Study on the mechanisms of defective spermatogenesis induced by TiO2 NPs based on 3D blood-testis barrier microfluidic chip.

Titanium dioxide nanoparticles (TiO2 NPs) can reduce sperm number, but the mechanisms of defective spermatogenesis induced by TiO2 NPs have not been studied through cell-cell interactions at present. A kind of biomimetic three-dimensional blood-testis barrier microfluidic chip capable of intercellular communication was constructed with soft lithography techniques, including Sertoli cell (TM4), spermatogonia (GC-1) and vascular endothelial cell units, to study the mechanisms of TiO2 NPs-induced defective spermatogenesis. TM4 and GC-1 cells cultured in TiO2 NPs exposure and control chips were collected for transcriptomics and metabonomics analysis, and key proteins and metabolites in changed biological processes were validated. In TM4 cells, TiO2 NPs suppressed glucose metabolism, especially lactate production, which reduced energy substrate supply for spermatogenesis. TiO2 NPs also decreased the levels of key proteins and metabolites of lactate production. In GC-1 cells, TiO2 NPs disturbed chemokine signaling pathways regulating cell proliferation and interfered with glutathione metabolism. The Cxcl13, Stat3 and p-Stat3 levels and cell proliferation rate were decreased, and the GSR, GPX4 and GSH contents were increased in GC-1 cells in chips under TiO2 NPs treatment. The decrease in energy substrate supply for spermatogenesis and inhibition of spermatogonia proliferation could be the main mechanisms of defective spermatogenesis induced by TiO2 NPs.

Chemical composition of Ecstasy tablets seized in Poland between 2005 and 2020.

PURPOSE: The most commonly associated substance found in Ecstasy tablets is MDMA (3,4-methylenedioxymethamphetamine). In our study, we showed how the composition of psychoactive ingredients in Ecstasy tablets seized on the drug market in Poland has changed in the years 2005-2020. METHODS: The study material consisted of nearly 20,000 single Ecstasy tablets seized by representatives of law enforcement (the police, prosecutors) from 2005 to 2020 and analysed by the Institute of Forensic Research, Krakow, Poland. The analysis of the tablets was carried out by gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography with diode array detection (HPLC-DAD) and ultra-high-performance liquid chromatography with photodiode array detection (UHPLC-PDA). RESULTS: Currently, new types of MDMA tablets are introduced onto the market, available in various colours and shapes. Our study showed that tablets sold on the street as Ecstasy have variable purity and sometimes contain little or no MDMA. The mean content of MDMA in one tablet seized in 2005-2011 decreased from 90 to 50 mg. In 2013, Ecstasy tablets with a very high MDMA content (average 195 mg per tablet) appeared on the market, but in the next 2 years, the MDMA content decreased again. From 2016, the average MDMA content began to rise again, ranging from 60 to 280 mg. CONCLUSION: Tablets sold as Ecstasy also contained completely different psychoactive substances, including new psychoactive substances (NPS) (found in almost 20% of all examined tablets sold as Ecstasy) belonging to different chemical groups or their dangerous combinations (i.e. phenylethylamines, piperazines, tryptamines, cathinones, arylalkylamines, arylcyclohexylamines and piperidines). Such a large variety of psychoactive substances in Ecstasy tablets is associated with a high risk for users unaware of their composition.

Identification of N-piperidinyl etonitazene in alternative keratinous matrices from a decomposing cadaver.

This short report describes research on N-piperidinyl etonitazene, also known as etonitazepipne, in keratinous matrices (hair and nails) after death related to a suspected opioid overdose. Etonitazepipne belongs to the family of benzimidazole opioids, a class of new synthetic opioids that has penetrated the illicit drug market. Analysis in the case under study showed the presence of etonitazepipne in both hair and nails, confirming that the substance accumulates in the body with repeated intake.

Cell Wall Binding Strategies Based on Cu3SbS3 Nanoparticles for Selective Bacterial Elimination and Promotion of Infected Wound Healing.

