The association of blood urea nitrogen-to-creatinine ratio and in-hospital mortality in acute ischemic stroke patients with atrial fibrillation: data from the MIMIC-IV database.

Objective: This research aimed to investigate the association between the blood urea nitrogen-to-creatinine (BUN/Cr) ratio and the rate of in-hospital mortality in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF), who are also receiving care in intensive care unit (ICU). Methods: A retrospective study was conducted using the MIMIC-IV database. We collected data on BUN/Cr levels at admission for patients with AIS and concurrent AF. To assess the association between BUN/Cr and in-hospital mortality rate, statistical analysis was conducted employing multivariable logistic regression models and restricted cubic spline models. These models were utilized to investigate the potential relationship and provide insights into the impact of BUN/Cr on the likelihood of in-hospital mortality. Interaction and subgroup analyses were performed to evaluate the consistency of the correlation. Results: There were a total of 856 patients (age ≥ 18 years) with a median age of 78.0 years, of which 466 (54.4%) were female. Out of 856 patients, 182 (21.26%) died in the hospital. Upon controlling for confounding factors, the multivariable logistic regression analysis elucidated that patients falling within the third trisection (Q3 > 22.41 mg/dL) exhibited a noticeably increased susceptibility to in-hospital mortality when contrasted with their counterparts positioned in the second trisection (Q2: 17.2-22.41 mg/dL) (OR = 2.02, 95% CI: 1.26-3.26, p = 0.004). A non-linear J-shaped relationship was observed between BUN/Cr at ICU admission and in-hospital mortality rate (p = 0.027), with a turning point at 19.63 mg/dL. In the threshold analysis, there was a 4% rise in in-hospital mortality for each 1 mg/dL increase in BUN/Cr (OR: 1.04, 95% CI: 1.01-1.06, p = 0.012). Conclusion: In patients with AIS complicated by AF, BUN/Cr at admission shows a J-shaped correlation with in-hospital mortality rate. When BUN/Cr exceeds 19.63 mg/dL, the in-hospital mortality rate increases.

Human health and ecological risk assessment of heavy metals in topsoil of different peatland use types.

Peatlands, known for their ability to retain and immobilize heavy metals due to unique waterlogged conditions and organic matter, face challenges when subjected to disturbances such as land use changes. These disruptions alter the organic matter, redox potential, and pH of the peatsoil, potentially influencing the migration, mobilization, and increased availability of stored heavy metals. Peatsoil samples from various peatland use types (improved and semi-natural grassland, forest, industrial cutaway bog) were collected to assess the human health and ecological risk associated with heavy metals (Cd, Cu, Hg, Pb, and Zn) in Co-Offaly, Ireland. Results reveal variations in heavy metal concentrations across peatland use types, with Cd, Hg, and Pb in improved and semi-natural grassland peatsoils exceeding the World Health Organization (WHO) permissible safety limits. Contamination factors (CF) were higher in improved grassland, especially for Cd and Pb, exceeding one. Hakanson potential ecological risk assessment indicates acceptable overall risk levels, though variations exist between improved grassland, unimproved grassland, forest, and industrial cutaway bog. Combined exposure routes (dermal, ingestion and inhalation routes) to all heavy metals do not exceed safe exposure levels (indicating low non-carcinogenic risks. However, the cancer risk (CR) exceeds acceptable thresholds across all use types, with higher CR in improved grassland, especially for children. Overall, the findings emphasize the need for careful consideration of heavy metal risks associated with land use changes in peatlands, particularly in the improved grassland areas.

Advances in Nanomaterials and Colorimetric Detection of Arsenic in Water: Review and Future Perspectives.

