By planting LEDs on the surfaces of orifice baffles, a novel batch oscillatory baffled photoreactor (OBPR) together with polymer-supported Rose Bengal (Ps-RB) beads are used to investigate reaction kinetics of a photo-oxidation reaction between α-terpinene and singlet oxygen (1O2). In the widely used NMR data analysis for this reaction, α-terpinene and ascaridole are treated as a reaction pair, assuming kinetically singlet oxygen is in excess or constant. We have, for the first time, examined the validity of the method, discovered that increasing α-terpinene initially leads to an increase of ascaridole, indicating that the supply of singlet oxygen is in excess. Applying kinetic analysis, a pseudo first order reaction kinetics is confirmed, supporting this assumption. We have subsequently initiated a methodology of estimating the 1O2 concentrations based on the proportionality of ascaridole concentrations with respect to its maximum under these conditions. With the help of the estimated singlet oxygen data, the efficiency of 1O2 utilization and the photo efficiency of converting molecular oxygen to 1O2 are further proposed and evaluated. We have also identified conditions where further increase of α-terpinene has caused decreases in ascaridole, implying kinetically that 1O2 has now become a limiting reagent, the method of treating α-terpinene and ascaridole as a reaction pair in the data analysis would no longer be valid under those conditions.

Phthalates are esters of Pthalic acid, compounds mainly used as plasticisers. Phthalates are widely used chemicals which are of significant research interest as their exposure causes various consequences for human health. There are several categories of phthalates extensively used in many commercial productions with diverse uses, physicochemical properties and toxicological effects. This chapter discusses the toxicity of Phthalates and its potential risks to human health.

Stimuli-responsive polymeric materials have attracted significant attentions in a variety of high-value-added and industrial applications during the past decade. Among various stimuli, light is of particular interest as a stimulus due to its unique advantages such as precisely spatiotemporal control, mild conditions, ease of use, and tunability. In recent years, a lot of effort toward synthesis of biocompatible and biodegradable polypeptide has resulted in many examples of photo-responsive nanoparticles. Depending on the specific photochemistry, those polypeptide derived nano-assemblies are capable of crosslinking, disassembling, or morphing into other shapes upon light irradiation. In this mini-review, we aim to assess the current state of photo-responsive polypeptide based nanomaterials. First, those “smart” nanomaterials will be categorized by their photo-triggered events (i.e., crosslinking, degradation, and isomerization) which are inherently governed by photo-sensitive functionalities including o-nitrobenzyl, coumarin, azobenzene, cinnamyl, and spiropyran. In addition, the properties and applications of those polypeptide nanomaterials will be highlighted as well. Finally, the current challenges and future directions of this subject will be evaluated.

We experimentally investigate power-sensitive photo-thermal tuning (PTT) of two-dimensional (2D) graphene oxide (GO) films coated on integrated optical waveguides. We measure the light power thresholds for reversible and permanent GO reduction in silicon nitride (SiN) waveguides integrated with 1 and 2 layers of GO. Raman spectra at different positions of a hybrid waveguide with permanently reduced GO are characterized, verifying the inhomogeneous GO reduction along the direction of light propagation through the waveguide. The differences between the PTT induced by a continuous-wave laser and a pulsed laser are also compared, confirming that the PTT mainly depend on the average input power. These results reveal interesting features for 2D GO films coated on integrated optical waveguides, which are of fundamental importance for the control and engineering of GO’s properties in hybrid integrated photonic devices.

Bio-devices are designed to allow biological matter to perform in vitro almost the same functions it performs in vivo. Therefore, they can benefit from the specificities of such materials and are expected to perform better than traditional devices. On the other hand, the integration of biological material with electronic/electrochemical instrumentation requires careful attention and can produce unconventional results. In this paper, we describe the impedance response of an electrochemical cell that converts sunlight into electrical power. It uses the photosynthetic system known as Reaction Center, which is the core of photosynthesis in several living beings. Under illumination, an abrupt transformation drives the cell electrical response from insulator to conductor and a photocurrent is observed. The impedance spectrum shows a peculiar shape which significantly modifies with the protein activation. It has been analyzed by means of a graphical/analytical/ numerical procedure. The modelling identifies an analogue electrical circuit, whose parameters give quantitative information about the underlying process. Finally, an appropriate normalization of data is proposed which validates data in dark and light and can be useful as a fast screening of measurements.

Using structured light to drive colloidal motors, due to its advantages of remote manipulation, energy tunability, programmability, and controllability of spatiotemporal distribution, has been attracting much attention in the fields of targeted drug delivery, environmental control, chemical agent detection, and smart device design. Here, we focus on studying the group control of colloidal made from a photo-responsive organic polymer molecule NO-COP (N,O-Covalent organic polymer). These colloidal motors mainly respond to the light intensity patterns. We chose a digital micromirror device (DMD) to modulate the structured light field shining on the sample, by considering its merit of fast refreshing speed, good programmability, and high-power threshold. It is found that under ultraviolet or green light modulation, such colloidal motors exhibit various group behaviors including group diffusion, group patterning, and group migration. The qualitative interpretation is also provided for these observations.

On-chip integration of two-dimensional (2D) materials with unique structures and distinctive properties endow integrated devices with new functionalities and improved performance. With a high flexibility in modifying its properties and a strong compatibility with various integrated platforms, graphene oxide (GO) becomes an attractive 2D material for implementing functional hybrid integrated devices. Here, we demonstrate novel functionalities that go beyond the capabilities of conventional photonic integrated circuits, by harnessing the photo-thermal effects in 2D GO films integrated onto them. These include all-optical control and switching, optical power limiting, and non-reciprocal light transmission. The 2D layered GO films are on-chip integrated with precise control of their thicknesses and sizes. Benefitting from the broadband response of 2D GO films, all the three functionalities feature a very wide operational bandwidth. By fitting the experimental results with theory, we also extract the changes in material properties induced by the photo-thermal effects, which reveal interesting insights about 2D GO films. These results highlight the versatility of 2D GO films in implementing functional integrated photonic devices for a range of applications.

In this study, we investigate the structural changes, electronic properties, and charge redistribution within azo-bithiophene (Azo-BT) chemisorbed monolayers under different light stimuli using density functional theory and molecular dynamics simulations. We consider two types of switches, Azo-BT and BT-Azo, with different arrangements of the Azo and BT blocks counting from the anchor thiol group. The chemisorbed monolayers of pure cis- and trans-isomers with a surface concentration of approximately 2.7 molecules per nm2 are modeled on a gold surface using classical all-atom molecular dynamics. Our results reveal significant shrinkage of the BT-Azo layer under UV illumination, whereas the thicknesses of the Azo-BT layer remain comparable for both isomers. This difference in behavior is attributed to the ordering of the trans-molecules in the layers, which is more pronounced for Azo-BT, leading to a narrow distribution of the inclination angle to the gold surface. Conversely, both layers consisting of cis-switches exhibit disorder, resulting in similar brush heights. To study charge transfer within the immobilized layers, we analyze each snapshot of the layer and calculate mean charge transfer integrals using Nelsen’s algorithm for a number of interacting neighboring molecules. Combining these integrals with reorganization energies defined for the isolated molecules, we evaluate the charge transfer rates and mobilities for electron and hole hopping within the layers at room temperature based on Marcus’ theory. This research offers new perspectives for the innovative design of electrode surface modifications and provides insights into controlling charge transfer within immobilized layers using light triggers. Additionally, we identify molecular properties that are enhanced through specific molecular design, which contributes to the development of more efficient molecular switches for various electronic applications.

Nanoparticles (NPs) are commonly used in healthcare and nano therapy, but their toxicity at high concentrations is well-known. Recent research has shown that NPs can also cause toxicity at low concentrations, disrupting various cellular functions and leading to altered mechanobiological behavior. While researchers have used different methods to investigate the effects of NPs on cells, including gene expression and cell adhesion assays, the use of mechanobiological tools in this context has been underutilized. This review emphasizes the importance of further exploring the mechanobiological effects of NPs, which could reveal valuable insights into the mechanisms behind NP toxicity. Such investigations could aid in developing new strategies to mitigate NP toxicity and improve their safety for biomedical applications. Moreover, understanding how NPs affect cell cytoskeletal functions through mechanobiology could have significant implications, including the development of innovative drug delivery systems and tissue engineering techniques. In summary, this review highlights the significance of incorporating mechanobiology into the study of NP toxicity and demonstrates the potential of this interdisciplinary field to advance our knowledge and practical use of NPs.

Silicon-based photoelectrochemical (PEC) conversion system has recently gained attention with its ability to provide cost-efficient and superior photoresponsive behavior in regard to other various semiconductor photoelectrodes. Carbon-based co-catalysts have always shared the spotlight for being rendered as alternative metal-free electrocatalysts intended for hydrogen evolution reaction (HER). In particular, a representative carbon-derived material, reduced Graphene Oxide (rGO) has attracted much attention as a non-metal catalyst for efficient and durable HER. Herein, we have deposited rGO on silicon nanowire (SiNW) structure which shows the highest reduction in the overpotential for HER up to date. This could be attributed to the synergistic effects of rGO and SiNW with unique anisotropic morphology, facile tuning capabilities, and scalable fabrication methods. Combined with nanostructured photocathode, rGO deposited SiNW showed better applied bias photon to current conversion efficiency of 3.16%, which is 158 times higher than that of bare planar Si system. In regard to this development we believe that rGO-SiNW photoelectrodes would pave the way for state-of-the-art highly efficient non-metal catalysts for energy conversion technologies.

In this research paper a novel Ultra Violet Photo Catalyst Oxidation (UVPCO) sensor for air and surface sanitization using Common Source (CS) amplifier is presented. The ultra violet photo catalysis is the process in which the highly reactive radicals like H+, OH-and peroxides ions are produced from air in the presence of the ultra violet radiation and photo catalyst. In this process, the free radicals outbreaks the bio aerosols like bacteria, fungus and volatile organic compounds (VOCs) and destroy them. The proposed system is relies on the fast operation of PCS which operates under sub-threshold conditions and reduced computation time. The properties of common source amplifier like very high voltage gain and input output resistance increased the sensitivity as well as stability of the circuit. The system is more user friendly and the outcomes of simulation are fairly in agreement with the theoretical estimation. Keywords: bio aerosol, Photo Catalytic Oxidation (PCO), hydroxyl, hydrogen peroxide, SPICE, surface sanitizer.

