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Epoxide-bearing filter paper was first prepared by surface-initiated reversible addition-fragmentation chain transfer (RAFT) copolymerization of glycidyl methacrylate (GMA) and poly(ethylene glycol)methacrylate (PEGMA). Without the need for activation step, the capture peptide nucleic acid (PNA) probes carrying a C-terminal lysine modification can be directly immobilized on the surface-grafted poly[glycidyl methacrylate-ran-poly(ethylene glycol)methacrylate] (P(GMA-ran-PEGMA)) through ring-opening of epoxide groups in the GMA repeating units by amino groups in the PNA's structure. The success of P(GMA-ran-PEGMA) grafting on the filter paper and subsequent PNA immobilization was confirmed by fluorescence microscopy, Fourier transform-infrared spectroscopy and X-ray photoelectron spectroscopy. Colorimetric detection with signal amplification upon DNA hybridization relies on sandwich-hybridization assay employing another biotinylated PNA strand as a reporter probe together with streptavidin-horseradish peroxidase conjugate (SA-HRP) and o-phenylenediamine (OPD) substrate. It was found that increasing ionic strength during the DNA hybridization step by addition of NaCl can increase the signal intensity, which can be visualized by naked eye. The sensing platform showed the best performance in preventing non-specific adsorption from the non-complementary DNA and discriminating between complementary and single-mismatched targets of at least 50 fmol without the requirement for stringent hybridization or washing condition. This superior ability to suppress non-specific adsorption of non-target DNA as well as other non-DNA components may be explained as a result of hydrophilic PEGMA repeating units in the surface-grafted copolymer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cationic paper was prepared by reaction of paper with 2,3-epoxypropyltrimethylammonium chloride in aqueous suspension, and tested as low-cost adsorbent for wastewater treatment. The experimental results revealed that anionic dyes (Acid Orange 7, Acid Red 18, and Acid Blue 92) were adsorbed on the cationic paper nicely. The maximum amount of dye Acid Orange 7 adsorbed on cationic paper was 337.2 mg/g in experimental conditions. The effects of initial dye concentration, temperature, and initial pH of dye solution on adsorption capacity of cationic paper were studied. The pseudo-first-order and pseudo-second-order kinetic models were applied to describe the kinetic data. The Freundlich and Langmuir adsorption models were used to describe adsorption equilibrium. The thermodynamic data indicated that the adsorption process of dye on cationic paper occurred spontaneously.

The properties of space charge and breakdown in epoxy/paper composites are studied in this paper. The results show that the breakdown voltage of the epoxy/paper composite is lower than that of the epoxy under AC voltage but is higher under DC voltage. In order to explain this phenomenon, the space charge behavior is investigated. In epoxy/paper composites, the space charges easily accumulate at the epoxy/paper interface at low fields, and the electric field distribution is highly deformed. However, the amount of interface charges decreases with increasing voltage, leading to a more uniform field distribution in the composites. This behavior is different from that of the pure epoxy, resulting in the different breakdown properties of pure epoxy and epoxy/paper composites. © 2015 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur-containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)-catalyzed enantioselective ring-opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl- and alkyl-substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large-scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy., (© 2022 Wiley-VCH GmbH.)

Propylene oxide (PO) is a direct-acting mutagen and rodent carcinogen. We have studied how PO modifies 2'-deoxynucleosides at pH 7.0-7.5 and 37 degrees C for 10 h. PO reacts as an SN2 alkylating agent by forming the following 2-hydroxypropyl (HP) adducts: N6-HP-dAdo (7% yield), 7-HP-Gua (37%) and 3-HP-dThd (4%). Alkylation at N-3 of dCyd resulted in conversion of the adjacent exocyclic imino group at C-4 to an oxygen (hydrolytic deamination) with the formation of a dUrd adduct, 3-HP-dUrd (14%). Ultraviolet spectroscopy and mass spectrometry were used for the structural determination of these adducts. Confirmation of the unexpected 3-HP-dUrd adduct was provided by an accurate mass measurement technique where diagnostic ions in the mass spectra of 3-HP-dUrd were measured to within 0.0005 atomic mass units of the predicted mass. PO was reacted in vitro with calf thymus DNA (pH 7.0-7.5, 37 degrees C, 10 h) and yielded N6-HP-dAdo (1 nmol/mg DNA), 3-HP-Ade (14 nmol/mg DNA), 7-HP-Gua (133 nmol/mg DNA) and 3-HP-dUrd (13 nmol/mg DNA). A mechanism for the hydrolytic deamination of 3-HP-dCyd to 3-HP-dUrd involving the OH on the HP side chain is proposed. This cytosine to uracil conversion may play a role in the mutagenic and carcinogenic activity of this epoxide.