Arsenic, existing in various chemical forms such as arsenate (As(V)) and arsenite (As(III)), demands serious attention in water and environmental contexts due to its significant health risks. It is classified as "carcinogenic to humans" by the International Agency for Research on Cancer (IARC) and is listed by the World Health Organization (WHO) as one of the top 10 chemicals posing major public health concerns. This widespread contamination results in millions of people globally being exposed to dangerous levels of arsenic, making it a top priority for the WHO. Chronic arsenic toxicity, known as arsenicosis, presents with specific skin lesions like pigmentation and keratosis, along with systemic manifestations including chronic lung diseases, liver issues, vascular problems, hypertension, diabetes mellitus, and cancer, often leading to fatal outcomes. Therefore, it is crucial to explore novel, cost-effective, and reliable methods with rapid response and improved sensitivities (detection limits). Most of the traditional detection techniques often face limitations in terms of complexity, cost, and the need for sophisticated equipment requiring skilled analysts and procedures, which thereby impedes their practical use, particularly in resource-constrained settings. Colorimetric methods leverage colour changes which are observable and quantifiable using simple instrumentation or even visual inspection. This review explores the colorimetric techniques designed to detect arsenite and arsenate in water. It covers recent developments in colorimetric techniques, and advancements in the role of nanomaterials in colorimetric arsenic detection, followed by discussion on current challenges and future prospects. The review emphasizes efforts to improve sensitivity, selectivity, cost, and portability, as well as the role of advanced materials/nanomaterials to boost the performance of colorimetric assays/sensors towards combatting this pervasive global health concern.

Review of Detection Limits for Various Techniques for Bacterial Detection in Food Samples.

Foodborne illnesses can be infectious and dangerous, and most of them are caused by bacteria. Some common food-related bacteria species exist widely in nature and pose a serious threat to both humans and animals; they can cause poisoning, diseases, disabilities and even death. Rapid, reliable and cost-effective methods for bacterial detection are of paramount importance in food safety and environmental monitoring. Polymerase chain reaction (PCR), lateral flow immunochromatographic assay (LFIA) and electrochemical methods have been widely used in food safety and environmental monitoring. In this paper, the recent developments (2013-2023) covering PCR, LFIA and electrochemical methods for various bacterial species (Salmonella, Listeria, Campylobacter, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)), considering different food sample types, analytical performances and the reported limit of detection (LOD), are discussed. It was found that the bacteria species and food sample type contributed significantly to the analytical performance and LOD. Detection via LFIA has a higher average LOD (24 CFU/mL) than detection via electrochemical methods (12 CFU/mL) and PCR (6 CFU/mL). Salmonella and E. coli in the Pseudomonadota domain usually have low LODs. LODs are usually lower for detection in fish and eggs. Gold and iron nanoparticles were the most studied in the reported articles for LFIA, and average LODs were 26 CFU/mL and 12 CFU/mL, respectively. The electrochemical method revealed that the average LOD was highest for cyclic voltammetry (CV) at 18 CFU/mL, followed by electrochemical impedance spectroscopy (EIS) at 12 CFU/mL and differential pulse voltammetry (DPV) at 8 CFU/mL. LOD usually decreases when the sample number increases until it remains unchanged. Exponential relations (R2 > 0.95) between LODs of Listeria in milk via LFIA and via the electrochemical method with sample numbers have been obtained. Finally, the review discusses challenges and future perspectives (including the role of nanomaterials/advanced materials) to improve analytical performance for bacterial detection.

Biogenic Synthesis of Selenium and Copper Oxide Nanoparticles and Inhibitory Effect against Multi-Drug Resistant Biofilm-Forming Bacterial Pathogens.

