Search Results (168)

This study presents an economic risk evaluation of buildings in Samoa exposed to extreme sea level (ESL)-driven episodic flooding and permanent inundation from relative sea level (RSL) rise. A spatiotemporal risk analysis framework was applied at the building object level to calculate monetary loss, expressed as the exceedance probability loss (EPL) and average annual loss (AAL). Economic risk was enumerated at national and district levels between the period 2020 and 2140 based on RSL projections for medium confidence Shared Socioeconomic Pathways (SSPs). Over this century, national AAL for buildings from ESL flooding in 2020 is expected to double by 2100 (USD 47–51 million). Under high emissions scenarios SSP3-7.0 and SSP5-8.5, AAL rates decelerate after 2100 as permanent inundation loss increases. District level risk variability is evident. For example, Tuamasaga on Upolu Island accounted for 44% of national 100-year annual recurrence interval losses, while AAL for Aiga-i-le-Tai and Va’a-o-Fonoti over this century reaches 8% of total district building replacement values. Our model approach has potential future applications to evaluate spatiotemporal risk distribution for a broader range of socioeconomic impacts that may occur beyond directly affected flood inundation areas. Full article

Background/Objectives: Ferroptosis, an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation, has been implicated in various acute and chronic brain disorders, including epilepsy. Although 1,4-naphthoquinone derivatives have been reported to regulate ferroptosis, their mechanistic roles in the nervous system remain underexplored. Here, we investigated the protective effects of 8-hydroxy-2-anilino-1,4-naphthoquinone (8-HANQ) on ferroptotic neuronal death in vitro and seizure behaviors in vivo. Methods: HT22 hippocampal cells were exposed to ferroptosis inducers including glutamate, glutamate plus iron, or RSL3. Lipid reactive oxygen species (ROS), ferroptosis markers, and its related molecules were assessed by flow cytometry and Western blotting. In a kainate (KA)-induced seizure model, 8-HANQ was delivered intracerebroventricularly, followed by behavioral seizure scoring and analysis of hippocampal levels of PSD95, cathepsin-B, and FGFR1 at 72 h post-seizure. Results: 8-HANQ attenuated ferroptotic death in HT22 cells, reducing lipid ROS accumulation and abnormal acyl-coA synthetase long chain family member 4 (ACSL4), suggesting 8-HANQ’s anti-ferroptotic action. Moreover, 8-HANQ also prevented aberrant STAT3-dependent cathepsin-B overexpression while modulating soluble N-cadherin-mediated FGFR1 activation. In vivo, 8-HANQ decreased KA-induced seizure behavior, restored hippocampal cathepsin-B and PSD95 expression, and partially alleviated dysregulation of FGFR1 activation. Conclusions: 8-HANQ prevents ferroptotic neuronal death and synaptic deficits involving FGFR1/STAT3/cathepsin-B-driven ferroptosis while lowering seizure severity, suggesting that 8-HANQ may serve as a potential anti-ferroptotic and anti-seizure agent. Full article

As a driver of neurodegenerative disorders, ischemic injuries, and acute organ dysfunction, ferroptosis represents a therapeutic target, and its inhibition may provide novel therapies. In our ongoing efforts to discover ferroptosis inhibitors from fungal strains, chemical investigation of the strain Diaporthe searlei CS-HF-1 led to the isolation of four polyketide-derived alkaloids (1–3 and 17) and fourteen polyketides (4–16 and 18), including three new isoindolone derivatives (1–3), a new phthalide (4), a new butyrolactone derivative (10), and three new nonenolides (11–13). The structures were determined by comprehensive spectroscopic analysis. The structures of 1, 2, and 10 were confirmed by comparison of experimental and calculated ¹³C NMR chemical shifts. The absolute configurations of compounds 10, 11, and 14 were assigned by ECD calculations, while those of 12 and 13 were assigned based on their biogenetic relationship with 14. Notably, compound 1 represents the first isoindolone featuring a primary amide group attached to the lactam nitrogen, while compound 2 is the first naturally occurring isoindolone dimer. These compounds were assessed for the anti-ferroptotic activity. As a result, asperlactone A (15) exhibited inhibition on RSL3-induced ferroptosis in HT22 cells with an EC₅₀ of 11.3 ± 0.4 μM. Preliminary mechanistic study revealed that 15 attenuated lipid peroxidation, as evidenced by reduced MDA levels, elevated GSH content, and suppression of lipid radical generation. This study offers a new chemotype for the development of novel ferroptosis inhibitors. Full article

