Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes.

For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling and antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there has been limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal senescence, brain volume loss, the attenuation of gamma oscillations in electroencephalograms, and the oxidation of lipids in the plasma and mitochondrial membranes. We surmise that the aberrant activation of the aryl hydrocarbon receptor by toxins derived from gut microbes or the environment drives premature cellular and neuronal senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including the impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: (1) to summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders, and (2) to discuss novel strategies for improving long-term outcomes in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor antagonists.

It is time to reconsider the use of naturally-occurring endotoxins in endotoxin recovery studies: Part 2 of a BioPhorum harmonized endotoxin recovery study.

The evaluation of Naturally Occurring Endotoxins (NOEs) for Low Endotoxin Recovery (LER) studies has been a topic in the industry and regulatory agencies have been hesitant to endorse NOE use in LER studies over purified Lipopolysaccharide (LPS) standards such as Control Standard Endotoxin (CSE) or Reference Standard Endotoxin (RSE). In a recent study involving 11 BioPhorum member companies across 13 sites, NOEs prepared in high and low nutrient conditions were evaluated in two common monoclonal antibody buffer formulations: 10 mM Sodium Citrate, 0.05 % Polysorbate 80, pH 6.0 and 20 mM Histidine, 0.05 % Polysorbate 80, pH 6.0. 12 g-negative bacterial isolates were used to prepare NOE analytes, which were spiked into the formulation buffers. Additionally, the NOEs were spiked into Limulus Amebocyte Lysate (LAL) reagent water as controls and purified LPS into the citrate/polysorbate buffer as the LER control. Results showed the average of three runs per organism was >50 % recovery, at the conclusion of the 7-day period, regardless of nutrient culture preparation conditions. Furthermore, purified LPS controls became undetectable (<50 % recovery) in the citrate/polysorbate buffer, highlighting the presence of LER. These findings highlight the potential value of using NOEs from relevant manufacturing facilities to assess overall risk when purified LPS recovery is insufficient.

Anti-biofilm activities and antibiotic synergy of naturally occurring compounds against drug-resistant rapidly growing mycobacteria.

Some naturally occurring compounds, known for their antimicrobial activities, have been employed as food additives. However, their efficacy in treating infections caused by antibiotic-resistant bacteria is yet to be fully explored. Rapidly growing mycobacteria (RGM), a category within nontuberculous mycobacteria (NTM), are prevalent in various environments and can lead to infections in humans. The rise of antimicrobial resistance within RGM is a documented concern. In this study, we reported that four specific natural compounds effectively inhibited the growth and biofilm formation of three key RGM pathogens M. abscessus, M. fortuitum, and M. chelonae. We screened 12 natural compounds for their effectiveness against antibiotic-resistant clinical strains of RGM. Four compounds showed significant inhibitory effects from the most effective to least: trans-cinnamaldehyde, carvacrol, gentisaldehyde, and phloroglucinaldehyde. In the analysis of time-killing kinetics, gentisaldehyde and phloroglucinaldehyde displayed bactericidal activity while trans-cinnamaldehyde and carvacrol exhibited bacteriostatic effects. At 1× minimal inhibition concentrations, these compounds significantly reduced biofilm formation in all three RGM species to levels between 2.9% and 20.5% relative to controls. Checkerboard assays indicated synergistic interactions between these four compounds and antibiotics such as amikacin, clarithromycin, and linezolid. Of these 12 compound-antibiotic combinations, the pairs of carvacrol-linezolid, carvacrol-amikacin, and gentisaldehyde-clarithromycin demonstrated the most synergy against multiple RGM strains. Moreover, two other compounds citral and geraniol showed synergism with all three test antibiotics. Time-killing assays further confirmed most of synergistic combinations identified in the checkerboard tests. Our research suggests the potential of these essential oils and phenolic aldehydes, both individually and in combination with antibiotics, in treating RGM infections. In addition, this work illuminates applications of these natural compounds in environmental remediation to mitigate bacterial persistence for the control of infectious diseases. IMPORTANCE: The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus, M. fortuitum, and M. chelonae. We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.