Utilizing nanomaterials as an alternative to antibiotics, with a focus on maintaining high biosafety, has emerged as a promising strategy to combat antibiotic resistance. Nevertheless, the challenge lies in the indiscriminate attack of nanomaterials on both bacterial and mammalian cells, which limits their practicality. Herein, Cu3SbS3 nanoparticles (NPs) capable of generating reactive oxygen species (ROS) are discovered to selectively adsorb and eliminate bacteria without causing obvious harm to mammalian cells, thanks to the interaction between O of N-acetylmuramic acid in bacterial cell walls and Cu of the NPs. Coupled with the short diffusion distance of ROS in the surrounding medium, a selective antibacterial effect is achieved. Additionally, the antibacterial mechanism is then identified: Cu3SbS3 NPs catalyze the generation of O2•-, which has subsequently been conversed by superoxide dismutase to H2O2. The latter is secondary catalyzed by the NPs to form •OH and 1O2, initiating an in situ attack on bacteria. This process depletes bacterial glutathione in conjunction with the disruption of the antioxidant defense system of bacteria. Notably, Cu3SbS3 NPs are demonstrated to efficiently impede biofilm formation; thus, a healing of MRSA-infected wounds was promoted. The bacterial cell wall-binding nanoantibacterial agents can be widely expanded through diversified design.

Biosynthesis of zinc oxide nanoparticles via neem extract and their anticancer and antibacterial activities.

In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.

Biosynthesis of TiO2 nano particles by using Rosemary (Rosmarinus officinalis) leaf extracts and its application for crystal dye degradation under sunlight.

Titanium dioxide (TiO2) nanoparticles were prepared through Rosmarinus-officinalis leaf extracts at 90 and 200°C. In this research, the degradations of methylene blues by using TiO2 nanoparticles Sun light radiations were studied. The synthesized materials were characterized using XRDs, UV-Vis, PL, SEM, TEM, EDS and XPS. The results displayed that bio-synthesis temperatures intrude the shapes and sizes of TiO2 nanoparticles. For TiO2-90, micrographs show separable crystalline with irregular morphologies and agglomerate cubic particles. For the other TiO2-200 sample, SEM and TEM micro-imaging shows crumbly agglomerated cubic structures. The XRD shows that the intense peaks observed at angles of 25.37°, 37.19°, 47.81° and 53.89° confirming a highly crystalline oriented as (004), (200), and (105) planes respectively. The optical properties of TiO2 nanoparticles synthesized were conveyed by PL and UV-Vis. The energy band gap calculated was 3.0 eV for both samples; that indicates heating temperature didn't influence the band gap of the samples. The elemental composition Ti and O2 is shown by EDS and XPS. Photo-catalytic experiments discovered that TiO2-90 nanoparticles were well-organized in photo-degradations of MB, likened to TiO2-200. The great activities of TiO2-90 were because of better physicochemical characteristics associated with TiO2-200 effectively degrading MB under photo-light. Photo-degradations of dye under sunlight as plentifully obtainable energy sources by TiO2, synthesized by simpler techniques, can be hopeful to grow an eco-friendly and economical process.

Activity-based detection of synthetic cannabinoid receptor agonists in plant materials.

BACKGROUND: Since late 2019, fortification of 'regular' cannabis plant material with synthetic cannabinoid receptor agonists (SCRAs) has become a notable phenomenon on the drug market. As many SCRAs pose a higher health risk than genuine cannabis, recognizing SCRA-adulterated cannabis is important from a harm reduction perspective. However, this is not always an easy task as adulterated cannabis may only be distinguished from genuine cannabis by dedicated, often expensive and time-consuming analytical techniques. In addition, the dynamic nature of the SCRA market renders identification of fortified samples a challenging task. Therefore, we established and applied an in vitro cannabinoid receptor 1 (CB1) activity-based procedure to screen plant material for the presence of SCRAs. METHODS: The assay principle relies on the functional complementation of a split-nanoluciferase following recruitment of ß-arrestin 2 to activated CB1. A straightforward sample preparation, encompassing methanolic extraction and dilution, was optimized for plant matrices, including cannabis, spiked with 5 µg/mg of the SCRA CP55,940. RESULTS: The bioassay successfully detected all samples of a set (n = 24) of analytically confirmed authentic Spice products, additionally providing relevant information on the 'strength' of a preparation and whether different samples may have originated from separate batches or possibly the same production batch. Finally, the methodology was applied to assess the occurrence of SCRA adulteration in a large set (n = 252) of herbal materials collected at an international dance festival. This did not reveal any positives, i.e. there were no samples that yielded a relevant CB1 activation. CONCLUSION: In summary, we established SCRA screening of herbal materials as a new application for the activity-based CB1 bioassay. The simplicity of the sample preparation, the rapid results and the universal character of the bioassay render it an effective and future-proof tool for evaluating herbal materials for the presence of SCRAs, which is relevant in the context of harm reduction.