Antimicrobial resistance (AMR), caused by microbial infections, has become a major contributor to morbid rates of mortality worldwide and a serious threat to public health. The exponential increase in resistant pathogen strains including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) poses significant hurdles in the health sector due to their greater resistance to traditional treatments and medicines. Efforts to tackle infectious diseases caused by resistant microbes have prompted the development of novel antibacterial agents. Herein, we present selenium and copper oxide monometallic nanoparticles (Se-MMNPs and CuO-MMNPs), characterized using various techniques and evaluated for their antibacterial potential via disc diffusion, determination of minimum inhibitory concentration (MIC), antibiofilm, and killing kinetic action. Dynamic light scattering (DLS), scanning electron microscopy (SEM/EDX), and X-ray diffraction (XRD) techniques confirmed the size-distribution, spherical-shape, stability, elemental composition, and structural aspects of the synthesized nanoparticles. The MIC values of Se-MMNPs and CuO-MMNPs against S. aureus and E. coli were determined to be 125 µg/mL and 100 µg/mL, respectively. Time-kill kinetics studies revealed that CuO-MMNPs efficiently mitigate the growth of S. aureus and E. coli within 3 and 3.5 h while Se-MMNPs took 4 and 5 h, respectively. Moreover, CuO-MMNPs demonstrated better inhibition compared to Se-MMNPs. Overall, the proposed materials exhibited promising antibacterial activity against S. aureus and E. coli pathogens.

Biosensor-Enhanced Organ-on-a-Chip Models for Investigating Glioblastoma Tumor Microenvironment Dynamics.

Glioblastoma, an aggressive primary brain tumor, poses a significant challenge owing to its dynamic and intricate tumor microenvironment. This review investigates the innovative integration of biosensor-enhanced organ-on-a-chip (OOC) models as a novel strategy for an in-depth exploration of glioblastoma tumor microenvironment dynamics. In recent years, the transformative approach of incorporating biosensors into OOC platforms has enabled real-time monitoring and analysis of cellular behaviors within a controlled microenvironment. Conventional in vitro and in vivo models exhibit inherent limitations in accurately replicating the complex nature of glioblastoma progression. This review addresses the existing research gap by pioneering the integration of biosensor-enhanced OOC models, providing a comprehensive platform for investigating glioblastoma tumor microenvironment dynamics. The applications of this combined approach in studying glioblastoma dynamics are critically scrutinized, emphasizing its potential to bridge the gap between simplistic models and the intricate in vivo conditions. Furthermore, the article discusses the implications of biosensor-enhanced OOC models in elucidating the dynamic features of the tumor microenvironment, encompassing cell migration, proliferation, and interactions. By furnishing real-time insights, these models significantly contribute to unraveling the complex biology of glioblastoma, thereby influencing the development of more accurate diagnostic and therapeutic strategies.

Improved empirical mode decomposition method based on amplitude-frequency characteristic of vortex signals.

The vortex flowmeter occupies a vital position in flow measurement with its unique advantages. It is essentially a fluid vibration instrument, and its measurement process is susceptible to interference, which seriously affects measurement accuracy. In particular, at low flow rates, it is an urgent problem to extract vortex signals from the complex noise. Among many signal processing methods, Empirical Mode Decomposition (EMD) is a time-frequency analysis method suitable for nonlinear, non-stationary signals. EMD can adaptively decompose noisy signals into noise and useful signal components arranged from high frequency to low frequency. For the above problems, an innovative, improved EMD method is proposed in this paper. The digital filter is designed according to the amplitude-frequency characteristic of vortex signals. After filtering, the vortex signal is adjusted to a fixed value, and high-frequency noise is filtered. According to the consistency of the filtered signal's amplitude, we design a decomposition stop criterion for EMD to process the output signal of the vortex sensor. This method not only maintains the characteristic of adaptive decomposition in EMD but also completes the automatic extraction of the vortex signal under complex noise. It provides a new comprehensive method for realizing high-precision and anti-interference vortex flowmeters.

Advances in Diagnostic Tools and Therapeutic Approaches for Gliomas: A Comprehensive Review.