Developing an SNP dataset for efficiently evaluating soybean germplasm resources using the genome sequencing data of 3,661 soybean accessions.

BACKGROUND: Single nucleotide polymorphism (SNP) markers play significant roles in accelerating breeding and basic crop research. Several soybean SNP panels have been developed. However, there is still a lack of SNP panels for differentiating between wild and cultivated populations, as well as for detecting polymorphisms within both wild and cultivated populations. RESULTS: This study utilized publicly available resequencing data from over 3,000 soybean accessions to identify differentiating and highly conserved SNP and insertion/deletion (InDel) markers between wild and cultivated soybean populations. Additionally, a naturally occurring mutant gene library was constructed by analyzing large-effect SNPs and InDels in the population. CONCLUSION: The markers obtained in this study are associated with numerous genes governing agronomic traits, thus facilitating the evaluation of soybean germplasms and the efficient differentiation between wild and cultivated soybeans. The natural mutant gene library permits the quick identification of individuals with natural mutations in functional genes, providing convenience for accelerating soybean breeding using reverse genetics.

Plants, Microorganisms and Their Metabolites in Supporting Asbestos Detoxification-A Biological Perspective in Asbestos Treatment.

Many countries banned asbestos due to its toxicity, but considering its colossal use, especially in the 1960s and 1970s, disposing of waste containing asbestos is the current problem. Today, many asbestos disposal technologies are known, but they usually involve colossal investment and operating expenses, and the end- and by-products of these methods negatively impact the environment. This paper identifies a unique modern direction in detoxifying asbestos minerals, which involves using microorganisms and plants and their metabolites. The work comprehensively focuses on the interactions between asbestos and plants, bacteria and fungi, including lichens and, for the first time, yeast. Biological treatment is a prospect for in situ land reclamation and under industrial conditions, which can be a viable alternative to landfilling and an environmentally friendly substitute or supplement to thermal, mechanical, and chemical methods, often characterized by high cost intensity. Plant and microbial metabolism products are part of the green chemistry trend, a central strategic pillar of global industrial and environmental development.

The common marmoset as a translational model of age-related osteoarthritis.

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression. The purpose of this study was to determine whether the common marmoset is a faithful model of human age-related knee OA. Semi-quantitative microCT scoring revealed greater radiographic OA in geriatric versus adult marmosets, and the age-related increase in OA prevalence was similar between marmosets and humans. Quantitative assessments indicate greater medial tibial cortical and trabecular bone thickness and heterogeneity in geriatric versus adult marmosets which is consistent with an age-related increase in focal subchondral bone sclerosis. Additionally, marmosets displayed an age-associated increase in synovitis and calcification of the meniscus and patella. Histological OA pathology in the medial tibial plateau was greater in geriatric versus adult marmosets driven by articular cartilage damage, proteoglycan loss, and altered chondrocyte cellularity. The age-associated increase in medial tibial cartilage OA pathology and meniscal calcification was greater in female versus male geriatric marmosets. Overall, marmosets largely replicate human OA as evident by similar 1) cartilage and skeletal morphology, 2) age-related progression in OA pathology, and 3) sex differences in OA pathology with increasing age. Collectively, these data suggest that the common marmoset is a highly translatable model of the naturally occurring, age-related OA seen in humans.

Assessment of environmental radiological impact in former metallic mines in Extremadura (Spain): A case study.

