Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Inducing Cellular Senescence in Mouse Embryonic Fibroblasts (MEFs).

Inducing cellular senescence in mouse embryonic fibroblasts (MEFs) is a robust tool to study the molecular mechanisms underlying senescence establishment and their heterogeneity. This protocol provides a detailed guide to generate MEFs and routinely induce senescence in MEFs using several DNA damage-dependent and DNA damage-independent induction methods.

Apple polyphenols prevent patulin-induced intestinal damage by modulating the gut microbiota and metabolism of the gut-liver axis.

Patulin (PAT), a foodborne toxin, causes severe intestinal damage. To mitigate this health threat, mice were pretreated with apple polyphenols (AP) in their drinking water (0.01 % and 0.05 %) for eight weeks, followed by exposure to PAT during the last two weeks. Subsequently, histopathological and biochemical evaluations of intestinal tissues were conducted, alongside assessments of alterations in gut microbiota, colonic content metabolome, and hepatic metabolome. Consequently, AP alleviated PAT-induced villus and crypt injury, mucus depletion, GSH level decline, GSH-Px and SOD activity reduction, and MPO activity elevation. Notably, AP counteracted PAT-mediated microbiota disruptions and promoted the abundance of beneficial bacteria (Dubosiella, Akkermansia, Lachnospiraceae, and Lactobacillus). Furthermore, AP counteracted PAT-induced metabolic disorders in the colonic contents and liver. Ultimately, AP prevented intestinal injury by regulating the gut microbiota and amino acid, purine, butanoate, and glycerophospholipid metabolism in the gut-liver axis. These results underscore the potential of AP to prevent foodborne toxin-induced intestinal damage.

Protonated carbon nitride for rapid photocatalytic sterilization via synergistic oxidative damage and physical destruction.

Photocatalytic disinfection is an eco-friendly strategy for countering bacterial pollution in aquatic environments. Numerous strategies have been devised to facilitate the generation of reactive oxygen species (ROS) within photocatalysts, ultimately leading to the eradication of bacteria. However, the significance of the physical morphology of photocatalysts in the context of sterilization is frequently obscured, and the progress in the development of physical-chemical synergistic sterilization photocatalysts has been relatively limited. Herein, graphitic carbon nitride (g-C3N4) is chemically protonated to expose more sharp edges. PL fluorescence and EIS results indicate that the protonation can accelerate photogenerated carrier separation and enhance ROS production. Meanwhile, the sharp edges on the protonated g-C3N4 facilitate the physical disruption of cell walls for further promoting oxidative damage. Protonated C3N4 demonstrated superior bactericidal performance than that of pristine g-C3N4, effectively eliminating Escherichia coli within 40 minutes under irradiation. This work highlights the significance of incorporating physical and chemical synergies in photocatalyst design to enhance the disinfection efficiency of photocatalysis.

Shikonin Stimulates Mitochondria-Mediated Apoptosis by Enhancing Intracellular Reactive Oxygen Species Production and DNA Damage in Oral Cancer Cells.

Phytotherapy has rendered a new insight towards the treatment of various cancers, including oral cancer with fewer side effects, over the traditional chemotherapeutic drugs to overcome chemoresistance. Shikonin (Shk) is a natural biologically active alkaloid found in the Lithospermum erythrorhizon plant's root. It has potent cytotoxic activities against various cancers. Our study revealed the release time and anticancer potential of Shk on the SCC9 and H357 oral cancer cell lines. We investigated the antiproliferative, antimigratory, cell cycle arresting and apoptosis promoting activity of Shk in oral cancer cells by performing MTT and morphological assay, colony, and tumor sphere formation assay, AO/EtBr and DAPI staining, Annexin V-FITC/PI staining, assay for reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) measurement, comet assay, qRT-PCR, and western blot analysis. We also checked the interaction of DNA and Shk by docking and CD spectroscopy and EtBr displacement assay. As a result, we found that Shk reduced the viability, proliferation, and tumorigenicity of SCC9 and H357 cells in a time and concentration-dependent manner. We obtained half-maximal inhibitory concentration (IC50) at 0.5 µM for SCC9 and 1.25 µM for H357. It promotes apoptosis via overexpressing proapoptotic Bax and caspase 3 via enhancing ROS that leads to MMP depletion and DNA damage and arrests cells at the G2/M & G2/S phase. The antimigratory activity of Shk was performed by analyzing the expression of markers of epithelial-mesenchymal transition like E-cadherin, ZO-1, N-cadherin, and vimentin. These overall results recommended that Shk shows potent anticancer activity against oral cancer cell lines in both in vitro and ex vivo conditions. So, it could be an excellent agent for the treatment of oral cancer.