The metabolism of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone) has been studied in man and the rat using gas phase analytical methods. Seven new metabolites formed by the epoxide-diol pathway were detected in human urine after methaqualone administration. Five of these compounds were characterized as dihydrodiols and two as hydroxydihydrodiols. The seven dihydrodiol metabolites were present in the nonhydrolyzed fraction isolated from urine. After intraperitoneal administration of methaqualone to the rat (40 mg/kg) the major monohydroxyl metabolites of the drug in hydrolyzed urine were identified as 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone (I) and 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone (II). Two dihydroxyl metabolites were also present, but only trace amounts of a dihydrodiol were detected. The major monohydroxyl metabolites of methaqualone detected in human urine after enzymic hydrolysis were I, II, 2-methyl-3-(3'-hydroxy-2'-methylphenyl)-4(3H)-quinazolinone (III), and 2-methyl-3-(4'-hydroxy-2'-methylphenyl)-4(3H)-quinazolinone (IV). Hydroxylation of the tolyl moiety of methaqualone probably occurs by way of an epoxide intermediate. The phenols, III and IV, may be formed from an epoxide or from the dihydrodiol(s) by enzymic or nonenzymic reactions. The results obtained suggest that epoxidation of methaqualone represents a major pathway of metabolism in the human.

The exploitation of light-weight paper-based cellulosic materials (PBCM) is beneficial for protecting the environment, cutting production cost and improving utilization efficiency of cellulose. In this study, a simple reaction using PEI (Polyethyleneimine) and KH560 was reported to improve the physical performance and hydrophobicity of PBCM. FTIR spectra indicated that the epoxide group of KH560 disappeared during reaction with PEI. Physical properties and hydrophobicity of the dried PBCM were determined after impregnation with the mixture of enzymatic starch and PEI-KH560. Compared with the control, the dry tensile index, wet tensile index and folding endurance of PBCM were increased by 27.1, 61.4 and 137.5%, respectively, when the dosage of PEI-KH560 was 1.35%. If starch (6.35 g/m2) was added together with PEI-KH560 (1.35%), the dry tensile index could increase by 98.6%. The pH and alkaline reserve value of PBCM were also improved. The addition of PEI-KH560 improved the thermal stability of starch, thus was beneficial for the increase of thermal stability of PBCM. This novel method adopted in this study to improve the physical performance, hydrophobicity and alkaline reserve value of PBCM provided a cost-efficient and simple way to broaden its potential application fields. [ABSTRACT FROM AUTHOR]

An investigation on the effect of epoxidation and maleated natural rubber (MNR) on fatigue and rubber-filler interaction properties of paper sludge filled natural rubber composites was elucidated. Paper sludge loading was varied from 0 to 40 phr and conventional vulcanisation system was used while compounding was carried out on a laboratory sized two roll mill. Two different types of natural rubber, SMR L and ENR 50 having 0 and 50 mole% of epoxidation were used in order to investigate the effect of epoxidation on the composites. Results indicate that, at a fixed filler loading, ENR 50 vulcanizates exhibit higher fatigue life than SMR L vulcanizates especially at filler loading below 20 phr which might be associated with better rubber-filler interaction. In the case of composites with the addition of maleated natural rubber (MNR), a higher fatigue life was observed due to presence of physical and/or chemical linkages, which increases the interfacial adhesion. Scanning electron microscopy (SEM) micrographs of fatigue fracture surfaces and rubber-filler interaction study supported the observed result on fatigue life. [ABSTRACT FROM AUTHOR]

The aim of this work is to assess the opportunity to use untreated waste office paper, alone and in combination with jute fabric, as a reinforcement in epoxy composites. Five different stacking sequences were manufactured and tested. Adding untreated waste office paper sheets has been revealed to increase both flexural and tensile strength of the neat resin and of the untreated jute fabric reinforced composites. The effect of the hybridization on tensile and flexural behavior has been evaluated through scanning electron microscopy observations and acoustic emission. The results confirm that waste office paper sheets can be used as a reinforcement for an epoxy resin, thus representing a viable alternative to paper recycling. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Abstract: Single-walled carbon nanotube (SWCNT) and multi-walled carbon nanotube (MWCNT) membranes (buckypaper) and carbon nanofiber (CNF) paper were incorporated onto the surface of epoxy carbon fiber composites, as proposed fire shields. Their flammability behaviors were investigated by a cone calorimeter. SWCNT buckypaper and CNF paper did not show notable improvement on fire retardancy. However, MWCNT buckypaper acted as an effective flame-retardant shield, reducing the peak heat release rate by more than 60% and reducing smoke generation by 50% during combustion. The pore structures of buckypapers and CNF paper were characterized by scanning electron microscopy (SEM), mercury intrusion porosimetry, and N2 adsorption isotherms. Gas permeability of buckypaper and carbon nanofiber paper was measured. The correlation between buckypaper and CNF paper properties and their fire retardancy was discussed. [Copyright &y& Elsevier]

For nearly 50 years immunogold labeling on ultrathin sections has been successfully used for protein localization in laboratories worldwide. In theory and in practice, this method has undergone continual improvement over time. In this study, we carefully analyzed circulating protocols for postembedding labeling to find out if they are still valid under modern laboratory conditions, and in addition, we tested unconventional protocols. For this, we investigated immunolabeling of Epon-embedded cells, immunolabeling of cells treated with osmium, and the binding behavior of differently sized gold particles. Here we show that (in contrast to widespread belief) immunolabeling of Epon-embedded cells and of cells treated with osmium tetroxide is actually working. Furthermore, we established a "speed protocol" for immunolabeling by reducing antibody incubation times. Finally, we present our results on three-dimensional immunogold labeling., (© 2020 The Authors. Microscopy Research and Technique Published by Wiley Periodicals, Inc.)