Metal mining in the Extremadura region was very important in the 19th and 20th centuries. However, due to different reasons the great majority of mines ceased operations, leading to plenty of abandoned mining sites, most of them with on-site waste dumps. Although metal extraction is not radioactive per se, it is considered a NORM activity. In this study, three former mining sites, in which Pb-V-Zn-Ag, Pb-Ag, and Pb-Zn were extracted, were selected to assess the radiological impact on the population and the environment. The external γ exposure was estimated by determining the effective dose and elaborating isodose maps of the sites. The presence of the mining sites increased up to 0.41 mSv/y the effective dose over the surrounding background, which is below the reference value of 1 mSv/y. In only one mining site, the uranium and radium activity concentration of waste dumps were higher than the surrounding soil. The soil to plant (wild grass) transfer factors were similar to other reported values without the influence of NORM activities. So, no enhanced transfer of radionuclides was observed. The radiological impact on the environment was assessed by the risk to non-human biota using the tiered approach developed in ERICA Tool. The sum of the risk quotients of all considered radionuclides in the most conservative Tier 1 was below 1. Total dose rates for several terrestrial Reference Animal and Plants (RAPs) were estimated using Tier 3, obtaining values below 40 µGy/h. Therefore, the impact on non-human biota can be considered as negligible.

Fractionation of environmental radioactivity in road dust from a megacity: external and internal health risks.

Naturally occurring radioactive materials (NORMs: 232Th, 226Ra, 40K) can reach our respiratory system by breathing of road dust which can cause severe health risks. Targeting the pioneering consideration of health risks from the NORMs in road dust, this work reveals the radioactivity abundances of NORMs in road dust from a megacity (Dhaka) of a developing country (Bangladesh). Bulk chemical compositions of U, Th, and K obtained from neutron activation analysis were converted to the equivalent radioactivities. Radioactivity concentrations of 226Ra, 232Th, and 40K in road dust ranged from 60-106, 110-159, and 488-709 Bq kg-1 with an average of 84.4 ± 13.1, 126 ± 11, and 549 ± 48 Bq kg-1, respectively. Estimated 226Ra, 232Th, and 40K radioactivities were, respectively, 1.7-3.0-, 3.7-5.3-, and 1.2-1.8-folds greater than the affiliated world average values. Mechanistic pathway of NORMs' enrichment and fractionation relative to the major origin (pedosphere) were evaluated concerning the water logging, relative solubility-controlled leaching and translocation, climatic conditions, and aerodynamic fractionations (dry and wet atmospheric depositions). Computation of customary radiological risk indices invokes health risks. Noticing the ingress of NOMR-holding dust into the human respiratory system along with the associated ionizing radiations, the computed radiological indices represent only the least probable health hazards. Nevertheless, in real situations, α-particles from the radioactive decay products of 232Th and 238U can create acute radiation damages of respiratory system. Policymakers should emphasize on limiting the dust particle evolution, and public awareness is required to alleviate the health risks.

Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers.

Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.

Naturally Occurring and Widespread Resistance to Bioactive Natural Products.

Naturally occurring resistances diminish the effectiveness of antibiotics, and present significant challenges to human health. Human activities are usually considered as the main drivers of the dissemination of antibiotic resistance, however, the origin of the clinical antibiotic resistance can be traced to the environmental microbes, and the clinically relevant resistance determinants have already pre-existed in nature before the antibiotics come into clinic. In this concept, we present the naturally occurring and widespread resistance determinants recently discovered during the biosynthesis study of bioactive compounds. These widely prevalent resistances in environmental microbes, including antibiotic producers and non-producers, advance the understanding of the origin of resistance, and provide prediction for the clinically relevant resistance to aid in the rational design of more effective drug analogues to combat resistance.

The Dynamical Hypothesis in Situ: Challenges and Opportunities for a Dynamical Social Approach to Interpersonal Coordination.

Over the past three decades, Van Gelder's dynamical hypothesis has been instrumental in reconceptualizing the ways in which perception-action-cognition unfolds over time and in context. Here, I examine how the dynamical approach has enriched the theoretical understanding of social dynamics within cognitive science, with a particular focus on interpersonal coordination. I frame this review around seven principles in dynamical systems: three that are well-represented in interpersonal coordination research to date (emergent behavior, context-sensitive behavior, and attractors) and four that could be useful opportunities for future growth (hysteresis, sensitivity to initial conditions, equifinality, and reciprocal compensation). In addition to identifying specific promising lines of theoretical inquiry, I focus on the significant potential afforded by computationally intensive science-especially in naturally occurring data or trace data. Building on the foundation laid over the past three decades, I argue that looking to increasingly situated and naturalistic settings (and data) is not only necessary to realize the full commitment to the dynamical hypothesis but is also critical to building parsimonious and principled theories of social phenomena.

