Safety Assessment Research Articles

Functional genomic characterization reveals the probiotic tendency and safety assessment of Exiguobacterium acetylicum G1–33 isolated from the gut of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂)

Functional genomic characterization reveals the probiotic tendency and safety assessment of Exiguobacterium acetylicum G1–33 isolated from the gut of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂)

Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with immunotherapy in early-stage triple-negative breast cancer.

This study aimed to assess safety and efficacy of a modified KEYNOTE 522 protocol, which incorporated pembrolizumab every 6weeks, allowing for concomitant dose-dense (14day) doxorubicin and cyclophosphamide (ddAC). By optimizing this dosing, the intention of this modified protocol was to improve pathologic complete response (pCR) rates in a population associated with a poorer prognosis. This was a retrospective, single-center, cohort study. Patients were included if they had early stage, triple-negative breast cancer, and received at least one dose of AC. The entire cohort received neoadjuvant chemotherapy including weekly carboplatin and paclitaxel with pembrolizumab every 3weeks for 12weeks (4 cycles). The group then received either ddAC with pembrolizumab 400mg every 6weeks, or AC with pembrolizumab 200mg every 3weeks. The primary objective was pCR rate at time of surgery. This study assessed outcomes in 25 patients over 34months. The pCR rate in the pembrolizumab, AC 3-week cohort was 64.3% versus 81.8% in the ddAC and 6-week pembrolizumab group. No pembrolizumab-associated grade 3-4 adverse events occurred in the either cohort. Despite seeing an increased incidence of grade 3-4 toxicities in the ddAC arm, this did not result in additional chemotherapy delays or dose reductions. This study demonstrated tolerability and a potential for favorable outcomes with this patient population, making this modified KEYNOTE 522 protocol a reasonable treatment approach. Larger, prospective studies are warranted to assess the feasibility of this dosing and true optimization of patient outcomes given the small sample size of this study.

A novel approach to runway overrun risk assessment using FRAM and flight data monitoring

Abstract Runway overruns (ROs) are the result of an aircraft rolling beyond the end of a runway, which is one of the accident’s types that most frequently occurs on aviation. The risk of an RO arises from the synergistic effect among its precursors, such as unstable approaches, long touchdowns and inadequate use of deceleration devices. To analyse this complex socio-technical system, the current work proposes a customised functional resonance analysis method, called FRAM-FDM, as traditional techniques of risk and safety assessment do not identify the interactions and couplings between the various functional aspects of the system itself, especially regarding human and organisational components. Basically, FRAM-FDM is the coupling of a traditional FRAM with flight data monitoring (FDM) techniques, used here to quantify the variabilities of the flight crew performance while executing the required activity (i.e. the landing). In this proposal, these variabilities (i.e. the FRAM functions aspects) are aggregated by the addend of a logistic regression, resulting in a model to evaluate the flare operations and the brake application profile effect on the remaining distance to the end of the runway, used as a reference to classify the landing as acceptable or not. The present application of the FRAM-FDM assesses the operational risk of a sample fleet in overrunning the runway during landing, highlighting the brake pedal application profile as the most relevant contributor. The model improves the knowledge about the system behaviour, being useful to direct flight crew training.

Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization.

Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo-fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material- and pregnancy stage-specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO2) and titanium dioxide (TiO2) NPs) and environmental NPs (diesel exhaust particles, DEPs). This includes a multitude of secreted inflammatory, vascular, and endocrine placental factors as well as extracellular vesicle (EV)-associated proteins. Moreover, conditioned media (CM) from NP-exposed explants induce pronounced anti-angiogenic and anti-vasculogenic effects, while early neurodevelopmental processes are only marginally affected. These findings underscore the potential of metal oxide NPs and DEPs for widespread interference with the placental secretome and identify vascular morphogenesis as a sensitive outcome for the indirect developmental toxicity of different NPs. Overall, this work has profound implications for the future safety assessment of NPs for industrial, commercial, or medical applications in pregnancy, which should consider placenta-mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies.