A multinuclear magnetic resonance investigation, supported by density functional theory calculations, has been synergically used to investigate the configurational stability, reactivity and aggregation states of alpha-lithiated styrene oxide in THF at 173 K. NMR studies on alpha-lithiated [alpha,beta-(13)C(2)]styrene oxide (also in an enantiomerically enriched form) proved that in THF this oxiranyllithium is mainly present as a solvated monomeric species in equilibrium with a complex mixture of stereoisomeric dimeric aggregates, as well as with bridged and tetrameric aggregates. The fact that some C(alpha)-Li bonds are partially broken in some stereoisomers reduces their symmetry and complicates the NMR spectra: two diastereoisomers each having a pair of diastereotopic carbon atoms slowly inverting at the lithium atom in absence of tetramethylethylenediamine (TMEDA) have been detected. A ((13)C,(7)Li)-HMQC experiment to correlate (7)Li and (13)C resonances of the various aggregates has been performed for the first time. From natural bond analysis, the monomeric aggregate was proven to have a lower carbenoid character with respect to bridged O-coordinated dimeric aggregates. The employment of suitable experimental conditions in terms of concentration, temperature and the presence or not of TMEDA are crucial to mitigate at the best the "carbene-like" reactivity of lithiated styrene oxide toward intermolecular C-Li insertions, eliminative dimerisation reactions and ring-opening reactions. A two-step mechanism for the deprotonation of styrene oxide by sBuLi in THF has been proposed and discussed as well as competitive side reactions.

Regioselective synthesis of halohydrin esters was achieved by (1) the reaction of acyl halides with epoxides and (2) the rhodium-catalyzed three-component coupling reaction of alkyl halides, carbon monoxide, and epoxides. [ABSTRACT FROM AUTHOR]

The article reports two cases of allergic contact dermatitis due to diethylenetriamine. After one month of the installation of a new machine to be used in the manufacturing of microcapsulecoated carbonless copy paper (CCP), in a paper factory, a man developed hand dermatitis. Patch testing showed two positive allergic test reaction with 2 of 19 of the CCP tested. The testing was then performed with the ingredients used for CCP production. Capsule dispersion substance and microcapsule paste gave a 2 positive allergic reaction.

Bisphenols, bisphenol A diglycidyl ether (BADGE), and bisphenol F diglycidyl ether (BFDGE) are commonly used as raw materials or additives in the production of several industrial and consumer products. However, information regarding the occurrence and distribution of these industrial chemicals in freshwater ecosystem is limited. In this study, four bisphenols, six BADGEs, and three BFDGEs were determined in abiotic and biotic samples collected from the Dongjiang River basin in southern China. Among the four bisphenols, BPA was widely present in all samples analyzed including surface water (median: 1.81 ng/L), sediment (3.1 ng/g dw), aquatic plants (3.69 ng/g dw), algae (7.57 ng/g dw), zooplankton (6.17 ng/g dw), and fish muscle (5.28 ng/g dw). Among the nine BADGEs and BFDGEs analyzed, BADGE, BADGE•H 2 O, BADGE·HCl·H 2 O and BADGE•2H 2 O was found in all sample types. Although the median concentration of BADGE•2H 2 O in surface water was below LOQ, this compound was found at median concentrations of 2.61, 3.59, 1.03, 1.69, and 49.8 ng/g dw in sediment, plants, algae, zooplankton, and fish muscle, respectively. Significant positive linear correlations were found among logarithmic transformed concentrations of BPA, BADGE, BADGE•H 2 O, BADGE•HCl•H 2 O, and BADGE•2H 2 O in sediment. The bioconcentration factor (logBCF) values of BADGE, BADGE•H 2 O, BADGE•HCl, BADGE•HCl•H 2 O, BADGE•2H 2 O, and BADGE•2HCl in fish, plants, algae, and zooplankton were > 3.3 L/kg (wet weight), indicating that these chemicals possess moderate bioaccumulation potential. The estimated daily total intake of bisphenols and BADGEs through fish consumption was 75.1 ng/kg bw/day for urban adult residents. The study provides baseline information on the occurrence of bisphenols, BADGEs, and BFDGEs in a freshwater ecosystem., 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.)