Evaluation of soil radioactivity in the areas of underground nuclear explosions at the Pomuk gas field site in Uzbekistan.

This study investigates soil radioactivity at the Pomuk gas field in Uzbekistan, a region with history of underground nuclear activity. Using a NaI (Tl) scintillation gamma spectrometer, soil samples were analyzed for concentrations of 232Th, 226Ra, 40K, and 137Cs. Concentrations were found to be in the range of 19.0-31.0 Bq/kg for 232Th, 12.0-32.0 Bq/kg for 226Ra, 450.0-634.0 Bq/kg for 40K, and 2.4-11.0 Bq/kg for 137Cs. Surface radon flux density was measured using a coal sorbent-based passive method, with values ranging from 26.1 to 79.0 mBq/m2s. Mean activity values for radium equivalent (Raeq) and gamma representative level index (Iγ) were calculated to be 75.2-96.5 Bq/kg and 0.3-0.4 Bq/kg, respectively. The absorbed airborne gamma dose rates (GDR) varied between 41.0 and 52.0 nGy/h, while annual effective dose rates (AEDR) were 0.3-0.4 µSv/year. The radiological risk assessment indicates the area is within safe limits for the population and environment, providing a foundation for future radiological monitoring programs.

Modeling naturally-occurring Vibrio parahaemolyticus in post-harvest raw shrimps.

There is little known about the growth and survival of naturally-occurring Vibrio parahaemolyticus in harvested raw shrimps. In this study, the fate of naturally-occurring V. parahaemolyticus in post-harvest raw shrimps was investigated from 4℃ to 30℃ using real-time PCR combined with propidium monoazide (PMA-qPCR). The Baranyi-model was used to fit the growth and survival data. A square root model and non-linear Arrhenius model was then used to quantify the parameters derived from the Baranyi-model. The results showed that naturally-occurring V. parahaemolyticus were slowly inactivated at 4℃ and 7℃ with deactivation rates of 0.019 Log CFU/g/h and 0.025 Log CFU/g/h. Conversely, at 15, 20, 25, and 30 °C, the average maximum growth rates (µmax) of naturally-occurring V. parahaemolyticus were determined to be 0.044, 0.105, 0.179 and 0.336 Log CFU/g/h, accompanied by the average lag phases (λ) of 15.5 h, 7.3 h, 4.4 h and 3.7 h. The validation metrics, Af and Bf, for both the square root model and non-linear, indicating that the model had a good ability to predict the growth behavior of naturally-occurring V. parahaemolyticus in post-harvest raw shrimps. Furthermore, a comparative exploration between the growth of artificially contaminated V. parahaemolyticus in cooked shrimps and naturally-occurring V. parahaemolyticus in post-harvest raw shrimps revealed intriguing insights. While no substantial distinction in deactivation rates emerged at 4 °C and 7 °C (P > 0.05), a discernible disparity in growth rates was observable at 15 °C, 20 °C, 25 °C, and 30 °C, with the former surpassing the latter. Which indicated the risk of V. parahaemolyticus using models derived from cooked shrimps may be biased. Our study also unveiled a discernible seasonal effect. The µmax and λ of V. parahaemolyticus in shrimps harvested in summer were similar to those harvested in autumn, while the initial and maximum bacterial concentration harvested in summer were higher than those harvested in autumn. This predictive microbiology model of naturally-occurring V. parahaemolyticus in raw shrimps provides relevance to modelling growth in situ.

Assessing the exposure situations with naturally occurring radioactive materials across European countries by means of the e-NORM survey.

