Safety Testing Research Articles

Determination of immunogenicity of an inactivated ND-vaccine developed experimentally with Newcastle disease virus (Genotype VII.2) local isolates of Bangladesh

BackgroundNewcastle disease virus (NDV) genotype VII severely affects poultry, causing respiratory and neurological symptoms with a high rate of morbidity and mortality. The research aimed to develop an inactivated ND vaccine using local isolates (Genotype VII.2) and assess its immunogenicity compared to other commercial live ND vaccines.MethodsAn inactivated vaccine using a candidate NDV (GenBank: OR924274.1) was developed according to WOAH guidelines following inactivation, sterility, purity, and safety tests. The birds were vaccinated through subcutaneous (SC) and intramuscular (IM) routes using three doses (0.25, 0.5, and 1.0 ml/bird). Immunogenicity and protective potentiality of the experimentally developed inactivated ND vaccine and live commercial ND vaccine (intra-ocularly/IO) were compared by challenge studies using three vaccination schedules: killed-followed-killed, live-followed-killed, and live-followed-live.ResultsThe birds vaccinated with 1.0 ml/bird SC showed higher antibody titers compared to those of IM-vaccinated groups. Birds vaccinated with the live-followed-killed commercial ND vaccines had slightly higher antibody titers compared to those vaccinated with killed-followed-killed and live-followed-live vaccines. Birds vaccinated with the killed-followed-killed ND vaccine showed a higher protection rate (100%) compared to live-followed-killed (83±5.77%) and live-followed-live (57±5.77%) vaccines. Birds vaccinated with killed-followed-killed group showed a slower decline rate of antibody titers than other groups. This regimen provided significantly better immunity, highlighting its potential in controlling ND outbreaks in Bangladesh's poultry.ConclusionThe study found that the inactivated ND vaccine, developed with the locally circulating isolate of genotype-VII.2 of NDV, might play an important role in effective control and management of ND in the commercial poultry population in Bangladesh.

Strategic Dual Approach for the Management of a Symptomatic Giant Partially Thrombosed Aneurysm at the Basilar Tip - Integrating Intrasaccular Flow Diversion and Endovascular Flow Reversal.

Managing giant partially thrombosed intracranial aneurysms presents significant challenges due to their unfavorable natural history and the lack of standardized treatment approaches. Conventional treatments, whether open surgical or endovascular, often struggle to manage these aneurysms effectively, resulting in high recurrence rates or significant morbidity. The patient was a 62-year-old male with a symptomatic giant partially thrombosed aneurysm at the tip of the basilar artery, presenting with left-sided hemiparesis and dysarthria. Diagnostic imaging revealed a giant aneurysm with a wide-necked, canalized portion. A two-stage endovascular treatment was conducted, involving a balloon occlusion test (BOT) and intraoperative monitoring (IOM) for maximum patient safety. The treatment utilized stent-assisted Woven EndoBridge (WEB) embolization and serial bilateral vertebral artery trapping. The procedure successfully isolated the aneurysm and postoperative imaging confirmed the absence of recanalization, preserving the intact posterior circulation. The patient showed stable recovery and no neurological deficits during the 12-month follow-up period. This technical note demonstrates the feasibility and efficacy of strategically integrating intrasaccular flow diversion using a WEB device and flow reversal through bilateral vertebral artery trapping for treating giant partially thrombosed aneurysms.

The Current State of Biotransformation Science - Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends.