Oxidative stress occurs within bovine when exposed to harmful stimuli, accompanied by substantial accumulation of reactive oxygen species. Without timely clearance, these reactive oxygen species attack vascular endothelial cells, concurrently inducing extensive production of lipid peroxides within the vascular endothelium, and thereby triggering ferroptosis. Aspirin eugenol ester (AEE) showed pharmacological activity against oxidative stress-induced vascular endothelial damage. However, whether it could alleviate vascular endothelial damage by inhibiting ferroptosis remains unclear. This study aimed to evaluate the effects of AEE on vascular endothelial ferroptosis and elucidate its underlying molecular mechanisms. This study established vascular endothelial damage models in vitro and in vivo to explore the ability of AEE to inhibit ferroptosis and oxidative stress by measuring ferroptosis- and oxidative stress-related biomarkers. Transcriptomic and network pharmacology analyses were performed to identify AEE-regulated pathways and key targets. Validation of the pathways were conducted using molecular docking, cellular thermal shift assay, and specific protein agonists/inhibitors. AEE inhibited oxidative stress and ferroptosis in bovine aortic endothelial cells induced by hydrogen peroxide (H₂O₂) or RSL3 via suppressing the upregulation of ferroptosis-related genes and enhancing the expression of antioxidant genes. Transcriptomic and network pharmacology analyses identified JNK as a core target of AEE in regulating ferroptosis. JNK agonists enhanced H₂O₂-induced ferritinophagy; on the contrary, JNK inhibitors alleviated it. AEE suppressed H₂O₂-induced phosphorylation of JNK/c-Jun and ferritinophagy. In a carrageenan-induced rat aortic vascular endothelial damage model, AEE alleviated vascular endothelial damage and ferroptosis-related gene changes, promoted antioxidant gene expression, and inhibited JNK/c-Jun phosphorylation and ferritinophagy. AEE inhibited vascular endothelial ferroptosis by enhancing antioxidant ability, blocking downstream ferritinophagy, and reducing ferrous ion release. Full article

The extensive distribution of quaternary sediments and the extraction of underground resources in the Yellow River Delta (YRD) have resulted in significant land subsidence, which accelerates relative sea level (RSL) rise and heightens the risk of coastal inundation. This study uses Sentinel-1A (S1A) imagery and the time-series synthetic aperture radar interferometry (TS-InSAR) method to obtain subsidence information for the YRD. By integrating data from groundwater level monitoring wells, hydrogeological conditions, extensometer monitoring, and drilling wells, we analyze the causes of subsidence and the deformation response to the groundwater level changes in the corresponding aquifers. For the first time in the YRD, this study introduces the high accuracy CoastalDEM v2.1 digital elevation model, combined with absolute sea level (ASL) data, to construct a coastal inundation simulation. This simulation maps the land inundation caused by RSL rise along the YRD in different scenarios. The results indicate significant subsidence bowls in coastal and inland regions, primarily attributed to shallow brine and deep groundwater extraction, respectively. The main subsidence layers in inland towns have been identified, and residual deformation has been observed. Currently, land subsidence has caused a maximum elevation loss of 141 mm/yr in coastal YRD areas, significantly contributing to RSL rise. Seawater inundation simulations suggest that if subsidence continues unabated, 12.84% of the YRD region will be inundated by 2100, with 8.74% of the built-up areas expected to be inundated. Compared to global warming-induced ASL rise, ongoing subsidence is the primary driver of inundation in the YRD coastal areas. Full article

