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A major hallmark of cancer is successful evasion of regulated forms of cell death. Ferroptosis is a recently discovered type of regulated necrosis which, unlike apoptosis or necroptosis, is independent of caspase activity and receptor-interacting protein 1 (RIPK1) kinase activity. Instead, ferroptotic cells die following iron-dependent lipid peroxidation, a process which is antagonised by glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1). Importantly, tumour cells escaping other forms of cell death have been suggested to maintain or acquire sensitivity to ferroptosis. Therefore, therapeutic exploitation of ferroptosis in cancer has received increasing attention. Here, we systematically review current literature on ferroptosis signalling, cross-signalling to cellular metabolism in cancer and a potential role for ferroptosis in tumour suppression and tumour immunology. By summarising current findings on cell biology relevant to ferroptosis in cancer, we aim to point out new conceptual avenues for utilising ferroptosis in systemic treatment approaches for cancer.

Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, and their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved in mediating constitutive mitochondrial fission and has been implicated in mitochondrial cell death pathways. During ferroptosis, a recently identified type of regulated necrosis driven by excessive lipid peroxidation, mitochondrial fragmentation has been observed. Yet, how this is regulated and whether it is involved in ferroptotic cell death has remained unexplored. Here, we provide evidence that Drp1 is activated upon experimental induction of ferroptosis and promotes cell death execution and mitochondrial fragmentation. Using time-lapse microscopy, we found that ferroptosis induced mitochondrial fragmentation and loss of mitochondrial membrane potential, but not mitochondrial outer membrane permeabilization. Importantly, Drp1 accelerated ferroptotic cell death kinetics. Notably, this function was mediated by the regulation of mitochondrial dynamics, as overexpression of Mitofusin 2 phenocopied the effect of Drp1 deficiency in delaying ferroptosis cell death kinetics. Mechanistically, we found that Drp1 is phosphorylated and activated after induction of ferroptosis and that it translocates to mitochondria. Further activation at mitochondria through the phosphatase PGAM5 promoted ferroptotic cell death. Remarkably, Drp1 depletion delayed mitochondrial and plasma membrane lipid peroxidation. These data provide evidence for a functional role of Drp1 activation and mitochondrial fragmentation in the acceleration of ferroptotic cell death, with important implications for targeting mitochondrial dynamics in diseases associated with ferroptosis.

Regional flood frequency analysis (RFFA) is a cornerstone for estimating design floods at ungauged or data-scarce sites by pooling information within hydrologically homogeneous regions. This study proposes and evaluates a hybrid RFFA framework that integrates the Index-Flood (IF) technique with a bivariate logistic extreme-value model whose marginal distributions are formulated under both stationary and non-stationary assumptions. Non-stationarity is incorporated through a covariate-dependent location parameter, using time and large-scale climate indices—the Pacific Decadal Oscillation (PDO) and the Southern Oscillation Index (SOI)—as explanatory variables. The proposed approach is applied to two contrasting hydrological regions in Mexico—RH10 (Sinaloa) and RH23 (Chiapas Coast)—to assess its performance under differing climatic and hydrological regimes. Model adequacy and stability are evaluated using likelihood-based goodness-of-fit criteria (log-likelihood and Akaike Information Criterion) and a leave-one-out (jackknife) cross-validation scheme embedded within the IF regionalization workflow. Results indicate that non-stationary bivariate formulations dominate model selection at most stations and yield stable regional growth curves, providing robust and engineering-relevant performance under cross-validation. Overall, the proposed framework offers a conservative and operational pathway for regional flood quantile estimation that bridges local data scarcity and regional hydrological characterization in environments influenced by climate variability and long-term change.

The odor-active volatile compounds of yellow tamarillo fruit (S. betaceum Cav.) were identified and quantified by using a sensomics approach, combining a gentle volatile extraction (solvent-assisted flavor evaporation (SAFE)), gas chromatography-mass spectrometry (GC-MS), and sensory analyses (gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA)). The medium-term purpose of this work is to evaluate the change of odor-active volatiles during processing. Thus, (Z)-3-hexenal, hexanal, and ethyl butanoate were identified as key aroma compounds of yellow tamarillo. The C6-aliphatic compounds, aliphatic esters, and terpenols were characterized as the volatiles responsible for the herbal-green, fruity, and fresh-mint odor notes of this variety, respectively. Additionally, one non-volatile compound contributing to the residual bitter taste of this fruit was isolated by a bioguided (taste sensory analyses) fractionation. The freeze-dried fruit was sequentially liquid-liquid partitioned with solvents of different polarity, and then the ethyl acetate fraction was submitted to size exclusion chromatography. Then, its structure was elucidated as rosmarinic acid, by using common spectroscopic methods (mass spectrometry (MS) and nuclear magnetic resonance (NMR)). The amount of rosmarinic acid was quantified as 46.17 ± 1.20 mg/100 g of dried fruit, by the external standard method. Its bitter taste threshold value was determined by using the 3AFC (alternative forced choice) method to be 37.00 ± 1.25 mg/L.