Effects of Vegan and Omnivore Diet on Post-Downhill Running Economy and Muscle Function.

OBJECTIVES: The objective of this study was to examine the difference between the extent of muscle damaging exercise on muscle function variables of vegans and omnivores. METHODS: Twenty recreationally trained participants completed the study. Participants were assigned to either vegan (n = 10) or omnivore (n = 10) groups. Subjects completed a consent visit followed by 2 visits consisting of running exercise sessions and test familiarization. They returned to the laboratory for visit 4 3-5 days after visit 3 to complete the testing battery. Following the testing, the participants performed a downhill run on the treadmill at -15% grade and approximately 70% of their speed at VO2peak and repeated the testing battery upon completion. Participants were asked to track their food intake. Visits 5, 6, and 7 took place 24, 48, and 72 h following the downhill running protocol, respectively, and consisted of the same testing battery used during visit 4. The detection of differences was performed using two-way (group x time) mixed factorial ANOVA with repeated measures. RESULTS: No group x time interactions were noted for running economy or any of the dependent variables. Main effects of time were found for muscle thickness (p<.001) with small effect sizes (d=-0.194 to d=-0.265), pain pressure threshold (p=.002) with medium effect sizes (d=.460 to d=.461), NPRS scale (p<.001) with large effect sizes (d = -0.776 to d=-1.520), and jump height (p<.002) with small to medium effect sizes (d=.304 to d=.438). Nutritional analysis compared the two groups revealed no difference (p>.05) between relative intake of macronutrients and that both exceeded typical recommendations for protein (vegan group - 1.4 g/kg, omnivore group - 1.6 g/kg). CONCLUSION: The lack of differences in recovery between the groups suggests that nutritional adequacy may play a role in recovery. Recovery from downhill running might be influenced by several factors beyond diet, such as exercise protocol intensity, individual fitness levels, and age.

Diabetes Mellitus and Neurovascular Pathology: A Comprehensive Review of Retinal and Brain Lesions.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by persistent hyperglycemia, which significantly impacts vascular health. This review comprehensively analyzes the neurovascular complications associated with DM, focusing on retinal and brain lesions. Diabetes is categorized into type 1 DM, type 2 DM, and gestational DM, each presenting unique challenges and risks. The condition accelerates vascular damage through mechanisms such as endothelial dysfunction, inflammation, and oxidative stress, leading to severe microvascular complications. Diabetic retinopathy is a primary concern, with its progression from non-proliferative to proliferative stages potentially resulting in vision loss. Concurrently, diabetes contributes to neurovascular damage in the brain, increasing the risk of cognitive decline and cerebrovascular events. This review examines the pathophysiological mechanisms underlying these complications, evaluates current diagnostic and management strategies, and highlights recent advancements in imaging technologies and therapeutic approaches. Integrating these insights is crucial for improving early detection, treatment, and management of diabetes-related neurovascular issues. Future research should focus on innovative preventive measures and therapeutic interventions to mitigate the long-term impact of diabetes on vascular health. By enhancing our understanding of these complex interactions, this review aims to contribute to better clinical practices and improved patient outcomes in diabetes care.

Comprehensive Profiling of Transcriptome and m6A Epitranscriptome Uncovers the Neurotoxic Effects of Yunaconitine on HT22 Cells.

Objective: To explore different mRNA transcriptome patterns and RNA N6-methyladenosine (m6A) alteration in yunaconitine (YA)-treated HT22 mouse hippocampal neuron, and uncover the role of abnormal mRNA expression and RNA m6A modification in YA-induced neurotoxicity. Methods: HT22 cells were treated with 0, 5, 10, and 50 µM of YA for 72 h to evaluate their viability and GSH content. Subsequently, mRNA-seq and MeRIP-seq analyses were performed on HT22 cells treated with 0 and 10 µM YA for 72 h, and molecular docking was used to simulate interactions between YA and differentially expressed m6A regulators. The mitochondrial membrane potential was examined using the JC-10 probe, and RT-qPCR was conducted to verify the expression levels of differentially expressed m6A regulatory factors, as well as to assess alterations in the mRNA expression levels of antioxidant genes. Results: YA treatment significantly reduced the viability of HT22 cells and decreased GSH content. The mRNA-seq analysis obtained 1018 differentially expressed genes, KEGG and GO enrichment results of differentially expressed genes mainly comprise the nervous system development, cholinergic synapse, response to oxidative stress, and mitochondrial inner membrane. A total of 7 differentially expressed m6A regulators were identified by MeRIP-seq. Notably, molecular docking results suggested a stable interaction between YA and most of the differentially expressed m6A regulators. Conclusion: This study showed that YA-induced HT22 cell damage was associated with the increased methylation modification level of target gene m6A and abnormal expression of m6A regulators.