Embedded within the field of drug metabolism and pharmacokinetics (DMPK), biotransformation is a discipline that studies the origins, disposition, and structural identity of metabolites to provide a comprehensive safety assessment, including the assessment of exposure coverage in toxicological species. Spanning discovery and development, metabolite identification (metID) scientists employ various strategies and tools to address stage-specific questions aimed at guiding the maturation of early chemical matter into drug candidates. During this process, the identity of major (and minor) circulating human metabolites is ascertained to comply with the regulatory requirements such as the Metabolites in Safety Testing (MIST) guidance. Through the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the "Translatability of MetID In Vitro Systems Working Group" was created within the Translational and ADME Sciences Leadership Group. The remit of this group was to objectively determine how accurate commonly employed in vitro systems have been with respect to prediction of circulating human metabolites, both qualitatively and quantitatively. A survey composed of 34 questions was conducted across 26 pharmaceutical companies to obtain a foundational understanding of current metID practices, preclinically and clinically, as well as to provide perspective on how successful these practices have been at predicting circulating human metabolites.The results of this survey are presented as an initial snapshot of current industry-based metID practices, including our perspective on how a harmonized framework for the conduct of in vitro metID studies could be established. Future perspectives from current practices to emerging advances with greater translational capability are also provided.

Isolation and identification of probiotic Bacillus subtilis AJQ03 from the intestinal tract of Anguilla japonica (Japanese eel)

In recent years, the use of fish-derived probiotics in aquaculture has become more widespread. However, research on Anguilla japonica-derived probiotics is still limited. To evaluate the potential of probiotics for disease control in eel aquaculture, isolates were obtained from the intestinal tract of healthy Anguilla japonica. These isolates were assessed for their adhesion properties, inhibition of pathogen adhesion, and hydrolytic enzyme production. Morphological characteristics and 16S rRNA sequence analysis were used for identification. Results showed that the AJQ03 strain adhered to the intestinal mucus and inhibited common pathogenic bacteria through adhesion inhibition, and further produced amylase, lipase, protease, and cellulase. Based on morphological characteristics and 16S rRNA sequencing, AJQ03 was identified as Bacillus subtilis. The strain demonstrated tolerance to various extreme conditions, as well as survival in simulated gastrointestinal fluids and superior growth in intestinal fluid compared to Luria-Bertani (LB) broth. In vitro safety tests showed that AJQ03 was not resistant to 32 antibiotics and exhibited γ hemolysis on blood plate. In vivo safety tests demonstrated a 100% survival rate for the fish, with stable organ indices, reduced bacterial loads in the liver and spleen, and complete bacterial clearance by day 7 without residue. Intestinal bacterial load results confirmed effective colonization by strain AJQ03. Analysis of the impact of AJQ03 on the gut microbiota of A. japonica revealed a significant increase in the relative abundance of Bacillus at the genus level, corroborating the colonization efficiency of AJQ03. Additionally, the relative abundances of Klebsiella, Pseudomonas, and Aeromonas were significantly lower compared to the controls, indicating that strain AJQ03 effectively reduced harmful bacteria and improved gut microbiota composition. This study confirms that B. subtilis AJQ03, isolated from the intestine of A. japonica, can serve as a probiotic candidate in A. japonica aquaculture.

Probe-based dual-chip digital loop-mediated isothermal amplification for the simultaneous detection of Staphylococcus aureus and Salmonella enteritidis in livestock and aquatic products

Staphylococcus aureus and Salmonella are common pathogens causing foodborne diseases, posing a serious threat to food safety. Accurate detection of foodborne pathogens is particularly critical. This study developed a probe-based dual-chip digital loop-mediated isothermal amplification (cdLAMP) technique that enables the simultaneous detection of Staphylococcus aureus and Salmonella in food samples. The chip contains 20,000 wells, each with a micro-reaction unit volume of approximately 1 nL. The dual-detection is achieved through the dual-color fluorescence channel equipped on the imaging analyzer. Compared with qPCR, the cdLAMP demonstrates superior sensitivity. In the detection of pure cultures and spiked food samples, the detection limit of two foodborne pathogens is 2 CFU/mL. In the detection of field samples, it is capable of detecting single colonies of both pathogens. The dynamic detection range spans 5 logs. In conclusion, the probe-based cdLAMP technique emerges as a user-friendly tool for detecting foodborne pathogens, providing a powerful platform for food safety testing.

Isolation, Potential Beneficial Properties, and Assessment of Storage Stability of Direct-Fed Microbial Consortia from Wild-Type Chicken Intestine.