Flood frequency analysis is essential for designing resilient hydraulic infrastructure, but traditional stationary models fail to capture the influence of climate variability and land-use change. This study applies a bivariate logistic model with non-stationary marginals to eight gauging stations in Sinaloa, Mexico, each with over 30 years of maximum discharge records. We compared stationary and non-stationary Gumbel and Generalized Extreme Value (GEV) distributions, along with their bivariate combinations. Results show that the non-stationary bivariate GEV–Gumbel distribution provided the best overall performance according to AIC. Importantly, GEV and Gumbel marginals captured site-specific differences: GEV was most suitable for sites with highly variable extremes, while Gumbel offered a robust fit for more regular records. At station 10086, where a significant increasing trend was detected by the Mann–Kendall and Spearman tests, the stationary GEV estimated a 50-year return flow of 772.66 m3/s, while the non-stationary model projected 861.00 m3/s for 2075. Under stationary assumptions, this discharge would be underestimated, occurring every ~30 years by 2075. These findings demonstrate that ignoring non-stationarity leads to systematic underestimation of design floods, while non-stationary bivariate models provide more reliable, policy-relevant estimates for climate adaptation and infrastructure safety.

The purpose of this study was to determine the mean propulsive velocity (MVP) at various percentages of one repetition maximum (1RM) in the full squat and chest press exercises. A total of 96 young women and 256 young men (recreational athletes) performed an incremental test (50–60–70–80% 1RM) comprising the bench press and full squat exercises in two different sessions. The individual load and velocity ratios were established through the MPV. Data were analyzed using SPSS software version 25.0, with the significance level set at 5%. The following findings were revealed: highly linear load-velocity relationships in the group of women (r = 0.806 in the squat, and r = 0.872 in the bench press) and in the group of men (r = 0.832 and r = 0.880, respectively); significant differences (p < 0.001) in the MPV at 50–70–80% 1RM between the bench press and the full squat in men and at 70–80% 1RM in women; and a high variability in the MPV (11.49% to 22.63) in the bench press and full squat (11.58% to 25.15%) was observed in women and men (11.31% to 21.06%, and 9.26% to 24.2%) at the different percentages of 1RM evaluated. These results suggest that the load-velocity ratio in non-strength-trained subjects should be determined individually to more precisely establish the relative load to be used in a full squat and bench press training program.

The retina is a highly heterogeneous tissue, both cell-wise but also regarding its extracellular matrix (ECM). The stiffness of the ECM is pivotal in retinal development and maturation and has also been associated with the onset and/or progression of numerous retinal pathologies, such as glaucoma, proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), epiretinal membrane (ERM) formation or uveitis. Nonetheless, much remains unknown about the biomechanical milieu of the retina, and specifically the role that Müller glia play as principal mechanosensors and major producers of ECM constituents. So far, new approaches need to be developed to further the knowledge in the field of retinal mechanobiology for ECM-target applications to arise. In this review, we focus on the involvement of Müller glia in shaping and altering the retinal ECM under both physiological and pathological conditions and look into various biomaterial options to more accurately replicate the impact of matrix stiffness in vitro.

A number of causes have been proposed to account for the occurrence of gelatinous zooplankton (both jellyfish and ctenophore) blooms. Jellyfish species have a complex life history involving a benthic asexual phase (polyp) and a pelagic sexual phase (medusa). Strong environmental control of jellyfish life cycles is suspected, but not fully understood. This study presents a comprehensive analysis on the physicochemical conditions that control the survival and phase transition of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the Mediterranean Sea. Laboratory experiments indicated that the influence of temperature on strobilation and polyp survival was the critical factor controlling the capacity of this species to proliferate. Early life stages were less sensitive to other factors such as salinity variations or the competitive advantage provided by zooxanthellae in a context of coastal eutrophication. Coherently with laboratory results, the presence/absence of outbreaks of this jellyfish in a particular year seems to be driven by temperature. This is the first time the environmental forcing of the mechanism driving the life cycle of a jellyfish has been disentangled via laboratory experimentation. Projecting this understanding to a field population under climatological variability results in a pattern coherent with in situ records.

Introduction: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. Methods: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. Results: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64–92.5) vs. 99 (88–105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467–600) vs. 611 (550–650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VCO2 slope 32 (28.1–37.4) vs. 29.4 (26.9–31.4); p = 0.022) and high PETCO2 (34.5 (32–39) vs. 38 (36–40); p = 0.025). Interpretation: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

The purpose of this pilot study was to examine the feasibility of a fundamental motor skills (FMS) intervention with two groups on the acquisition of FMS of children with autism spectrum disorders (ASD). We randomly assigned families (n = 15) of children with ASD aged 4–11 years into two groups (a workshop or a home-based group) focused on FMS development. Both groups participated in a 10-week intervention and were given the same instructional manual and adapted physical activity equipment. The workshop group also attended four in-person workshops targeting the needs of children with ASD and their parents. Children were tested on their FMS using the third edition of the Test of Gross Motor Development at the start and end of the intervention and then three months following the intervention. The recruitment rate was 50%, and the retention rate was 80% for all participants. The intervention for groups was safe and accepted by the participants as evaluated by post-program interviews. The outcomes of this pilot study suggest that parents can facilitate the acquisition of FMS of their children with ASD. Although these results are positive, there is a need to further identify effective interventions for FMS development in children with ASD.