The Safety and Efficacy of Hypertonic Saline in Achieving Primary Fascial Closure Following Damage Control Laparotomy: A Systematic Review and Meta-Analysis.

Effective fluid management is critical in patients undergoing damage control laparotomy (DCL) for trauma and sepsis. Hypertonic saline (HTS) has been proposed as an alternative to isotonic fluids to enhance primary fascial closure rates and optimize fluid balance. This systematic review and meta-analysis aims to evaluate the efficacy and safety of HTS compared to isotonic fluids in patients undergoing DCL. A comprehensive literature search was conducted across multiple databases up to the 14th of June 2024, identifying studies that compared HTS to isotonic fluids in adult patients undergoing DCL for trauma or sepsis. Eligible studies included randomized controlled trials and observational studies reporting outcomes such as early primary fascial closure (EPFC) rates, time to fascial closure, fluid requirements, electrolyte imbalances, renal function, and mortality. Data extraction and quality assessment were performed independently by two reviewers, and pooled analyses were conducted using fixed-effect models where appropriate. Four studies encompassing 375 patients met the inclusion criteria, with 100 patients receiving HTS and 275 receiving isotonic fluids. HTS administration was associated with a significantly higher EPFC rate compared to isotonic fluids (odds ratio (OR): 0.314; 95% confidence interval (CI): 0.142-0.696; p=0.004). The mean time to fascial closure was also significantly reduced in the HTS group by approximately eight hours (mean difference (MD): 8.007 hours; 95% CI: 5.558-10.596; p<0.001). Patients receiving HTS required significantly less total fluid over 48 hours (MD: 1.055 liters; 95% CI: 0.713-1.398; p<0.001). While HTS use led to higher peak sodium levels (MD: -4.318 mEq/L; 95% CI: -4.702 to -3.934; p<0.001), there were no significant differences in peak creatinine levels, need for inpatient renal replacement therapy, or 28-day mortality between the groups. HTS appears to be effective in improving EPFC rates and reducing both time to closure and overall fluid requirements in patients undergoing DCL for trauma and sepsis. Although associated with higher serum sodium levels, HTS did not increase the risk of renal dysfunction or mortality. These findings suggest that HTS is a safe and efficacious alternative to isotonic fluids in the management of critically ill patients requiring DCL. Further large-scale, randomized controlled trials are warranted to confirm these results and inform clinical guidelines.

Age and blood pressure stratified healthy vascular aging, organ damage and prognosis in the community-dwelling elderly: insights from the North Shanghai Study.

BACKGROUND: This study aimed to investigate the prognostic value of age and blood pressure stratified healthy vascular aging (HVA) defined in the North Shanghai Study (NSS), and illustrate its relationship with organ damage (OD). METHODS: This study enrolled 3590 community-dwelling elderly Chinese aged over 65 years and finally 3234 participants were included. 3230 individuals were included in the final analysis, with 4 participants lost to follow-up. NSS HVA was defined as low carotid-femoral pulse wave velocity (PWV) which had a higher cutoff value with advanced age and level of blood pressure. OD was thoroughly assessed and classified into vascular, cardiac and renal OD. Primary endpoints were major adverse cerebrocardiovascular events (MACCE) and all-cause mortality. RESULTS: Nine hundred seventy-eight participants out of 3234 participants (43.1%) were identified as having NSS HVA. The NSS HVA group exhibited a younger age, lower blood pressure levels, lower body mass index, and milder OD compared to the non-NSS HVA group. Over follow-up of 5.7 ± 1.8 years, 332 MACCE (1.82 per 100 person-year) and 212 all-cause deaths (1.14 per 100 person -year) occurred. NSS HVA was associated with a reduced risk of MACCE (HR [95% CI] = 0.585, 0.454-0.754) and all-cause death (HR [95%CI] = 0.608 [0.445, 0.832]), especially in those subgroups without clinical diagnosed cardiovascular disease (CVD) or diabetes mellitus but with at least one type of OD. Moreover, NSS HVA exhibited improved prognostic value for MACCE, all-cause death and CVD death compared to other definitions of HVA. CONCLUSIONS: Age and blood pressure stratified NSS HVA could serve as an improved indicator against serious adverse events in the community-dwelling elderly Chinese. TRIAL REGISTRATION: Prognosis in the Elderly Chinese: The Northern Shanghai Study (NSS), NCT02368938, https://clinicaltrials.gov/study/NCT02368938?cond=NCT02368938&rank=1 .