Despite the EU states being under the umbrella of the European Directive 2013/59/Euratom, a certain degree of heterogeneity may be noticed in the implementation of EU recommendations concerning regulation and handling of NORM into national legislation and practice. This is mainly a result of the still existing incomplete international knowledge about different phenomena related to NORM. Therefore, the attempt to advance the understanding of the behaviour and exposure of NORM is at the core of the European RadoNorm project. Within this context, an international survey on NORM has been prepared. The goals of the survey were to gather information and data from European countries that will contribute making an updated and/or new (a) systematic overview of NORM exposure situations and their analysis with respect to different radiation protection aspects, (b) knowledge about applied radioecological models in a variety of NORM exposure situations to improve evaluation of possible exposure doses and risk for population and workers, as well as of environmental risk, and (c) overview of overall mitigation measures applied in NORM involving industries, and possible remediation activities applied at NORM affected legacy sites. The survey is built upon an extended list of NORM-involving industries and processes, covers general aspects of NORM, presence of multi-stressors, as well as practical procedures applied in management and regulation, also in the context of a circular economy. The survey responses were obtained from 19 countries. An analysis of survey responses proved that NORM control is still a complex issue for many countries, and the recently-introduced regulatory solutions require further interpretation for developing procedures and good practices. The present work provides a detailed analysis of the survey responses with respect to regulation, management and investigation of NORM.

Excess lifetime cancer risk due to ingestion of fish from a dam reservoir associated with a nuclear facility in Brazil.

Fish from a Funil dam reservoir associated with a Nuclear Fuel Factory were sampled aiming to assess the radiological risk due to ingestion. Funil dam reservoir is a strategic site, once it receives effluent from the industrial complex that performs isotopic enrichment of uranium and conversion of UF6. The mean activity concentrations obtained for 40K, 226Ra, 228Ra and 228Th were 57.81, 0.41, 0.92 and 0.49 Bq·kg-1, respectively. Lifetime cancer risk was estimated in ∼10-5 and no action needs to be taken.

Unleashing nature's potential and limitations: Exploring molecular targeted pathways and safe alternatives for the treatment of multiple sclerosis (Review).

Driven by the limitations and obstacles of the available approaches and medications for multiple sclerosis (MS) that still cannot treat the disease, but only aid in accelerating the recovery from its attacks, the use of naturally occurring molecules as a potentially safe and effective treatment for MS is being explored in model organisms. MS is a devastating disease involving the brain and spinal cord, and its symptoms vary widely. Multiple molecular pathways are involved in the pathogenesis of the disease. The present review showcases the recent advancements in harnessing nature's resources to combat MS. By deciphering the molecular pathways involved in the pathogenesis of the disease, a wealth of potential therapeutic agents is uncovered that may revolutionize the treatment of MS. Thus, a new hope can be envisioned in the future, aiming at paving the way toward identifying novel safe alternatives to improve the lives of patients with MS.

The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson's Disease.

The accumulation and aggregation of alpha-synuclein (α-Syn) are pathological processes associated with Parkinson's disease, indicating that the regulation of protein is a crucial etiopathological mechanism. Interestingly, human serum and cerebrospinal fluid contain autoantibodies that recognize α-Syn. This potentially demonstrates an already existing, naturally decomposing, and protective system. Thus, quantitative or qualitative alterations, such as the modified antigen binding of so-called naturally occurring autoantibodies against α-Syn (nAbs-α-Syn), may induce disease onset and/or progression. We investigated the serum titers and binding characteristics of nAbs-α-Syn in patients suffering from sporadic Parkinson's disease (n = 38), LRRK2 mutation carriers (n = 25), and healthy controls (n = 22). METHODS: Titers of nAbs-α-Syn were assessed with ELISA and binding affinities and kinetics with SPR. Within the patient cohort, we discriminated between idiopathic and genetic (LRRK2-mutated) variants. RESULTS: ELISA experiments revealed no significant differences in nAbs-α-Syn serum titers among the three cohorts. Moreover, the α-Syn avidity of nAbs-α-Syn was also unchanged. CONCLUSIONS: Our findings indicate that nAbs-α-Syn concentrations or affinities in healthy and diseased persons do not differ, independent of mutations in LRRK2.