Stability of new psychoactive substances in crude wastewater.

Those involved in drug testing continue to grapple with the dynamic nature of emerging psychoactive substances (NPS) and their rapid infiltration into society. The challenge extends beyond merely detecting and measuring NPS using analytical tools; it also encompasses the complexities arising from the formation and presence of metabolites and degradation products. This study utilises liquid chromatography time-of-flight mass spectrometry to investigate the stability of new psychoactive substances in wastewater. Seven NPS compounds including 25C-NBOMe, 5F-APINACA 4-hydroxyphenyl, AB-PINACA, APINACA 4-hydroxyphenyl, fentanyl, norfentanyl and MDPV, along with their corresponding internal standard, were examined. Reference material for each NPS compound was introduced into a wastewater sample from a Wessex water treatment plant. The sample was then exposed to four different environments: room temperature, refrigerator temperature, acidification to pH 2, and the introduction of sodium metabisulfite. The findings highlight the critical dependence of storage conditions on target analytes, emphasizing the paramount importance of the time elapsed between collection and analysis for NPS wastewater analysis. Notably, synthetic cannabinoids exhibit limited stability in wastewater whereas cathinone-like substances demonstrate greater stability. Furthermore, metabolites prove to be more stable in wastewater than the parent drug, suggesting that focusing on metabolite detection may be more favourable for future analysis.

Silver nanoparticles incorporated with superior silica nanoparticles-based rice straw to maximize biogas production from anaerobic digestion of landfill leachate.

Treating hazardous landfill leachate poses significant environmental challenges due to its complex nature. In this study, we propose a novel approach for enhancing the anaerobic digestion of landfill leachate using silver nanoparticles (Ag NPs) conjugated with eco-friendly green silica nanoparticles (Si NPs). The synthesized Si NPs and Ag@Si NPs were characterized using various analytical techniques, including transmission electron microscopy, X-ray diffraction, and Fourier-transform infrared spectroscopy. The anaerobic digestion performance of Si NPs and Ag@Si NPs was tested by treating landfill leachate samples with 50 mg/L of each NP. The results demonstrated an enhancement in the biogas production rate compared to the control phase without the nanocomposite, as the biogas production increased by 14% and 37% using Si NPs and Ag@Si NPs. Ag@Si NPs effectively promoted the degradation of organic pollutants in the leachate, regarding chemical oxygen demand (COD) and volatile solids (VS) by 58% and 65%. Furthermore, microbial analysis revealed that Ag@Si NPs enhanced the activity of microbial species responsible for the methanogenic process. Overall, incorporating AgNPs conjugated with eco-friendly green Si NPs represents a sustainable and efficient approach for enhancing the anaerobic digestion of landfill leachate.

Investigation of the efficacy of Zn/Ce-CuO nanoparticles for enhanced photocatalytic, antibacterial, and antioxidant activities.

The world is dealing with unprecedented environmental challenges, leading to a growing urgency to limit environmental damage. So, this study focuses on the synthesis of pure CuO, Zn, Ce, and Zn/Ce dual-doped CuO nanoparticles (NPs) using extract of Citrus limon leaves as reductant via simple co-precipitation method. The X-ray diffraction (XRD) characterization was employed to analyze structural characteristics of synthesized samples which confirm influence of Zn or Ce doping on crystallite size, dislocation density, and strain. The role of functional groups, changes in force constant, and bond length on addition of dopants was indicated by FTIR results. The SEM and TEM results showed variation in morphology from irregular to spherical. The zeta-potential and BET analysis confirmed surface potential as well as surface area characteristics. The change in energy gap values from 1.81 to 1.45 eV of Zn/Ce-doped CuO NPs computed from UV-vis analysis elevated its photocatalytic performance and reduced the chances of recombination of electron-hole pair due to presence of trapping levels between valence and conduction bands. The enhanced photo-degradation of Congo red (CR) and rhodamine B (RhB) with 91 and 94%, respectively, for Zn/Ce-doped CuO NPs was observed. The so-obtained samples have also exhibited good antibacterial and antioxidant activities.