Gliomas, a prevalent category of primary malignant brain tumors, pose formidable clinical challenges due to their invasive nature and limited treatment options. The current therapeutic landscape for gliomas is constrained by a "one-size-fits-all" paradigm, significantly restricting treatment efficacy. Despite the implementation of multimodal therapeutic strategies, survival rates remain disheartening. The conventional treatment approach, involving surgical resection, radiation, and chemotherapy, grapples with substantial limitations, particularly in addressing the invasive nature of gliomas. Conventional diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), play pivotal roles in outlining tumor characteristics. However, they face limitations, such as poor biological specificity and challenges in distinguishing active tumor regions. The ongoing development of diagnostic tools and therapeutic approaches represents a multifaceted and promising frontier in the battle against this challenging brain tumor. The aim of this comprehensive review is to address recent advances in diagnostic tools and therapeutic approaches for gliomas. These innovations aim to minimize invasiveness while enabling the precise, multimodal targeting of localized gliomas. Researchers are actively developing new diagnostic tools, such as colorimetric techniques, electrochemical biosensors, optical coherence tomography, reflectometric interference spectroscopy, surface-enhanced Raman spectroscopy, and optical biosensors. These tools aim to regulate tumor progression and develop precise treatment methods for gliomas. Recent technological advancements, coupled with bioelectronic sensors, open avenues for new therapeutic modalities, minimizing invasiveness and enabling multimodal targeting with unprecedented precision. The next generation of multimodal therapeutic strategies holds potential for precision medicine, aiding the early detection and effective management of solid brain tumors. These innovations offer promise in adopting precision medicine methodologies, enabling early disease detection, and improving solid brain tumor management. This review comprehensively recognizes the critical role of pioneering therapeutic interventions, holding significant potential to revolutionize brain tumor therapeutics.

pH and NaCl Optimisation to Improve the Stability of Gold and Silver Nanoparticles' Anti-Zearalenone Antibody Conjugates for Immunochromatographic Assay.

The aim of this research is to define optimal conditions to improve the stability of gold and silver nanoparticles' anti-zearalenone antibody conjugates for their utilisation in lateral flow immunochromatographic assay (LFIA). The Turkevich-Frens method was used to synthesise gold nanoparticles (AuNPs), which were between 10 and 110 nm in diameter. Silver nanoparticles (AgNPs) with a size distribution of 2.5 to 100 nm were synthesised using sodium borohydride as a reducing agent. The onset of AuNP and AgNP aggregation occurred at 150 mM and 80 mM NaCl concentrations, respectively. Stable Au and Ag nanoparticle-antibody conjugates were achieved at 1.2 mM of K2CO3 concentration, which corresponds to the pH value of ≈7. Lastly, the highest degree of conjugation between Au and Ag nanoparticles and anti-zearalenone antibodies was at 4 and 6 µg/mL of antibody concentrations. The optimisation of the conjugation conditions can contribute to better stability of nanoparticles and their antibody conjugate and can improve the reproducibility of results of bioreporter molecules in biosensing lateral flow devices.

Surface-Modified Silver Nanoparticles and Their Encapsulation in Liposomes Can Treat MCF-7 Breast Cancer Cells.

Silver nanoparticles (AgNPs) have emerged as a promising tool for cancer treatment due to their unique physicochemical and biological properties. However, their clinical applications are limited by their potential cytotoxicity caused due to oxidation stress and non-specific cellular uptake pathways. To overcome these barriers, surface modifications of AgNPs have been proposed as an effective strategy to enhance their biocompatibility and specificity toward cancer cells. In this study, AgNPs were synthesised using the chemical reduction method and subsequently conjugated with various capping agents such as Polyvinylpyrrolidone (PVP) and Bovine Serum Albumin (BSA). Further, this study involves the synthesis of liposomes by using dipalmitoyl phosphatidylcholine lipid (DPPC) and cholesterol to increase the biocompatibility and bioavailability of AgNPs to MCF-7 breast cancer cells. In vitro, cytotoxicity studies were performed to determine which surface modification method exhibited the highest cytotoxic effect on the MCF-7 breast cancer cells, which was determined through the MTT assay. The AgNPs conjugated with BSA exhibited the highest cytotoxicity at the lowest dosage, with an IC50 of 2.5 µL/mL. The BSA-AgNPs induced a dose-dependent rise in cytotoxicity through the enhancement of nucleophilic dissolution of the AgNPs in cancer cells. In comparison, the unmodified AgNPs had an IC50 value of 3.0 µL/mL, while the PVP-modified AgNPs had an IC50 of 4.24 µL/mL. AgNPs encapsulated in liposomes had an IC50 value of 5.08 µL/mL, which shows that the encapsulation of AgNPs in liposomes controls their entry into cancer cells. The findings of this research have provided insights into the potential use of surface-modified AgNPs and liposomal encapsulated AgNPs as novel therapeutic tools to overcome the conventional treatment limitations of breast cancer cells.

