BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

INTRODUCTION: Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. MATERIALS AND METHODS: Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. RESULTS: In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. CONCLUSIONS: BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems.

Hydrothermal conditioning of oleaginous yeast cells to enable recovery of lipids as potential drop-in fuel precursors.

BACKGROUND: Lipids produced using oleaginous yeast cells are an emerging feedstock to manufacture commercially valuable oleochemicals ranging from pharmaceuticals to lipid-derived biofuels. Production of biofuels using oleaginous yeast is a multistep procedure that requires yeast cultivation and harvesting, lipid recovery, and conversion of the lipids to biofuels. The quantitative recovery of the total intracellular lipid from the yeast cells is a critical step during the development of a bioprocess. Their rigid cell walls often make them resistant to lysis. The existing methods include mechanical, chemical, biological and thermochemical lysis of yeast cell walls followed by solvent extraction. In this study, an aqueous thermal pretreatment was explored as a method for lysing the cell wall of the oleaginous yeast Rhodotorula toruloides for lipid recovery. RESULTS: Hydrothermal pretreatment for 60 min at 121 °C with a dry cell weight of 7% (w/v) in the yeast slurry led to a recovery of 84.6 ± 3.2% (w/w) of the total lipids when extracted with organic solvents. The conventional sonication and acid-assisted thermal cell lysis led to a lipid recovery yield of 99.8 ± 0.03% (w/w) and 109.5 ± 1.9% (w/w), respectively. The fatty acid profiles of the hydrothermally pretreated cells and freeze-dried control were similar, suggesting that the thermal lysis of the cells did not degrade the lipids. CONCLUSION: This work demonstrates that hydrothermal pretreatment of yeast cell slurry at 121 °C for 60 min is a robust and sustainable method for cell conditioning to extract intracellular microbial lipids for biofuel production and provides a baseline for further scale-up and process integration.

BIO 300 Attenuates Whole Blood Transcriptome Changes in Mice Exposed to Total-Body Radiation.

Development of radiation medical countermeasures under the U.S. Food and Drug Administration Animal Rule requires the capability to translate an effective animal-to-human drug dose. One method of human dose translation is using a biomarker and determining drug doses that modulate the biomarker to the desired level. BIO 300 Oral Powder (BIO 300) is a prophylactic radiation medical countermeasure that is currently being developed following the Animal Rule. The present study aimed to identify biomarkers that can be used for human dose conversion by conducting transcriptomics of whole blood collected from BIO 300-treated CD2F1 mice in the presence and absence of total-body irradiation (TBI). Unirradiated mice were treated with vehicle or 50, 100, or 200 mg/kg BIO 300, and irradiated mice were treated with 200 mg/kg or BIO 300 or vehicle prior to TBI. Whole-blood samples were collected after the last dose of the drug and after irradiation. RNA sequencing demonstrated 100 and 200 mg/kg of BIO 300 doses caused significantly more differential gene expression at 48 h after drug dose compared to 50 mg/kg of BIO 300 (7648, 7680, and 55 significantly differently expressed genes, respectively). Interestingly, following TBI, there were no significantly differentially expressed genes between vehicle- and BIO 300-treated mice. Despite the lack of significant changes in gene expression, the transcriptomic profiles in both groups indicated differential changes in signaling pathways. Pathway analysis of the transcriptome profile from vehicle-treated/TBI mice revealed that many inflammatory signaling pathways were activated in these animals. Signaling pathways enriched in BIO 300-treated/TBI mice were involved in cellular stress and immune response and were predicted to be inhibited. In all, four signaling pathways of interest were identified that were differentially enriched in irradiated animals treated with BIO 300: pathogen-induced cytokine storm signaling, S100 family signaling, pulmonary fibrosis idiopathic signaling, and wound-healing signaling. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation.

The Human Monkeypox Virus and Host Immunity: Emerging Diagnostic and Therapeutic Challenges.