Green synthesis of zinc oxide nanoparticles (ZnO-NPs) by Streptomyces baarnensis and its active metabolite (Ka): a promising combination against multidrug-resistant ESKAPE pathogens and cytotoxicity.

Various eco-friendly techniques are being researched for synthesizing ZnO-NPs, known for their bioactivity. This study aimed at biosynthesizing ZnO-NPs using Streptomyces baarnensis MH-133, characterizing their physicochemical properties, investigating antibacterial activity, and enhancement of their efficacy by combining them with a water-insoluble active compound (Ka) in a nanoemulsion form. Ka is a pure compound of 9-Ethyl-1,4,6,9,10-pentahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione obtained previously from our strain of Streptomyces baarnensis MH-133. Biosynthesized ZnO-NPs employing Streptomyces baarnensis MH-133 filtrate and zinc sulfate (ZnSO4.7H2O) as a precursor were purified and characterized by physicochemical investigation. High-resolution-transmission electron microscopy (HR-TEM) verified the effective biosynthesis of ZnO-NPs (size < 12 nm), whereas dynamic light scattering (DLS) analysis showed an average size of 17.5 nm. X-ray diffraction (XRD) exhibited characteristic diffraction patterns that confirmed crystalline structure. ZnO-NPs efficiently inhibited both Gram-positive and Gram-negative bacteria (MICs: 31.25-125 µg/ml). The pure compound (Ka) was combined with ZnO-NPs to improve effectiveness and reduce dose using checkerboard microdilution. Niteen treatments of Ka and ZnO-NPs combinations obtained by checkerboard matrix inhibited Klebsiella pneumonia. Eleven combinations had fractional inhibitory concentration index (FICi) between 1.03 and 2, meaning indifferent, another five combinations resulted from additive FICi (0.625-1) and only one combination with FICi of 0.5, indicating synergy. In the case of methicillin-resistant S. aureus (MRSA), Ka-ZnO-NPs combinations yielded 23 treatments with varying degrees of interaction. The results showed eleven treatments with indifferent interaction, eight additive interactions, and two synergies with FICi of 0.5 and 0.375. The combinations that exhibited synergy action were transformed into a nanoemulsion form to improve their solubility and bioavailability. The HR-TEM analysis of the nanoemulsion revealed spherical oil particles with a granulated core smaller than 200 nm and no signs of aggregation. Effective dispersion was confirmed by DLS analysis which indicated that Ka-ZnO-NPs nanoemulsion droplets have an average size of 53.1 nm and a polydispersity index (PI) of 0.523. The killing kinetic assay assessed the viability of methicillin-resistant Staphylococcus aureus (MRSA) and K. pneumonia post-treatment with Ka-ZnO-NPs combinations either in non-formulated or nanoemulsion form. Results showed Ka-ZnO-NPs combinations show concentration and time-dependent manner, with higher efficacy in nanoemulsion form. The findings indicated that Ka-ZnO-NPs without formulation at MIC values killed K. pneumonia after 24 h but not MRSA. Our nanoemulsion loaded with the previously mentioned combinations at MIC value showed bactericidal effect at MIC concentration of Ka-ZnO-NPs combination after 12 and 18 h of incubation against MRSA and K. pneumonia, respectively, compared to free combinations. At half MIC value, nanoemulsion increased the activity of the combinations to cause a bacteriostatic effect on MRSA and K. pneumonia after 24 h of incubation. The free combination showed a bacteriostatic impact for 6 h before the bacteria regrew to increase log10 colony forming unit (CFU)/ml over the initial level. Similarly, the cytotoxicity study revealed that the combination in nanoemulsion form decreased the cytotoxicity against kidney epithelial cells of the African green monkey (VERO) cell line. The IC50 for Ka-ZnO-NPs non-formulated treatment was 8.17/1.69 (µg/µg)/ml, but in nano-emulsion, it was 22.94 + 4.77 (µg/µg)/mL. In conclusion, efficient Ka-ZnO-NPs nanoemulsion may be a promising solution for the fighting of ESKAPE pathogenic bacteria according to antibacterial activity and low toxicity.