Soil organic matter carbon chemistry signatures, hydrophobicity and humification index following land use change in temperate peat soils.

Peatlands play a critical role in the global carbon cycle, storing large amounts of carbon because of a net imbalance between primary production and the microbial decomposition of the organic matter. Nevertheless, peatlands have historically been drained for energy sources (e.g. peat briquettes), forestry, or agriculture - practices that could affect the quality of the soil organic matter (SOM) composition, hydrophobicity and humification index. This study compared the effect of land use change on the quality and composition of peatland organic material in Co-Offaly, Ireland. Specifically, drained and grazing peat (grassland), drained and forest plantation peat (forest plantation), drained and industrial cutaway peat (cutaway bog) and an undrained actively accumulating bog (as a reference for natural peatland) were studied. Fourier-transform infrared spectroscopy (FTIR) was used to examine the organic matter quality, specifically the degree of decomposition (DDI), carbon chemistry signatures, hydrophobicity and humification index. The ratio of hydrophobic to hydrophilic group intensities was calculated as the SOM hydrophobicity. In general, there is greater variance in the carbon chemistry signature, such as aliphatic methyl and methylene, C=O stretching of amide groups, aromatic C=C, strong H-bond C=O of conjugated ketones and O-H deformation and C- O stretching of phenolics and secondary alcohols of the peat samples from industrial cutaway bog samples than in the grassland and forest plantation samples. The hydrophobicity and the aromaticity of the soil organic matter (SOM) are significantly impacted by land use changes, with a trend of order active bog > forest plantation > industrial cutaway bog > grassland. A comparison of the degree of decomposition index of the peat from active bog showed a more advanced state of peat degradation in grassland and industrial cutaway bog and, to a lesser extent, in forest plantation.

Surface-Enhanced Raman Analysis of Uric Acid and Hypoxanthine Analysis in Fractionated Bodily Fluids.

In recent years, the disease burden of hyperuricemia has been increasing, especially in high-income countries and the economically developing world with a Western lifestyle. Abnormal levels of uric acid and hypoxanthine are associated with many diseases, and therefore, to demonstrate improved methods of uric acid and hypoxanthine detection, three different bodily fluids were analysed using surface-enhanced Raman spectroscopy (SERS) and high-performance liquid chromatography (HPLC). Gold nanostar suspensions were mixed with series dilutions of uric acid and hypoxanthine, 3 kDa centrifugally filtered human blood serum, urine and saliva. The results show that gold nanostars enable the quantitative detection of the concentration of uric acid and hypoxanthine in the range 5-50 µg/mL and 50-250 ng/mL, respectively. The peak areas of HPLC and maximum peak intensity of SERS have strongly correlated, notably with the peaks of uric acid and hypoxanthine at 1000 and 640 cm-1, respectively. The r2 is 0.975 and 0.959 for uric acid and hypoxanthine, respectively. Each of the three body fluids has a number of spectral features in common with uric acid and hypoxanthine. The large overlap of the spectral bands of the SERS of uric acid against three body fluids at spectra peaks were at 442, 712, 802, 1000, 1086, 1206, 1343, 1436 and 1560 cm-1. The features at 560, 640, 803, 1206, 1290 and 1620 cm-1 from hypoxanthine were common to serum, saliva and urine. There is no statistical difference between HPLC and SERS for determination of the concentration of uric acid and hypoxanthine (p > 0.05). For clinical applications, 3 kDa centrifugal filtration followed by SERS can be used for uric acid and hypoxanthine screening is, which can be used to reveal the subtle abnormalities enhancing the great potential of vibrational spectroscopy as an analytical tool. Our work supports the hypnosis that it is possible to obtain the specific concentration of uric acid and hypoxanthine by comparing the SER signals of serum, saliva and urine. In the future, the analysis of other biofluids can be employed to detect biomarkers for the diagnosis of systemic pathologies.