Emergency Decision Support Techniques for Nuclear Power Plants: Current State, Challenges, and Future Trends

Emergency decision support techniques play an important role in complex and safety-critical systems such as nuclear power plants (NPPs). Emergency decision-making is not a single method but a framework comprising a combination of various technologies. This paper presents a review of various methods for emergency decision support systems in NPPs. We first discuss the theoretical foundations of nuclear power plant emergency decision support technologies. Based on this exposition, the key technologies of emergency decision support systems in NPPs are presented, including training operators in emergency management, risk assessment, fault detection and diagnosis, multi-criteria decision support, and accident consequence assessment. The principles, application, and comparative analysis of these methods are systematically described. Additionally, we present an overview of emergency decision support systems in NPPs across different countries and feature profiles of prominent systems like the Real-Time Online Decision Support System for Nuclear Emergencies (RODOS), the Accident Reporting and Guiding Operational System (ARGOS), and the Decision Support Tool for Severe Accidents (Severa). Then, the existing challenges and issues in this field are summarized, including the need for better integration of risk assessment, methods to enhance education and training, the acceleration of simulation calculations, the application of large language models, and international cooperation. Finally, we propose a new decision support system that integrates Level 1, 2, and 3 probabilistic safety assessment for emergency management in NPPs.

Challenging the safety and efficacy of topically applied chlorogenic acid, apigenin, kaempferol, and naringenin by HET-CAM, HPLC-TBARS-EVSC, and laser Doppler flowmetry

The integumentary system, a vital organ, constitutes a multifaceted barrier against pathogens and environmental factors, crucial for maintaining homeostasis. Intrinsic and extrinsic factors can accelerate skin aging and compromise its homeostatic functions and solar rays, particularly ultraviolet (UV) radiation, pose a significant risk for skin cancer. Polyphenols are molecules that donate hydrogen or electrons, preventing the oxidation of substances, such as lipids, or the formation of inflammatory mediators by cyclooxygenase enzymes. This study explored the in vitro safety, by HET-CAM (hen’s egg test on chorioallantoic membrane), and protective effects of polyphenols (chlorogenic acid, apigenin, kaempferol, and naringenin) against stratum corneum UV-induced lipid peroxidation using an innovative method, the HPLC-TBARS-EVSC (high-performance liquid chromatography–thiobarbituric acid reactive substances–ex vivo stratum corneum), and a stress test using methyl nicotinate and laser Doppler flowmetry to establish in vivo the samples’ topical anti-inflammatory ability. An aqueous gel containing 0.1% w/w of each polyphenol was formulated using ammonium acryloyldimethyltaurate/VP copolymer. Through the utilization of the HET-CAM assay for in vitro safety assessment, chlorogenic acid, apigenin, kaempferol, and naringenin were classified as non-irritating active ingredients. This classification was based on their lack of adverse reactions within the vascularization of the chorioallantoic membrane. To assess the protective capabilities of four polyphenols against lipid peroxidation in the stratum corneum, the HPLC-TBARS-EVSC protocol was conducted. It was observed that only naringenin exhibited a significant reduction in epidermal lipoperoxidation, indicating superior anti-radical potential. Conversely, chlorogenic acid, apigenin, and kaempferol displayed a pro-oxidant profile under the specified test conditions. The laser Doppler flowmetry suggested the anti-inflammatory potential of naringenin, kaempferol, and chlorogenic acid, with naringenin showing superior efficacy involving all parameters quantified. Naringenin emerged as the only polyphenol capable of reducing the intensity of the inflammatory response induced by methyl nicotinate solution in the participants, compared to the blank gel and the untreated area. This comprehensive investigation underscores the diverse protective roles of polyphenols in skin health, emphasizing naringenin’s notable anti-radical and anti-inflammatory properties.