In order to improve contrast and restore color for underwater image captured by camera sensors without suffering from insufficient details and color cast, a fusion algorithm for image enhancement in different color spaces based on contrast limited adaptive histogram equalization (CLAHE) is proposed in this article. The original color image is first converted from RGB color space to two different special color spaces: YIQ and HSI. The color space conversion from RGB to YIQ is a linear transformation, while the RGB to HSI conversion is nonlinear. Then, the algorithm separately operates CLAHE in YIQ and HSI color spaces to obtain two different enhancement images. The luminance component (Y) in the YIQ color space and the intensity component (I) in the HSI color space are enhanced with CLAHE algorithm. The CLAHE has two key parameters: Block Size and Clip Limit, which mainly control the quality of CLAHE enhancement image. After that, the YIQ and HSI enhancement images are respectively converted backward to RGB color. When the three components of red, green, and blue are not coherent in the YIQ-RGB or HSI-RGB images, the three components will have to be harmonized with the CLAHE algorithm in RGB space. Finally, with 4 direction Sobel edge detector in the bounded general logarithm ratio operation, a self-adaptive weight selection nonlinear image enhancement is carried out to fuse YIQ-RGB and HSI-RGB images together to achieve the final fused image. The enhancement fusion algorithm has two key factors: average of Sobel edge detector and fusion coefficient, and these two factors determine the effects of enhancement fusion algorithm. A series of evaluate metrics such as mean, contrast, entropy, colorfulness metric (CM), mean square error (MSE) and peak signal to noise ratio (PSNR) are used to assess the proposed enhancement algorithm. The experiments results showed that the proposed algorithm provides more detail enhancement and higher values of colorfulness restoration as compared to other existing image enhancement algorithms. The proposed algorithm can suppress effectively noise interference, improve the image quality for underwater image availably.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

On Feb. 6^th, 2020, FDA implemented the enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products’ attraction to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and re-established attractions. Both the sales of e-cigarettes and posts on social media suggested that the manufacturers’ strategies are likely “successful”. The re-established attraction causes not only a public health issue, but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes that are likely added in tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco free nicotine, and these other flavors are associated with higher clinical symptoms not often induced by only natural traditional tobacco flavors. The additional health risks posed by the flavorants are pronounced even without considering the interactions of toxicology of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for regulation of these emerging products.

Optimal conditions for maximum efficacy of photoinitiated polymerization are theoretically presented. Analytic formulas are shown for the crosslink time, crosslink depth and efficacy function. The roles of photoinitiator (PI) concentration, diffusion depth and light intensity on the polymerization spatial and temporal profiles, for both uniform and non-uniform cases, are presented. For optimal efficacy, a strategy via controlled PI concentration is proposed, where re-supply of PI in high light intensity may achieve a combined-efficacy similar to low light intensity, but has a much faster procedure. A new criterion of efficacy based on the polymerization (crosslink) [strength] and [depth] is introduced. Experimental data are analyzed for the role of PI concentration and light intensity on the gelation time and efficacy.

Traditional phase change composites usually suffer poor mechanical property and easy collapsing in the phase changing process. Herein, a highly flexible phase change composite is fabricated using thermoplastic elastomer as the basic gel and the expanded graphite/paraffin as the filler. This new phase change composite shows a tensile strength of 2.1 MPa and a breaking elongation of 220%. It has a melting enthalpy of 145.4 J•g^-1 and a thermal conductivity of 2.2 W•m^-1•K^-1 with 70% of expanded graphite/paraffin. The thermoplastic elastomer based phase change composite exhibits great reversible property after 200 heating/cooling cycles. This flexible phase change composite demonstrates good photo-thermal energy charging/discharging property and shows great potential to be applied in the solar thermal energy systems.

The kinetics and efficacy profiles of photoinitiated polymerization are theoretically presented. For the same dose, lower light intensity achieves a higher steady-state-efficacy (SSE) in type-I; in contrast, type-II has an equal SSE. Higher light intensity has a faster rising efficacy, due to faster depletion of photoinitiator (PS) concentration. However, type-II process is also affected by the available oxygen. Higher light intensity produces more efficient singlet oxygen, resulting a higher transient efficacy, in which all intensities reach the same SSE when oxygen is completely depleted. With external oxygen, type-II efficacy increases with time, otherwise, it is governed only by the light dose, i.e., same dose achieves same efficacy. Moreover, type-II has an efficacy follows Bunsen Roscoe law (BRL), whereas type-I follows non-BRL. The measured type-I efficacy and gelation profile are analyzed by our analytic formulas. Schematics of the photocrosslinking stage defined by the availability of oxygen is developed, where both type-I and –II coexist until the oxygen is depleted. The overall efficacy may be enhanced by resupply of PS or oxygen during the light exposure. The roles of light dose and PS concentration on the efficacy of photoinitiated polymerization should be are governed a new concept of a volume efficacy (Ve), defined by the product of the crosslink (or gelation) depth (CD) and local [efficacy].

Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin^TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner, across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or pre-mature release of viral genomes as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than smoking. The intestinal absorption of Cd involves the transporters for iron, zinc, copper, and calcium. These metal transporters essentially determine the body burden of Cd because only 0.001-0.005% of Cd accumulated in the body can be excreted in urine each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen. Current evidence, however, suggests that environmental Cd may increase the prevalence of many types of cancer, notably lung, liver, breast, pancreas, and kidney. A two-year bioassay that mimics a lifelong exposure demonstrates Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cell lines underwent malignant cell transformation, when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it can profoundly affect gene expression through its interactions with various proteins, and Cd can thus be viewed as a transcription modulator. The present review highlights epidemiological studies that connected an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is on the impact of body iron stores on the absorption rate of Cd, and its implications for breast cancer prevention in highly susceptible subpopulation groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer-cell transformation, under in vitro conditions, are briefly discussed. The potential role for ZnT1 efflux transporter in cellular acquisition of tolerance to Cd cytotoxicity are highlighted.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

Solvents are widely-used in all aspects of chemical sciences. One of the disadvantages of conventional solvents is attributed to the adverse impacts they pose on human health and ecological systems. Emerging class of solvents such as ionic liquids have been proposed to alleviate this problem. In this study, aquatic toxicity and biodegradability of two common industrial solvents are compared to those of two ionic liquids. Results from this study highlight the importance of solvent selection considering the information on the toxicity, biodegradability and fate and transport properties of selected solvents altogether.

Since a large amount of sewage sludge (WSS) has been generated daily, it is necessary to explore effective methods for utilizing WSS. Although a photo-fermentation system sometimes alters the characteristics of microbial functions, there are no attempts to perform the photo-fermentation using WSS which is regularly treated under a dark-fermentation style. In this study, the effect of photo-fermentation (photo-irradiation) on anaerobic digestion using WSS was revealed. Photo-irradiation during the anaerobic digestion of WSS significantly reduced the amount of organic acids and hydrogen sulfide and methane production was also suppressed. However, it was shown that the activity of sulfate-reducing bacteria in WSS under the light treatment increased. Photo-irradiation also stimulated the growth of green-sulfur bacteria and induced anoxygenic photosynthesis, by which the fermented samples turned green linking with the consumption of hydrogen sulfide. Finally, a dark/light switching fermentation was able to reduce only hydrogen sulfide while methane production remained the same.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

The manuscript presents the comprehensive integrative theory of the etiology and pathogenesis of Alzheimer’s disease - the amyloid degradation toxicity hypothesis - and describes the logic that underlies it.The analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies suggest that AD diagnosis is associated with higher cellular uptake of beta-amyloid. Uptake of beta-amyloid by cells is needed for its cytotoxicity, so the uptake rate should correlate with the rate of neurodegeneration. Also, the initial step in forming extracellular aggregates cannot occur in the interstitial fluid due to the extremely low concentration of beta-amyloid but can occur intralysosomally. Therefore, the density of extracellular aggregates should positively correlate with the rate of cellular amyloid uptake. The model, which considers that both cytotoxicity and aggregation of beta-amyloid are defined by cellular uptake, successfully reproduces the probability distribution of AD diagnosis in the population. Cellular uptake of beta-amyloid is mediated by endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage. Lysosomal permeabilization explains ion disturbances, such as an accumulation of intracellular calcium, caused by cell exposure to extracellular beta-amyloid. Some amyloid fragments, produced from beta-amyloid by lysosomal proteases, can form membrane channels in lysosomal membranes, which are large enough to leak cathepsins to the cytoplasm. Appearance of proteases in the cytoplasm results in necrosis and/or initiation of apoptosis. If the cell survives, the damage of lysosomes leads to autophagy failure and slow recycling of mitochondria, promoting the production of reactive oxygen species and potentiating cell damage.Considering the above, the integrative theory of AD etiology and pathogenesis can be formulated. The etiology of AD is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization by giant membrane channels, which leak lysosomal proteases into the cytoplasm. The correlation between the density of amyloid aggregates and the probability of AD appears because the intensity of cellular uptake defines both aggregation rates in vivo and cytotoxicity of beta-amyloid.The amyloid degradation toxicity hypothesis is the integrative theory of Alzheimer’s disease (AD). It successfully interprets multiple phenomena and paradoxes associated with AD pathobiology at various levels, from molecular and cellular to biomarkers. The hypothesis explains the limitations of currently used biomarkers of AD and proposes etiology-related parameters. These parameters could be measured in humans and become novel diagnostic and prognostic clinical tools. Based on the proposed framework, we foresee the development of effective medications to treat, stall the progression of, or prevent disease development.