Design and Development of Magnetic Iron Core Gold Nanoparticle-Based Fluorescent Multiplex Assay to Detect Salmonella.

Salmonella is a bacterial pathogen which is one of the leading causes of severe illnesses in humans. The current study involved the design and development of two methods, respectively using iron oxide nanoparticle (IONP) and iron core gold nanoparticle (ICGNP), conjugated with the Salmonella antibody and the fluorophore, 4-Methylumbelliferyl Caprylate (4-MUCAP), used as an indicator, for its selective and sensitive detection in contaminated food products. Twenty double-blind beverage samples, spiked with Salmonella enteritidis, Staphylococcus aureus, and Escherichia coli, were prepared in sterile Eppendorf® tubes at room temperature. The gold layer and spikes of ICGNPs increased the surface areas. The ratio of the surface area is 0.76 (IONPs/ICGNPs). The comparative sensitivity and specificity of the IONP-based and the ICGNP-based methods to detect Salmonella were determined. The ICGNP method shows the limit of detection is 32 Salmonella per mL. The ICGNPs had an 83.3% sensitivity and a 92.9% specificity value for the presence and detection of Salmonella. The IONP method resulted in a limit of detection of 150 Salmonella per mL, and a 66.7% sensitivity and 83.3% specificity for the presence and detection of Salmonella. The higher surface area of ICGNPs increases the efficiency of detection. The monitoring of Salmonella can thus be achieved by a rapid magnetic fluorescent assay using a smartphone for image capture and analyze, providing quantitative results. The findings from the present study would help to detect Salmonella rapidly in water. It can improve the microbial quality of water and food safety due to the presence of Salmonella in the water environment.

Short-term but not long-term perennial mugwort cropping increases soil organic carbon in Northern China Plain.

Perennial cropping has been an alternative land use type due to its widely accepted role in increasing soil carbon sequestration. However, how soil organic carbon (SOC) changes and its underlying mechanisms under different cropping years are still elusive. A chronosequence (0-, 3-, 6-, 20-year) of perennial mugwort cropping was chosen to explore the SOC dynamics and the underlying mechanisms in agricultural soils of Northern China Plain. The results revealed that SOC first increased and then decreased along the 20-year chronosequence. The similar patterns were also found in soil properties (including soil ammonium nitrogen, total nitrogen and phosphorus) and two C-degrading hydrolytic enzyme activities (i.e., α-glucosidase and ß-glucosidase). The path analysis demonstrated that soil ammonium nitrogen, total nitrogen, and plant biomass affected SOC primarily through the indirect impacts on soil pH, total phosphorus availability, and C-degrading hydrolytic enzyme activities. In addition, the contributions of soil properties are greater than those of biotic factors (plant biomass) to changes in SOC across the four mugwort cropping years. Nevertheless, the biotic factors may play more important roles in regulating SOC than abiotic factors in the long run. Moreover, SOC reached its maximum and was equaled to that under the conventional rotation when cropping mugwort for 7.44 and 14.88 years, respectively, which has critical implications for sustainable C sequestration of agricultural soils in Northern China Plain. Our observations suggest that short-term but not long-term perennial mugwort cropping is an alternative practice benefiting soil C sequestration and achieving the Carbon Neutrality goal in China.

