Concentration-dependent Changes Research Articles

The impact of varying sizes of silver nanoparticles on the induction of cellular damage in Klebsiella pneumoniae involving diverse mechanisms

Abstract Silver nanoparticles (AgNPs) are extensively studied as potent antibacterial agents targeting antibiotic-resistant pathogens. Cellular damage induced through various mechanisms that can affect multiple cell components like the outer membrane, enzymes, and proteins is closely linked to their chemical and morphological characteristics. We investigated the impact of AgNPs’ size on their antibacterial effectiveness using two differently sized nanoparticles: silver nanoparticle-Citrus limon (AgCL) with an average size of 21 nm and silver nanoparticle-Citrus sinensis (AgCS) with an average size of 13 nm, derived from C. limon and C. sinensis through environmentally friendly methods. The study evaluated their antibacterial effects by assessing morphology changes via scanning electron microscopy, metabolic alterations using Fourier transform infrared (FT-IR) spectroscopy, and oxidative stress responses through biochemical markers in Klebsiella pneumoniae cells exposed to AgNPs. The results showed that both AgCL and AgCS exhibited remarkable antibacterial activity, evidenced by inhibition zones of 14 ± 1.5 and 16 ± 1.0 mm, respectively. Morphological changes in K. pneumoniae cells treated with AgNPs were size dependent, with notable alterations noted. FT-IR spectroscopy revealed size and concentration-dependent biochemical changes, particularly in shifts in functional groups involved in the fluidity of cell wall lipid, and protein structure. Exposure to AgNPs led to increased oxidative stress markers like lipid peroxides and reduced levels of enzymatic and non-enzymatic antioxidants, more prominently observed with smaller AgCS nanoparticles (13 nm). AgNPs induce oxidative stress and morphological changes in K. pneumoniae strains, with smaller nanoparticles demonstrating greater efficacy. These findings underscore the importance of nanoparticle size in optimizing the antibacterial properties against pathogens.

Rapid Single-Step Detection of Polyfluoroalkyl Substances (PFAS) Using Electropolymerized Phenoxazine Dyes.

Per- and polyfluoroalkyl substances (PFAS) are highly stable ubiquitous contaminants that have been recently added to the list of regulated chemicals. While methods for PFAS detection exist, analysis is difficult, involving a tedious protocol and expensive instrumentation. Here, we demonstrate the first implementation of a phenoxazine dye as a sensing probe that facilitates rapid and inexpensive detection of representative PFAS, e.g., perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), at sensitivity levels covering the recently established Environmental Protection Agency (EPA) limits. The method comprises an electrode modified with a stable redox film of Meldola blue (MB) in its electropolymerized form (epMB), which provides amino sites for electrostatic interactions with PFAS. Long-chain PFAS bind specifically to the epMB, inducing a hydrophobic-type cluster formation through ion-pair and F-F interactions. This binding generates concentration-dependent changes in the epMB/epMB+ oxidation, enabling rapid and sensitive quantification in a single step with high sensitivity, reaching a limit of detection of 0.4 ppt for PFOS and 1.65 ppt for PFOA. The sensor demonstrates good selectivity toward common interfering compounds like humic acid, sodium chloride and fluoride, metallic ions (Cu, Hg, As), as well as pesticides. In addition to PFOS and PFOA, the sensors can measure other perfluoroalkyl compounds, demonstrating potential as a tool for rapid quantification of a total PFAS index, with affinity for long-chain PFAS. This work highlights the integration of redox receptors into an electrochemical sensor to solve the grand challenge of PFAS analysis using a rapid and inexpensive procedure, with potential for field deployment.