The widespread use of the herbicide glyphosate has resulted in the global presence of its degra-dation product, aminomethylphosphonic acid (AMPA), in the global environment. AMPA is commonly found in water bodies, including freshwater systems. We investigated the effects of chronic and acute AMPA exposure on the survivorship, regenerative abilities, and locomotion of the brown planarian (Girardia tigrina), a water-dwelling flatworm commonly found in freshwa-ter ecosystems. We exposed planarians to two concentrations of AMPA, consistent with the high and low ranges of concentrations observed in US water systems. We measured endpoints includ-ing survivorship, regenerative abilities of head and tail segments, eyespot regeneration, and swimming speed. Compared to the control group, we found that planarians chronically exposed to AMPA exhibited (1) modestly reduced survivorship while regenerating and (2) slower regen-eration from the tail segment. No significant differences were observed in intact body growth during chronic exposure. Our findings highlight the potential ecological impacts of AMPA con-tamination on planarian populations. Understanding the effects of AMPA exposure on planarians contributes to our understanding of the ecological consequences of glyphosate use in freshwater ecosystems.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

Following the occurrence of a typhoon, quick damage assessment related to residents can facilitate quick dispatch of house repair and disaster insurance works. Employing a deep learning method, this study used aerial photos of the Chiba prefecture obtained following the Typhoon Faxai in 2019 to automatically detect and evaluate the roof damage. This study comprised three parts: training deep learning model, detecting the roof damage using trained model, and classifying the level of roof damage. The detection object comprised roof outline, blue tarps, and roof completely destroyed. The roofs were divided into three categories: roof without damage, roof with blue tarps and roof completely destroyed. the F value obtained using the proposed method was higher than those obtained using other methods. In addition, it can be further divided into 5 levels from level 0 to 4. Finally, the spatial distribution of the roof damage was analyzed using ArcGIS tools. The proposed method is expected to provide certain reference for the real-time detection of the roof damage after the occurrence of a typhoon.

As a photo-catalytic titanium oxide film deposition process, thermal spray is hoped to be utilized practically on the condition that it is relatively easy to deposit anatase rich films. However, because of its high equipment and feedstock powder costs, it is very difficult to introduce thermal spray equipment into small companies. In this study, to develop a low cost thermal spray system, low power atmospheric suspension plasma spray equipment with titanium hydroxide suspension created by hydrolysis of titanium tetra iso butoxide using Ar, N2 as working gases. For avoiding sedimentation of the hydroxide particles in the suspension, mechanical milling of the suspension was conducted to create colloidal suspension before using it as feedstock. Moreover, an Ultrasonic wave container was used to keep the suspension particles moving while the spray process was conducted. After the film deposition, with As for the coating, anatase rich TiO2 film could be obtained. For characterization of the film, microstructure observation by optical microscope and X-ray diffraction was carried out. Consequently, by creation of colloidal suspension, deposition could be conducted without sedimentation of the hydroxide particle in the suspension during operation. Besides, it was proved the film had enough photo-catalytic property to decolor methylene-blue droplet

Use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated to exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally lower. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the tran-scriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP.

A significant amount of data is available for bench-scale fire assessments. However, there is little surrounding large-scale tests and even less so for bench-to-large scale comparisons. Large-scale tests require more material, time and preparation, making them more expensive than bench-scale assessments. However, large-scale testing is an essential component to bench-scale fire testing. The bench-scale tests must be representative of both large-scale and real fire behaviour to provide an insight into how a material or product will behave in the event of a fire during its end use application. The few existing studies reviewed in this study show more guidance and data is needed, especially on a large-scale. Unfortunately, the data that is presented is done so in an inconsistent manner using various means of presentation, statistical analysis, and modelling that doesn’t show clear comparisons between bench and large scale. Currently, no bench-scale method shows good agreement with large-scale fire behaviour. Overall, there is a need for more large-scale testing and data for direct comparisons to be made.

This article aims to provide a comprehensive understanding of vaping from various perspectives that contributes to the origin, development, achievement, and consequences of the greed of e-cigarette manufacturers. In our analysis, multiple elements of the social landscape, including economic, cultural, moral, psychological, and philosophical dimensions, contributed to the origin and development of the vaping greed and shaped people’s behaviors. Further discussion was made on how the specific characteristics of e-cigarette products and the marketing strategies of the companies, especially social media marketing, fostered the growth of such greed. Through interviews, we have also discussed the unfolding of this greed within the community of teenage vapers. The growth of the vaping greed was manifested in the large market share taken by the companies, but these all significantly harm people’s health and the communities. Nicotine and other chemicals in e-liquids promote each other’s negative effects in the mechanism leading to pulmonary symptoms and addiction, which are not limited to the physical level. We described that addiction could be transgenerational and can induce trauma both at an individual level and a community level. Overall, the greed of the vaping industry is a very complex system. The treatment of the greed shall be complicated as well: Besides the public health measures taken to treat the symptoms of the greed, we should educate individuals to be aware of their unfulfilled needs to regain authenticity and establish an infallible authority to enforce universal morality, which eradicates the complications of addiction and the root of the capitalists’ greed, respectively.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

Increasing environmental distress is associated with a growing asthma incidence and, with no treatments available, montelukast (MTK) – an antagonist of the cysteinyl leukotrienes receptor 1 – is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions. Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as modulator of leukotriene pathways and systematize the knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Silicon nanoparticles (SiNPs) are highly promising for biological and biomedical applications, including bioimaging, due to their unique opltical properties (i.e. strong fluorescence and very high photostability). Their low or negligible in vitro toxicity has been reported, but in vivo toxicity and biological effects of SiNPs are still uncertain. Uncoated SiNPs were dispersed in distilled water via sonication, and their rapid aggregation was observed (319.0 ± 2.4 nm particle size). In vivo toxicity was studied using Danio rerio embryos and larvae. Rapid aggregation in their incubation medium was observed; besides that, SiNPs at 25 mg/L or higher concentration induced swim bladder malformation and/or death of the fish. The estimated LC50 value for 7-day larvae was 180 mg/L. This is the first in vivo toxicity study of uncoated and unfunctionalized SiNPs. To achieve better stability in biological media and lower toxicity, SiNPs should be covered with hydrophilic layers, but their absorption by cellular membranes may be weaker in this case.

The Ce0.5Y0.35Tb0.15F3 nanoparticles with CeF3 hexagonal structure were synthesized by co-precipitation technique. The average nanoparticle diameter was 14±1 nm. The luminescence decay curves of Ce0.5Y0.35Tb0.15F3 nanoparticles (λem = 541 nm, 5D4 – 7F5 transition of Tb3+) conjugated with Radachlorin by means of polyvinylpyrrolidone coating as well as without Radachlorin were detected. Efficient nonradiative energy transfer from Tb3+ to the Radachlorin was demonstrated. The maximum energy transfer coefficient for nanoparticles conjugated with Radachlorin via polyvinylpyrrolidone and without the coating were 82% and 55%, respectively. The average distance between nanoparticle surface and Radachlorin was R0 =4.5 nm. The best results for X-ray induced cytotoxicity was observed for NP-PVP-Rch sample at the lowest Rch concentration. In particular, after X-ray irradiation the survival A 549 human lung carcinoma cells decreased by ~12%.

In a world where conventional sources of energy are fast depleting, the quest for alternative energy sources may hold the key for the survival of humanity. In the present work, emphasis has been given to the idea of producing energy from perovskite based solar cells. In order to bring this idea into fruition, a unique and novel nano structured perovskite material n-propyl ammonium lead chloride (C₃H₇NH₃⁺PbCl₃⁻) was prepared through a unique co-precipitation route using n-propyl amine (n-C₃H₇NH₂) and hydrochloric acid as the starting precursors with aqueous solution of Pb(CH₃COO)₂3H₂O. Finally acetic acid was added to the solution and this solution was allowed to concentrate and then gradually cooled down to room temperature. After math, the synthesized material was spin-coated on TiO₂ film to fabricate the solar cell. The device was then undergone systematic analysis using XRD, SEM, UV and Photo Conversion to get a transparent idea regarding its structural, electrical and optical properties. When experimentally applied, this perovskite-based solar cell has shown energy conversion efficiency (η) of around 6.01 % which is noticeably good. Thus it can be concluded that this material is promising for fabrication of vastly efficient solar cells. This technology can be tried in large scale as an alternative of conventional energy in the near future.

Despite great strides in diagnosis and treatment, cardiac diseases remain the number one cause of mortality in the developed world, with rates catching up at an alarming rate in the developing world. Targeted delivery of therapeutics, specifically to cardiomyocytes, would open up new frontiers. Our prior work using a combinatorial in vitro and in vivo phage display methodology identified a 12-amino acid long peptide that targets cardiomyocytes selectively after an intravenous injection in as little as 5 mins, and hence was termed cardiac targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension for development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed on the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10µM of Cyanine-5.5 labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by more extensive studies performed by Eurofins in stably transfected cell lines for an extensive list of GPCR-coupled receptors. Positive data for GPCR-coupled receptors was interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting 60, 6-week-old, wild-type CD1, male/female mice (1:1) injected with CTP (150 µg/Kg) intravenously. Mice were weighed immediately before injections and daily thereafter. Cohorts of mice were euthanized on day 0, 1, 2, 7 and 14 with inhalational CO2, followed by opening of the chest cavity, collection of blood via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after injections of CTP (150 µg/Kg) to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. In the Eurofins Cardiac Profiler Qube, no significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed by RT-qPCR. There was no change in blood pressures before and after injections with CTP at 10 mg/Kg. Blood counts and chemistries showed no evidence of significant hematological, hepatic or renal toxicities. Lastly, there was no significant difference in cardiac function, size or mass before and after CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies, in good laboratory practices fashion, are needed with more prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of &lt;1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Mercury toxicity significantly threatens aquatic ecosystems, particularly impacting fish populations and human well-being. This article exposes the effects of mercury contamination on aquatic life and their habitats. Mercury primarily originates from natural degassing and anthropogenic activities and accumulates in aquatic organisms, most notably in predatory fish, through bio-accumulation and bio-magnification. This bio-accumulation, driven by microbial transformation to methyl-mercury, leads to elevated concentrations in top-level predators. The consequences of mercury exposure on fish physiology are stunted growth, reproductive impairments, and compromised immunity, with potential ramifications for population dynamics and ecosystem resilience. This study delves into specific impacts of mercury on fish, ranging from bone deformities to liver damage, developmental anomalies, neurotoxic effects, and disruptions in reproductive systems. The interplay between ecological, physiological, and human health effects underscores the need for a comprehensive understanding of mercury's underlying mechanisms. Monitoring mercury levels in aquatic systems emerges as a crucial strategy for ensuring fish populations' health and ecosystems' sustainability. Urgent collaborative efforts are imperative to address this global concern, promote harmonious coexistence between human activities and aquatic environments, and secure the availability of safe and nutritious fish for future generations. In conclusion, this article highlights the urgent necessity for targeted interventions and informed decision-making to mitigate the influence of mercury contamination on aquatic ecosystems.