Effect of (R)-(-)-Linalool on endothelial damage: Sex differences.

Oxidative stress and inflammation are responsible for endothelial damage displaying many sex differences. Lipopolysaccharide (LPS) is a pathogenic stimulus that can trigger inflammation, contributing to endothelial dysfunction. Given the scientific evidence on the effectiveness of herbal extracts in managing endothelial dysfunction, we considered the (R)-(-)-Linalool (LIN), an aromatic monoterpene alcohol, as a bioactive phytochemical compound that could prevent and improve endothelial injury. In this study, we evaluated the effect of the LIN on LPS-induced damage in female and male human umbilical vein endothelial cells (FHUVECs and MHUVECs), measuring cell viability, cytokines release (IL-6 and TNF-α), malondialdehyde (MDA), and nitrites. LPS significantly reduced viability both in MHUVECs and FHUVECs. Moreover, LPS increased the IL-6, TNF-α, and MDA level only in FHUVECs if compared to basal value; despite that, LPS reduced nitrites only in MHUVECs. LIN alone did not affect the parameters measured except for an increase in nitrites in FHUVECs. Nevertheless, LIN reduced damage and restored endothelium viability reduced by LPS without a clear sex difference. Under LPS, LIN inhibited IL-6 release and reduced MDA levels only in FHUVECs. The present data confirm the existence of sex differences in the behavior of HUVECs under LPS conditions. The administration of LIN seems to have a more evident effect on FHUVECs after damage induced by LPS. These LIN effects are important to conduct further well-designed studies on the sex-specific use of this compound on vascular endothelial injury.

Telomere maintenance and the DNA damage response: a paradoxical alliance.

Telomeres are the protective caps at the ends of linear chromosomes of eukaryotic organisms. Telomere binding proteins, including the six components of the complex known as shelterin, mediate the protective function of telomeres. They do this by suppressing many arms of the canonical DNA damage response, thereby preventing inappropriate fusion, resection and recombination of telomeres. One way this is achieved is by facilitation of DNA replication through telomeres, thus protecting against a "replication stress" response and activation of the master kinase ATR. On the other hand, DNA damage responses, including replication stress and ATR, serve a positive role at telomeres, acting as a trigger for recruitment of the telomere-elongating enzyme telomerase to counteract telomere loss. We postulate that repression of telomeric replication stress is a shared mechanism of control of telomerase recruitment and telomere length, common to several core telomere binding proteins including TRF1, POT1 and CTC1. The mechanisms by which replication stress and ATR cause recruitment of telomerase are not fully elucidated, but involve formation of nuclear actin filaments that serve as anchors for stressed telomeres. Perturbed control of telomeric replication stress by mutations in core telomere binding proteins can therefore cause the deregulation of telomere length control characteristic of diseases such as cancer and telomere biology disorders.

MRI-based microplastic tracking in vivo and targeted toxicity analysis.

Microplastics (MPs) as an emerging pollutant have raised significant concerns in environmental health. However, elucidating the distribution of MPs in living organisms remains challenging due to their trace residue and tough detection problems. In this study, a novel magnetic resonance imaging (MRI)-based tracking method was employed to monitor functionalized MPs biodistribution in vivo. Our results identified that the liver is the primary accumulation site of polystyrene microplastics (PS-MPs) in biological systems through continuous in vivo monitoring spanning 21 days. Biochemical tests were performed to assess the toxicological effects of functionalized MPs on the liver tissue, revealing hepatocyte death, inflammatory cell infiltration, and alterations in alkaline phosphatase levels. Notably, positively charged MPs exhibited more severe effects. A combined metabolomics-proteomics analysis further revealed that PS-MPs interfered with hepatic metabolic pathways, particularly bile secretion and ABC transporters. Overall, this study effectively assessed the distribution of functionalized MPs in vivo utilizing MRI technology, validated toxicity in targeted organ, and conducted an in-depth study on underlying biotoxicity mechanism. These findings offer crucial scientific insights into the potential impact of MPs in the actual environment on human health.