Chemical Characteristics of Zirconium Chloride and Zirconium Oxide Nanoparticles Driving Toxicity on Lemna minor

The increasing global production and utilization of zirconium (Zr) compounds, including zirconium chloride (ZrCl4) and zirconium oxide nanoparticles (NPs-ZrO2), raises concerns about their potential environmental impact. This study investigated the toxicity mechanisms of ZrCl4 and NPs-ZrO2 on the aquatic plant Lemna minor. The physicochemical properties of NPs-ZrO2 in the test medium were characterized, revealing concentration-dependent changes in the hydrodynamic diameter, zeta potential, and solubility over time. The analysis of Zr speciation showed the predominance of Zr(OH)4(aq) species from ZrCl4. Plants of L. minor exposed to ZrCl4 and NPs-ZrO2 exhibited differential Zr bioaccumulation, growth inhibition, oxidative stress, and antioxidant responses. ZrCl4 induced a higher toxicity than NPs-ZrO2, with bioaccumulation strongly correlating with adverse effects. The differential toxicity impact between these two Zr-compounds was also determined by the lowest observed-effect doses for growth and biochemical parameters. The scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy confirmed internalization of NPs-ZrO2 and Zr uptake in the L. minor plant. Therefore, these findings highlighted the importance of chemical speciation, environmental transformations, and biological responses in assessing the ecological impact of Zr-compounds for effective risk assessment and management strategies for protecting aquatic ecosystems.

NADPHnet: a novel strategy to predict compounds for regulation of NADPH metabolism via network-based methods.

Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies. However, the complex nature of NADPH metabolism poses challenges in achieving this goal. In this study, we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods. Different from traditional approaches only focusing on one single protein, NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view. Specifically, NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods, and characterized the impact of natural products on NADPH metabolism using a combined score, NADPH-Score. NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set. This approach was further employed along with molecular docking to identify 27 compounds from a natural product library, 6 of which exhibited concentration-dependent changes of cellular NADPH level within 100 μM, with Oxyberberine showing promising effects even at 10 μM. Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer. Overall, NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases.

NIR-Sensitive Squaraine Dye-Peptide Conjugate for Trypsin Fluorogenic Detection.

Trypsin enzyme has gained recognition as a potential biomarker in several tumors, such as colorectal, gastric, and pancreatic cancer, highlighting its importance in disease diagnosis. In response to the demand for rapid, cost-effective, and real-time detection methods, we present an innovative strategy utilizing the design and synthesis of NIR-sensitive dye-peptide conjugate (SQ-3 PC) for the sensitive and selective monitoring of trypsin activity by fluorescence ON/OFF sensing. The current research deals with the design and synthesis of three unsymmetrical squaraine dyes SQ-1, SQ-2, and SQ-3 along with a dye-peptide conjugate SQ-3-PC as a trypsin-specific probe followed by their photophysical characterizations. The absorption spectral investigation conducted on both the dye alone and its corresponding dye-peptide conjugates in water, utilizing SQ-3 and SQ-3 PC respectively, reveals enhanced dye aggregation and pronounced fluorescence quenching compared to observations in DMSO solution. The absorption spectral investigation conducted on dye only and corresponding dye-peptide conjugates in water utilizing SQ-3 and SQ-3 PC, respectively, reveals not only the enhanced dye aggregation but also pronounced fluorescence quenching compared to that observed in the DMSO solution. The trypsin-specific probe SQ-3 PC demonstrated a fluorescence quenching efficiency of 61.8% in water attributed to the combined effect of aggregation-induced quenching (AIQ) and fluorescence resonance energy transfer (FRET). FRET was found to be dominant over AIQ. The trypsin-mediated hydrolysis of SQ-3 PC led to a rapid and efficient recovery of quenched fluorescence (5-fold increase in 30 min). Concentration-dependent changes in the fluorescence at the emission maximum of the dyes reveal that SQ-3 PC works as a trypsin enzyme-specific fluorescence biosensor with linearity up to 30 nM along with the limit of detection and limit of quantification of 1.07 nM and 3.25 nM, respectively.

Increasing salinity sequentially induces salt tolerance responses in Szarvasi-1 energy grass