The Role of Risk Analysis in EU Food Governance: Balancing Scientific Food Safety Factors and External Factors that Inform Risk Management for Healthier Food Systems

Abstract Scientific consensus links dietary choices to health outcomes, highlighting the urgency to prioritise healthy food production in food systems. At the EU level, however, defining healthy food and integrating it into food governance remains a challenge, particularly regarding the inclusion of health-related characteristics in food safety assessments. While the EU primarily relies on the risk analysis principle to address food safety concerns, the process still exhibits weaknesses that hinder its direct impact on fostering a healthier food production landscape. This review demonstrates how the risk analysis process, particularly scientific opinions in risk assessment and external factors (economic and political) in risk management, impact food governance and the healthiness of food systems. We find that while external factors play a crucial role in risk management decisions by incorporating non-food safety considerations, they often stem from an imbalance of power favouring major industry and political stakeholders. This imbalance disproportionately influences decision-making, often overshadowing nutritional and health aspects. To address these challenges, we recommend directing research towards filling knowledge gaps and exploring minority scientific findings, and separating external factors from risk management’s decision-making process, to ensure that food governance prioritises public health and healthy food production.

Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington's disease.

Huntington's disease (HD) is a paradigm of a genetic neurodegenerative disorder characterized by the expansion of CAG repeats in the HTT gene. This extensive review investigates the molecular complexities of HD by highlighting the pathogenic mechanisms initiated by the mutant huntingtin protein. Adverse outcomes of HD include mitochondrial dysfunction, compromised protein clearance, and disruption of intracellular signaling, consequently contributing to the gradual deterioration of neurons. Numerous therapeutic strategies, particularly precision medicine, are currently used for HD management. Antisense oligonucleotides, such as Tominersen, play a leading role in targeting and modulating the expression of mutant huntingtin. Despite the promise of these therapies, challenges persist, particularly in improving delivery systems and the necessity for long-term safety assessments. Considering the future landscape, the review delineates promising directions for HD research and treatment. Innovations such as Clustered regularly interspaced short palindromic repeats associated system therapies (CRISPR)-based genome editing and emerging neuroprotective approaches present unprecedented opportunities for intervention. Collaborative interdisciplinary endeavors and a more insightful understanding of HD pathogenesis are on the verge of reshaping the therapeutic landscape. As we navigate the intricate landscape of HD, this review serves as a guide for unraveling the intricacies of this disease and progressing toward transformative treatments.

Barriers and strengthening strategies on the Korea safety laws for the application of hydrogen and ammonia as power generation fuels based on the expert survey

Hydrogen and ammonia have emerged as prominent next-generation clean energy sources pivotal for realizing a decarbonized society. However, their adoption has been marred by incidents ranging from leaks to fires, and explosions, underscoring the imperative for heightened safety protocols when utilizing these novel fuels. In light of this, this study scrutinizes Korean laws and regulations to assess the institutional framework governing the safe utilization of hydrogen and ammonia in power plants. Through this examination, four key limitations are identified: hydrogen laws do not comprehensively cover the entire hydrogen business sector, regulations regarding the revised usage of hydrogen and ammonia are either weak or absent, safety assessments in certain laws exclude new fuels, and there is a relaxation in requirements for appointing safety managers. This prompted an expert survey aimed at delineating strategies for improvement. A bespoke questionnaire, tailored to address the shortcomings of current legislation, was administered to 50 experts in the realms of decarbonized fuels or safety. Quantitative analysis of their responses revealed a consensus regarding the elevated risk posed by hydrogen and ammonia compared to conventional fuels, with hydrogen (72) deemed riskier than ammonia (65) and LNG (50). Moreover, a pressing need for bolstering the existing safety legal framework was highlighted. Notably, the survey underscored specific areas requiring attention, ranked in order of priority: the enactment of an Ammonia Act (78), augmentation of qualification requirements for safety managers under the Hydrogen Act (73), reinforcement of regulatory and technical standards, implementation of emergency response drills, classification of ammonia as a Class 4 hazardous material (70), and enhancement of criteria for appointing safety managers (59). Insights gleaned from the expert survey culminated in four improvements geared towards enhancing safety measures. There is a need to enact a stand-alone law specifically for ammonia, to strengthen standards for risk assessment and the appointment of safety managers. Additionally, there is a necessity to expand the scope of safety laws to include prevention and education initiatives, while also attempting to consolidate scattered laws for better coherence and effectiveness. This study advocates for comprehensive safety management systems to be established through extensive research preceding the commercialization of power plants utilizing new fuels.