Glitter particles are considered a model of microplastics, which are used in a wide range of products. In this study, we evaluated the toxicity of green and white glitter dispersions on the embryonic development of the sea urchins Echinometra lucunte, Arbacia lixula, and the mussel Perna perna. The Toxicity Identification and Evaluation (TIE) approach was used to identify possible chemicals related to toxicity. Glitter dispersions were prepared using 0.05% ethanol. The tested dispersions ranged from 50 to 500 mg/L. The white glitter was composed of a vinyl chloride-methyl acrylate copolymer. The effective concentrations of green glitter to 50% embryos (EC50) were 246.1 (235.8 – 256.4) mg/L to A. lixula, 23.0 (20.2 - 25.8) mg/L to P. perna and 105.9 (61.2 - 150.2) mg/L, whereas the EC50 of white glitter to E. lucunter was 272.2 (261.5 – 282.9) mg/L. The EC50 for P. perna could not be calculated; however, the lowest effect concentration was 10 mg/L. The filtered suspension of green glitter had Ag levels exceeding the legal standards for marine waters. TIE showed that metals, volatiles, and oxidant compounds contribute to toxicity. The results showed that glitter may adversely affect marine organisms; however further studies are necessary to determine its environmental risks.

The cork oak (Quercus suber L.), endemic essence of the Mediterranean Basin, is commonly used in traditional pharmacopoeia. The main objective of this work is to enhance the valorization of this plant species through the study of the anticandidosic activity of cork oak bark methalonic extracts in order to develop an efficient natural formulation for Candidiasis treatment.The anticandidosic activity of methanolic extracts of Q. suber bark stemming from decoction, maceration and Soxhlet methods of extraction in was tested on five different Candida albicans strains. Our results showed that all the tested extracts displayed an inhibitive activity, which varies according to the obtained extract and the tested strain. The best anticandidosic potential was observed with extracts obtained with Soxhlet method. The study of the acute toxicity showed that the lethal dose is 1150 mg/kg in mice, which remained moderately toxic according to Hodge and Sterner classification scale. Thus, this extract can be used in phytotherapy without danger in doses that are below 300 mg/kg of corporal weight. Based on these results, we can conclude that Cork oak bark extracts can be used to treat Candida albicans infections.

Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people around the world. Neuronal death in AD is initiated by the toxic action of oligomeric amyloid-β (Aβ) peptides. The formation of membrane channels by Aβ is a primary molecular action and does not require any other proteins. Channels are formed by short amyloid fragments faster and more frequently than by full-length peptides. The channel formation is dependent on an electrostatic interaction between a positively charged peptide and a negatively charged membrane. Negative membranes can be found in several locations of a cell – the inner leaflet of plasma membrane, mitochondria, and lysosomes, which all are well-known cellular targets in AD. Considering that the amyloid enters a cell by endocytosis and is exposed to lysosomal enzymes, we propose the amyloid degradation toxicity hypothesis. Endopeptidases degrade the endocytosed peptide. Produced fragments form membrane channels, which can transfer various ions (including protons) and even relatively large compounds. The neutralization of lysosomal content inactivates enzymes, which fails the whole system of recycling cellular content, including autophagy. The permeabilization of lysosomes could also lead to cell death through necrotic and apoptotic mechanisms. We discuss several mechanisms that describe how amyloid degradation products reach plasma and mitochondrial membranes, and form membrane channels. The pathogenesis of AD is discussed at various levels in a context of how the primary molecular mechanism of membrane channel formation could progress into the disease state. The discussion starts at the molecular level and extends to why the development of a disease takes years and is closely associated with aging. The proposed hypothesis offers an interpretation to several clinical observations such as the involvement of iron metabolism and an inverse association between developing Alzheimer's disease and cancer. Predictions about potential biomarkers and effectiveness of future treatments are discussed.

Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

Terpenoids, including monoterpenoids (C₁₀), norisoprenoids (C₁₃) and sesquiterpenoids (C₁₅), constitute a large group of plant-derived naturally occurring secondary metabolites which chemical structure is highly diverse. A quantitative structure-activity relationship (QSAR) model to predict the terpenoids toxicity and to evaluate the influences of their chemical structure, was developed in this study, by assessing the toxicity of 27 terpenoid standards using Gram-negative bioluminescent Vibrio fischeri, in real time. Under the test conditions, at concentration of 1 µM, the terpenoids showed a toxicity level lower than five %, with exception of geraniol, citral, (S)-citronellal, geranic acid, (±)-α-terpinyl acetate and geranyl acetone. Moreover, the standards tested displayed a toxicity level higher than 30 % at concentration of 50 to 100 µM, with the exception of (+)-valencene, eucalyptol, (+)-borneol, guaiazulene, β-caryophellene and linalool oxide. Regarding the functional group, the terpenoids toxicity was observed in the following order: alcohol > aldehyde ~ ketone > ester > hydrocarbons. CODESSA software was employed to develop the QSAR models based on the correlation of terpenoids toxicity and a pool of descriptors related to each chemical structure. The QSAR models, based on t-test values, showed that terpenoids toxicity was mainly attributed to geometric (e.g., asphericity) and electronic (e.g., max partial charge for a C atom [Zefirov's PC]) descriptors. Statistically, the most significant overall correlation was the four-parameter equation with training and test coefficient correlation higher than 0.810 and 0.535, respectively, and square coefficient of cross-validation (Q²) higher than 0.689. According to the obtained data, the QSAR models are a suitable and a rapid tool to predict the terpenoids toxicity in a diversity of food products.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

This article presents, for the first time, the efficacy and curing depth analysis of photo-thermal dual polymerization in metal (Fe) polymer composites for 3D printing of a 3-component (A/B/M) system based on the proposed mechanism of our group, in which the co initiators A and B are Irgacure-369, and charge-transfer complexes (CTC), respectively; and the monomer M is filled by Fe. Our formulas show the depth of curing (Zc) is an increasing function of the light intensity, but a decreasing function of the Fe and photoinitiator concentrations. Zc is enhanced by the additive [B] which produces extra thermal radical for polymerization under high temperature. The heat (or temperature) increase in the system has two components : (i) due to the light absorption of Fe filler, and (ii) heat released from the exothermic photopolymerization of the monomer. The heat is transported to the additive (or co-initiator) [B] to produce extra radical R' and enhance the monomer conversion function (CF). The Fe filler leads to temperature increase, but also limits the light penetration leading to lower CF and Zc, which could be overcome by the additive initiator [B] in thick polymers. Optimal Fe for maximal CF and Zc are explored theoretically.

The low relative humidity (RH) levels in a greenhouse during the daytime in a strawberry (Fragaria × ananassa Duch) cultivation period negatively affect the growth of strawberry related to photo-physiology. Therefore, this study was conducted to confirm an efficient RH management method by analyzing the phenotypic characteristics related to photo-physiology by controlling the RH in a greenhouse during the daytime with a fog system. Strawberry plants were grown respectively in a greenhouse affected by natural RH changes (control) and in a greenhouse with 40% ~ 50% RH adjusted during the daytime using a fog system. In the greenhouse, with controlled RH, the temperature decreased, and the RH was higher in the initial growth stage of strawberry planting than the control. It was observed a significant increase in the survival rate of the strawberry plant, as well as the incidence of powdery mildew, was lowered. In addition, the photosynthetic rate and OJIP chlorophyll a fluorescence transients related to photosystem II efficiency of strawberry leaves were significantly higher in the fog treatment than in the control. In winter, during the day, the number of days on which the temperature dropped below 20℃ has increased, the greenhouse temperature with controlled RH was lower due to the fog system. When the yield per strawberry plant in January and February was investigated, the control was higher than the RH treatment. Therefore, RH management using a fog system must be controlled at a level where a temperature range is adequate for plant growth, in which the efficient control of these parameters increases strawberry productivity.

A Invasive emerging pollutants from wastewater effluent discharge, such as dyes, pesticides, etc., pose a serious threat to the ecosystem. Advanced oxidation processes (AOPs) under visible light irradiation have emerged as a promising technology to overcome toxic and recalcitrant organic compounds. In this work, the impact of operational factors, including the concentration of Fe3+ or Fe2+, [H2O2], the molar ratio (Oxalate/ Fe3+ or Fe2+), and the initial pH, was studied to obtain high efficiency in the degradation and mineralization of such a food dye to reduce their pollution. The study deals with the comparison of the efficiency of UV, LED, and sunlight irradiation on the photocatalytic degradation of the dye using Fe3+/Lig and Fe2+/Lig complexes. The results showed that sunlight irradiation gave a very rapid kinetic and higher degradation efficiency of over 70%. The optimized conditions for the maximum elimination of the dye with a photocatalytic degradation efficiency (98%) and a mineralization rate of 96% were obtained with the Fe3+/Lig complex, based on the Box Benhken surface design analysis. In the presence of H2O2, the degradation reached an equilibrium stage after 15 min (97.57%) for the Fe(III)/Lig system. Moreover, the inhibition effect of inorganic ions on the photo-Fenton performance of Fe3+/Lig and Fe2+/Lig was studied. The study suggests that the use of nanocrystals of hematite as a Fenton reagent for treating textile effluents needs further investigation. The results showed that the proposed models were well-suited to batch treatment under sunlight. This study not only proposes a Fe3+/Lig and Fe2+/Lig system for the elimination of a food dye without adjusting the pH of the medium, but it also provides insight into the best source of light irradiation for the photocatalytic degradation process.