This article explores the Human Monkeypox Virus (MPV), a contagious virus that causes disease in both vertebrates and insects. It originated in Denmark in 1958 and expanded beyond Africa during the 1970s. The virus was initially detected in the United States in 2003 following the hospitalisation of a toddler who had been bitten by a prairie dog. The article examines the identification of the virus, its categorization into two genetic groups with dif-ferent levels of harmfulness, and its genetic changes over time due to specific influences. Additionally, it investigates the immunological reaction to MPXV, encompassing both the innate and adaptive systems. The essay also addresses the diagnostic difficulties presented by MPXV's resemblance to other orthopoxviruses and the progress made in molecular diagnos-tics. The paper analyses different therapeutic interventions, such as tecovirimat, an antiviral medication, and JYNNEOS, a vaccine, in terms of their efficacy, potential drawbacks, and the difficulties encountered in managing outbreaks. The future outlook emphasises the ne-cessity of inventive research methodologies, worldwide monitoring, and individualised med-ical treatments to counteract the dissemination of MPXV and alleviate its consequences on public health.

Resecting Lower Segment Inferior Vena Cava Leiomyosarcoma With Middle Segment Extension While Avoiding Renal Morbidity.

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare and aggressive mesenchymal tumor, with less than 400 reported cases to date. Complete resection of the tumor with clear margins is the only proven curative treatment, providing survival benefits. Nonetheless, leiomyosarcomas in the middle segment or those extending up to it within the inferior vena cava (IVC) frequently necessitate renal reimplantation or nephrectomy, with rates varying between 56% and 75%. In this case report, we present a 65-year-old female with lower segment IVC leiomyosarcoma with middle segment extension, successfully resected and reconstructed while avoiding associated renal reimplantation or nephrectomy morbidity.

ABLs and transmembrane kinases shape extracellular auxin perception.

Auxin is a key phytohormone, but the mechanism underlying apoplastic auxin perception has remained elusive. Yu et al. recently demonstrated that the interaction of two novel apoplast-localized auxin-binding protein 1 (ABP1)-like proteins, ABL1 and ABL2, with transmembrane kinases (TMKs) shapes extracellular auxin perception in both an overlapping and an ABP1-independent manner.

Unveiling the Metabolic Maze: FDG PET/CT Findings in Peritoneal Carcinomatosis - A Case Series.

Peritoneal carcinomatosis (PC), the spread of cancer cells in the peritoneum, is a significant concern in advanced gastrointestinal and gynecological cancers. This case series includes findings on the appearance and pattern of PC on 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT). The primary sources of peritoneal dissemination are direct invasion from abdominal or pelvic tumors and metastatic spread from distant tumors. The accurate preoperative diagnosis and quantification of PC play a vital role in determining the appropriate treatment approach, with a particular emphasis on surgical planning. Several imaging modalities have been employed in preoperative evaluation, such as computed tomography (CT), magnetic resonance imaging (MRI), and 18F-FDG PET/CT. Among these modalities, 18F-FDG PET/CT has demonstrated improved anatomical localization and accurate information about the nature of pathological findings. The case series showcases four cases that illustrate the imaging characteristics of PC on FDG PET/CT. FDG PET/CT plays a vital role in diagnosing and assessing PC, aiding in its detection, staging, and treatment planning. It surpasses conventional imaging techniques in identifying and characterizing lesions and detecting the primary tumor site in cases where its location is unknown. Furthermore, FDG PET/CT additionally assists in evaluating treatment response and monitoring disease progression, providing insights into treatment effectiveness and guiding patient management decisions.

Enhancement of Cognitive Function by Andrographolide-Loaded Lactose ß-Cyclodextrin Nanoparticles: Synthesis, Optimization, and Behavioural Assessment.

This study investigates whether Andrographolide-loaded Lactose ß-Cyclodextrin (ALN-ßCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to ß-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-ßCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements (p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-ßCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials.

Optimizing CaCl2-mediated transformation of Pseudomonas aeruginosa SDK-6 with pJN105 using OFAT: A novel and efficient cloning approach.

Cloning and expression of a gene in the desired host is required for optimum production in recombinant strains. The present research is the first attempt to optimize the physiological conditions for the transformation of Pseudomonas aeruginosa SDK-6 with pJN105. Different factors, such as inoculum size, incubation period, heat shock temperature, and heat shock time were optimized using one factor at a time (OFAT) followed by the selection of transformants using gentamicin resistance marker. The maximum number of transformants (2.002 ± 0.077 × 105 cfu/ µg of plasmid DNA) were reported with 0.5% (v/v) inoculum, an incubation period of 3 h, and heat shock treatment at 50 °C for 1 min. An overall 12-fold increase in transformation efficiency was observed. The presence of a 6055 bp band on agarose gel confirmed the transformation of Pseudomonas aeruginosa with the vector pJN105.