An Assessment of Semaglutide Safety Based on Real World Data: From Popularity to Spontaneous Reporting in EudraVigilance Database

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treatment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obesity in patients with or without T2DM (liraglutide—LIR, semaglutide—SEM, and tirzepatide—TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analyzed the Google queries related to SEM to assess people’s interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. The data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a hi3gh tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the risks of ADRs, the off-label use should be reduced and carefully monitored.

Importance of Examining Incidentality in Vaccine Safety Assessment

The author believes that the principles of statistical methods for vaccine safety can be divided into three categories: comparison of adverse event incidence rates between vaccinated and unvaccinated groups, analysis of incidentality in the vaccinated group, and a combination of both. The first category includes the cohort study; the second, the self-controlled risk interval design (SCRI); and the third, the self-controlled case series method. A single p-value alone should not determine a scientific conclusion, and analysis should be performed using multiple statistical methods with different principles. The author believes that using both the cohort study and the SCRI for analysis is the best method to assess vaccine safety. When the cohort study may not detect a significant difference owing to a low incidence rate of an adverse event in the vaccinated group or a high one in the unvaccinated group, the SCRI may detect it. Because vaccines must have a higher level of safety than the pharmaceuticals used for treatment, vaccine safety is advisable to be assessed using methods that can detect a significant difference even for any value of the incidence rate of an adverse event. The author believes that the analyses of COVID-19 vaccine safety have areas for improvement because the proportion of papers that used the cohort study and the SCRI was negligible.

Assessment of safety and efficacy of transarterial chemoembolization combined with camrelizumab and donafenib in patients with hepatocellular carcinoma at BCLC stage C: A study of 20 cases.

Camrelizumab, donafenib, and transarterial chemoembolization (TACE) are recommended for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear. From July 2021 to January 2023, 20 Barcelona Clinic Liver Cancer stage C HCC patients were prospectively enrolled. Inclusion criteria were Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh Score ≤ 7, and Barcelona Clinic Liver Cancer B or C. Surgical candidates were excluded. The treatment included TACE, camrelizumab, and donafenib. Endpoints were median overall survival, progression-free survival, and adverse events (AEs) related to donafenib. Among 20 patients, 85% experienced AEs from targeted therapy and programmed cell death protein-1, with 40% having grade 3 AEs. No grade 4 or 5 AEs occurred. Median follow-up was 9 months, with 15% achieving complete response, 65% partial response, and 15% stable disease. Disease control rate was 90%. Median progression-free survival and overall survival were 9 and 14 months, respectively. TACE, camrelizumab, and donafenib combination therapy in Chinese advanced HCC patients show effectiveness in extending survival with low severe AEs incidence.

Ablating Myocardium Using Nanosecond Pulsed Electric Fields: Preclinical Assessment of Feasibility, Safety and Durability.

Background:Unlike "conventional" microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation (nsPFA) in swine. Methods: A novel endocardial nsPFA system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Swine were survived for <1 (n=1), ~2 (n=7), ~7 (n=6), 14 (n=2), or ~28 (n=9) days and venous isolation assessed before sacrifice. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathological examination. Results: All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed and all 13 (100%) were transmural (depth 6.4±0.4mm). Ventricular lesions were 14.7±4.5mm wide and 7.1±1.3mm deep, with high-dose lesions deeper than low-dose (7.9±1.2mm vs 6.2±0.8mm, p=0.007). The esophagus revealed non-transmural adventitial surface lesions in 5 of 5 (100%) animals sacrificed early (2 days) post-ablation. In the 10 animals sacrificed later (14-28 days), all animals demonstrated significant esophageal healing - 8 with complete resolution, and 2 with only trace fibrosis. Conclusions: A novel, endocardial nanosecond PFA system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and non-transmural esophageal lesions can occur with worst case assessments suggesting limits to PFA tissue selectivity and the need for dedicated assessments during clinical studies.