Cancer remains one of the greatest global health concerns. This is especially true for gynecological cancers, which include cervical, ovarian, and endometrial cancers, and breast cancer. Natural products used for cancer treatment offer some unique advantages. Triptolide (TPL) is a biologically active terpenoid extracted from Tripterygium wilfordii, which exhibits anti-inflammatory, immunosuppressive, antitumor, and other pharmacological activities. However, clinical applications of TPL are restricted because of poor water solubility and severe cytotoxicity; to overcome these limitations, various TPL derivatives and drug delivery systems, especially nanocarriers, have been used. Furthermore, various preclinical and clinical studies have demonstrated that TPL and its derivatives exhibit excellent antitumor effects by targeting proteins involved in multiple signaling pathways. Here, we review the progress regarding novel drug delivery systems, antitumor activities, and molecular mechanisms of action of TPL and its derivatives against gynecological and breast cancers. TPL and its derivatives inhibit tumor growth, suppress tumor metastasis, and enhance the drug sensitization of resistant cancers. In addition, TPL and its derivatives exert synergistic antitumor effects against gynecological and breast cancers when combined with existing antitumor drugs, such as carboplatin, cisplatin, and PI3K inhibitors. Moreover, we highlight the clinical potential of TPL analogs against cancer from bench to bedside and their prospects for future applications in gynecologic and breast cancers., Competing Interests: Declaration of Competing Interest The authors state that they have no known competing financial interests that could have appeared to influence this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This paper presents an inverse design methodology that utilizes artificial intelligence (AI)-driven experiments to optimize the chemoenzymatic epoxidation of soyabean oil using hydrogen peroxide and lipase (Novozym 435). First, experiments are conducted using a systematic 3-level, 5-factor Box-Behnken design to explore the effect of input parameters on oxirane oxygen content (OOC (%)). Based on these experiments, various AI models are trained, with the support vector regression (SVR) model being found to be the most accurate. SVR is then used as a fitness function in particle swarm optimization, and the suggested optimal conditions, upon experimental validation, resulted in a maximum OOC of 7.19 % (∼98.5 % relative conversion of oil to epoxy). The results demonstrate the superiority of the proposed approach over existing methods. This framework offers a general intensified process optimization strategy with minimal resource utilization that can be applied to any other process., 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.)

Triple-negative breast cancer (TNBC) is the most aggressive and fatal subtype of breast cancer with disappointing treatment and high mortality. Tumor microenvironment (TME) plays an important role in the invasion and metastasis of TNBC through multiple complex processes. Most anti-metastatic therapies only focus on cancer cells themselves or interfering with single factors of the metastasis process, which is often related to poor outcomes. Thus, effective TNBC treatment relies on regulating multiple key metastasis-related aspects of the TME. Herein, a self-targeting Metal-Organic Frameworks (MOFs) nanoplatform (named as MTX-PEG@TPL@ZIF-8) was designed to improve treatment of TNBC through tumor microenvironment remodeling and chemotherapy potentiation. The self-targeting MOF nanoplatform is consist of ZIF-8 nanoparticles loaded triptolide (TPL) and followed by the coating with methotrexate-polyethylene glycol conjugates (MTX-PEG). Due to MTX's affinity for the overexpressed folate receptor on tumor cell surfaces, MTX-PEG@TPL@ZIF-8 enables effective accumulation and deep penetration in the tumor area by an MTX-mediated self-targeting strategy. This MOF nanoplatform could promptly release the medication after penetrating the tumor cell, due to pH-triggered degradation. Its anti-metastasis mechanism is to inhibit tumor invasion and metastasis by down-regulating the expression of Vimentin, MMP-2 and MMP-9 and increasing the expression of E-cadherin, upregulation of cleaved caspase-3 and cleaved caspase-9 protein expression promote the apoptosis of tumor cells, thereby reducing their migration. It also downregulated the expression of VEGF and CD31 protein to inhibit the generation of neovascularization. Overall, these findings suggest the self-targeting MOF nanoplatform offers new insights into the treatment of metastatic TNBC by TME remodeling and potentiating chemotherapy., 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.)

3-Monochloropropane-1,2-diol (3-MCPD), 2-monochloropropane-1,2-diol (2-MCPD) and 2,3-epoxy-1-propanol (glycidol), in their free form or esterified to fatty acids, are food contaminants formed during the refinement of oils and fats. We conducted a survey to quantify the levels of these compounds in 130 food items, in order to assess the exposure to them in food and the consequent health risk for consumers. Food samples, including infant formula, were analysed by gas-chromatography mass spectrometry with the indirect method, and we used the latest open access food consumption database for the Italian population for a probabilistic assessment of exposure. We adopted an in silico approach to fill the gap for the toxicity of 2-MCPD. The occurrence values for the three contaminants in food were in most cases lower than or comparable to those reported in previous surveys. Exposure assessment for the most exposed individuals (95 th percentiles of consumers only) of different age groups, gave values below the tolerable daily intake recommended by the European Food Safety Authority for 3-MCPD and below the simulated or predicted toxicity thresholds for 2-MCPD, indicating a negligible risk due to dietary exposure to these contaminants. For glycidol, however, estimated exposure indicated a non-negligible increase in cancer risk, and a margin of exposure <25,000 for younger population groups, indicating a potential health concern., 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.)

Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-associated death globally with a lack of efficient therapy. The pathogenesis of HCC is a complex and multistep process, highly reliant on de novo lipogenesis, from which tumor cells can incorporate fatty acids to satisfy the necessary energy demands of rapid proliferation and provide survival advantages. Triptolide (TP) is a bioactive ingredient exhibiting potent abilities of anti-proliferation and lipid metabolism regulation, but its clinical application is constrained because of its toxicity and non-specific distribution. The present study has developed galactosylated bovine serum albumin nanoparticles loaded with TP (Gal-BSA-TP NPs) to alleviate systemic toxicity and increase tumor-targeting and antitumor efficacy. Furthermore, Gal-BSA-TP NPs could inhibit de novo lipogenesis via the p53-SREBP1C-FASN pathway to deprive the fuel supply of HCC, offering a specific strategy for HCC treatment. In general, this study provided a biocompatible delivery platform for targeted therapy for HCC from the perspective of de novo lipogenesis., 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.)

This study focuses on the development a green synthesis of epoxy fatty acids (EFAs) which are commonly used as the plasticizer in polymer industries. The intracellular lipases of Candida catenulata cells as a whole-cell biocatalyst (WCB) were examined in the bio-epoxidation of free fatty acids (FFAs) with hydrogen peroxide. The FFAs in soybean soap stock, an industrial by-product of vegetable oil factories, was used as the feedstock of the process. To remove phosphates from soap stock a degumming process was tested before the bio-epoxidation reaction and results revealed that the EFAs yield was improved using the degummed fatty acids (DFAs). The attachments of magnetic Fe 3 O 4 nanoparticles to the surface of WCBs facilitated the recovery of the biocatalyst, and were improved stabilities. The activation energy for the magnetic whole-cell biocatalysts (MWCB) was 48.54 kJ mol -1 , which was lower than the WCB system (51.28 kJ mol -1 ). The EFA yield was about 47.1 % and 33.8 % after 3 h for the MWCBs and 2 h for the WCBs, respectively. The MWCBs displayed acceptable reusability in the repetitious bio-epoxidation reaction with maintaining 59 % of the original activity after 5 cycles whereas the performance of the WCBs was 5.9 % at the same conditions. The effects of influential factors such as reaction time, molar ratio of H 2 O 2 to CC, and batch and semi-batch operations were investigated for both biocatalyst systems. The quality of EFAs was characterized by FTIR and GC-MS analyses., 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.)

Triptolide (TP) is a major bioactive compound derived from Tripterygium wilfordii Hook. F. (TwHF) known for its medicinal properties, but it also exhibits potential toxic effects. It has been demonstrated to induce severe male reproductive toxicity, yet the precise mechanism behind this remains unclear, which limits its broad clinical application. This study aimed to investigate the mechanisms underlying testicular damage and spermatogenesis dysfunction induced by TP in mice, using both mouse models and the spermatocyte-derived cell line GC-2spd. In the present study, it was found that TP displayed significant testicular microstructure damaged and spermatogenesis defects including lower concentration and abnormal morphology by promoting ROS formation, MDA production and restraining GSH level, glutathione peroxidase 4 (GPX4) expression in vivo. Furthermore, Ferrostatin-1 (FER-1), a ferroptosis inhibitor, was found to significantly reduce the accumulation of lipid peroxidation, alleviate testicular microstructural damage, and enhance spermatogenic function in mice. Besides, notably decreased cell viability, collapsed mitochondrial membrane potential, and elevated DNA damage were observed in vitro. The above-mentioned phenomenon could be reversed by pre-treatment of FER-1, indicating that ferroptosis participated in the TP-mediated spermatogenesis dysfunction. Mechanistically, TP could enhance GPX4 ubiquitin degradation via triggering K63-linked polyubiquitination of GPX4, thereby stimulating ferroptosis in spermatocytes. Functionally, GPX4 deletion intensified ferroptosis and exacerbated DNA damage in GC-2 cells, while GPX4 overexpression mitigated ferroptosis induced by TP. Overall, these findings for the first time indicated a vital role of ferroptosis in TP induced-testicular injury and spermatogenic dysfunction through promoting GPX4 K63-linked polyubiquitination, which hopefully offers a potential therapeutic avenue for TP-related male reproductive damage. In addition, this study also provides a theoretical foundation for the improved clinical application of TP or TwHF in the future., 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.)

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic., 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.)