Soil salinity causes severe physiological disorders, decline in biomass, and crop production worldwide becoming more critical with global climate change. Consequently, salt-tolerant varieties received major focus in all sectors of agriculture. Biomass plants such as Szarvasi-1 energy grass (Elymus elongatus subsp. ponticus cv. Szarvasi-1) may play an important role in energy production if they are tolerant to environmental stresses. In this study, Szarvasi-1 energy grass has been investigated to reveal its tolerance to 50–200 mM NaCl in hydroponics. Significant decline in stomatal conductance appeared at 100 mM NaCl treatment but fresh and dry weight and the maximal quantum efficiency of PSII decreased only at 200 mM NaCl. Relative water content and total chlorophyll concentration did not change compared to the control. Leaf water potential was maintained at the control level for one week NaCl exposure, decrease became significant only after two weeks. Malondialdehyde concentration did not refer to oxidative stress. In the element composition of the plants, remarkable increase was found only for Mo whereas Ca, K, S, P, Mn decreased compared to the control. K to Na ratio remained higher than one in the shoot even at 200 mM NaCl. Salt treatment caused temporal and concentration-dependent changes in the expression of genes in the phenylpropanoid pathway, Na transport, photosynthesis, and cellular protection and repair. Szarvasi-1 was found to be fairly tolerant to NaCl which induced a sequential response switching on vacuolar compartmentalization at 50 mM, Na efflux at 100 mM, and cellular protection and repair at 200 mM.

Enhanced Neurotransmitter Detection with Biorecognition Element-Functionalized Organic Electrochemical Transistors

The United States National Academies of Science and Engineering have issued a grand challenge to “reverse-engineer the brain”. Addressing this challenge requires a more complete understanding of how connections between individual neurons and groups of neurons are formed and maintained, as well as a more thorough elucidation of the signaling processes that drive neural network optimization. However, to achieve these goals, it is first necessary to develop the appropriate fundamental tools and protocols for adaptive biointerfacing, bottom-up neuroscience, and neuromodulation.To address this challenge, our research team has developed neurotransmitter-specific biosensors based on organic electrochemical transistors (OECT), which are electrolyte-gated devices that permit large signal amplification, ionic-to-electronic signal transduction, and controllable variable resistance. Given that their porous channel materials enable volumetric interaction with the adjacent electrolyte, OECT offer increased detection sensitivity compared to other electrolyte-gated devices such as field-effect transistors (FET). Although these OECT devices have demonstrated utility in a wide range of applications, from neuromorphic computing to bioelectronic devices, they are still in an early stage of development.We report enhanced electrochemical sensing of dopamine, mediated by functionalizing the OECT gate electrode with dopamine-specific biorecognition elements (BRE, i.e., aptamers). To optimize these devices, our team tested a variety of electrode functionalization approaches (e.g. alkane-thiol or silane chemistry, layer-by-layer, and covalent modification). The operational principle of BRE-functionalized OECT gate electrode biosensing is based on changes in gate electrode surface potential caused by target-binding to the BRE. When the target binds to the BRE, the event alters the capacitance at the surface of the functionalized gate electrode. The change in surface potential at the gate electrode shifts the applied potential on the OECT channel, which alters the doping state of the OECT channel. The channel materials are mixed ionic/electronic conductors, so changes in the doping state of the channel will directly affect the transconductance of the channel, which alters the OECT transfer characteristic and thereby permits sensing. The large transconductance of the OECT channel allows small changes in doping state to amplify the signal caused by binding of the target to the surface-attached BRE.In this study, we directly compare the dopamine biosensing performance of BRE-functionalized gold electrodes tested in two different sensing configurations:(i) traditional amperometric biosensor with a BRE-functionalized working electrode(ii) OECT with BRE-functionalized gate electrodeWe confirm the operational principles outlined above, and quantitatively assess the biosensing performance through a variety of analytical and electroanalytical techniques, such as cyclic voltammetry, open-circuit potentiometry, electrochemical impedance spectroscopy (EIS), square-wave and differential pulse voltammetry (DPV), and electrochemical quartz crystal microbalance (EQCM). We also compare the observed concentration-dependent changes in OECT transfer characteristics to the changes predicted by a theoretical analysis of surface potential.Finally, we will present the steps we have taken to implement these devices within organ-on-a-chip systems, both for traditional neurotransmitter biosensing and to demonstrate the utility of our devices for studying the formation and longitudinal evolution of neural networks within in vitro neuronal colonies.

Ethanolic Extract of Salvia officinalis Leaves Affects Viability, Survival, Migration, and the Formation and Growth of 3D Cultures of the Tumourigenic Murine HPV-16+-Related Cancer Cell Line.