Direct-fed microorganisms (DFM) are recognized as an alternative to antibiotic-based growth promoters in poultry production due to their health benefits. DFM, however, should undergo rigorous safety testing to ensure they meet the criteria to be "Generally Recognized as Safe." This study assessed eight bacterial consortia (BC) isolated from the ileal and cecal intestinal regions of wild-type chickens, subjecting them to probiotic tests. Subsequently, they were spray- and freeze-dried to evaluate their storage stability for 30days. BC5-I and BC7-I, isolated from the ileum, emerged as promising DFM, displaying a high content of Lactobacillales using a selective medium and higher susceptibility to Gram-positive and Gram-negative antibiotics. These BC showed a high tolerance to temperature (> 90%), pH > 4 (88-98%), and antagonist effects against Escherichia coli and Salmonella. BC5-I exhibited superior survival in the simulated gastric conditions and satisfactory intestine mucus adhesion. Freeze-drying was the best method to obtain BC5-I and BC7-I powders, with a survival efficiency of 80.3% and 73.2%, respectively, compared to the beginning of storage. BC5-I presented the lowest cell death rate and prolonged half-life through survival storage kinetics. BC5-I only contained Lactobacillus, and Limosilactobacillus reuteri was the predominant species in liquid (78.3%) and freeze-dried (59.8%) forms. BC5-I stands out as a promising Lactobacillus-based DFM that could improve chicken intestinal health and enhance meat and egg production.

Wine industry by-products as a source of active ingredients for topical applications

AbstractThe wine industry is responsible for a considerable amount of waste produced by agricultural activities worldwide, which impacts both the economic sector and the environment through pollution and ecosystem imbalance. There are several examples of by-products generated during the winemaking process, such as grape pomace, vine leaves, grape stalks, or wine lees. These can be recovered and reused by the cosmetic industry, which is actively seeking natural and greener products. There are active ingredients that come from by-products that have relevant bioactive properties such as antioxidant, antiaging, anti-hyperpigmentation, or cellular protection. Therefore, the use of by-products from the wine industry as a source of active ingredients for topical application has attracted attention from the scientific community, overcoming some of the drawbacks of the winemaking process. Further research into extraction processes and methods is essential, as they directly influence the quality and quantity of recovered active ingredients. While current cosmetic products on the market undergo safety and cytotoxicity testing, it is important to evaluate the effects of pesticide treatments applied before pruning and the toxicity of the by-products to ensure the safety of future formulations. This review addresses a critical discussion on this subject, assessing the potential benefits of their use in topical formulations. Graphical Abstract

The use of surrogate matrices in bioanalytical preclinical safety testing using chromatographic methods: a recommendation from the European Bioanalysis forum.

Within the bioanalytical community, the use of blank matrix from preclinical animals for bioanalytical method validation and sample analysis is common practice and required in the context of guidelines for bioanalytical method validation. At the same time, its use has been challenged by the scientific community for decades, since there is ample scientific evidence to allow the use surrogate matrices for this purpose. Nevertheless, legacy and current regulatory thinking continues to be reluctant to allow the use of surrogate matrices in bioanalytical testing except for so-called rare matrices. As part of ongoing discussions in relation to the ICH M10 Guideline, the European Bioanalysis Forum re-challenges the unnecessary use of blank matrices from preclinical animals and believes that, as part of community responsibility and ethical standards and when supported by data, the use of surrogate matrices should become widely accepted. It is in this context that targeted experiments were conducted within the European Bioanalysis Forum to gather additional data and re-open the discussions with all involved and that it should become acceptable to use surrogate matrices wherever possible.

The use of dance to improve the health and wellbeing of older adults: A global scoping review of research trials.