Herein we foremost detailed the numerical modeling of the double absorber layer- methyl ammonium lead iodide– carbon nitride layer solar cell and subsequently provided in-depth insight on the active layer associated with dominant radiative and non-radiative recombination losses limiting the efficiency ( ) of the solar cell. Under recombination kinetics phenomena, we explored the influence of Radiative recombination, Auger recombination, Shockley Read Hall recombination, the energy distribution of defects; Band Tail recombination (Hoping Model), Gaussian distribution, metastable defect states including single donor (0/+), single acceptor (-/0), Double Donor (0/+/2+), double acceptor (2/-/0-), and the interface layer defects on the output characteristics of the solar cell. Setting defect (or trap) density to with uniform energy distribution of defects for all the layers, we achieved the of 24. 16 %. A considerable enhancement in power conversion efficiency was perceived as we reduced the trap density to for the absorber layers. Further, it was observed that for the absorber layer with double donor defect states, the active layer should be carefully synthesized to reduce crystal order defects to keep the total defect density as low as to achieve efficient device characteristics

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second-largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter in monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

Abstract This study focuses on the toxicity assessment of various flavonoids, with particular emphasis on Hesperidin. Among the investigated compounds, Hesperidin exhibits notable potential and low toxicity in both short and long-term evaluations. The toxicity parameters for Hesperidin include a low Max. Tolerated Dose (Human) (0.525 log mg/kg/day), indicative of its minimal potential harm to humans. Additionally, its Oral Rat Acute Toxicity (LD50) (2.506 mol/kg) suggests a relatively low acute toxicity level. The Oral Rat Chronic Toxicity (LOAEL) (3.167 log mg/kg_bw/day) signifies a higher dose threshold for observing adverse effects over the long term. Furthermore, Hesperidin demonstrates low Minnow Toxicity (7.131 log mM), suggesting minimal impact on aquatic organisms. Overall, this comprehensive assessment positions Hesperidin as a promising flavonoid with favorable properties and minimal toxicity.

Biosensors based on an oxygen electrode, a mediator electrode and a mediator microbial biofuel cell (MFC) using on the bacteria Gluconobacter oxydans B-1280 have been formed and tested to determine the integral toxicity. G. oxydans bacteria exhibit high sensitivity to the toxic effects of phenol, 2,4-dinitrophenol, salicylic and trichloroacetic acid and a number of heavy metal ions. The system “G. oxydans bacteria – ferrocene – graphite-paste electrode” is superior in sensitivity to biosensors formed using an oxygen electrode and MFC, in particular regarding heavy metal ions (EC50 of chromium (II), manganese (II) and cadmium (II) was 0.8 mg/dm3, 0.3 mg/dm3 and 1.6 mg/dm3, respectively). It has been determined that the period of stable functioning of electrochemical systems during measurements is reduced by half due (from 30 to 15 days) due to changes in the enzyme system of microbial cells when exposed to toxicants. Samples of products made from polymeric materials were analyzed using developed biosensor systems and standard biotesting methods based on inhibiting the growth of duckweed L. minor, reducing the motility of bull sperm and quenching the luminescence of the commercial test system "Ecolum". The developed bioelectrocatalytic systems are comparable in sensitivity to commercial biosensors, which made it possible to correlate the results and identify by all methods a highly toxic sample containing diphenylmethane-4,4'-diisocyanate according to GC-MS data.

Brassicaceae are well known as non-arbuscular mycorrhizal (AM) host plants. This study was aimed to examine effects of two Brassica; cabbage (Brassica oleracea L. cv. cabitata) and mustard (B. juncea Coss.) on three AM species (Acaulospora, Entrophospora and Glomus) and to examine effect of root incorporation into soil on root AM infectivity in maize growing in iron toxicity soil. Experiment 1, cabbage and mustard crop reduced spore density of Acaulospora, but there was no effect on spore density of Entrophospora. While, mustard crop had more effect on Glomus spore density than cabbage crop. Experiment 2, AM spore from two conditions; without and with 6 weeks of root residues (cabbage, mustard and maize) incorporation was examined for its infectivity in maize roots. At D21, without root incorporated, the infectivity of Acaulospora, Entrophospora and Glomus were not different. By contrast, cabbage and mustard root incorporation depressed infec-tivity of Acaulospora but, there was no effect on Entrophospora. Whereas, cabbage root incorporation only depressed infectivity of Glomus. However, AM infectivity was recovered at D42. These results suggested that Brassica root incorporated into soil was the actual effect on the viability of AM spore resulting in reduction of AM infectivity at the early stage.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

Alginate extraction is from seaweed, and lignin separation is from by-product corn (stalks and leaves). Alginate/lignin is a synthetic polymer rich in biological activity of great interest. Antioxidant activities of alginate/lignin were evaluated, such as total antioxidant activity, reducing power activity, DPPH free radical scavenging activity, and α – glucosidase inhibition activity. The test of anticancer activity was on four cell lines (Hep G2, fibroblast, MCF-7, and NCI H460). Determination of physical-chemistry characteristics of alginate/lignin was through FTIR, DSC, SEM_EDS, SEM_EDS mapping, XRD, XRF, and 1H-NMR. A study of acute toxicity of alginate/lignin was on Swiss albino mice. The results showed alginate/lignin possessed antioxidant activity such as total antioxidant activity, reducing power activity, especially, α – glucosidase inhibition activity, and no free radical scavenging activity. Alginate/lignin did not be typical in cancer cell lines. Alginate/lignin existed in a thermally stable regular spherical shape in the investigated thermal region. Some specific functional groups of alginate and lignin did not exist in alginate/lignin crystal. Elements such as C, O, Na, and S were popular in the alginate/lignin structure. LD0 and LD100 of alginate/lignin in mice were 3.91 g/kg and 9.77 g/kg, respectively. Alginate/lignin is the potential for application as pharmaceutical materials, functional foods, and supporting diabetes treatment.

This work is related to the environmental toxicology risk assessment and evaluation of possible transformation of carbon-based nanomaterials (CNMs) after the contact with marine microalgae. The materials used in the study represent common and widely applied multiwalled carbon nanotubes (CNTs), fullerene (C60), graphene (Gr), and graphene oxide (GrO). The toxicity was evaluated as growth rate inhibition, esterase activity, membrane potential, and reactive oxygen species generation changes. The measurement was performed with flow cytometry after 3, 24, 96 h, and 7 days. Biotransformation of nanomaterials were evaluated after 7 days of microalgae cultivation with CNMs by FTIR and Raman spectroscopy. The calculated toxic level (EC50 in mg/L, 96 h) of ued CNMs reduced in the following order: CNTs (18.98) &gt; GrO (76.77) &gt; Gr (159.40) &gt; C60 (414.0). Oxidative stress and membrane depolarization was the main toxic action of CNTs and GrO. At the same time, Gr and C60 decreased the toxic action with time and had no negative impact on microalgae even at concentration of 125 mg/L. Moreover, C60 and Gr after seven days of the contact with microalgae cells obtained structural deformations.

Introduction: Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These smokeless tobacco products are being marketed for usage all over as Snus containing tobacco-derived nicotine (Natural) or as tobacco-free nicotine (Synthetic) as substitutes for other tobacco products that are limited in public places. ONPs have become popular tobacco products among adolescents/young adults and over 50% of young adult users of ONP use flavored ONP, such as menthol/mint, tobacco, dessert/candy, and fruity, being the most popular flavors. Various new ONP flavors are currently popular locally as well in the online market. Tobacco, Menthol, and fruit-flavored ONPs could motivate cigarette smokers to alteration to ONPs. Methods: We expanded our knowledge on natural/synthetic ONP flavors wheels to available data on ONPs, describing in detail their flavors and brands (US and Europe) in both natural/Synthetic ONP categories. We classified over 152 snus and 228 synthetic ONPs into the following flavor categories: “Tobacco”, “Menthol/Mint”, “Fruity”, “Candy/Deserts”, “Drink”, “Aroma”, “Spices” and “Mixed Flavors”. Results: Based on total numbers, wefound that the most popular ONPs flavor sold as tobacco and menthol to be among natural ONPs, among synthetic ONPs fruity and menthol as the most prominent flavors with varying concentrations of nicotine and other flavoring chemicals including coolant WS-23. We also illustrated possible molecular targets and toxicities due to exposure to ONPs activating several signaling cascades like AKT and NF-B might possibly lead to apoptosis and epithelial mesenchymal transition (EMT). Conclusions: Considering the marketing of ONP products with various flavor profiles and most of these products containing tobacco/menthol/fruit flavor, it is likely to have regulation and marketing disclaimer on some of these products. Further, it would be logical to determine how the market reacts in terms of compliance and non-compliance with flavor restrictions by the regulatory agencies.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

Mouse models are frequently used to study Huntington’s disease (HD). Onset and severity of neuronal and behavioral pathologies vary greatly between HD mouse models, which results from different huntingtin expression levels and different CAG repeat length. HD pathology appears to depend also on strain background of mouse models. Thus, behavioral deficits of HD mice are more severe in the FVB than in the C57BL/6 background. Alterations in medium spiny neuron (MSN) morphology and function has been well documented in young YAC128 mice in the FVB background. We here tested the relevance of strain background for mutant huntingtin (mHTT) toxicity on the cellular level by investigating HD pathologies in YAC128 mice in the C57BL/6 background (YAC128/BL6). Morphology, spine density, synapse function and membrane properties were not or only subtly altered in MSNs of 12-month-old YAC128/BL6 mice. Despite the mild cellular phenotype, YAC128/BL6 mice showed deficits in motor performance. More pronounced alterations in MSN function were found in the HdhQ150 mouse model in the C57BL/6 background (HdhQ150/BL6). Consistent with the differences in HD pathology, the number of inclusion bodies was considerably lower in YAC128/BL6 mice than HdhQ150/BL6 mice. This study highlights the relevance of strain background for mHTT toxicity in HD mouse models.