Salvia officinalis (SO) is one of the most widely used plants in traditional medicine worldwide. In the present study, the effect of an ethanolic extract of S. officinalis leaves on hallmarks of cancer of HPV-16-positive cancer tumorigenic cells, TC-1, was analyzed in vitro. Phytochemical and spectroscopic analysis were performed. Additionally, the extract's flavonoid content, reducing iron, and antioxidant capacity were determined. In regard to the in vitro tests, the cytotoxic activity and its effect on the replicative capacity and on the cell migration of TC-1 cells were analyzed by viability and clonogenic, survival, and wound healing assays. The effect of a pre-treatment or treatment on 3D culture formation, growth, and reversion capacity was also examined. The results of the phytochemical analysis allowed the detection of tannins, saponins, steroids, and flavonoids. The flavonoids content was found to be 153.40 ± 10.68 µg/mg of extract. Additionally, the extract exhibited an antioxidant capacity and a ferric-reducing capacity of around 40% compared to the ascorbic acid. Thin layer chromatographic (TLC) analysis and spectroscopic tests showed the presence of compounds similar to quercetin and catechin flavonoids in the extract. In the in vitro assays, the SO extract induced in a concentration-dependent way changes in cell morphology, the decrease of cell viability, survival, and migration. At a concentration of 125 µg/mL, the extract inhibited spheroid formation, reduced their growth, and affected their reversion to 2D. Ethanolic extract of S. officinalis leaves had inhibitory effects on hallmarks of the cancer line HPV-16+. This suggests that the phytochemicals present in it may be a source of chemotherapeutics against cervical cancer.

Development of MnWO4:Ag nanodilute magnetic semiconductors with tunable magnetic and optoelectronic properties

The bandgap engineered MnWO4 nanoparticles doped with Ag were developed using a facile one-pot synthesis method. The impurity doping concentration of Ag was varied from 1 to 5 wt percentages to tune the interactions between manganese tungstate and silver ions to obtain desirable magnetic and optoelectronic properties. The structural properties of the MnWO4 particles with various concentrations of Ag were investigated using X-ray diffraction. The optical properties of the pristine and Ag-doped MnWO4 particles were determined using UV‒Vis and photoluminescence spectroscopy. The impurity concentration-dependent structural transformations and changes in the vibrational modes, lattice dynamics, electronic transitions and optoelectronic properties of the prepared materials were analyzed using Raman spectroscopy. The topology, morphology and elemental analysis of the synthesized nanoparticles were elucidated using HRTEM, SAED, SEM and EDX techniques. The magnetic properties of the MnWO4:Ag nanoparticles were measured using a vibrating sample magnetometer (VSM). The obtained results suggested that Ag-doped MnWO4 nanosystems show enhanced and tunable magnetic properties suitable for nanodilute magnetic semiconductor (nDMS) applications. The presented work opens a range of possibilities for the development of advanced materials with applications in optoelctronics, nanomedicine, energy-efficient electronic devices and energy conversion.

Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice

BackgroundRespiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear.PurposeThe present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism.Study design and methodsLung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria.ResultsIn the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota.ConclusionZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

Quantifying Chemical Reactions and Interfacial Properties at Buried Polymer/Polymer Interfaces.

Maleic anhydride (MAH)-modified polymers are used as tie layers for binding dissimilar polymers in multilayer polymer films. The MAH chemistry which promotes adhesion is well characterized in the bulk; however, only recently has the interfacial chemistry been studied. Sum frequency generation vibrational spectroscopy (SFG) is an interfacial spectroscopy technique which provides detailed information on interfacial chemical reactions, species, and molecular orientations and has been essential for characterizing the MAH chemistry in both nylon and ethyl vinyl alcohol copolymer (EVOH) model systems and coextruded multilayer films. Here, we further characterize the interfacial chemistry between MAH-modified polyethylene tie layers and both EVOH and nylon by investigating the model systems over a range of MAH concentrations. We can detect the interfacial chemical reaction products between MAH and the barrier layer at MAH concentrations of ≥0.022 wt % for nylon and ≥0.077 wt % for EVOH. Additionally, from the concentration-dependent reaction reactant/product SFG peak positions and the product imide or ester/acid C═O group tilt angles extracted from the polarization-dependent SFG spectra, we quantitatively observe concentration-dependent changes to both the interfacial chemistry and interfacial structure. The interfacial chemistry and molecular orientation as a function of MAH concentration are well correlated with the adhesion strength, providing important quantitative information for the future design of MAH-modified tie layers for a variety of important applications.