Pharmacological Potential of Bioactive Peptides for the Treatment of Diseases Associated with Alzheimer's and Brain Disorders.

Bioactive peptides are a promising class of therapeutics for the treatment of diseases associated with Alzheimer's and brain disorders. These peptides are derived from naturally occurring proteins and have been shown to possess a variety of beneficial properties. They may modulate neurotransmitter systems, reduce inflammation, and improve cognitive performance. In addition, bioactive peptides have the potential to target specific molecular pathways involved in the pathogenesis of Alzheimer's and brain disorders. For example, peptides have been shown to interact with amyloid-beta, a major component of amyloid plaques found in Alzheimer's disease, and have been shown to reduce its accumulation in the brain. Furthermore, peptides have been found to modulate the activity of glutamate receptors, which are important for memory and learning, as well as to inhibit the activity of enzymes involved in the formation of toxic amyloid-beta aggregates. Finally, bioactive peptides have the potential to reduce oxidative stress and inflammation, two major components of many neurological disorders. These peptides could be used alone or in combination with traditional pharmacological treatments to improve the management of diseases associated with Alzheimer's and brain disorders.

Stimuli-responsive (nano)architectures for phytochemical delivery in cancer therapy.

The use of phytochemicals for purpose of cancer therapy has been accelerated due to resistance of tumor cells to conventional chemotherapy drugs and therefore, monotherapy does not cause significant improvement in the prognosis and survival of patients. Therefore, administration of natural products alone or in combination with chemotherapy drugs due to various mechanisms of action has been suggested. However, cancer therapy using phytochemicals requires more attention because of poor bioavailability of compounds and lack of specific accumulation at tumor site. Hence, nanocarriers for specific delivery of phytochemicals in tumor therapy has been suggested. The pharmacokinetic profile of natural products and their therapeutic indices can be improved. The nanocarriers can improve potential of natural products in crossing over BBB and also, promote internalization in cancer cells through endocytosis. Moreover, (nano)platforms can deliver both natural and synthetic anti-cancer drugs in combination cancer therapy. The surface functionalization of nanostructures with ligands improves ability in internalization in tumor cells and improving cytotoxicity of natural compounds. Interestingly, stimuli-responsive nanostructures that respond to endogenous and exogenous stimuli have been employed for delivery of natural compounds in cancer therapy. The decrease in pH in tumor microenvironment causes degradation of bonds in nanostructures to release cargo and when changes in GSH levels occur, it also mediates drug release from nanocarriers. Moreover, enzymes in the tumor microenvironment such as MMP-2 can mediate drug release from nanocarriers and more progresses in targeted drug delivery obtained by application of nanoparticles that are responsive to exogenous stimulus including light.

Airborne gamma-ray mapping using fixed-wing vertical take-off and landing (VTOL) uncrewed aerial vehicles.

Low-cost uncrewed aerial vehicles (UAVs) are replacing manned aircraft for airborne radiation mapping applications such as nuclear accident response scenarios or surveying ore deposits and mine sites because of their cost-effectiveness and ability to conduct surveys at lower altitude compared to manned counterparts. Both multi-rotor UAVs and fixed-wing UAVs are well established technologies for aerial radiation mapping applications, however, both also have drawbacks: multi-rotor UAVs are very limited in flight time and range, and fixed-wing UAVs usually require facilities for take-off and landing. A compromise solution is introduced in this work, using a fixed-wing vertical take-off and landing (VTOL) UAV that combines the flexibility of a multi-rotor UAV with the range and flight time of a fixed-wing UAV. The first implementation of a VTOL with radiation mapping capabilities is presented, based on a commercial WingtraOne UAV augmented with CsI scintillator and CZT semiconductor gamma spectrometers. The radiation mapping capabilities of the prototype are demonstrated in a case study, mapping the distribution of radionuclides around the South Terras legacy uranium mine in the south of England, United Kingdom, and the results are compared with previous studies using multi-rotor and manned aircraft to survey the same area.