Evaluation of the teratogenic potency of bulk zinc oxide and its nanoparticles on embryos of the freshwater snail, Helisoma duryi.

Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC50, studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails' embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs.

Antibacterial Mechanism of d-Cysteine/Polyethylene Glycol-Functionalized Gold Nanoparticles and Their Potential for the Treatment of Bacterial Infections.

Bacterial infection has always posed a severe threat to public health. Gold nanoparticles (Au NPs) exhibit exceptional biocompatibility and hold immense potential in biomedical applications. However, their antibacterial effectiveness is currently unsatisfactory. Herein, a chiral antibacterial agent with high stability was prepared by the modification of Au NPs with d-cysteine with the assistance of polyethylene glycol (PEG). The as-synthesized d-cysteine/PEG-Au NPs (D/P-Au NPs) exhibited a stronger (99.5-99.9%) and more stable (at least 14 days) antibacterial performance against Gram-negative (Escherichia coli and Listeria monocytogenes) and Gram-positive (Salmonella enteritidis and Staphylococcus aureus) bacteria, compared with other groups. The analysis of the antibacterial mechanism revealed that the D/P-Au NPs mainly affected the assembly of ribosomes, the biosynthesis of amino acids and proteins, as well as the DNA replication and mismatch repair, ultimately leading to bacterial death, which is significantly different from the mechanism of reactive oxygen species-activated metallic antibacterial NPs. In particular, the D/P-Au NPs were shown to effectively accelerate the healing of S. aureus-infected wounds in mice to a rate comparable to or slightly higher than that of vancomycin. This work provides a novel approach to effectively design chiral antibacterial agents for bacterial infection treatment.

ZnO Doped Silica Nanoparticles (ZnO@SiO2) for Enhanced Electrochemical Detection of Cd2+ Ions in Real Samples.

Pollution by heavy metal ions has a serious impact on human health and the environment, which is why the monitoring of heavy metal ions is of great practical importance. In this work, we describe the development of an electrochemical sensor for the detection of cadmium (Cd2+) involving the doping of porous SiO2 spheres with ZnO nanoparticles. Zinc oxide is chosen as the central dopant in the composite material to increase the conductivity and thus improve the electrochemical detection of Cd2+ ions with the SiO2 spheres. The resulting composite is characterized by electrochemical spectroscopic XRD and microscopic methods. As a result, the developed sensor shows good selectivity towards the targeted Cd2+ ions compared to other divalent ions. After optimization of the experimental conditions, the electrochemical sensor shows two different linear ranges between 2.5 × 10-11 molL-1 to 1.75 × 10-10 molL-1 and 2 × 10-9 molL-1 to 1.75 × 10-9 molL-1, indicating a change from diffusion-controlled to surface-controlled oxidation of Cd2+. A detection limit was reached at 4.4 × 10-11 molL-1. In addition, it offers good repeatability and recovery, and can detect accurate trace amounts of Cd2+ ions in real samples such as tap water or seawater by spiking these samples with known Cd2+ concentrations. This setup also provides satisfactory recovery rates in the range of 89-102%.

Harnessing Walnut-Based Zinc Oxide Nanoparticles: A Sustainable Approach to Combat the Disease Complex of Meloidogyne arenaria and Macrophomina phaseolina in Cowpea.