Review on treatment of pleural metastasis and malignant pleural effusion with Pressurized IntraThoracic Aerosol Chemotherapy (PITAC)

Abstract Background Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe shortness of breath. Current first-line treatment options include pleural drainage using catheters as well as pleurodesis. However, these treatment modalities are often inefficient and patients need repeated procedures. Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive procedure, where antineoplastic agents are nebulized under pressure into the pleural space. Content We present the preliminary safety, feasibility, and response assessment data for PITAC based on a comprehensive literature review. Summary Five retrospective studies reported data on 38 PITACs in 21 patients. Data were heterogeneous and incomplete on several important aspects such as procedure, safety, local effect and long-term outcomes. PITAC seems technically feasible with a low risk of complications and may provide some reduction in MPE in selected cases. Outlook PITAC seems feasible, but prospective phase I and II studies are needed to define safety, indications, and efficacy.

A Model-Informed Drug Development Approach to Design a Phase 3 Trial of Teverelix Drug Product in Advanced Prostate Cancer Patients with Increased Cardiovascular Risk.

Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach. Data from 9 phase 2 studies (229 patients) was utilized to develop a population pharmacokinetic (PK) model that described the concentration profile accommodating both IM and SC routes of administration. A 2-compartment model with sequential first-order absorption (slow and fast) and lag times best described the PK profiles of teverelix following SC and IM administration. An indirect response model with inhibition of production rate was fit to describe testosterone (T) concentrations based on physiological relevance. The final population PK-pharmacodynamic model was used to conduct simulations of various candidate dosing regimens to select the optimal dosing regimen to achieve clinical castration (T<0.5ng/mL by day 28) and to sustain clinical castration for 26 weeks. Model simulation showed that a loading dose of 360mg SC and 180mg IM with a maintenance dose of 360mg SC 6-weekly (Q6W) starting at day 28 can achieve a ≥95% castration rate up to 52 weeks. This dose regimen was selected for phase 3 clinical development, which includes cardiovascular safety assessment in comparison to a GnRH agonist.

Investigating and Improving Pedestrian Safety in an Urban Environment of a Low- or Middle-Income Country: A Case Study of Yaoundé, Cameroon

In Yaoundé, Cameroon, where walking dominates transport modes, pedestrian safety remains an issue as pedestrians account for a fair share of road traffic casualties, partly due to the lack of walking policies and pedestrian facilities safety data, hindering targeted intervention. This study used a pedestrian safety index (PSI) and the Global Walkability Index (GWI) to investigate 12 road segments frequented by diverse pedestrian groups. Indexes were graded from E—lowest to A—highest and analyzed using description and rank correlation. Main safety issues included lack of adequate and accessible sidewalks, bollards, pedestrian crossings, signage, shade, and street lighting. Only one segment (R7) achieved grade C, while the remainder scored D or E, indicating poor pedestrian safety conditions and an unpleasant walking experience. The correlation coefficient (0.69) between the PSI and GWI at a 99% significance level validated the safety assessment, providing confidence in the results. A seven-year (2024–2030) safety strategy is proposed to improve all roads to grade B. This strategy contains several interventions, including engineering improvement, which have been proven effective. This study offers evidence for city officials to improve pedestrian safety and informs walking policies and the implementation of upcoming projects. Future research should quantify the recommendations’ benefits and validate indexes with crash or conflict data.

Understanding the transition to viable but non-culturable state in Escherichia coli W3110: a comprehensive analysis of potential spectrochemical biomarkers.