Background/Objectives: Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and holds promise as a therapeutic strategy against cancers with elevated iron metabolism. However, many tumors evade ferroptosis through the upregulation of specialized antioxidant defense mechanisms. Here, we investigated ferroptosis susceptibility and resistance mechanisms in TSC models and in ovarian and breast cancer cell lines, aiming to identify potential therapeutic targets. Methods: Ferroptosis sensitivity was assessed using RSL3 and erastin. We explored the contribution of ferroptosis defense pathways using inhibitors of NRF2 (ML385) and FSP1 (iFSP1). RNA sequencing was performed to evaluate the expression of ferroptosis resistance genes and to explore NRF2-regulated transcriptional programs. Results: TSC2-deficient cells were resistant to RSL3- and erastin-induced ferroptosis. This resistance correlated with upregulation of ferroptosis defense genes, including NRF2 and its downstream targets. Pharmacological inhibition of NRF2 resensitized TSC2-deficient cells to ferroptosis, confirming a protective role for NRF2. However, FSP1 inhibition did not restore ferroptosis sensitivity in TSC2-deficient angiomyolipoma cells. In contrast, FSP1 knockdown significantly enhanced ferroptosis sensitivity in ovarian (PEO1, PEO4, OVCAR3) and breast (MDA-MB-436) cancer cells. Notably, in MDA-MB-436 cells, FSP1 knockdown was more effective than NRF2 inhibition to enhance ferroptosis sensitivity. FSP1 expression was not regulated by NRF2, suggesting that NRF2-targeted therapies alone may be insufficient to overcome ferroptosis resistance in certain cancer contexts. Conclusions: TSC2-deficient cells resist ferroptosis via an adaptive antioxidant response that protects against elevated iron-mediated lipid peroxidation. Our findings identify NRF2 and FSP1 as key, but mechanistically distinct, regulators of ferroptosis resistance. The differential efficacy of targeting these pathways across cancer types highlights the potential need for patient stratification. Dual targeting of NRF2 and FSP1 may offer an effective therapeutic strategy for iron-dependent, ferroptosis-resistant cancers. Full article

Soybean (Glycine max), as an important crop for both oil and grains, is a major source of high-quality plant proteins for humans. Among various natural disasters affecting soybean production, waterlogging is one of the key factors leading to yield reduction. It can cause root rot and seedling death, and in severe cases, even total crop failure. Given the significant differences in responses to waterlogging stress among different soybean varieties, traditional single-trait indicators are insufficient to comprehensively evaluate flood tolerance. In this study, relative seedling length (RSL) was used as a comprehensive evaluation index for flood tolerance. Using a chromosome segment substitution line (CSSL) population derived from SN14 and ZYD00006, we successfully identified seven quantitative trait loci (QTLs) associated with seed waterlogging tolerance. By integrating RNA-Seq transcriptome sequencing and phenotypic data, the functions of candidate genes were systematically verified. Phenotypic analysis indicated that Suinong14 had significantly better flood tolerance than ZYD00006. Further research revealed that the Glyma.05G160800 gene showed a significantly up-regulated expression pattern in Suinong14; qPCR analysis revealed that this gene exhibits higher expression levels in submergence-tolerant varieties. Haplotype analysis demonstrated a significant correlation between different haplotypes and phenotypic traits. The QTLs identified in this study can provide a theoretical basis for future molecular-assisted breeding of flood-tolerant varieties. Additionally, the functional study of Glyma.05G161800 in regulating seed flood tolerance can offer new insights into the molecular mechanism of seed flood tolerance. These findings could accelerate the development of submergence-tolerant rice varieties, enhancing crop productivity and stability in flood-prone regions. Full article