Zinc oxide nanoparticles (ZnO NPs) exhibit diverse applications, including antimicrobial, UV-blocking, and catalytic properties, due to their unique structure and properties. This study focused on the characterization of zinc oxide nanoparticles (ZnO NPs) synthesized from Juglans regia leaves and their application in mitigating the impact of simultaneous infection by Meloidogyne arenaria (root-knot nematode) and Macrophomina phaseolina (root-rot fungus) in cowpea plants. The characterization of ZnO NPs was carried out through various analytical techniques, including UV-visible spectrophotometry, Powder-XRD analysis, FT-IR spectroscopy, and SEM-EDX analysis. The study confirmed the successful synthesis of ZnO NPs with a hexagonal wurtzite structure and exceptional purity. Under in vitro conditions, ZnO NPs exhibited significant nematicidal and antifungal activities. The mortality of M. arenaria juveniles increased with rising ZnO NP concentrations, and a similar trend was observed in the inhibition of M. phaseolina mycelial growth. SEM studies revealed physical damage to nematodes and structural distortions in fungal hyphae due to ZnO NP treatment. In infected cowpea plants, ZnO NPs significantly improved plant growth parameters, including plant length, fresh mass, and dry mass, especially at higher concentrations. Leghemoglobin content and the number of root nodules also increased after ZnO NP treatment. Additionally, ZnO NPs reduced gall formation and egg mass production by M. arenaria nematodes and effectively inhibited the growth of M. phaseolina in the roots. Furthermore, histochemical analyses demonstrated a reduction in oxidative stress, as indicated by decreased levels of reactive oxygen species (ROS) and lipid peroxidation in ZnO NP-treated plants. These findings highlight the potential of green-synthesized ZnO NPs as an eco-friendly and effective solution to manage disease complex in cowpea caused by simultaneous nematode and fungal infections.

The Therapeutic Role of NPS-1034 in Pancreatic Ductal Adenocarcinoma as Monotherapy and in Combination with Chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in terms of diagnosis and treatment, with limited therapeutic options and a poor prognosis. This study explored the potential therapeutic role of NPS-1034, a kinase inhibitor targeting MET and AXL, in PDAC. The investigation included monotherapy with NPS-1034 and its combination with the commonly prescribed chemotherapy agents, fluorouracil and oxaliplatin. Our study revealed that NPS-1034 induces cell death and reduces the viability and clonogenicity of PDAC cells in a dose-dependent manner. Furthermore, NPS-1034 inhibits the migration of PDAC cells by suppressing MET/PI3K/AKT axis-induced epithelial-to-mesenchymal transition (EMT). The combination of NPS-1034 with fluorouracil or oxaliplatin demonstrated a synergistic effect, significantly reducing cell viability and inducing tumor cell apoptosis compared to monotherapies. Mechanistic insights provided by next-generation sequencing indicated that NPS-1034 modulates immune responses by inducing type I interferon and tumor necrosis factor production in PDAC cells. This suggests a broader role for NPS-1034 beyond MET and AXL inhibition, positioning it as a potential immunity modulator. Overall, these findings highlight the anticancer potential of NPS-1034 in PDAC treatment in vitro, both as a monotherapy and in combination with traditional chemotherapy, offering a promising avenue for further in vivo investigation before clinical exploration.

Evaluating long-term impacts of land use/land cover changes on pollution loads at a catchment scale.

Evaluating how pollutant loads react to changes in land use/land cover (LULC) is a challenging task due to the intricate relationships among the many elements within a watershed. However, the difficulty in connecting LULC change and nonpoint source (NPS) pollution loads to streams may be lessened by combining hydrological modeling with geospatial tools and multivariate statistics. The objective of this study was to investigate the long-term effects of LULC change on NPS pollution loads in a highly human-dominated catchment, in central Ethiopia. In the study, hydrologic modeling was used to estimate the NPS parameters from multispectral Landsat images, and multivariate statistical techniques were then used to extract major LULC types that explain the variances of NPS loads between 1981 and 2020. The results demonstrated that there were human-induced LULC changes in the area, as the built-up and agricultural landscapes are rising (186.4% and 5.8%, respectively), and shrub and forest lands are decreasing (67.1% and 41%, respectively). As a result of these changes, the concentrations of nitrate (NO3), total P, total N, organic N, and organic P loads were increased by 69.41, 19.83, 18.45, 18.88, and 24.05%, respectively. Reductions in natural vegetation, as well as agriculture intensification, are the major contributors to the NPS pollutant losses to surface water sources. The result also revealed that pollution nutrients are strongly related to deforestation and agricultural land expansion. Proper adaptation strategies should be implemented to minimize the negative impact of LULC changes in the area.

Impact of ZnO NPs on photosynthesis in rice leaves plants grown in saline-sodic soil.