This review article seeks to provide relevant information about the applicability of cell-based assays in assessing cytotoxicity of phytochemicals in light of several traditional methods available. Phenolic compounds and other phytochemicals are significant resources for drug discovery and development, thus underlining the enormous potentials of plant-derived natural products for the prevention and management of oxidative stress associated with cancer and other diseases. These effects have been linked to the content of phytochemicals such as phenolic compounds and their antioxidant properties. The abundance and complexity of these bio-constituents highlight the need for well-defined methods for the in vitro characterization and quantification of extracts and/or preparations that can translate to in vivo effects. Cell culture systems provide a useful model for basic research and a wide range of clinical in vitro studies and physiological processes as well as assessing the toxicity and therapeutic potential of compounds including plant extracts with potential medicinal benefits. Their use in cancer research provide a useful insight into possible therapeutic properties of phytochemicals at the cellular level. This approach has been instrumental in the initial stages of developing chemotherapeutic agents where human cancer cell lines are used as experimental models. These models have continued to contribute to elucidating specific requirements for certain biochemical events associated with proliferation, metabolism, loss of cell viability/apoptosis. Cell culture systems remain a promising tool in natural product development.

Nicotine is a pharmacologically active component of tobacco which adversely affects the male reproductive system and fertility and Icariin (ICA) is the main active ingredient of Epimedium herba which has been used to treat several male reproductive problems. This study was aimed at investigating the protective or ameliorative effect of ICA against reproductive toxicity induced by intraperitoneal injection of nicotine in mice. Forty male mice were randomly divided into 4 groups: control, nicotine (0.75 mg/kg intraperitoneally), icariin (ICA, 75 mg/kg), and icariin plus nicotine (ICA + nicotine) group. After 35 days of treatment, the mice were weighed, sacrificed, and their reproductive organs were collected and examined for further studies. In the nicotine-treated group, epididymal sperm density and serum testosterone concentrations significantly decreased relative to the control group. Nicotine also caused oxidative damage as shown by significant reduction in the activities of antioxidant enzymes and an elevation in Malondialdehyde (MDA) levels. Icariin on the other hand, improved the reduction in sperm characteristics, hormone levels, and activities of antioxidant enzymes alterations observed in the nicotine treated mice. These findings indicate that the nicotine-induced reproductive toxicity and oxidative damages on male reproductive tissues can be effectively attenuated by icariin.

Water pollution is the main problem in the current scenario which is being faced by mankind due to the industrial and commercial effects. Industrial effluents contain heavy metals and inorganic ions like nitrates and phosphate ions. These ions are being included in waterways through industrial runoff. When the concentration of these hazardous pollutants increases in aquatic flora and fauna causes severe health problems. So remediation of these toxicants from water reserves is of chief importance. Conventional processes along with modern processes are being used for the treatment of industrial wastes. Photo-degradation is a modern method used for the degradation of inorganic ions due to its environmentally friendly nature and cost-effectiveness. In a recent study Aluminum oxide (Al2O3) nanoparticles were synthesized via a green approach at different pH by using Cymbopogan citratus (lemongrass) plant extract and these nanoparticles were used for the removal of inorganic ions from wastewater. The nanoparticles of different pH showed different % degradation of the inorganic ions in acidic medium removal of inorganic waste was less, in basic media % degradation was more as compared to acidic media but maximum % degradation was observed in neutral media like that average % degradation 91% and 81% was observed for nitrate and phosphate ions. The maximum absorbance occurred at 212nm and Al2O3 nanoparticles showed absorbance from 210nm-217nm. The R2 values of pseudo1st, 2nd, and BMG models were 0.956, 0.837, 0.7007 0.95, 0.896, and 0.756 for the nitrate and phosphate ions. Characterizations of synthesized particles were investigated by using UV-visible spectroscopy and other analytical methods like X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The statistical analyses were done using Simple Linear regression (SLR).

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

Background. Intravenous iron therapy is used in treatment of anemia in uremic pa-tients. In patients treated with peritoneal dialysis iv. infused iron diffuses into the peritoneal cavity and may cause injury to the mesothelial cell. Methods. We studied effect of Iron Isomaltoside (IIS) in presence of NF-κβ inhibitor dehydroxymethyepoxyquinmicin (DHMEQ) on function of the peritoneal mesothelial cells. Experiments were performed on human peritoneal mesothelial cells in in vitro culture ex-posed to IIS 15 ug/dL ± DHMEQ 1 ug/mL. Intracellular oxidative stress, secretory activity and collagen synthesis in the cells were studied. Results. IIS induced oxidative stress in the mesothelial cells and that effect was weaker in presence of DHMEQ (-52%,p<0.001). In cells exposed to IIS increased expression of genes for IL6 (+74%,p<0.001), PAI-1 (+43%, p<0.01) and TGFβ (+53%,p<0.001) was observed and reduced for tPA (-36%,p<0.01). In presence of IIS increased secretion of IL6 (+56%, p<0.001), TGFβ (+49%,p<0.001) and PAI-1 (+51%, p<0.001) was observed whereas secretion of tPA was reduced (-25%, p0.001). DHMEQ reduced changes in genes and secre-tory activity caused by IIS. In presence of IIS synthesis of collagen in mesothelial cells was increased (+45%,p<0.001) and that effect was weaker (-25% vs. IIS, p<0001) when simulta-neously DHMEQ was used. Discussion. IIS induces proinflammatory changes in mesothelial cells, deteriorates their fibrinolytic activity and stimulates synthesis of collagen. All these effects are reduced when simultaneously NF-κβ inhibitor – DHMEQ is used.

Boron (B) toxicity is an important stress that negatively affects maize yield and quality production. The excessive B content in agricultural lands is a growing problem due to the increase in arid and semi-arid areas because of climate change. Recently, two Peruvian maize landraces, Sama and Pachía, were physiologically characterized based on their tolerance to B toxicity, the former being more tolerant to B excess than Pachía. However, many aspects regarding the molecular mechanisms of these two maize landraces against B toxicity are still unknown. In this study, a leaf proteomic analysis of Sama and Pachía was performed. Out of a total of 2793 proteins identified only 303 proteins were differentially accumulated. Functional analysis indicated that many of these proteins are involved in transcription and translation processes, amino acids metabolism, photosynthesis, carbohydrate metabolism, protein degradation, and protein stabilization and folding. Compared to Sama, Pachía had a higher number of differentially expressed proteins related to protein degradation, and transcription and translation processes under B toxicity conditions, which might reflect the greater protein damage caused by B toxicity in Pachía. Our results suggest that higher tolerance to B toxicity of Sama can be attributed to more stable photosynthesis that would avoid damage caused by stromal over-reduction under this stress condition.

Advanced Hepatocellular carcinoma (HCC) is no longer a terminal illness. This change was mainly attributed to the development of new treatments including tyrosine-kinase inhibitors (TKIs), vascular endothelial growth factor (VEGF) inhibitors and immune checkpoint inhibitors (ICPIs) but the financial toxicity of treating advanced HCC is of a major concern specially in low middle-income countries (LMICs) where the patients are still battling for their most basic rights. Most of advanced HCC patients in LMICs have very limited accessibility to the new treatments including ICPIs. Searching for out of the box solutions to improve access to treatments -mainly ICPIs- is an utmost necessity for LMICs advanced HCC patients.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

Streptococcus suis is a zoonotic pathogen causing serious infections in both swine and humans. Although metals are essential for life, excess amounts of metals they are toxic to bacteria. when accumulated in excess amounts. Except for zinc, Transcriptome-level data of the mechanisms for resistance to metal-induced toxicity in S. suis are available for no metals other than zinc. have not been investigated from the transcriptome level in S. suis. Herein, we explored the transcriptome-level changes of in S. suis in response to ferrous iron and cobalt toxicity by RNA sequencing. Many A lot of genes were differentially expressed in the presence of excess ferrous iron and cobalt. Most of the genes in response to cobalt toxicity showed the same expression trends as those were expressed in the same trend in response to ferrous iron toxicity. qRT-PCR analysis of the selected genes confirmed the accuracy of RNA sequencing results. Bioinformatics analysis of the differentially expressed genes indicated that ferrous iron and cobalt have similar impacts effects on the cellular processes of S. suis. Treatment with ferrous Ferrous iron treatment resulted in down-regulation of several oxidative stress tolerance-related genes involved in oxidative stress tolerance and up-regulation of the genes in an amino acid ABC transporter operon. Expression of the several genes in the arginine deiminase system was down-regulated in the presence of after ferrous iron and cobalt treatment. Collectively, our results suggested that S. suis alters the expression of a lot of multiple genes to respond to ferrous iron and cobalt toxicity.

Biopolymers are of growing interest, but to improve some of their poor properties and performance, it is required the formulation of bio-based blends and/or adding of nanoparticles. For this purpose, in this work, two different metal oxides, such as zinc oxide (ZnO) and titanium dioxide (TiO2), at different concentrations (0.5, 1 and 2 %wt.) have been added in polylactic acid (PLA) and polylactic acid/polyamide 11 (PLA/PA11) blends to establish their effects on solid-state properties, morphology, melt behaviour, and photo-oxidation resistance. It seems that the addition of ZnO in PLA leads to a significant reduction of its rigidity probably due to an inefficient dispersion in the melt state, while the addition of TiO2 does not penalise PLA rigidity. Interestingly, the addition of both ZnO and TiO2 in PLA/PA11 blend has a positive effect on the rigidity because of blend morphology refinement and leads to a slight increase in film hydrophobicity. The photo-oxidation resistance of neat PLA and PLA/PA11 blend is significantly reduced due to the presence of both metal oxides, and this must be considered when designing the potential applications. The last results suggest that both metal oxides could be considered as photo-sensitive degradant agents for biopolymer and biopolymer blends.