The olive oil-production sector engages with the environment on multiple levels, and the valorization of olive pomace (OP) has emerged as a key strategy to improve the entire system’s sustainability. Numerous studies have investigated the biological effects of OP phenolic fraction for nutraceutical applications, highlighting its antioxidant properties. This study aimed to assess the effect of an OP extract (OPE) and its phenolic content on ferroptosis induced by RAS-selective lethal 3 (RSL3), an inhibitor of glutathione peroxidase 4. After characterization of OPE phenolic composition, its antioxidant properties were confirmed through the Fenton reaction assay. Subsequently, we examined the effect of OPE on ter-butyl hydroperoxide-induced ROS generation and lipid peroxidation in TPH-1 and HIECs cells and found that OPE reduced ROS and lipid peroxidation. RSL3 decreased the number of vital cells, which was associated with an elevation in ROS and lipid peroxidation, and a reduction in GSH. Interestingly, all these detrimental effects were reversed by OPE. Furthermore, OPE was also found to significantly increase GSH and the GSH/GSSG ratio per se. In conclusion, the fact that OPE decreases ROS and lipid peroxidation induced by RSL3 and augments GSH and cell viability suggests that OPE has potential as a ferroptosis inhibitor. Full article

Numerous dark linear recurrent features called Recurring Slope Lineae (RSL) are observed on Martian surfaces, hypothesized as footprints of high-salinity liquid flow. This paper experimentally examined this “wet hypothesis” by analyzing the aspect ratios (length/width) of the flow traces on the granular material column to investigate how they vary with the granular material column, liquid and its flow rate, and inclination. While pure water produced low aspect ratios (<1.0) on the Martian regolith simulant column, high-salinity fluid (CaCl₂(aq)) traces exhibited significantly higher aspect ratios (>4.0), suggesting that pure water alone is insufficient to explain RSL formulation. Furthermore, the aspect ratios of high-salinity fluid traces on Martian regolith simulants were among the highest observed across all studied granular materials with similar particle sizes, aligning closely with actual RSL observed on Martian slopes. The results further suggest that variable ARs of actual RSL at the given slope can partly be explained by variable flow rates of high-salinity flow as well as salinity (i.e., viscosity) of flow. The results can be attributed to the unique granular properties of Martian regolith, characterized by the lowest permeability and Beavers–Joseph slip coefficient among the studied granular materials. This distinctive microstructure surface promotes surface flow over Darcy flow within the regolith column, leading to a narrow and long-distance feature with high aspect ratios observed in Martian RSL. Thus, our findings support that high-salinity flows are the primary driver behind RSL formation on Mars. Our study suggests the presence of salts on the Martian surface and paves the way for further investigation into RSL formulation processes. Full article

Multiple myeloma (MM) is an incurable malignancy of plasma cells that accounts for 10% of all haematological malignancies diagnosed worldwide. The poor outcome of patients with MM highlights the ongoing need for novel treatment strategies. Ferroptosis is a recently characterised form of non-apoptotic programmed cell death. Phospholipids (PLs) containing polyunsaturated fatty acids (PUFAs) play a crucial role as ferroptosis substrates when oxidised to form toxic lipid reactive oxygen species (ROS). Using a range of scientific techniques, we demonstrate a strong correlation between the PL profile of MM and diffuse large B cell lymphoma (DLBCL) cells with their sensitivity to ferroptosis. Using this PL profiling, we manufacture liposomes that are themselves composed of PL-PUFA ferroptosis substrates relatively deficient in MM cells, with and without the GPX4 inhibitor, RSL3, for investigation of their ferroptosis-inducing potential. PL-PUFAs were more abundant in DLBCL than MM cell lines, consistent with greater ferroptosis sensitivity. In contrast, MM cells generally contained a significantly higher proportion of PLs containing monounsaturated fatty acids. Altering the lipid composition of MM cells through exogenous supplementation with PL-PUFAs induced ferroptosis-mediated cell death and further sensitised these cells to RSL3. Liposomes predominantly comprising PL-PUFAs were subsequently manufactured and loaded with RSL3. Uptake, cytotoxicity and lipid ROS studies demonstrated that these novel liposomes were readily taken up by MM cells. Those containing RSL3 were more effective at inducing ferroptosis than empty liposomes or free RSL3, resulting in IC₅₀ values an average 7.1-fold to 14.5-fold lower than those for free RSL3, from the micromolar to nanomolar range. We provide a better understanding of the mechanisms associated with ferroptosis resistance of MM cells and suggest that strategies such as liposomal delivery of relatively deficient ferroptosis-inducing PL-PUFAs together with other targeted agents could harness ferroptosis for the personalised treatment of MM and other cancers. Full article