Sensitive Detection of Perfluoroalkyl Substances Using MXene-AgNP-Based Electrochemical Sensors.

Per- and polyfluoroalkyl substances (PFAS) pose a significant threat to the environment due to their persistence, ability to bioaccumulate, and harmful effects. Methods to quantify PFAS rapidly and effectively are essential to analyze and track contamination, but measuring PFAS down to the ultralow regulatory levels is extremely challenging. Here, we describe the development of a low-cost sensor that can measure a representative PFAS, perfluorooctanesulfonic acid (PFOS), at the parts per quadrillion (ppq) level within 5 min. The method combines the ability of PFOS to bind to silver nanoparticles (AgNPs) embedded within a fluorine-rich Ti3C2-based multilayered MXene, which provides a large surface area and accessible binding sites for direct impedimetric detection. Fundamentally, we show that MXene-AgNPs are capable of binding PFOS and other long-chain PFAS compounds, though the synergistic action of AgNPs and MXenes via electrostatic and F-F interactions. This binding induced concentration-dependent changes in the charge-transfer resistance, enabling rapid and direct quantification with extremely high sensitivity and no response to interferences. The sensor displayed a linear range from 50 ppq to 1.6 ppt (parts per trillion) with an impressively low limit of detection of 33 ppq and a limit of quantification of 99 ppq, making this sensor a promising candidate for low-cost screening of the PFAS content in water samples, using a simple and inexpensive procedure.

Chitosan-mediated tailoring of cadmium sulphide nanoparticle: Synthesis, properties, and interactive mechanisms

This study explores the synergistic effects of chitosan-coated cadmium sulphide (CdS) nanoparticles (NPs) at varying concentrations on their structural, optical, and photocatalytic properties. CdS NPs are known for their promising photocatalytic potential, but their practical application often requires stability enhancement and reduced toxicity. Chitosan, a natural biopolymer, offers unique advantages such as biocompatibility and heavy metal adsorption capabilities, making it an attractive candidate for surface modification of CdS NPs. Our investigation reveals that chitosan-coated CdS NPs exhibit concentration-dependent changes in their crystalline structure, bandgap energy, particle size, and vibrational characteristics. Notably, CdS NPs synthesized with 1.5 g chitosan concentration display the smallest bandgap and particle size, suggesting optimal photocatalytic activity. This research provides valuable insights into tailoring CdS NPs for efficient visible light photocatalysis, with implications in environmental remediation and energy conversion.

A comprehensive study on the surface property changes of antibodies on interacting with Ti3C2Tx, V2CTx, or Mo2TiC2Tx MXenes

MXenes are nanomaterials composed of layered transition metal carbides and nitridesand are considered to have considerable potential in the biomedical translation field. However, the biological and toxicological behaviours of nanomaterials (NMs) are regulated by protein-corona formation, which leads to conformational changes in proteins and impacts their biological functions. Thus, in this work, we synthesized four different MXenes (multi-layered titanium carbide (Ti3C2Tx-ML); single-layered titanium carbide (Ti3C2Tx-SL); single-layered molybdenum titanium carbide (Mo2TiC2Tx-SL); and multi-layered vanadium carbide (V2CTx-ML)) and studied their physicochemical interactions with a model protein immunoglobin G (IgG) from human serum. The conformational, thermal, and colloidal stabilities of IgG were investigated after exposing IgG to MXenes for 15 min at IgG/MXene ratios of 40:1 and 20:1. Circular dichroism (CD) spectroscopy revealed that the secondary structure of IgG underwent a concentration-dependent conformational change after exposure to all four MXenes. ζ-potential studies showed that Ti3C2Tx-ML MXene had the highest negative surface charge due to the presence of abundant fluorine (F) surface groups. However, this increased the hydrophilicity of IgG/MXene solution and eventually caused IgG aggregation and destabilization. Furthermore, Ti3C2Tx-ML MXene had a greater tendency to produce protein coronas than the other MXenes. This study describes a versatile means of examining the properties of MXenes responsible for protein coronas and lays a foundation for establishing the connection between protein corona formation and the biological functions of MXenes.