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides like glyphosate, malathion, and permethrin have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other nontarget organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of permethrin, malathion, and glyphosate. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid permethrin is the most toxic pesticide tested, followed by organophosphate malathion and glyphosate. Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylamino)(phenyl) phosphonium iodides (bromides) 1 containing one, two, or three diethylamino groups were obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions and high yields. The structure of compounds 1 was established by NMR and XRD. In vitro a high cytotoxicity against the lines M-Hela, HuTu 80, PC3, DU-145, PANC-1 and MCF-7 was found. Selectivity index are in the range of 0.06-4.0 M (SI 17-277) for the most active compounds. ROS production, mitochondrial localization and the process of cellular apoptosis were investigated. Decorated by 1 of lipid systems (liposomes and solid lipid nanoparticles) improve the cytotoxicity and a decrease in toxicity against normal cell lines. Compounds 1 induce apoptosis proceeding along the mitochondrial pathway. Aminophosphonium salts 1 also exhibit a high selective activity against the Gram-positive bacteria strains S. aureus 209P, B. segeus 8035, including methicillin-resistant strains of S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead compounds.

Ants of the genus Solenopsis are important invasive pests in the world. Due to their high dispersion capacity, aggressive behavior and because they feed on various sources of vegetable and animal protein, these insects have caused serious damage to public health and agriculture. The control has usually been carried out through the use of organosynthetic insecticides. However, due to the ecological and environmental impacts caused by the use these products, more sustainable alternatives have been sought for their control. Faced with these problems and due to the scarcity of registered products for the control of these insects, we aimed with this study to synthesize and evaluate the anticidal potential of carvacrol derivatives. The lethal and sublethal effects caused by these derivatives were compared with the essential oil of Lippia gracilis (50.7% carvacrol) and with the base molecule — carvacrol. Carvacryl benzoate was the most toxic derivative to Solenopsis sp. with an LD50 of 3.20 g/ mg. This compound was about 2 and 7.6 times, more toxic than carvacrol at the doses needed to kill 50 and 90% of populations, respectively. The workers of Solenopsis sp. showed a rapid reduction in survival when exposed to carvacrol (LT50 = 8.43h) and carvacryl benzoate (LT50 = 8.87h). Insects treated with sublethal doses of the compounds did not show significant effects on self-cleaning, allogrooming and aggregation, with the exception of those treated with L. gracilis essential oil. The oil increased self-cleaning and reduced allogrooming and aggregation. Ants treated with carvacrol and carvacryl benzoate showed greater distance and speed when compared to the control. These compounds decreased meanders and angular velocity. When live workers were exposed to dead individuals at the LD90 of the compounds, carvacryl benzoate was the derivative that most reduced insects survival, due to horizontal transfer. These results show the potential of the carvacrol derivative — carvacryl benzoate — for the alternative management of ants of the genus Solenopsis sp.

Metal bioaccumulation and metallothionein (MT) expression were investigated in gills and liver of the red-blooded Antarctic teleost Trematomus hansoni with the aim to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper or cadmium concentrations in the environment. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory condi-tions. The two treatments lead to a significant accumulation of both metals and an increase of gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in speci-mens exposed to Cd, but the majority of these proteins were soon oxidized, probably because they were involved in cell protection against the risk of oxidative stress, by reactive oxygen spe-cies scavenging. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species evolved in an environment characterized by natural high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming every day more toxic.

Metal toxicity in soils, along with water runoff, are increasing environmental problems that affect agriculture directly and, in turn, human health. In light of finding a suitable and urgent solution, research on plant treatments with specific compounds that can help mitigate these effects has increased, and thus the exogenous application of melatonin (MET) and its role in alleviating the negative effects of metal toxicity in plants, have become more important in the last few years. MET is an important plant-related response molecule involved in growth, development, and reproduction, and in the induction of different stress-related key factors in plants. It has been shown that MET plays a protective role against the toxic effects induced by different metals (Pb, Cd, Cu, Zn, B, Al, V, Ni, La, As, and Cr) by regulating both the enzymatic and non-enzymatic antioxidant plant defense systems. In addition, MET interacts with many other signaling molecules, such as reactive oxygen species (ROS) and nitric oxide (NO), and participates in a wide variety of physiological reactions. Furthermore, MET treatment enhances osmoregulation and photosynthetic efficiency and increases the concentration of other important antioxidants such as phenolic compounds, flavonoids, polyamines (PAs), and carotenoid compounds. Some recent studies have shown that MET appeared to be involved in the regulation of metal transport in plants, and lastly, various studies have confirmed that MET significantly upregulated stress tolerance-related genes. Despite all the knowledge acquired over the years, there is still more to know about how MET is involved in the metal toxicity tolerance of plants.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

Knowledge on the health of banana trees is critical for farmers to profit from banana cultivation. Fusarium wilt and banana blood diseases (BDB), two significant diseases infecting banana trees, are caused by Fusarium oxysporum and Ralstonia syzygii, respectively. They have successfully caused a decline in crop yield as they destroy the trees, starting sequentially from the pseudostem to the fruits. The entire distribution of BDB and Fusarium on a plantation can be understood using advanced geospatial information obtained from multispectral aerial photographs taken using an unmanned aerial vehicle (UAV), combined with the reliable data field of infected trees. Vegetation and soil indices derived from a multispectral aerial photograph, such as normalized difference vegetation index, modified chlorophyll absorption ratio index, normalized difference water index (NDWI) and soil pH, may have to be relied on to explain the precise location of these two diseases. In this study, a random forest algorithm was used to handle a large dataset consisting of two models: the banana diseases multispectral model and the banana diseases spectral model. The results show that the soil indices, soil pH and NDWI are the most important variables for predicting the spatial distribution of these two diseases. Simultaneously, the plantation area affected by BDB is more extensive than that affected by Fusarium, if the variation of planted banana cultivars is not considered.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

As smoke toxicity is unregulated outside of the mass transport industry, there is no set methodology for assessing smoke toxicity of construction products, like OSB, on a large-scale. This research aims to assess the novel design of a modified ISO 9705 room corner test designed for smoke toxicity quantification. Three tests conditions will be assessed to determine if restriction of ventilation is enough to force a fire to transition to under-ventilated flaming, or if the fuel loading is much more important in affecting the fire severity and fire condition. The research found that fuel loading and test geometry has more significant impact on the fire condition than restricting the ventilation. While imposing restrictions on the test rooms ventilation did increase the equivalence ratio, it was not sufficient enough to force the transition into under-ventilated flaming. The addition of a door to the test room did not force the fire to transition to under-ventilated flaming. When doubling the fuel loading, there was sufficient fuel for the fire to transition to under-ventilated flaming. This research has provided the experimental methodologies to assess smoke toxicity at a range of ventilation conditions on a large-scale.

Aluminum (Al) toxicity is the most common factor limiting the growth of alfalfa in acidic soil conditions. Melatonin (MT), a significant pleiotropic molecule present in both plants and animals, has shown promise in mitigating Al toxicity in various plant species. This study aims to elucidate the underlying mechanism by which melatonin alleviates Al toxicity in alfalfa through a combined physiological and transcriptomic analysis. The results reveal that 5 μM MT significantly alleviates Al-induced growth inhibition and preserves the morphology of root tip cells. Moreover, MT application reduces Al accumulation in alfalfa roots and shoots by 28.6% and 27.6%, respectively. Additionally, MT plays a crucial role in scavenging Al-induced excess H2O2 by enhancing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), consequently reducing malondialdehyde (MDA) levels. The RNA-seq results reveal that MT application significantly upregulates the expression of xyloglucan endotransglucosylase/hydrolase (XTH) and carbon metabolism-related genes, including those involved in the glycolysis process, as well as sucrose and starch metabolism, suggesting that MT application may mitigate Al toxicity by facilitating the binding of Al to the cell walls, thereby reducing intracellular Al accumulation, and by improving respiration and the content of sucrose and trehalose. Taken together, our study demonstrates that MT alleviates Al toxicity in alfalfa by restoring redox homeostasis, enhancing Al binding to the cell wall, and modulating carbon metabolism. This research advances our understanding of the mechanisms underlying MT's effectiveness in mitigating Al toxicity, offering potential strategies for reducing Al accumulation in alfalfa.

The EPA has banned PFOA and PFOS as persistent organic pollutants, but their residues in environment should not be underestimated. Based on the demand for healthy aquaculture and safe aquatic products, it is necessary to explore alleviative methods for the toxicity of PFOA and PFOS to fish. This study is the first to investigate the protective effects of Lactobacillus rhamnosus against oxidative damage, neurotoxicity, and gut microbial dysbiosis induced by PFOA and PFOS in adult zebrafish. The results showed that L. rhamnosus effectively alleviated PFOA- and PFOS-induced oxidative stress by restoring superoxide dismutase (SOD), catalase (CAT), and lactate dehydrogenase (LDH) levels. Both PFOA and PFOS caused intestinal tissue damage, and the degree of damage is PFOA+PFOS>PFOS>PFOA. L. rhamnosus can restore damaged intestinal villi and lymphocyte numbers and also have a restorative effect on intestinal tissue damage. The up-regulated proportion of beneficial Firmicutes and Actinobacteria was also found after L. rhamnosus feeding. These findings provide new insights for L. rhamnosus to alleviate the toxicity of PFOA and PFOS to zebrafish and promote the progress of research on the successful use of probiotics in freshwater aquaculture.