Hydrogel on a Smart Nanomaterial Interface to Carry Therapeutics for Digitalized Glioma Treatment.

Glioma is considered the primary brain tumor to cause brain illnesses, and it is difficult to treat and shows resistance to various routine therapeutics. The most common treatments to cure glioma are the surgical removal of tumors followed by adjuvant chemotherapy and radiation therapy. The latest biocompatible interfaces have been incorporated into therapeutic modalities such as the targeted delivery of drugs using hydrogels to treat and manage brain glioma. This review illustrates the applications of the multimodal hydrogel as the carrier of therapeutics, gene therapy, therapeutic tactics, and glioma devices. The scientific articles were retrieved from 2019 to 2022 on Google Scholar and the Scopus database and screened to determine whether they were suitable for review. The 20 articles that fit the study are summarized in this review. These studies indicated that the sizes of the hydrogel range from 28 nm to 500 nm. There are 16 out of 20 articles that also explain the post-surgical application of hydrogels, and 13 out of 20 articles are employed in 3D culture and other structural manifestations of hydrogels. The pros of the hydrogel include the quick formulation for a sufficient filling of irregular damage sites, solubilizing hydrophobic drugs, continuously slowing drug release, provision of a 3D cell growth environment, improving efficacy, targetability of soluble biomolecules, increasing patient compliance, and decreased side effects. The cons of the hydrogel include difficult real-time monitoring, genetic manipulations, the cumbersome synchronized release of components, and lack of safety data. The prospects of the hydrogel may include the development of electronic hydrogel sensors that can be used to enhance guidance for the precise targeting patterns using patient-specific pathological idiosyncrasies. This technology has the potential to revolutionize the precision medicine approaches that would aid in the early detection and management of solid brain tumors.

Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the drug-loaded gold nanogels are spherical and exist in the size of 180 nm. The single and combinatorial toxicity effects of curcumin- and piperine-loaded Lignin-g-p (NIPAM-co-DMAEMA) gold nanogels were studied against U-251 MG GBM cells. A cytotoxicity analysis displayed anticancer properties. IC50 of curcumin- and piperine-loaded gold nanogels were recorded at 30 µM and 35 µM, respectively. Immunostaining and Western blot analysis confirmed the protein expression of caspase-3 and cleaved caspase-3 in cells treated with drug-loaded nanogels. Kinetic drug release revealed 86% release of hybrid curcumin-piperine from gold nanogel after 250 min at pH 4. Atomic absorption spectroscopic analysis confirmed that the drug-loaded nanogels have better internalization or association with the cancer cells than the GNPs or nano-gels alone. Morphological studies further confirmed that the curcumin and piperine nanogels penetrate the cells via endocytic pathways and induce caspase-3-related apoptosis. The experimental evidence shows the enhanced properties of combinatorial curcumin-piperine gold nanogels (IC50: 21 µM) to overcome the limitations of conventional chemotherapeutic treatments of glioma cells.

Enhanced pyrazolopyrimidinones cytotoxicity against glioblastoma cells activated by ROS-Generating cold atmospheric plasma.

Pyrazolopyrimidinones are fused nitrogen-containing heterocyclic systems, which act as a core scaffold in many pharmaceutically relevant compounds. Pyrazolopyrimidinones have been demonstrated to be efficient in treating several diseases, including cystic fibrosis, obesity, viral infection and cancer. In this study using glioblastoma U-251MG cell line, we tested the cytotoxic effects of 15 pyrazolopyrimidinones, synthesised via a two-step process, in combination with cold atmospheric plasma (CAP). CAP is an adjustable source of reactive oxygen and nitrogen species as well as other unique chemical and physical effects which has been successfully tested as an innovative cancer therapy in clinical trials. Significantly variable cytotoxicity was observed with IC50 values ranging from around 11 µM to negligible toxicity among tested compounds. Interestingly, two pyrazolopyrimidinones were identified that act in a prodrug fashion and display around 5-15 times enhanced reactive-species dependent cytotoxicity when combined with cold atmospheric plasma. Activation was evident for direct CAP treatment on U-251MG cells loaded with the pyrazolopyrimidinone and indirect CAP treatment of the pyrazolopyrimidinone in media before adding to cells. Our results demonstrated the potential of CAP combined with pyrazolopyrimidinones as a programmable cytotoxic therapy and provide screened scaffolds that can be used for further development of pyrazolopyrimidinone prodrug derivatives.