Ferroptosis, a regulated form of iron-dependent lipid peroxidation-induced cell death, has emerged as a compelling therapeutic strategy to overcome treatment resistance in head and neck cancer (HNC). Glutathione peroxidase 4 (GPX4), a selenoenzyme responsible for detoxifying phospholipid hydroperoxides, plays a central role in blocking ferroptosis and is frequently upregulated in therapy-resistant HNC subtypes. In this review, we examine the multifaceted regulation of GPX4 expression and function, including transcriptional, post-transcriptional, epigenetic, and proteostatic mechanisms. We explore how GPX4 suppression through pharmacologic inhibitors (e.g., RSL3, withaferin A, statins), metabolic stress, or combined therapies (e.g., radiotherapy, EGFR inhibitors, immunotherapy) induces ferroptosis and resensitizes resistant tumors. We also summarize emerging biomarkers, including GPX4, ACSL4, SLC7A11, and NCOA4, that predict ferroptosis sensitivity and may guide patient selection for ferroptosis-targeted therapies. Single-cell and spatial transcriptomics reveal significant intratumoral heterogeneity in ferroptosis susceptibility, underscoring the need for precision approaches. Despite promising preclinical data, challenges such as drug delivery, toxicity, and resistance mechanisms remain. Nevertheless, the ferroptosis-GPX4 axis represents a unique vulnerability in HNC that can be therapeutically exploited. Integrating ferroptosis modulation into personalized oncology may transform outcomes for patients with refractory disease. Full article

In the continuous pursuit of minimally invasive interventions while ensuring a radical excision of lesions, Radio-Guided Surgery (RGS) has been for years the standard for image-guided surgery procedures, such as the Sentinel Lymph Node biopsy (SLN), Radio-guided Seed Localization (RSL), etc. In RGS, the lesion has to be identified precisely, in terms of position and extension. In such a context, going beyond the current one-point probes, introducing portable but high-resolution cameras, handholdable by the surgeon, would be highly beneficial. We developed and tested a novel compact, low-power, handheld gamma camera for radio-guided surgery. This is based on a particular position-sensitive Silicon Photomultiplier (SiPM) technology—the FBK linearly graded SiPM (LG-SiPM). Within the camera, the photodetector is made up of a 3 × 3 array of 10 × 10 mm² SiPM chips having a total area of more than 30 × 30 mm². This is coupled with a pixelated scintillator and a parallel-hole collimator. With the LG-SiPM technology, it is possible to significantly reduce the number of readout channels to just eight, simplifying the complexity and lowering the power consumption of the readout electronics while still preserving a good position resolution. The novel gamma camera is light (weight), and it is made to be a fully stand-alone system, therefore featuring wireless communication, battery power, and wireless recharge capabilities. We designed, simulated (electrically), and tested (functionally) the first prototypes of the novel gamma camera. We characterized the intrinsic position resolution (tested with pulsed light) as being ~200 µm, and the sensitivity and resolution when detecting gamma rays from Tc-99m source measured between 134 and 481 cps/MBq and as good as 1.4–1.9 mm, respectively. Full article

Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is regulated by key mediators including glutathione peroxidase 4 (GPX4) and nuclear factor erythroid 2-related factor 2 (Nrf2). Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes latency-associated nuclear antigen (LANA), a multifunctional protein critical for viral persistence. Although studies reported that KSHV infection enhanced cellular resistance to ferroptosis, the specific role of LANA in this process remains unexplored. Here, we demonstrate that LANA unexpectedly promotes ferroptosis. In KSHV-positive iSLK.219 cells, LANA knockdown significantly attenuated RSL-3-induced ferroptosis, whereas LANA overexpression sensitized HeLa cells to ferroptotic death. Quantitative analysis revealed that LANA-depleted cells exhibited significantly elevated ROS accumulation (p < 0.01), whereas LANA-overexpressing cells maintained reduced ROS levels during challenge with the ferroptosis inducer RSl-3. Mechanistically, LANA suppressed glutathione peroxidase 4 (GPX4) expression, reduced nuclear factor erythroid 2-related factor 2 (Nrf2) expression and impaired its nuclear translocation, and upregulated mouse double minute 2 homolog (MDM2) expression. Pharmacological inhibition of Nrf2 (ML385) or MDM2 (nutlin3a) reversed the ferroptotic effects of LANA knockdown or overexpression, respectively. These findings reveal a pro-ferroptotic role of LANA via Nrf2/GPX4 suppression and MDM2 activation. Full article

Oxidative stress plays a critical role in regulating sperm function, yet species-specific antioxidant mechanisms remain poorly understood. This study compared hydrogen peroxide (H₂O₂) tolerance in horse and human sperm and investigated the roles of catalase and glutathione peroxidase (GPx) in horses. A H₂O₂ dose–response assay (0–2000 µM) showed that horse sperm were significantly more resistant to oxidative damage, with an IC₅₀ for progressive motility over 14-fold higher than that of human sperm (391.6 µM vs. 27.3 µM). Horse sperm also accumulated more intracellular H₂O₂ without loss of motility or viability. DNA damage assays (Halo and SCSA) revealed H₂O₂-induced fragmentation in human but not horse sperm. Enzyme inhibition experiments in horse sperm using 3-amino-1,2,4-triazole (catalase inhibitor) and (1S,3R)-RSL3 (GPx inhibitor) at 250 µM H₂O₂ showed that catalase inhibition severely impaired motility and increased intracellular H₂O₂ > 100-fold, while GPx inhibition had a milder effect (~5-fold increase). Immunocytochemistry localized catalase to the sperm head, particularly the post-acrosomal region, challenging the notion that sperm lack peroxisomes. The dependence of horse sperm on oxidative phosphorylation may drive the need for enhanced antioxidant defenses. These findings reveal species-specific oxidative stress adaptations and highlight catalase as a key antioxidant in equine sperm. Full article

Robotics has widespread applications throughout industrial automation, autonomous vehicles, agriculture, and more. For these reasons, undergraduate education has begun to focus on preparing engineering students to directly contribute to the design and use of such systems. However, robotics is inherently multi-disciplinary and requires knowledge of controls and automation, embedded systems, sensors, signal processing, algorithms, and artificial intelligence. This makes training the future robotics workforce a challenge. In this paper, we evaluate our experiences with project-based learning approaches to teaching robotics at the undergraduate level at Miami University. Specifically, we analyze three consecutive years of capstone design projects on increasingly complex robotics design problems for multi-robot systems. We also evaluate the laboratories taught in our course “ECE 314: Elements of Robotics”. We have chosen these four experiences since they focus on the use of “cheap” first-principled robots, meaning that these robots sit on the fringe of embedded system design in that much of the student time is spent on working with a micro-controller interfacing with simple and cheap actuators and sensors. To contextualize our results, we propose the Robotic System Levels (RSL) model as a structured way to understand the levels of abstraction in robotic systems. Our main conclusion from these case studies is that, in each experience, students are exposed primarily to a subset of levels in the RSL model. Therefore, the curriculum should be designed to emphasize levels that align with educational objectives and the skills required by local industries. Full article