Bifenthrin (BF) is a new highly effective broad-spectrum insecticide that has gained widespread use. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. In this research, Chinese giant salamanders (CGS) were exposed to three different concentrations of BF (0, 0.04, and 4 g/L BF) for 1-week to investigate the toxic effects. Behavioral changes, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results showed that exposure to BF (0.04 and 4) significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and 8-hydroxydeoxyguanosine (8-OHdG) contents in the brain, liver, and kidney of CGS, whereas the malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased. The liver tissue showed considerable inflammatory reactions and structural malformations. RNAseq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS, which affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior and detoxification significantly up-regulated, resulting the differential genes were significantly enriched in calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. These results indicated that BF induced the abnormal production of free radicals to exceed the potential of the self-defense system, causing different degrees of oxidative damage and lipid peroxidation in the body, resulting in oxidative stress, abnormal lipid metabolism, DNA damage, tissue inflammation, and abnormal behavior. This work provides a theoretical basis for the rational use of pyrethrin and environmental risks assessment, and scientific guidance for the conservation of amphibian populations.

Fluorescent semiconductor nanocrystals called quantum dots (QDs) have gained attention in biomedical applications, including imaging, molecular tracking, and drug delivery, due to their unique optical properties. However, their use is limited because of safety issues. This study was aimed at assessment the acute toxicity of QDs with different core chemical compositions and surface charges in mice. In addition, the immunotoxicity of CdSe/ZnS QDs was estimated. CdSe/ZnS, PbS/CdS/ZnS, and CuInS2/ZnS QDs were synthesized and modified with PEG derivatives. The hydrodynamic diameters and surface charges of solubilized QDs were characterized. The QD acute toxicity has been shown to depend on both surface charge and core composition. The immunotoxicity of CdSe/ZnS-PEG-OH QDs in mice was assessed after a single intravenous administration of 0.2 LD100 of the QDs. The QDs have been found to increase the spleen weight and cause spleen, thymus, and bone marrow cell depletion. However, these changes are reversible. A transient increase in the levels of proinflammatory cytokines (MCP1 and IL-6) indicates an acute inflammatory response to a single low dose of QDs. Thus, systemic comparative analysis of QD toxicity has shown how the QD core composition and surface properties affect living organisms.

Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H2O2) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH-, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH- to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases in DUOX mRNA and protein expression when treated with DNMT inhibitors. PDAC cells treated with P-AscH- + DNMT inhibitors demonstrated increased DUOX expression, increased intracellular oxidation, and increased cytotoxicity in vitro and in vivo compared to either treatment alone. These findings suggest a potential therapeutic, epigenetic mechanism to treat PDAC.

Rapid industrialization, urbanization, and population explosion in sub-Saharan Africa escalate environmental Lead levels with subsequent elevation of blood Lead levels in children. Nutrition status, age, and genetics govern one’s susceptibility to Lead toxicity. This study expounded this susceptibility by relating blood Lead levels, d-aminolevulinic acid dehydratase enzyme activity (ALAD), and genetic variations of proteins that code for ALAD enzyme in urban children of Uganda. Spectrophotometric analysis for blood Lead (BL), hemoglobin levels, and determination d-levels aminolevulinic acid dehydratase enzyme activity of the blood samples from 198 children were performed prior to a polymerase chain reaction and restriction fragment length digestion for ALAD polymorphism was done. Up to 99.5% of samples coded for the ALAD1 allele whereas 0.05% coded for ALAD2. Genotypes ALAD2-2 members had elevated BLL (mean 14.1 µg/dL) and reduced ALAD enzyme activity compared to others. This, therefore, implies that the majority of children hoard BL which may affect them later in life.

The bloom-forming toxic dinoflagellate Alexandrium catenella was first detected in Southern Chile (39.5–55°S) 50 years ago and is responsible for most of the area’s cases of paralytic shellfish poisoning (PSP). Given the complex life history of A. catenella, which includes benthic sexual cysts, in this study we examined the potential link between latitude, toxicity, and sexual compatibility. Nine clones isolated from Chilean Patagonia were used in self- and out-crosses in all possible combinations (n=45). The effect of latitude on toxicity, reproductive success indexes, and cyst production was also determined. Although the toxin profiles were similar for all strains, consisting of C1, C2, GTX4, GTX1, GTX3, and NeoSTX, a latitudinal gradient was determined for their proportions (%) and content per cell (pg cell⁻¹), with the more toxic strains occurring in the north (−40.6°S). Reproductive success also showed a latitudinal tendency and was lower in the north. None of the self-crosses yielded resting cysts. Rather, the production of resting cysts was highest in pairings of clones separated by distances of 1000–1650km. Our results contribute to a better understanding of PSP outbreaks in the region and demonstrate the importance of resting cysts in fueling new toxic events. They also provide additional evidence that the introduction of strains from neighboring regions is a cause for concern.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

Plant sulfite oxidase )SO( is a molybdo-enzyme responsible for the oxidation of excess SO₂/sulfite into non-toxic sulfate. The effect of toxic sulfite level on leaves and fruits was studied in tomato plants with different SO expression levels: wild-type (WT), SO overexpression (OE) and SO RNA interference (Ri) plants. Leaf discs and ripe fruit of plants lacking SO were more susceptible, whereas SO OE plants were more resistant as revealed by remaining chlorophyll content and tissue damage levels. Application of molybdenum further enhanced the tolerance of leaf discs to sulfite by enhancing SO activity in SO OE lines, but not in WT or Ri plants. Notably, incubation with tungsten, the molybdenum antagonist, overturned the effect of molybdenum spray in SO OE plants, revealed by remaining chlorophyll content and SO activity. The results indicate that SO determines, in tomato leaves and ripe fruits, the resistance to toxic sulfite and the application of molybdenum enhances sulfite resistance in OE plants by increasing SO activity. The results suggest that overexpressing SO mechanism can be employed in agriculture with or without molybdenum application, for the development of more tolerate crops and vegetables to higher concentrations of sulfite/SO₂ containing postharvest treatments.

The toxic effects of 4-octylphenol (4-OP) have been studied in species such as mouse and fish; however, the toxic effects of 4-OP in male specific niche cells has not been researched. In this study, we investigated the molecular mechanism of toxicity of 4-OP in mouse TM4 Sertoli cells. TM4 cells were treated with four concentrations (0, 10, 30, and 50 µM/mL) of 4-OP at time points 24, 48, and 72 h. Cell viability and apoptosis assay was conducted following exposure. 4-OP significantly decreased cell viability in a concentration- and time-dependent manner, and increased apoptosis. Quantitative PCR analysis showed that Bad, Bax, and Bak mRNA expression levels were higher in exposed cells than in the control, but Bcl-2 expression was decreased. Western blotting revealed that 4-OP induced activities of caspase-3 and phosphorylation of Bad in a concentration- and time-dependent manner. Additionally, cytochrome C protein did not colocalize with mitochondria marker dye by 24 h. Cytochrome c protein expression increased in a time-dependent manner with 50 µM/mL. These results suggest that 4-OP induces mitochondria-mediated apoptosis by regulation of Bcl-2 family proteins and caspase-3 activation in male Sertoli cells.

In this present study, we conducted untargeted metabolic profiling using Gas Chromatography-Mass Spectrometry (GC-MS) analysis of ascidian Didemnum bistratum to assess the chemical constituents by searching in NIST library with promising biological properties against anti-bacterial and Zika virus vector mosquitocidal Properties. Metabolites, steroids and fatty acids are abundant in crude compounds of ascidian D. bistratum and showed potential zone growth inhibition against bacterial strains Kluyvera ascorbate (10 mm). The active crude compounds of D. bistratum exhibited prominent larvicidal activity against the Zika vector mosquitoes of Aedes aegypti and Cluex quinquefasciatus (LC₅₀ values of 0.4436 to 2.23 mg/mL). The findings of this study provide a first evidence of the biological properties exhibited by D. bistratum extracts, thus increasing the knowledge about the Zika virus vector mosquitocidal properties of ascidian. Overall, ascidian D. bistratum are promising and biocontrol or eco-friendly tool against A. aegypti and C. quinquefasciatus with prospective toxicity against non-target organisms.

Nanoparticles (NPs) are widely used in diverse disciplines, including biology, medicine science. The central question that need to be answered is whether NPs have toxic effects on biological cells and molecules or are they safe. The safety of NPs including targeted drug delivery is critical and so is their toxicity in the environment. In recent years, in vitro and in vivo research on animals has generated abundant information about the toxicity of NPs. However, due to varying laboratory conditions, the comparison of the results from ensuing studies is somewhat unreliable. It should be noted that, depending on the type of production, NPs can enter the body through inhalation, skin and via digestive routes. Due to the diversity of NPs and their properties, there is paucity of accurate information on their toxicological effects; particle size, shape, surface area and the chemical levels are considered as key factors in creating health and toxicological effects. Consequently, there is a need for reliable information about their effects on various organs so as to deal with NPs effectively and their impact on health and the environment. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

Spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real time proliferation assay. Comet assay was used to determine oxidative damage of UCNPs. In vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. Proliferation assay revealed that L-UCNPs were less toxic than S-UCNPs. The viability of rat mesenchymal stem cells (rMSCs) incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. Oxidative damage measured by the Comet assay showed that neat L-UCNPs caused oxidative damage to rMSCs more than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

Organophosphate pesticides (OPs) are toxic substances that contaminate aquatic environments, interfere with the development of the nervous system, and induce Neurodevelopmental Toxicity (NDT) in animals and humans. The canonical mechanism of OP neurotoxicity involves the inhibi-tion of acetylcholinesterase (AChE), but other mechanisms non-AChE are also involved and not fully understood. We used network toxicology and molecular docking to identify molecular targets and toxicity mechanisms common to OPs. Targets related to diazinon-oxon, chlorpyrifos oxon, and paraoxon OPs were predicted using the Swiss Target Prediction and PharmMapper databases. Targets related to NDT were compiled from GeneCards and OMIM databases. In order to construct the protein-protein interaction (PPI) network, the common targets between OPs and NDT were imported into the STRING. Networks topological analyses identified EGFR, MET, HSP90AA1, and SRC as hub nodes common to the three OPs. Using Reactome pathway and gene ontology we found that signal transduction, axon guidance, cellular responses to stress, and glutamatergic signaling activation play key roles in OP-induced NDT.