Tracking and managing the water-food-environment-ecosystem (WFEE) nexus in groundwater irrigation districts using system dynamics modelling.

Groundwater irrigation districts, which play a crucial role in the Earth's critical zone, are confronted with numerous challenges, including water scarcity, pollution, and ecological degradation. These issues come from multiple systems and are linked to a groundwater-dominated water-food-environment-ecosystem nexus problem related to agricultural activities (WFEE). There is a pressing need for the scientific characterization and evaluation of the WFEE nexus in groundwater irrigation districts to assure high-quality, sustainable development. Furthermore, it is critical to provide practical and efficient regulations at the farmer level to uphold the health of this nexus. This paper presents a mapping network that focuses on groundwater irrigation districts. The network aims to convert the restriction indicators utilized to maintain the health of the WFEE nexus (at the irrigation district scale) into the targets employed to manage farmers' living and agricultural activities (at the farmer scale). Additionally, a system dynamics model is created to track and manage the interacting relationships between the WFEE nexus and farmers' living and agricultural activities. This proposed model employs a structured parameter system comprising targets, state parameters, regulatory parameters, and evaluation parameters. This system can get insight into the status of the WFEE nexus at the farmer level using state parameters, induce tailored management and regulation measures using regulatory parameters, assess the effectiveness of various measures using the evaluation parameters, and finally provide decision support to enhance the health of the WFEE nexus. The findings from the research conducted in the Yong'an groundwater irrigation district demonstrated that the model accurately described the relationship between the WFEE nexus and farmers' activities in groundwater irrigation districts. Furthermore, the model responded strongly to a variety of improvement strategies, including adjustments in planting area, optimization of planting pattern, improvement of irrigation method, and implementation of agronomic measures. As a result, it provided farmers with decision support for applying agricultural management methods and addressing the WFEE nexus problem in groundwater irrigation areas.

2D-Bio-FETs for sensitive detection of cardiovascular diseases.

The biosensing industry has seen exponential growth in the past decade. Impact of biosensors in the current scenario cannot be overlooked. Cardiovascular diseases (CvDs) have been recognized as one of the major causes for millions of deaths globally. This mortality can be minimized by early and accurate detection/diagnosis of CvDs with the help of biosensing devices. This also presents a global market opportunity for the development of biosensors for CvDs. A vast variety of biosensing methods and devices have been developed for this problem. Most of commercially available platforms for CvD detection rely on optical (fluorometric and colorimetric analysis) techniques using serum biomarkers since optical testing is the gold standard in medical diagnosis. Field effect transistors-based biosensors, termed as Bio-FETs, are the upcoming devices for blood or serum analyte detection due to excellent sensitivity, low operational voltage, handheld device structure and simple chip-based operation. Further, the discovery of two dimensional (2D) materials and their integration with conventional FETs has improved the overvoltage problem, sensitivity and strict operating conditions as compared to conventional FETs. Graphene-FETs based biosensing devices have been proven as promising candidates due to their attractive properties. Despite the severe threat of CvDs which has further increased in post-covid era, the Bio-FET sensor studies in literature are still rare. In this review, we aim to provide a comprehensive view of all the multidisciplinary concepts related to 2D-BioFETs for CvDs. A critical review of the different platforms has been covered with detailed discussions of related studies to provide a clear concept and present status of 2D-BioFETs based CvD biosensors.

Link between Plant Phosphate and Drought Stress Responses.

The menace of drought has persistently loomed over global crop production, posing a serious threat to agricultural sustainability. Research on drought stress highlights the important role of the phytohormone abscisic acid (ABA) in orchestrating plant responses to drought conditions. ABA regulates various drought/dehydration-responsive genes, initiates stomatal closure, and influences cellular responses to drought stress. Additionally, plants employ a phosphate starvation response (PSR) mechanism to manage phosphate (Pi) deficiency, with ABA playing a role in its regulation. However, despite intensive research in these fields, the precise connection among PSRs, drought stress, and ABA signaling still needs to be determined. Recently, PSR-related gene induction has been reported to occur before the induction of ABA-responsive genes under progressive mild drought. Mild drought decreases Pi uptake and contents in plants, triggering PSRs, which play an important role in plant growth during mild drought. Both ABA-responsive and PSR-related gene expression could indicate plant perception of external moisture conditions. Thus, integrating the information regarding their associated gene expression with soil moisture contents and thermographic data can enable timely irrigation optimization to mitigate the effect of drought on crop productivity.