The viable but non-culturable (VBNC) state is considered a survival strategy employed by bacteria to endure stressful conditions, allowing them to stay alive. Bacteria in this state remain unnoticed in live cell counts as they cannot proliferate in standard culture media. VBNC cells pose a significant health risk because they retain their virulence and can revive when conditions normalize. Hence, it is crucial to develop fast, reliable, and cost-effective methods to detect bacteria in the VBNC state, particularly in the context of public health, food safety, and microbial control assessments. This research examined the biomolecular changes in Escherichia coli W3110 induced into the VBNC state in artificial seawater under three different stress conditions (temperature, metal, and antibiotic). Initially, confirmation of VBNC cells under various stresses was done using fluorescence microscopy and plate counts. Subsequently, lipid peroxidation was assessed through the TBARS assay, revealing a notable increase in peroxidation end-products in VBNC cells compared to controls. ATR-FTIR spectroscopy and chemomometrics were employed to analyze biomolecular changes, uncovering significant spectral differences in RNA, protein, and nucleic acid concentrations in VBNC cells compared to controls. Notably, RNA levels increased, while protein and nucleic acid amounts decreased. ROC analyses identified the 995cm- 1 RNA band as a consistent marker across all studied stress conditions, suggesting its potential as a robust biomarker for detecting cells induced into the VBNC state under various stressors.

Innovative peptide architectures: advancements in foldamers and stapled peptides for drug discovery.

Peptide foldamers play a critical role in pharmaceutical research and biomedical applications. This review highlights recent (post-2020) advancements in novel foldamers, synthetic techniques, and their applications in pharmaceutical research. The authors summarize the structures and applications of peptide foldamers such as α, β, γ-peptides, hydrocarbon-stapled peptides, urea-type foldamers, sulfonic-γ-amino acid foldamers, aromatic foldamers, and peptoids, which tackle the challenges of traditional peptide drugs. Regarding antimicrobial use, foldamers have shown progress in their potential against drug-resistant bacteria. In drug development, peptide foldamers have been used as drug delivery systems (DDS) and protein-protein interaction (PPI) inhibitors. These structures exhibit resistance to enzymatic degradation, are promising for therapeutic delivery, and disrupt crucial PPIs associated with diseases such as cancer with specificity, versatility, and stability, which are useful therapeutic properties. However, the complexity and cost of their synthesis, along with the necessity for thorough safety and efficacy assessments, necessitate extensive research and cross-sector collaboration. Advances in synthesis methods, computational modeling, and targeted delivery systems are essential for fully realizing the therapeutic potential of foldamers and integrating them into mainstream medical treatments.

Non-clinical safety assessment of Annona atemoya leaf extract: evaluation of genotoxicity

Non-clinical safety assessment of Annona atemoya leaf extract: evaluation of genotoxicity

CorTAF-LBE: A full scale subchannel-level thermal-hydraulic characteristics analysis code for LBR core based on OpenFOAM

The lead-bismuth cooled fast reactor core adopts box-type design, and the fuel rod bundle is fixed by wrapping wires. The complex geometric structure of the fuel assemblies significantly affects the flow and heat transfer status of the liquid metal coolant. Building upon the open-source CFD platform, OpenFOAM, this work established conservation equations for liquid metal coolant, fuel rod thermal characteristic models, inter-wrapper coolant analysis models, and coupled heat transfer models, and developed the subchannel level thermal-hydraulic analysis code CorTAF-LBE for whole-core analysis of LBR core using the finite volume method. The wire-wrapped rod bundles internal flow and heat transfer experiments of lead-bismuth, carried out based on the THEADES and KYLIN-II circulation loops, were selected to perform verification and validation. The results match well with the experimental data and CFD fine-modeling prediction. The steady-state numerical simulation of three wire-wrapped rod bundle assemblies with inter-wrapper flow was carried out under normal operation condition. The temperature and pressure distributions of the coolant in each subchannel and inter-wrapper flow region, the temperature of cladding and other key thermal-hydraulic parameters were obtained. The role of the inter-wrapper coolant in heat removal from the fuel assemblies was revealed. The work in this paper has referential value for the optimization of lead-bismuth cooled fast reactor design and safety assessment during operation.