first to show that both solid phase Cu speciation and chalkophore adsorption can constrain methanotrophic Cu acquisition from marine sediments. Only for certain sediments did mb addition enhance dissolved Cu concentrations. Cu mobilisation by mb was not correlated to the total Cu content of the sediment, but was controlled by solid-phase Cu speciation. Cu was only mobilised from sediments containing a mono-Cu-sulphide (CuS x ) phase. We also show that mb adsorption to sediments limits Cu acquisition by mb to less compact (surface) sediments. Therefore, in sulphidic sediments, mb-mediated Cu acquisition is presumably constrained to surface-sediment interfaces containing mono-Cu-sulphide phases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Simeprevir and daclatasvir represent a cornerstone in the management of Hepatitis C Virus infection, a global health concern that affects millions of people worldwide. In this study, we propose a synergistic approach combining synchronous spectrofluorimetry and chemometric modeling i.e. Partial Least Squares (PLS-1) for the analysis of simeprevir and daclatasvir in different matrices. Moreover, the study employs firefly algorithms to further optimize the chemometric models via selecting the most informative features thus improving the accuracy and robustness of the calibration models. The firefly algorithm was able to reduce the number of selected wavelengths to 47-44% for simeprevir and daclatasvir, respectively offering a fast and sensitive technique for the determination of simeprevir and daclatasvir. Validation results underscore the models' effectiveness, as evidenced by recovery rates close to 100% with relative root mean square error of prediction (RRMSEP) of 2.253 and 2.1381 for simeprevir and daclatasvir, respectively. Moreover, the proposed models have been applied to determine the pharmacokinetics of simeprevir and daclatasvir, providing valuable insights into their distribution and elimination patterns. Overall, the study demonstrates the effectiveness of synchronous spectrofluorimetry coupled with multivariate calibration optimized by firefly algorithms in accurately determining and quantifying simeprevir and daclatasvir in HCV antiviral treatment, offering potential applications in pharmaceutical formulation analysis and pharmacokinetic studies for these drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human Hsp90 chaperones are implicated in various aspects of cancer. Due to this, Hsp90 has been explored as potential target in cancer treatment. Initial attempts to use Hsp90 inhibitors in drug trials failed due to toxicity and inefficacy. The next generation of drugs were less toxic but still insufficiently effective in a clinical setting. Recently, a lot of effort is being put into understanding the consequences of Hsp90 isoform selective inhibition, expecting that this might hold the key in targeting Hsp90 for disease treatment. Here we investigate a series of compounds containing the aryl-resorcinol scaffold with a 5-membered ring as a promising class of new human Hsp90 inhibitors, reaching nanomolar affinity. We compare how the replacement of 5-membered ring, from thiadiazole to imidazole, as well as a variety of their substituents, influences the potency of these inhibitors for Hsp90 alpha and beta isoforms. To further elucidate the dissimilarity in ligand selectivity between the isoforms, a mutant protein was constructed and tested against the ligand library. In addition, we performed a series of molecular dynamics (MD) and docking simulations to further explain our experimental findings as well as evaluated key compounds in cell assays. Our results deepen the understanding of Hsp90 isoform ligand selectivity and serve as an informative base for further Hsp90 inhibitor optimization., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DM and EK have patents on Hsp90 inhibitors that are not the focus of this study (EP2268626; US2011/0046387). The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Ovarian cancer cells are prone to acquire tolerance to chemotherapeutic agents, which seriously affects clinical outcomes. The development of novel strategies to enhance the targeting of chemotherapeutic agents to overcome drug resistance and minimize side effects is significant for improving the clinical outcomes of ovarian cancer patients., Methods: We employed folic acid (FA)-modified ZIF-90 nanomaterials (FA-ZIF-90) to deliver the chemotherapeutic drug, cisplatin (DDP), via dual targeting to improve its targeting to circumvent cisplatin resistance in ovarian cancer cells, especially by targeting mitochondria. FA-ZIF-90/DDP could rapidly release DDP in response to dual stimulation of acidity and ATP in tumor cells., Results: FA-ZIF-90/DDP showed good blood compatibility. It was efficiently taken up by human ovarian cancer cisplatin-resistant cells A2780/DDP and aggregated in the mitochondrial region. FA-ZIF-90/DDP significantly inhibited the mitochondrial activity and metastatic ability of A2780/DDP cells. In addition, it effectively induced apoptosis in A2780/DDP cells and overcame cisplatin resistance. In vivo experiments showed that FA-ZIF-90/DDP increased the accumulation of DDP in tumor tissues and significantly inhibited tumor growth., Conclusion: FA-modified ZIF-90 nanocarriers can improve the tumor targeting and anti-tumor effects of chemotherapeutic drugs, reduce toxic side effects, and are expected to be a novel therapeutic strategy to reverse drug resistance in ovarian cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Xing et al.)

Removing p-nitrophenol (PNP) from water resources is crucial due to its significant threat to the environment and human health. Herein, imidazolium ionic liquids with short/long alkyl chain ([C 2 VIm]Br and [C 8 VIm]Br) modified cellulose microspheres (MCC-[C 2 VIm]Br and MCC-[C 8 VIm]Br) were synthesized by radiation method. To examine the impact of adsorbent hydrophilicity on adsorption performance, batch and column experiments were conducted for PNP adsorption. The MCC-[C 2 VIm]Br and MCC-[C 8 VIm]Br, with an equivalent molar import amount of ionic liquids, exhibited maximum adsorption capacities of 190.84 mg/g and 191.20 mg/g for PNP, respectively, and the adsorption equilibrium was reached within 30 min. Both adsorbents displayed exceptional reusability. Integrating the findings from XPS and FTIR analyses, and AgNO 3 identification, the suggested adsorption mechanism posited that the adsorbents engaged with PNP through ion exchange, hydrogen bonds and π-π stacking. Remarkably, the hydrophobic MCC-[C 8 VIm]Br exhibited superior selectivity for PNP than the hydrophilic MCC-[C 2 VIm]Br, while had little effect on adsorption capacity and rate. MCC-[C 8 VIm]Br-2 with high grafting yield increased the adsorption capacity to 327.87 mg/g. Moreover, MCC-[C 8 VIm]Br-2 demonstrated efficient PNP removal from various real water samples, and column experiments illustrated its selective capture of PNP from groundwater. The promising adsorption performance indicates that MCC-[C 8 VIm]Br-2 holds potential for PNP removal from wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)