Dance is a promising health resource for older adults, but empirical evidence remains inconsistent. The lack of synthesised evidence regarding program design, dose, and delivery limits understanding of factors influencing participation and health outcomes. This scoping review aimed to map the scope, range, and effectiveness of dance programs for older people, and identify gaps and opportunities for future research and practice. Searches across five databases (September 2023) identified 148 studies evaluating 116 dance programs (≥4 weeks) for older adults (≥55 years, N = 8060), Dance interventions delivered to clinical groups were excluded. Intervention design and delivery were charted against the TIDieR reporting checklist. Program outcomes including adherence, safety, and positive tests were charted into established taxonomies. Demographic information, program details, and implementation were often insufficiently reported. Participant groups differed by age range, with underserved communities underrepresented. Programs varied extensively in key factors including dose, prospective 'active ingredients', delivery approach, facilitator expertise, and class size. While dance was physically safe, adherence rates in older adults are comparable to other community exercise programs. Less than 40% of health assessments showed positive change, with more consistent benefits to physical endurance, strength, and function, moderate impacts on psychosocial health, and limited benefits to cognitive and brain health, and falls and falls risk. Dance is a meaningful, safe, adaptable, and low-cost health resource for older adults. Key opportunities for advancing research include improved access for underserved groups, program suitability assessments, strategies to support adherence and engagement including theory-informed approaches, and incorporation of participant and practitioner insights. Identification of key 'active ingredients' and dance program factors may improve understanding of causal pathways and mechanisms to optimise engagement and health impacts. Stronger reporting practices will facilitate comparisons across studies and more robust evidence synthesis. This review provides a critical knowledge foundation to guide future approaches in dance for health and offers reporting recommendations.

Rapid identification of antibiotic residues in bovine kidney using coated blade spray-mass spectrometry.

The use of certain antibiotics in food-producing animals is allowed in Europe following Regulation (EU) 2017/625. However, use could result in antibiotic residues in foodstuffs of animal origin. Maximum residue limits (MRLs) are in place to protect consumers. For monitoring purposes, animal matrices are tested to verify their compliance with these MRLs. Initially, matrices of (slaughtered) food animals are screened, often using a microbiological assay. Faster screening tests for antibiotics would be an advantage for control laboratories. Therefore, the present study describes, for the first time, the use of coated blade spray (CBS) followed by direct mass spectrometry (MS) analysis for the screening of tetracyclines, sulfonamides, quinolones, and macrolides residues from the renal area of intact bovine kidneys. An optimized workflow using two different desorption/ionization solutions per blade allowed screening of target compounds within 1min per sample. The proof-of-principle of the CBS-MS method is validated according to (EU) 2021/808, presenting CCβ screening values of 0.1 × MRL for 43 analytes, 0.5 × MRL for 4 analytes, and 2.5µgkg-1 for the prohibited substance dapsone, respectively. The developed method was successfully applied to seven official control samples of bovine kidneys. One of these samples was found to be positive using the CBS-MS method, which was confirmed as a true positive by LC-MSMS analysis. The developed method demonstrates that CBS devices can directly extract and analyze kidney samples for food safety testing.

Development of Dual-Arm Human Companion Robots That Can Dance.

As gestures play an important role in human communication, there have been a number of service robots equipped with a pair of human-like arms for gesture-based human-robot interactions. However, the arms of most human companion robots are limited to slow and simple gestures due to the low maximum velocity of the arm actuators. In this work, we present the JF-2 robot, a mobile home service robot equipped with a pair of torque-controlled anthropomorphic arms. Thanks to the low inertia design of the arm, responsive Quasi-Direct Drive (QDD) actuators, and active compliant control of the joints, the robot can replicate fast human dance motions while being safe in the environment. In addition to the JF-2 robot, we also present the JF-mini robot, a scaled-down, low-cost version of the JF-2 robot mainly targeted for commercial use at kindergarten and childcare facilities. The suggested system is validated by performing three experiments, a safety test, teaching children how to dance along to the music, and bringing a requested item to a human subject.