Exploring the Binding Mechanism of 5-HT7 Specific Benzoxazolone alkyl Piperazinium Derivatives: A Comprehensive Analysis Using Spectroscopic and Computational Approaches.

Recently, the 5-HT7 receptor has achieved greater attention in research fraternity due to the involvement of neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in several neurological disorders. Targeting this neuroreceptor, we have synthesized six compounds named as butyl-benzoxazolone substituted piperazinium derivatives (BBOP) derivatives, abbreviated as L1-L6. These compounds have been evaluated for their binding interaction with BSA through photophysical and in-silico approaches. The UV absorption of these compounds with BSA at λmax = 280 nm, showed an optical density (O.D.) in the range of 0.5-0.9, i.e., 21%-53% (L1max = 1.4, L5min = 0.7385) at varied concentrations (17 µM-114 µM). For fluorescence studies, the Ksv value varied inversely with temperature, which confirmed the static mechanism of quenching with L1 showing maximum quenching. The parameters (ΔH, ΔS) obtained from the thermodynamic study for interaction between BSA and L1-L6 were correlated with in-silico (molecular docking) data. The in-silico docking study showed hydrophobic and the Van der Waals forces were the most significant forces. Amino acid residues ARG 217 & TRP 213 (Sudlow Site I) and LYS 116 & GLU 125 (Sudlow Site II) of BSA were primarily involved in H-bonding.Furthermore, the catalytic activity of BSA for hydrolyzingdifferent chemical entities have monitored in the presence of L1-L6 through esterase-like assay with p-NPA as a substrate, to get more insight about the interaction with catalytic residues (LYS 414, LYS 413, and TYR 411) in BSA at site II. These findings showed the potential of these 5-HT7 markers as promising ligands with appropriate drug likeliness characteristics.

An Overview of Radiation Countermeasure Development in Radiation Research from 1954 to 2024.

Preparation for medical responses to major radiation accidents, further driven by increases in the threat of nuclear warfare, has led to a pressing need to understand the underlying mechanisms of radiation injury (RI) alone or in combination with other trauma (combined injury, CI). The identification of these mechanisms suggests molecules and signaling pathways that can be targeted to develop radiation medical countermeasures. Thus far, the United States Food and Drug Administration (U.S. FDA) has approved seven countermeasures to mitigate hematopoietic acute radiation syndrome (H-ARS), but no drugs are available for prophylaxis and no agents have been approved to combat the other sub-syndromes of ARS, let alone delayed effects of acute radiation exposure or the effects of combined injury. From its inception, Radiation Research has significantly contributed to the understanding of the underlying mechanisms of radiation injury and combined injury, and to the development of radiation medical countermeasures for these indications through the publication of peer-reviewed research and review articles.

A comparative analysis of mycobacterial ribonucleases: Towards a therapeutic novel drug target.

Bacterial responses to continuously changing environments are addressed through modulation of gene expression at the level of transcription initiation, RNA processing and/or decay. Ribonucleases (RNases) are hydrolytic or phosphorolytic enzymes involved in a majority of RNA metabolism reactions. RNases play a crucial role in RNA degradation, either independently or in collaboration with various trans-acting regulatory factors. The genus Mycobacterium consists of five subgenera: Mycobacteroides, Mycolicibacterium, Mycobacterium, Mycolicibacter and Mycolicibacillus, which include 63 fully sequenced species (pathogenic/non-pathogenic) to date. These include 13 different RNases, among which 5 are exonucleases (RNase PH, PNPase, RNase D, nano-RNases and RNase AS) and 8 are endonucleases (RNase J, RNase H, RNase P, RNase III, RNase BN, RNase Z, RNase G and RNase E), although RNase J and RNase BN were later identified to have exoribonuclease functions also. Here, we provide a detailed comparative insight into the Escherichia coli and mycobacterial RNases with respect to their types, phylogeny, structure, function, regulation and mechanism of action, with the main emphasis on RNase E. Among these 13 different mycobacterial RNases, 10 are essential for cell survival and have diverse structures hence, they are promising drug targets. RNase E is also an essential endonuclease that is abundant in many bacteria, forms an RNA degradosome complex that controls central RNA processing/degradation and has a conserved 5' sensor domain/DNase-I like region in its RNase domain. The essential mycobacterial RNases especially RNase E provide a potential repertoire of drug targets that can be exploited for inhibitor/modulator screening against many deadly mycobacterial diseases.