Background: The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear., Purpose: To explore the molecular mechanisms by which minnelide exhibits antileukemic activity., Methods: AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis., Results: Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis., Conclusions: Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials., Competing Interests: Declaration of competing interest The authors declare that we have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Any perceived conflicts of interest are non-existent. The authors are motivated simply by pursuing knowledge and sharing scientific findings with the research community., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Epoxiconazole (EPX) is a world widely used chiral triazole fungicide in the agriculture field. The excessive application of this triazole may cause damage to lizards. However, limited information is known about the toxicokinetics of EPX on lizards. Our study aimed to investigate the enantioselective absorption, distribution, metabolism, and elimination (ADME) of EPX in lizards following low and high dose exposure (10 and 100 mg kg -1 bodyweitht (bw)). The results demonstrated that (+)-EPX was easier absorbed than (-)-EPX in lizard plasma. Both (+)-EPX and (-)-EPX were detected in the liver, gonad, kidney, skin, brain, and intestine, with (+)-EPX preferentially distributed in these tissues. The elimination of (-)-EPX was faster than that of (+)-EPX in lizard liver and kidney in the high dose groups. Chiral conversion was found between EPX enantiomers in lizard skin. Simultaneously, five metabolites including M2, M4, M10, M18 and M19 were detected in lizard liver and kidney after EPX enantiomers exposure. The relative concentrations of M2, M4, and M10 were higher in the liver and kidney of (-)-EPX groups than those produced from (+)-EPX groups. The metabolic enzymes CYP3A4 and SULT1A1 primarily mediated enantioselective metabolism of EPX. The conclusions drawn from this study significantly enhance our understanding of the enantioselective behaviors of chiral triazole fungicides in reptiles, offering essential guidance for assessing the risks associated with different enantiomers of triazole fungicides., 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.)

Background: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure., Methods: Male mice were subjected to TP at doses of 15, 30, and 60 μg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood-testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining., Results: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells., Conclusion: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes., 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 Inc. All rights reserved.)

Background: Myeloid-derived suppressor cells (MDSCs) negatively modulate immune activity. Prior investigations have shown much promise in using MDSCs-assisted immunotherapy for organ transplantation patients. Additionally, owing to its immunosuppressive activity, MDSCs can also be used to manage immune-associated disorders., Methods: Granulocyte-macrophage colony-stimulating factor (GM-CSF) was employed to stimulate myeloid progenitor cell differentiation. Triptolide (PG490) was introduced toward the later phases of in vitro MDSCs induction. Lastly, real-time PCR (RT-PCR) and flow cytometry were used to assess transcript expression and cell phenotype, and a mouse skin transplantation model was established to evaluate the MDSCs-mediated immune suppression in vivo., Results: Co-stimulation with PG490 and GM-CSF potently induced myeloid-derived monocytes to form MDSCs, with remarkable immune-suppressive activity. The underlying mechanism involved downregulation of T cell proliferation, activation, enhancement of inflammatory cytokine release, as well as T cell conversion to Treg cells. PG490 strongly enhanced iNOS expression in MDSCs, and iNOS inhibition successfully reversed the immune-suppression. The PG490- and GM-CSF-induced MDSCs substantially extended survival duration of murine skin grafts, thereby validating their strong immune-suppressive activity in vivo., Conclusions: Herein, we presented a new approach involving MDSCs-based immunosuppression in vitro. PG490 and GM-CSF co-treatment strongly induced immuno-suppressive activity in MDSCs both in vitro and in vivo. Our findings highlight the promise of applying MDSCs-based therapy in clinical organ transplantation treatment., 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.)

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC 50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC 50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of 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 Inc. All rights reserved.)

Epoxiconazole (EPX) is a triazole fungicide, which has been widely used in pest control of cereal crops. However, its extensive use has led to concerning levels of residue in water bodies, posing substantial risks to aquatic life. In this study, we characterized the toxicological effects of EPX on 6-month-old male and female zebrafish at 70 and 700 μg/L, respectively. The results revealed that EPX exposure markedly increased both body length and weight in zebrafish of both sexes, consequently elevating their condition factor. Besides, EPX exposure resulted in notable alterations in hepatic histopathology. These changes included loosened hepatocyte structure, ballooning degeneration, nucleolysis, and disappearance of cell line, with male zebrafish exhibiting more severe damage. High concentration of EPX also significantly increased hepatic lipid accumulation in male zebrafish, as well as increased hepatic triglyceride (TG) levels. Correspondingly, there was a notable alteration in the transcription of genes including cyp51, hmgcr, and PPAR-γ, which associated with cholesterol and lipid metabolism. Interestingly, with the hepatic transcriptomic analysis, high concentration of EPX produced 195 upregulated and 107 downregulated differential expression genes. Both KEGG and GO analyses identified significant enrichment of these genes in lipid and amino acid metabolism pathways. Notably, some key genes involved in the steroid synthesis pathway were marked upregulated. In addition, molecular docking study confirmed that EPX could bind CYP51 protein well (△G = -7.7 kcal/mol). Taken together, these findings demonstrated the multiple toxic effects of EPX on adult zebrafish., 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.)