Pedestrian safety behavior modeling method in human-vehicle-intelligence shared road space

In the context of the development of autonomous vehicles sharing road resources with traditional traffic participants in the future, modeling the safe behavior of pedestrians in the shared road space between people, vehicles and intelligence is crucial for the simulation development and reliability and safety testing of autonomous vehicles. To meet this demand, the safe movement behavior of pedestrians is first analyzed, and on this basis, the traditional pedestrian social force model is improved to construct a momentum model for the interactive movement of pedestrians with other pedestrians, traditional vehicles and autonomous vehicles in the shared road space; then, the safety parameters of the model are calibrated using a data set of human-vehicle interactive movement and a genetic algorithm, and a typical shared road space scenario is built to verify the effectiveness of the model. The simulation results show that the model can simulate the real safe movement behavior of pedestrians, and has better simulation effects when used in tasks such as human-vehicle-intelligence shared road space simulation.

Ultra-Low-Field Portable MRI and Extracorporeal Membrane Oxygenation: Preclinical Safety Testing.

Conventional MRI is incompatible with extracorporeal membrane oxygenation (ECMO) cannulas and pumps. Ultra-low-field portable MRI (ULF-pMRI) with 0.064 Tesla may provide a solution, but its safety and compatibility is unknown. ULF-pMRI does not cause significant displacement and heating of ECMO cannulas and does not affect ECMO pump function. ECMO cannulas in various sizes were tested ex vivo using phantom models to assess displacement force and heating according to the American Society for Testing and Materials criteria. ECMO pump function was assessed by pump flow and power consumption. In vivo studies involved five female domestic pigs (20-42 kg) undergoing different ECMO configurations (peripheral and central cannulation) and types of cannulas with an imaging protocol consisting of T2-weighted, T1-weighted, FLuid-Attenuated Inversion Recovery, and diffusion-weighted imaging sequences. Phantom models demonstrated that ECMO cannulas, both single lumen with various sizes (15-24-Fr) and double lumen cannula, had average displacement force less than gravitational force within 5 gauss safety line of ULF-pMRI and temperature changes less than 1°C over 15 minutes of scanning and ECMO pump maintained stable flow and power consumption immediately outside of the 5 gauss line. All pig models showed no visible motion due to displacement force or heating of the cannulas. ECMO flow and the animals' hemodynamic status maintained stability, with no changes greater than 10%, respectively. ULF-pMRI is safe and feasible for use with standard ECMO configurations, supporting its clinical application as a neuroimaging modality in ECMO patients.

Preclinical evaluation of a fully human, quadrivalent-hantavirus polyclonal antibody derived from a non-human source.

This candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world's most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.

Challenges of Conducting Point-Of-Care Testing Operations In The Municipal Public Health System Based Ambulatory Care Clinics In New York City

Abstract Introduction/Objective Our New York City Municipal Public Health System- based multisite ambulatory clinics that offer various waived POCT (point of care tests) and provider-performed microscopy (PPM) to our communities, ensure standardization and quality of POC testing across our health system. Our laboratory service conducts system-wide centralized implementation, monitoring and oversight of the POCT operations regarding regulatory compliance, test performance, quality control and training. With our day-to-day POCT operations, like all other clinical laboratories, our ambulatory care clinics encounter various hurdles and challenges. Here we elaborated on the issues we encounter and how we manage to overcome them. Methods/Case Report We identified and stratified the challenges that affect our managerial as well as field-level laboratory operations and devised ways to deal with those POCT operational issues. Results (if a Case Study enter NA) Among the staffing issues, rapid staff turnover causes significant delays or cessation of POCT operations in our ambulatory care clinics, due to orientation, re-education and ensuring competency to the staff, that conducts POCT in our clinics. Besides, supply shortages, staff shortages and absences due to illness and overwork are the issues, noted at the laboratory field operational level. Delays in the processing of paperwork and new staff recruitments and in the laboratory supply chains are notable management issues. Conclusion Even though the vastness and complexity of our multisite ambulatory care network sometimes affect our ambulatory care clinic POCT operation in various challenging way, our timely, planned and coordinated intervention, close monitoring and communication and rapid initiatives handle those issues very effectively to ensure the quality of POC testing for the patient safety and care across our health system, which is one of the largest municipal-based public health care, in the country.