An optimal deep learning model for the scoring of radiographic damage in patients with ankylosing spondylitis.

Background: Detecting vertebral structural damage in patients with ankylosing spondylitis (AS) is crucial for understanding disease progression and in research settings. Objectives: This study aimed to use deep learning to score the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) using lateral X-ray images of the cervical and lumbar spine in patients with AS in Asian populations. Design: A deep learning model was developed to automate the scoring of mSASSS based on X-ray images. Methods: We enrolled patients with AS at a tertiary medical center in Taiwan from August 1, 2001 to December 30, 2020. A localization module was used to locate the vertebral bodies in the images of the cervical and lumbar spine. Images were then extracted from these localized points and fed into a classification module to determine whether common lesions of AS were present. The scores of each localized point were calculated based on the presence of these lesions and summed to obtain the total mSASSS score. The performance of the model was evaluated on both validation set and testing set. Results: This study reviewed X-ray image data from 554 patients diagnosed with AS, which were then annotated by 3 medical experts for structural changes. The accuracy for judging various structural changes in the validation set ranged from 0.886 to 0.985, whereas the accuracy for scoring the single vertebral corner in the test set was 0.865. Conclusion: This study demonstrated a well-trained deep learning model of mSASSS scoring for detecting the vertebral structural damage in patients with AS at an accuracy rate of 86.5%. This artificial intelligence model would provide real-time mSASSS assessment for physicians to help better assist in radiographic status evaluation with minimal human errors. Furthermore, it can assist in a research setting by offering a consistent and objective method of scoring, which could enhance the reproducibility and reliability of clinical studies.

Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells.

OBJECTIVE: Radon ( 222 Rn) is a naturally occurring radioactive gas that has been closely linked with the development of lung cancer. In this study, we investigated the radon-induced DNA strand breaks, a critical event in lung carcinogenesis, and the corresponding DNA damage response (DDR) in mice and human bronchial epithelial (BEAS-2B) cells. METHODS: Biomarkers of DNA double-strand breaks (DSBs), DNA repair response to DSBs, ataxia-telangiectasia mutated (ATM) kinase, autophagy, and a cell apoptosis signaling pathway as well as cell-cycle arrest and the rate of apoptosis were determined in mouse lung and BEAS-2B cells after radon exposure. RESULTS: Repeated radon exposure induced DSBs indicated by the increasing expressions of γ-Histone 2AX (H2AX) protein and H2AX gene in a time and dose-dependent manner. Additionally, a panel of ATM-dependent repair cascades [i.e. non-homologous DNA end joining (NHEJ), cell-cycle arrest and the p38 mitogen activated protein kinase (p38MAPK)/Bax apoptosis signaling pathway] as well as the autophagy process were activated. Inhibition of autophagy by 3-methyladenine pre-treatment partially reversed the expression of NHEJ-related genes induced by radon exposure in BEAS-2B cells. CONCLUSIONS: The findings demonstrated that long-term exposure to radon gas induced DNA lesions in the form of DSBs and a series of ATM-dependent DDR pathways. Activation of the ATM-mediated autophagy may provide a protective and pro-survival effect on radon-induced DSBs.

Helmets with lattice liners can mitigate traumatic brain injury from impacts.

This study explores the effectiveness of architected lattice structures, specifically made of polyamide 12 (PA12) material, as potential helmet liners to mitigate traumatic brain injuries (TBI), with a focus on rotational acceleration. Evaluating three lattice unit cell topologies (simple cubic, dode-medium, and rhombic dodecahedron), the research builds upon prior investigations indicating that PA12 lattice liners may outperform conventional EPS liners. Employing a high-fidelity finite element male head model and utilizing direct and oblique impact scenarios, mechanical quantities, such as maximum principal strain (MPS) and shear strain, cumulative strain damage measure and intracranial pressure were measured at the tissue level in different brain regions. Results indicate that lattice liners, especially with dode-medium topology, exhibit promising reductions in brain tissue strains. On average, during oblique impacts, less than 1 % of the brain volume experienced an MPS level of 0.4 when the lattice liners were adopted, whereas that percentage was above 70 % with the expandable polystyrene (EPS) foam liners. Pressure-based assessments suggest that lattice liners may outperform EPS liners in oblique impacts, showcasing the limitations of EPS for effective TBI mitigation. Despite certain model limitations, this study emphasizes the need for advancements in helmet technology, particularly in the development of commercial lattice liners using additive manufacturing, to address the limitations of existing EPS liners in preventing rotational consequences of impacts and reducing TBI.