Investigation on structure and photoluminescence properties of Ho3+ doped Ca3(VO4)2 phosphors for luminescent devices.

This study focuses on the synthesis and characterization of Ho3+ doped Ca3(VO4)2 phosphor for potential application in solid-state lighting technology. A citrate-based sol-gel process is optimized to achieve sheet-like morphologies in the phosphor material. The investigation reveals UV absorption at 371 nm, indicating a band gap of 3.28 eV. Emission transitions at (506, 541, and 651) nm are observed when excited at 451 nm, with an optimal Ho3+ concentration of 0.05 mol resulting in robust green emission at 541 nm. The concentration quenching in Ca3(VO4)2:xHo3+ phosphors is discussed in detail with Blesse's and Dexter's models. The concentration quenching effect found in the studied samples is due to the dipole-dipole interactions. Judd-Ofelt intensity parameters were calculated from the excitation bands, and for Ω 2, Ω 4, and Ω 6 are (0.16, 0.17, and 0.36) × 10-20 cm2, respectively. The emission properties for the (5S2 + 5F4) → 5I8 and 5F5 → 5I8 transitions are also estimated with J-O parameters. The higher magnitude of branching ratios (83%) and emission cross-sections (1.6 × 10-21 cm2) suggest that the Ca3(VO4)2:0.05Ho3+ phosphor materials may be suitable for efficient green-emitting device applications. The CIE coordinates confirm the potential of Ho3+-doped phosphors for green emissions, making them suitable for solid-state lighting and display technology.

Optimizing feature selection with gradient boosting machines in PLS regression for predicting moisture and protein in multi-country corn kernels via NIR spectroscopy.

Differences in moisture and protein content impact both nutritional value and processing efficiency of corn kernels. Near-infrared (NIR) spectroscopy can be used to estimate kernel composition, but models trained on a few environments may underestimate error rates and bias. We assembled corn samples from diverse international environments and used NIR with chemometrics and partial least squares regression (PLSR) to determine moisture and protein. The potential of five feature selection methods to improve prediction accuracy was assessed by extracting sensitive wavelengths. Gradient boosting machines (GBMs), particularly CatBoost and LightGBM, were found to effectively select crucial wavelengths for moisture (1409, 1900, 1908, 1932, 1953, 2174 nm) and protein (887, 1212, 1705, 1891, 2097, 2456 nm). SHAP plots highlighted significant wavelength contributions to model prediction. These results illustrate GBMs' effectiveness in feature engineering for agricultural and food sector applications, including developing multi-country global calibration models for moisture and protein in corn kernels.

Development of a multi-objective reservoir operation model for water quality-quantity management.

This study aims to develop a multi-objective quantitative-qualitative reservoir operation model (MOQQROM) by a simulation-optimization approach. However, the main challenge of these models is their computational complexity. The simulation-optimization method used in this study consists of CE-QUAL-W2 as a hydrodynamic and water quality simulation model and a multi-objective firefly algorithm-k nearest neighbor (MOFA-KNN) as an optimization algorithm which is an efficient algorithm to overcome the computational burden in simulation-optimization approaches by decreasing simulation model calls. MOFA-KNN was expanded for this study, and its performance was evaluated in the MOQQROM. Three objectives were considered in this study, including (1) the sum of the squared mass of total dissolved solids (TDS), (2) the sum of the squared temperature difference between reservoir inflow and outflow as water quality objectives, and (3) the vulnerability index as a water quantity objective. Aidoghmoush reservoir was employed as a case study, and the model was investigated under three scenarios, including the normal, wet, and dry years. Results showed the expanded MOFA-KNN reduced the number of original simulation model calls compared to the total number of simulations in MOQQROM by more than 99%, indicating its efficacy in significantly reducing execution time. The three most desired operating policies for meeting each objective were selected for investigation. Results showed that the operation policy with the best value for the second objective could be chosen as a compromise policy to balance the two conflicting goals of improving quality and supplying the demand in normal and wet scenarios. In terms of contamination mass, this policy was, on average, 16% worse than the first policy and 40% better than the third policy in the normal scenario. In the wet scenario, it was, on average, 55% worse than the first policy and 16% better than the third policy. The outflow temperature of this policy was, on average, only 8.35% different from the inflow temperature in the normal scenario and 0.93% different in the wet scenario. The performance of the developed model is satisfactory.