Prevalence of Antibodies against Adeno-Associated Viruses (AAVs) in Göttingen Minipigs and Its Implications for Gene Therapy and Xenotransplantation

Adeno-associated viruses (AAV) are widely used as delivery vectors in clinical trials for in vivo gene therapy due to their unique features. Göttingen minipigs are a well-established animal model for several diseases and can be used for the efficacy and safety testing of AAV-based gene therapy. Pre-existing antibodies against AAV may influence the results of testing and, therefore, the animals should be tested for the presence of antibodies against relevant AAV serotypes. The detection of AAVs in pigs may be also important for the virus safety of xenotransplantation. In this study, we screened Göttingen minipigs from Ellegaard Göttingen Minipigs A/S, Denmark, and Marshall BioResources, USA, for antibodies against AAV1, AAV2, AAV6, AAV9 serotypes. Of the 20 animals tested, 18 had no neutralizing antibodies for all AAVs tested, none had antibodies against AAV9, only one had antibodies against AAV6, and the titers of antibodies against AAV1 and AAV2 were less than 1:100, with two exceptions. For total binding IgG, more individuals showed positivity for all the tested serotypes but, in general, the levels were low or zero. Three animals had no antibodies at all against the AAVs tested. Therefore, Göttingen minipigs could be considered an attractive animal model for gene therapy studies. Since some animals were negative for all AAVs tested, these may be selected and used as donor animals for xenotransplantation.

Rapid and Ultrasensitive Detection of H. aduncum via the RPA-CRISPR/Cas12a Platform.

Hysterothylacium aduncum is one of six pathogens responsible for human anisakiasis. Infection with H. aduncum can cause acute abdominal symptoms and allergic reactions and is prone to misdiagnosis in clinical practice. This study aims to enhance the efficiency and accuracy of detecting H. aduncum in food ingredients. We targeted the internal transcribed spacer 1 (ITS 1) regions of Anisakis to develop a visual screening method for detecting H. aduncum using recombinase polymerase amplification (RPA) combined with the CRISPR/Cas12a system. By comparing the ITS 1 region sequences of eight nematode species, we designed specific primers and CRISPR RNA (crRNA). The specificity of RPA primers was screened and evaluated, and the CRISPR system was optimized. We assessed its specificity and sensitivity and performed testing on commercial samples. The results indicated that the alternative primer ADU 1 was the most effective. The final optimized concentrations were 250 nM for Cas12a, 500 nM for crRNA, and 500 nM for ssDNA. The complete test procedure was achievable within 45 min at 37 °C, with a limit of detection (LOD) of 1.27 pg/μL. The amplified product could be directly observed using a fluorescence microscope or ultraviolet lamp. Detection results for 15 Anisakis samples were entirely consistent with those obtained via Sanger sequencing, demonstrating the higher efficacy of this method for detecting and identifying H. aduncum. This visual detection method, characterized by simple operation, visual results, high sensitivity, and specificity, meets the requirements for food safety testing and enhances monitoring efficiency.

Hybrid Sunscreen for Albinistic Skin Types Augmented by Terminalia Sericea Mediated Silver Doped Zinc Oxide Nanoparticles, Efficacy and Safety Investigation