Analysis of postdisaster economy using high-resolution disaster and economy simulations.

We present an integrated framework that utilizes high-resolution seamless simulations of disasters and national economies for estimating the economic impacts of disasters. The framework consists of three components: a physics-based simulator to simulate the disaster and estimate the response of the infrastructure; a tool that estimates the losses suffered by the infrastructure based on its response; and an agent-based economic model (ABEM) that simulates the national economy considering the infrastructure damage and postdisaster decisions of the economic entities. The ABEM used in the framework has been implemented in a high-performance computing environment to simulate large economies at 1:1 scale. Furthermore, it has been calibrated to the Japanese economy using publicly available macroeconomic data and validated to the Japanese economy under the business-as-usual scenario. We demonstrate the integrated framework by simulating a potential Nankai-trough earthquake disaster and estimating its impacts on the Japanese economy. The seismic response of 1.8 million buildings of the Osaka-bay area has been estimated using a large-scale earthquake disaster simulator and corresponding repair costs are estimated using the Performance Assessment Calculation Tool. As per our estimates, repair costs amount to approximately 15 trillion Yen. Considering the investments made by impacted households and firms toward recovery, the postdisaster economy is simulated using the ABEM for 5 years under two recovery scenarios. Industrial production is expected to recover in three quarters whereas 10-13 quarters will be required to finish all the repair work.

A low-kiloelectronvolt focused ion beam strategy for processing low-thermal-conductance materials with nanoampere currents.

Ion beam-induced heat damage in thermally low conductive specimens such as biological samples is gaining increased interest within the scientific community. This is partly due to the increased use of FIB-SEMs in biology as well as the development of complex materials, such as polymers, which need to be analyzed. The work presented here looks at the physics behind the ion beam-sample interactions and the effect of the incident ion energy (set by the acceleration voltage) on inducing increases in sample temperature and potential heat damage in thermally low conductive materials such as polymers and biological samples. The ion beam-induced heat for different ion beam currents at low acceleration voltages is calculated using Fourier's law of heat transfer, finite element simulations, and numerical modelling results and compared to experiments. The results indicate that with lower accelerator voltages, higher ion beam currents in the nanoampere range can be used to pattern or image soft material and non-resin-embedded biological samples with increased milling speed but reduced heat damage.

Comprehensive eco-geno-toxicity and environmental risk of common antiviral drugs in aquatic environments post-pandemic.

The eco-geno-toxicological impacts of the most widely used antiviral drugs against SARS-CoV2 - ribavirin, ritonavir, nirmatrelvir and tenofovir - were investigated in freshwater organisms. Ribavirin and tenofovir exhibited the highest acute toxicity in the rotifer Brachionus calyciflorus at concentrations of a few mg/L while ritonavir and nirmatrelvir showed similar effects at tens of mg/L; acute toxicity of ribavirin was also observed in the crustacean Ceriodaphnia dubia at similar concentrations. In contrast, the crustacean Thamnocephalus platyurus showed the lowest sensitivity to the antiviral drugs tested with no sublethal effects. Chronic toxicity tests revelead that these antivirals induced effects in consumers at concentrations of environmental concern (ng-µg/L). Ribavirin showed the highest toxicity to the alga Raphidocelis subcapitata, while ritonavir showed the highest toxicity to B. calyciflorus and C. dubia. DNA damage and oxidative stress were observed in C. dubia at 0.001 µg/L and 0.1 µg/L when exposed to ritonavir and nirmatrelvir respectively, and at 1 µg/L when exposed to ribavirin and tenofovir. Toxic and genotoxic environmental risks were assessed with risk quotients for ritonavir, tenofovir and ribavirin exceeding the threshold of 1, indicating significant environmental concern.