Chemical production wastewater contains large amounts of organic solvents (OSs), which pose a significant threat to the environment. In this study, a 10 g·L -1 styrene oxide tolerant strain with broad-spectrum OSs tolerance was obtained via adaptive laboratory evolution. The mechanisms underlying the high OS tolerance of tolerant strain were investigated by integrating physiological, multi-omics, and genetic engineering analyses. Physiological changes are one of the main factors responsible for the high OS tolerance in mutant strains. Moreover, the P-type ATPase GOX&#95;RS04415 and the LysR family transcriptional regulator GOX&#95;RS04700 were also verified as critical genes for styrene oxide tolerance. The tolerance mechanisms of OSs can be used in biocatalytic chassis cell factories to synthesize compounds and degrade environmental pollutants. This study provides new insights into the mechanisms underlying the toxicological response to OS stress and offers potential targets for enhancing the solvent tolerance of G. oxydans., 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.)

Tripterygium wilfordii (TW) preparations have been utilized in China for treating rheumatoid arthritis and autoimmune diseases. However, their clinical use is limited due to reproductive toxicity, notably premature ovarian failure (POF). Our study aimed to investigate the effect and mechanism of bergenin in attenuating POF induced by triptolide in mice. POF was induced in female ICR mice via oral triptolide administration (50 μg/kg) for 60 days. Mice received bergenin (25, 50, 100 mg/kg, i.g.) or estradiol valerate (EV) (0.1 mg/kg, i.g.) daily, 1 h before triptolide treatment. In vitro, ovarian granulosa cells (OGCs) were exposed to triptolide (100 nM) and bergenin (1, 3, 10 μM). Antioxidant enzyme activity, protein expression, apoptosis rate, and reactive oxygen species (ROS) levels were assessed. The results showed that triptolide-treated mice exhibited evident atrophy, along with an increase in atretic follicles. Bergenin (50, 100 mg/kg) and EV (0.1 mg/kg), orally administered, exerted significant anti-POF effect. Bergenin and EV also decreased apoptosis in mouse ovaries. In vitro, bergenin (1, 3, 10 μM) attenuated triptolide-induced OGCs apoptosis by reducing levels of apoptosis-related proteins. Additionally, bergenin reduced oxidative stress through downregulation of antioxidant enzymes activity and overall ROS levels. Moreover, the combined use with Sh-Nrf2 resulted in a reduced protection of bergenin against triptolide-induced apoptosis of OGCs. Together, bergenin counteracts triptolide-caused POF in mice by inhibiting Nrf2-mediated oxidative stress and preventing OGC apoptosis. Combining bergenin with TW preparations may effectively reduce the risk of POF., 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.)

This paper discusses web slenderness effects on the flexural behaviour of epoxy adhesive-bonded compound normal and high-strength steel beams. The compound beams were simply supported and consisted of an I-section connected, on its top flange, to a channel section using an epoxy adhesive. A non-linear three-dimensional finite-element modelling study was performed using Abaqus software for the analysis of the beams. The non-linear finite-element modelling was verified against tests on compound steel beams with different cross-sections. An extensive parametric study was carried out using the finite-element modelling to study the effects of the change in web slenderness, cross-sectional geometries, beam lengths and steel strengths on the flexural behaviour of compound steel beams. The failure moments predicted by the finite-element modelling were compared with the design moments predicted by the European code for steel beams in flexure. It is shown that the code generally overestimated the design failure moments for most of the epoxy adhesive-bonded compound steel beams investigated in this study. In addition, reliability analysis was performed to assess the reliability of the design rules of the code. Generally, it was found that the European code is unconservative and statistically unreliable for the epoxy adhesive-bonded compound beams investigated in this study. [ABSTRACT FROM AUTHOR]

One of the environmentally friendly methods is the intelligent utilization of natural one-dimensional nanomaterials as carriers to improve the CO2 catalytic performance of MOF materials. This paper reports an efficient composite catalyst preparation using a cheap and readily available magnesium–aluminosilicate nanometer, attapulgite (ATP), as a carrier for MOF materials. Due to its Lewis acidic site and unique alkaline pore structure, ATP exhibits excellent catalytic activity in the coupling reaction of CO2 with epoxy compounds, and its regular one-dimensional nanorod shape has tremendous potential as a carrier compared to other natural minerals. Given the diversity of MOF material types and structures, the design of this UIO-66/ATP nanocomposite catalyst provides both a new pathway for CO2 capture and conversion and a developmental space for the synthesis of such nanocomposites. [ABSTRACT FROM AUTHOR]