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis to Repair Oxidised Membrane and Enhance Uptake of Nanomaterial in Glioblastoma Multiforme Cells.

Cold atmospheric plasma (CAP) enhances uptake and accumulation of nanoparticles and promotes synergistic cytotoxicity against cancer cells. However, the mechanisms are not well understood. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP. CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidised lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrin-dependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. We demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake. This knowledge will underpin the development of new delivery strategies for theranostic nanoparticles into cancer cells.

Developing Gold Nanoparticles-Conjugated Aflatoxin B1 Antifungal Strips.

Lateral flow immunochromatographic assays are a powerful diagnostic tool for point-of-care tests, based on their simplicity, specificity, and sensitivity. In this study, a rapid and sensitive gold nanoparticle (AuNP) immunochromatographic strip is produced for detecting aflatoxin B1 (AFB1) in suspicious fungi-contaminated food samples. The 10 nm AuNPs were encompassed by bovine serum albumin (BSA) and AFB1 antibody. Thin-layer chromatography, gel electrophoresis and nuclear magnetic resonance spectroscopy were employed for analysing the chemical complexes. Various concentrations of AFB1 antigen (0-16 ng/mL) were tested with AFB1 antibody-BSA-AuNPs (conjugated AuNPs) and then analysed by scanning electron microscopy, ultraviolet-visible spectroscopy, and Zetasizer. The results showed that the AFB1 antibody was coupled to BSA by the N-hydroxysuccinimide ester method. The AuNPs application has the potential to contribute to AFB1 detection by monitoring a visible colour change from red to purple-blue, with a detection limit of 2 ng/mL in a 96-well plate. The lateral flow immunochromatographic strip tests are rapid, taking less than 10 min., and they have a detection capacity of 10 ng/g. The smartphone analysis of strips provided the results in 3 s, with a detection limit of 0.3 ng/g for AFB1 when the concentration was below 10 ng/g. Excellent agreement was found with AFB1 determination by high-performance liquid chromatography in the determination of AFB1 among 20 samples of peanuts, corn, rice, and bread.

A novel, rapid, seedless, in situ synthesis method of shape and size controllable gold nanoparticles using phosphates.

We hereby report a novel synthesis method of size and shape controllable gold nanoparticles that is rapid, in situ and seedless. Unlike most currently employed size and shape controllable synthesis methods, it takes place in a single step under room temperature within ~15 minutes. While mixtures of gold nanospheres around 70 nm and gold nanoplates with width ranging from 100 nm to 1000 nm can be synthesized in about 15 minutes by standard synthesis method using N-2-hydroxyethylpiperazine-N-2-ethanesulphonic acid (HEPES) to reduce Au(III), gold nanoflowers or mixtures of smaller gold nanospheres and nanoplates can be synthesized with the addition of disodium phosphate (Na2HPO4) or monosodium phosphate (NaH2PO4), respectively. Increasing the concentration of phosphate added significantly reduces the formation time of gold nanoparticles to seconds. By increasing the molar ratio of Na2HPO4: HEPES and NaH2PO4: HEPES, the size of gold nanoflowers and gold nanoparticle mixtures can be tuned from ~60 nm down to 1 nm and from ~70 nm to ~2.5 nm, respectively. The systematic structural changes are accompanied by similarly systematic colour changes associated with shifting of the surface plasmon resonance. The proposed mechanism of the synthesis process is also presented.