Saline-sodic stress restricts the absorption of zinc by rice, consequently impacting the photosynthesis process of rice plants. In this experiment, Landrace 9 was selected as the test material and the potting method was employed to investigate the influence of ZnO nanoparticles (ZnO NPs) on zinc absorption and chlorophyll fluorescence in rice grown in saline-sodic land. The research findings demonstrate that the application of ZnO NPs proves to be more advantageous for the growth of rice in saline-sodic soil. Notably, the application of ZnO NPs significantly decreases the levels of Na+ and MDA in rice leaves in saline-sodic soil, while increasing the levels of K+ and Zn2+. Additionally, ZnO NPs enhances the content of chloroplast pigments, specific energy flux, quantum yield, and the performance of active PSII reaction center (PIABS) in rice leaves under saline-sodic stress. Furthermore, the relative variable fluorescence (WK and VJ) and quantum energy dissipation rate (φDo) of rice are also reduced. Therefore, the addition of ZnO NPs enhances the transfer of electrons and energy within the rice photosystem when subjected to saline-sodic stress. This promotes photosynthesis in rice plants growing in saline-sodic land, increasing their resistance to saline-sodic stress and ultimately facilitating their growth and development.

Biogenic Synthesis and Characterisation of Novel Potassium Nanoparticles by Capparis spinosa Flower Extract and Evaluation of Their Potential Antibacterial, Anti-biofilm and Antibiotic Development.

Scientific researches on the synthesis, characterisation, and biological activity of potassium nanoparticles (K NPs) are extremely rare. In our study, we successfully synthesised a novel form of K NPs using Capparis spinosa (C. spinosa) flower extract as a reducing and capping agent. The formation of K NPs in new form (K2O NPs) was confirmed by UV-vis and XRD spectra. Furthermore, the FTIR results indicated the presence of specific active biomolecules in the C. spinosa extract which played a crucial role in reducing and stabilising K2O NPs. SEM imaging demonstrated that the K2O NPs exhibited irregular shapes with nanosizes ranging between 25 and 95 nm. Remarkably, the biosynthesised K2O NPs displayed considerable antibacterial activity against a wide range of multidrug-resistant (MDR) pathogenic bacteria. K2O NPs demonstrated considerable anti-biofilm activity against preformed biofilms produced by MDR bacteria. Combining K2O NPs with conventional antibiotics greatly improved their efficacy in compacting the MDR bacterial strains. Industrially, bulk form of potassium oxides was commonly used in the preparation of various antimicrobial compounds such as detergents, bleach, and oxidising solutions. The synthesis of potassium oxide in nanoform has shown remarkable biological efficacy, making it a promising therapeutic approach for pharmaceutical and medical applications.

Pharmacokinetic and molecular docking studies to pyrimidine drug using Mn3O4 nanoparticles to explore potential anti-Alzheimer activity.

Alzheimer disease (AD) is the cause of dementia and accounts for 60-80% cases. Tumor Necrosis Factor-alpha (TNF-α) is a multifunctional cytokine that provides resistance to infections, inflammation, and cancer. It developed as a prospective therapeutic target against multiple autoimmune and inflammatory disorders. Cholinergic insufficiency is linked to Alzheimer's disease, and several cholinesterase inhibitors have been created to treat it, including naturally produced inhibitors, synthetic analogs, and hybrids. In the current study, we tried to prepared compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's using manganese tetroxide nanoparticles (Mn3O4-NPs) as a catalyst to generate compounds with excellent reaction conditions. The Biginelli synthesis yields 4-(4-cyanophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile when the 4-cyanobenzaldehyde, ethyl cyanoacetate, and thiourea were coupled with Mn3O4-NPs to produce compound 1. This multi-component method is non-toxic, safe, and environmentally friendly. The new approach reduced the amount of chemicals used and preserved time. Compound 1 underwent reactions with methyl iodide, acrylonitrile, chloroacetone, ethyl chloroacetate, and chloroacetic acid/benzaldehyde, each of the synthetized compounds was docked with TNF-α converting enzyme. These compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's disease. The majority of the produced compounds demonstrated pharmacokinetic features, making them potentially attractive therapeutic candidates for Alzheimer's disease treatment.