Polyurethane (PU), with excellent physical and chemical properties and high designability, is one of the ideal materials for asphalt modification in the future. In this paper, based on the limitations of traditional asphalt modifiers, the preparation process, relative advantages and development prospects of PU as asphalt modifiers are described. Subsequently, the spatial structure, physical and chemical properties of PU synthetic raw materials were combined with the modification properties of PU to analyze the effect and influence of PU on asphalt modification. Specifically, polyurethane modified asphalt (PUMA) is divided into thermoplastic polyurethane modified asphalt (TP-PUMA) and thermosetting polyurethane modified asphalt (TS-PUMA). The gain effect of TPPUMA in high-temperature performance, low-temperature performance, aging resistance, fatigue resistance, weathering performance and bonding performance is obvious. In addition, it has good storage stability. With excellent road performance, TS-PUMA makes up for the shortcomings of epoxy asphalt in terms of lowtemperature performance and compatibility. Finally, due to the development trend of functional diversification of modified asphalt, the research basis and status of several new modified asphalts based on PU properties are described. Because the systematic study of PUMA is insufficient, this paper proposes corresponding research. To provide guidance and ideas for the research of PU modified asphalt. [ABSTRACT FROM AUTHOR]

FR901464 is a natural product that exhibits antiproliferative activity at single-digit nanomolar concentrations in cancer cells. Its tetrahydropyran-spiroepoxide covalently binds the spliceosome. Through our medicinal chemistry campaign, we serendipitously discovered that a bromoetherification formed a tetrahydrofuran. The tetrahydrofuran analog was three orders of magnitude less potent than the corresponding tetrahydropyran analogs. This study shows the significance of the tetrahydropyran ring that presents the epoxide toward the spliceosome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John C. Schmitz reports financial support was provided by UPMC Hillman Cancer Center NCI Cancer Center Support Grant Developmental Funds. 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 Ltd. All rights reserved.)

It reported a porous material prepared from microcrystalline cellulose (MCC), to achieve rapid preparation of adsorbents. The porous material was characterized by several tools including 1 H NMR, FTIR, XPS, and SEM. Two adsorbents were prepared and subjected to adsorption experiments. Dye adsorption experiments show that the adsorption driving is electrostatic interactions and the process is chemisorption. The maximum capacity of Microcrystalline cellulose-g-Poly (glycidyl methacrylate)-Tannins (MPT) reached 191.3 (Methylene blue), 123.7 mg g -1 (Rhodamine B), and Microcrystalline cellulose-g-Poly (glycidyl methacrylate)-Lysine (MPL) attained 425.8 (Methylene blue), 480.7 mg g -1 (Methyl orange). The results were followed the pseudo-second-order (PSO) and agreed with the Langmuir fit model. Adsorption-desorption cycling experiments further indicate that the adsorbent possesses outstanding reproducibility. At last, epoxidized bio-porous materials are positive in the preparation of dye adsorbents with critical adsorption properties., 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.)

This work presents the synthesis of Pd-loaded microporous titanosilicalite-1 (Pd/TS-1) and Pd-loaded hierarchical titanosilicalite-1 (Pd/HTS-1) with abundant mesopores (2-30 nm) inside the framework via hydrothermal method using polydiallydimethyl ammonium chloride as the non-surfactant mesopore template. XRD, N 2 sorption, FT-IR, FESEM-EDX, TEM, XPS, and DR-UV techniques were used to characterize the morphological and physicochemical properties of the synthesized materials. These materials were tested as heterogeneous catalysts, along with tetrapropylammonium bromide as co-catalyst, for cycloaddition reactions of CO 2 with epoxides to produce cyclic carbonates. It was found that the epoxide conversions were influenced by acidity and pore accessibility of the catalysts. Using Pd/HTS-1 facilitated bulky substrates to access active sites, resulting in higher conversions than Pd/TS-1. Over 85 % conversions were achieved for at least five consecutive cycles without significant loss in catalytic activity. The interaction between the Pd active surfaces and epichlorohydrin (ECH) was further studied by DFT calculations. The existence of Pd(200) was more influential on adsorbing epichlorohydrin (ECH) and subsequent formation of dissociated ECH (DECH) intermediate than Pd(111) surface. However, Pd(111) was dominant in enhancing the activity of DECH species for capturing CO 2 . Therefore, the co-existence of Pd(200) and Pd(111) surfaces was needed for cycloaddition of CO 2 with ECH., 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.)

This paper provides an overview of technical enhancements of current encapsulant materials (epoxy molding compound and underfill) and future deployment of graphene materials for better thermal and mechanical stress management in thin and complex memory packaging. Also, with the aim to study the key technical barriers, influencing of each epoxy molding compound (EMC) and underfill (UF) materials properties and its reliability performance of impacts on materials used in semiconductor device packaging, this paper lays out the importance of future graphene of its superior materials thermal dissipation and performances especially for future higher memory density and low power memory devices. This article briefly reviews key aspects of encapsulant materials reliability concerns, factors impacting package strength, package warpage and thermal dissipation for future miniatured memory device packaging. [ABSTRACT FROM AUTHOR]