Exposure to tungsten particles via inhalation triggers early toxicity marker expression in the rat brain

Objective Our work is focused on tungsten, considered as an emerging contaminant. Its environmental dispersion is partly due to mining and military activities. Exposure scenario can also be occupational, in areas such as the hard metal industry and specific nuclear facilities. Our study investigated the cerebral effects induced by the inhalation of tungsten particles. Methods Inhalation exposure campaigns were carried out at two different concentrations (5 and 80 mg/m3) in single and repeated modes (4 consecutive days) in adult rats within a nose-only inhalation chamber. Processes involved in brain toxicity were investigated 24 h after exposure. Results and discussion Site-specific effects in terms of neuroanatomy and concentration-dependent changes in specific cellular actors were observed. Results obtained in the olfactory bulb suggest a potential early effect on the survival of microglial cells. Depending on the mode of exposure, these cells showed a decrease in density accompanied by an increase in an apoptotic marker. An abnormal phenotype of the nuclei of mature neurons, suggesting neuronal suffering, was also observed in the frontal cortex, and can be linked to the involvement of oxidative stress. The differential effects observed according to exposure patterns could involve two components: local (brain-specific) and/or systemic. Indeed, tungsten, in addition to being found in the lungs and kidneys, was present in the brain of animals exposed to the high concentration. Conclusion Our data question the perceived innocuity of tungsten relative to other metals and raise hypotheses regarding possible adaptive or neurotoxic mechanisms that could ultimately alter neuronal integrity.

Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

Multifunctional Ionic Hydrogel-Based Transdermal Delivery of 5-Fluorouracil for the Breast Cancer Treatment.

Transdermal drug delivery systems (TDDS) are a promising and innovative approach for breast cancer treatment, offering advantages such as noninvasiveness, potential for localized and prolonged drug delivery while minimizing systemic side effects through avoiding first-pass metabolism. Utilizing the distinctive characteristics of hydrogels, such as their biocompatibility, versatility, and higher drug loading capabilities, in the present work, we prepared ionic hydrogels through synergistic interaction between ionic liquids (ILs), choline alanine ([Cho][Ala]), and choline proline ([Cho][Pro]) with oleic acid (OA). ILs used in the study are biocompatible and enhance the solubility of 5-fluorouracil (5-FU), whereas OA is a known chemical penetration enhancer. The concentration-dependent (OA) change in morphological aggregates, that is, from cylindrical micelles to worm-like micelles to hydrogels was formed with both ILs and was characterized by SANS measurement, whereas the interactions involved were confirmed by FTIR spectroscopy. The hydrogels have excellent mechanical properties, which studied by rheology and their morphology through FE-SEM analysis. The in vitro skin permeation study revealed that both hydrogels penetrated 255 times ([Cho][Ala]) and 250 times ([Cho][Pro]) more as compared to PBS after 48 h. Those ionic hydrogels exhibited the capability to change the lipid and keratin arrangements within the skin layer, thereby enhancing the transdermal permeation of the 5-FU. Both ionic hydrogels exhibit excellent biocompatibility with normal cell lines (L-132 cells) as well as cancerous cell lines (MCF-7 cells), demonstrating over 92% cell viability after 48 h in both cell lines. In vitro, the cytotoxicity of the 5-FU-loaded hydrogels was evaluated on MCF-7 and HeLa cell lines. These results indicate that the investigated biocompatible and nontoxic ionic hydrogels enable the transdermal delivery of hydrophilic drugs, making them a viable option for effectively treating breast cancer.

In Vivo Tissue Distribution of Polystyrene or Mixed Polymer Microspheres and Metabolomic Analysis after Oral Exposure in Mice.

Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored. This study aims to investigate the impacts of polymer microspheres on tissue metabolism in mice by assessing the microspheres ability to translocate across the gut barrier and enter into systemic circulation. Specifically, we wanted to examine microsphere accumulation in different organ systems, identify concentration-dependent metabolic changes, and evaluate the effects of mixed microsphere exposures on health outcomes. To investigate the impact of ingested microspheres on target metabolic pathways, mice were exposed to either polystyrene () microspheres or a mixture of polymer microspheres consisting of polystyrene (), polyethylene (), and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid) (). Exposures were performed twice a week for 4 weeks at a concentration of either 0, 2, or via oral gastric gavage. Tissues were collected to examine microsphere ingress and changes in metabolites. In mice that ingested microspheres, we detected polystyrene microspheres in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolic differences that occurred in the colon, liver, and brain, which showed differential responses that were dependent on concentration and type of microsphere exposure. This study uses a mouse model to provide critical insight into the potential health implications of the pervasive issue of plastic pollution. These findings demonstrate that orally consumed polystyrene or mixed polymer microspheres can accumulate in tissues such as the brain, liver, and kidney. Furthermore, this study highlights concentration-dependent and polymer type-specific metabolic changes in the colon, liver, and brain after plastic microsphere exposure. These results underline the mobility within and between biological tissues of MPs after exposure and emphasize the importance of understanding their metabolic impact. https://doi.org/10.1289/EHP13435.

Portable hydrogel kit driven by bimetallic carbon dots nanozyme for H2O2-self-supplying dual-modal monitoring of atmospheric CH3SH

Due to the typical volatility of gaseous pollutant methyl mercaptan (CH3SH), the development of a facile, reliable, and accurate onsite environmental surveillance of highly toxic CH3SH faces many challenges, but it is critical to environmental atmosphere assessment and safeguarding public health. Here, we prepared a novel bimetallic carbon dots (Fe&Cu@CDs) nanozyme with high peroxidase-mimicking activity to design a portable hydrogel kit for onsite visual H2O2-self-supplying enzymatic cascade catalytic colorimetric and photothermal signal synergistic amplification dual-modal monitoring of CH3SH in atmospheric environment. Assisted by alcohol oxidase (AOX), CH3SH could be specifically converted into H2O2 for oxidizing chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) catalyzed by Fe&Cu@CDs to produce dark blue ox-TMB with absorption at 652 nm and photothermal characters. Consequently, a CH3SH concentration-dependent change both in naked-eye color and photothermal effect-triggered temperature were observed. By hybridizing AOX-assisted Fe&Cu@CDs + TMB with agarose, a H2O2-self-supplying colorimetric and photothermal signal synergistic amplification sensory hydrogel kit integrated with Color Picker APP-installed smartphone and 660 nm laser-equipped handheld thermal imager for CH3SH was proposed with acceptable results in atmospheric environment around wastepile (e.g., solid waste and food waste piles), which exhibited great potentials to further develop commercial onsite monitoring platforms in warning-early abnormal atmospheric CH3SH for safeguarding environmental health.

Effect of glycation-induced concentration-dependent change in albumin structure and alteration in its binding capacity

Reducing sugars causes confirmatory alterations in albumin structure by the nonenzymatic glycation of the amino group of serum albumin. In this study, glucose and its hazardous metabolic products like glyoxal and methylglyoxal were incubated with bovine serum albumin (BSA). The confirmational changes in BSA molecule’s structure by glycating substances was investigated using a variety of spectroscopic methods, including deconvolutionFourier Transform Infra-red (FT-IR) spectroscopy, fluorescence spectroscopy, UV spectroscopy and circular dichroism (CD) spectroscopy. Dynamic fluorescence quenching was observed in the case of glucose, while static quenching was observed in the case of methyl glyoxal and glyoxal. Similarly, employing deconvolution FT-IR spectroscopy and CD spectroscopy for determination of change in secondary structures in terms signature of α-helix, β-turn, β-sheet and random coil modifications. Destabilization or unfolding of the albumin structure, due to the disruption of the hydrogen bonding pattern that stabilizes the albumin manifold, causes a 25-50% reduction in α-helix and a 2-fold increase in β-sheet and turns in glycated BSA. The competitive displacement interaction studies with warfarin were performed using the ultrafiltration technique and quantitative determination of free drug in ultrafiltrate using LC-MS/MS. The binding of carbamazepine (CBZ) or its active metabolite to proteins was unaffected by the glycation of BSA with glucose and methyl glyoxal. Nevertheless, with glyoxal-modified BSA, it changed the binding of selected analytes significantly. Based on in vitro observations and results, it could be anticipated that the serum CBZ concentration variation may be worsened in uncontrolled diabetes circumstances, with an overall variance of 30–40% possible. Communicated by Ramaswamy H. Sarma