Albinism is a congenital hypopigmentation disorder characterized by errors in melanisation leading to the partial or complete absence of melanin, the skin’s primary defense against actinic damage. Actinic damage in albinism summarizes all solar induced consequences from freckles to fatal skin cancers. Of the 16 sunscreens approved by regulators, 14 chemical sunscreens were stripped of GRASE (Generally Recognizable as Safe and Effective) status in 2020 by the FDA though Over-the-Counter Monograph M020, the remaining 2 physical sunscreens (ZnO and TiO2) are unaesthetic, leaving unpleasant persistent white casts. The hunt for new, effective and safe sunscreen agents is on and photoprotective polyphenolics from tropical plants including Terminalia sericea, maybe the solution. This study aimed to develop and evaluate the efficacy and safety of a novel sunscreen for albinistic skin, utilizing Terminalia sericea-mediated silver-doped ZnO nanoparticles, so as to leverage the novel sun protection efficacy of aesthetic ZnO-NPs with the antibacterial effects of Ag-NPs as well as the photoprotective effects from T. Sericea polyphenolics. Our observations from the study confirm that T. Sericea possesses abundant polyphenolic compounds capable of mediating bio-reducing and capping of metallic nanoparticles. UV-Vis identified the nanostructures as Ag-ZnONPs, TEM confirmed their cubic and oblong agglomerated morphology. DLS estimated the nanostructures to be between 30 and 40nm. The sunscreen achieved a high SPF of 30, showed significant photoprotective properties, and demonstrated negligible skin sensitization in safety tests following OECD guidelines. It was therefore concluded that the biosynthesis of multifunctional Ag doped ZnONPs mediated by T. Sericea, was feasible and that the resultant safe multifunctional emulsion was efficacious in retarding biomarkers of actinic damage and is a potential pioneering albinistic skin type actinic damage retarding sunscreen.

Mechanism and performance of choline-based ionic liquids in enhancing nasal delivery of glucagon

Proteins and peptides have been increasingly developed as pharmaceuticals owing to their high potency and low side effects. However, their administration routes are confined to injections, such as intra-muscular and intra-venous injections, making patient compliance a challenge. Hence, non-injectable delivery systems are crucial to expanding the clinical use of proteins and peptides. In this context, two choline-based ionic liquids (ILs), namely, choline geranic acid ([Ch][Ger]) and choline citric acid ([Ch][Cit]), have been identified as promising agents for enhancing the permeation and prolonging the retention time of glucagon (GC) after intra-nasal administration. Notably, intra-nasal delivery of GC via ILs (GC/ILs) elicited rapid and smooth reversal of acute hypoglycaemia without leading to rebound hyperglycaemia in type 1 diabetic rats subjected to insulin induction. In addition, ILs could improve the transcellular transport of GC through electrostatic interaction. ILs could also transiently open inter-cellular tight junctions transiently to facilitate the paracellular transport of GC. Safety tests indicated that continuous intra-nasal delivery of ILs led to reversible changes, such as epithelial cell inflammation, goblet cell overgrowth, and impacts on the distribution of nasal cilia. However, these changes could be alleviated by the innate self-repair ability of mucosal epithelial cells. This study highlights the considerable potential of ILs for long-term nasal delivery of biomacromolecules.

Study on fuel management strategy for accident-tolerant fuel on in-pile irradiation test

Within the context of the long-term development plan of batch loading of accident-tolerant fuel assemblies, an equivalent physical model of lead test assemblies is established based on the requirements of radiation testing and the applicability of analysis software. The quantitative assessment has been conducted on the impacts of parameters including zirconium alloy cladding coating and pellet additives on reactivity of fuel assembly. Concurrently, the fuel management strategy is optimized in alignment with the irradiation test objectives of ATF assemblies, leading to the creation of an evaluation process tailored for ATF assembly loading pattern. Focusing on the irradiation of the lead test assemblies into a nuclear power plant in China, three-cycle nuclear reactor loading pattern are designed, which are taking into account the economic, safety, and irradiation testing goals of the nuclear power plant. Simultaneously, the neutronic characteristics are also evaluated, quantitatively. The results show that the established equivalent physical model can effectively represent the characteristics of the lead test assemblies. The loading patterns designed based on the Optimised fuel management strategy achieve the desired goals in terms of economy, safety and radiation test requirements. The designed loading pattern evaluation process and equivalent model analysis method in this work provide guidance for the subsequent engineering design and application of irradiation testing for lead test assemblies.