Search Results (438)

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

Ferroptosis suppressor protein 1 (FSP1) has emerged as a critical regulator of ferroptosis, an iron-dependent form of programmed cell death with significant therapeutic potential in cancer treatment. Despite rapidly expanding research, current knowledge on FSP1 remains fragmented across various tumor types and experimental contexts. The aim of this review is to systematically integrate the latest evidence regarding the molecular structure, biological functions, and regulatory mechanisms controlling FSP1 expression, emphasizing its involvement in tumor progression and resistance to therapy. Readers can expect comprehensive coverage of FSP1’s structural characteristics, enzymatic roles, transcriptional and post-transcriptional regulation, and its pathological significance in hepatocellular carcinoma, colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, and leukemia. We further evaluate emerging therapeutic strategies targeting FSP1 aimed at overcoming resistance and improving clinical outcomes. Relevant studies were systematically identified by searching PubMed, Web of Science, and Embase databases, focusing particularly on the recent and impactful literature to guide future research directions. Full article

Continuous planting results in a higher occurrence rate of oriental melon Fusarium wilt caused by Fusarium oxysporum f. sp. melonis (FOM), and treatment with Trichoderma can considerably alleviate the incidence of disease. However, the tripartite interaction mechanisms among T. harzianum–melon–rhizosphere microorganisms remain poorly understood in current research. Pot experiments elucidate the growth-promoting, antagonistic, and rhizosphere-regulating effects of T. harzianum on oriental melon. The experiment consisted of two treatments: (1) water control (CK), and (2) T. harzianum inoculation (MM) with three repetitions per treatment. Illumina high-throughput sequencing was employed to analyze the microbial community and associated metabolic pathways. Additionally, a comprehensive correlation analysis clarified how T. harzianum-modulated physiological factors regulate soil microbial communities to enhance melon resistance to FOM. T. harzianum inoculation significantly promoted plant growth, decreased the incidence rate of Fusarium wilt by 41.85%, and increased rhizosphere nitrate-N, pH, EC, and soil enzyme activity (e.g., sucrose and alkaline phosphatase). Notably, T. harzianum inoculation altered the rhizosphere microbial community’s relative abundance and structure, with the most striking changes in the fungal community. Principal coordinate analysis showed this fungal restructuring accounted for 44.9% of total community variation (37% from PCo1, 7.9% from PCo2). Soil-borne pathogens (e.g., Fusarium, Verticillium, Phytophthora) decreased in relative abundance with the inoculation of T. harzianum. Meanwhile, the microbial community shifted from a “fungal-dominated” to “bacterial-dominated” state: fungal proportion decreased by 9.47% (from 23.95% in CK to 14.48% in MM), while bacterial proportion increased by 9.47% (from 76.05% in CK to 85.52% in MM). Microbial abundance shifts primarily impacted amino acid and cofactor biosynthesis metabolic pathways. The application of T. harzianum modified the soil environment, restructuring microbial communities through these changes, which in turn regulated microbial metabolic pathways, creating a soil environment conducive to melon growth and thereby enhancing oriental melon resistance to FOM, while mitigating the obstacles of continuous cropping. Full article

In the context of the valorization of agri-food by-products, tomato (Solanum lycopersicum L.) seeds represent a protein-rich matrix containing potential bioactives. The aim of the present work is to develop a biochemical pipeline for (i) achieving high protein recovery from tomato seed, (ii) optimizing the hydrolysis with different proteases, and (iii) characterizing the resulting peptides. This approach was instrumental for obtaining and selecting the most promising peptide mixture to test for antifungal activity. To this purpose, proteins from an alkaline extraction were treated with bromelain, papain, and pancreatin, and the resulting hydrolysates were assessed for their protein/peptide profiles via SDS-PAGE, SEC-HPLC, and RP-HPLC. Bromelain hydrolysate was selected for antifungal tests due to its greater quantity of peptides, in a broader spectrum of molecular weights and polarity/hydrophobicity profiles, and higher DPPH radical scavenging activity, although all hydrolysates exhibited antioxidant properties. In vitro assays demonstrated that the bromelain-digested proteins inhibited the growth of Fusarium graminearum and F. oxysporum f.sp. lycopersici in a dose-dependent manner, with a greater effect at a concentration of 0.1 mg/mL. The findings highlight that the enzymatic hydrolysis of tomato seed protein represents a promising strategy for converting food by-products into bioactive agents with agronomic applications, supporting sustainable biotechnology and circular economy strategies. Full article

Background: Type 2 diabetes (T2D) is a growing public health concern, particularly in low- and middle-income countries. Although prediabetes is a major risk factor for T2D, it remains largely underdiagnosed and untreated. Structured lifestyle interventions have proven effective in preventing diabetes, but their feasibility within the Brazilian public health system remains unclear. Methods: This multicenter pilot randomized controlled trial assessed the feasibility of a culturally adapted lifestyle intervention (PROVEN-DIA) across the five regions of Brazil. A total of 220 adults at high risk for T2D were randomized to an intervention group or a control group (usual care) and followed for three months. Both groups received similar educational content on healthy eating and physical activity, but the intervention group participated in a structured and personalized lifestyle program with regular follow-up sessions. The primary outcome was adherence to dietary recommendations, assessed using the BALANCE Index—a validated dietary score (range: 0–40) based on the Brazilian Cardioprotective Diet that classifies foods into color-coded groups according to nutritional quality—along with engagement in moderate-to-vigorous physical activity (MVPA). Secondary outcomes included diet quality (DQIR), anthropometric and metabolic parameters. Results: Feasibility was demonstrated by a 93.2% retention rate (n = 205). There was no significant difference in the primary outcome (simultaneous improvement in diet and MVPA). However, the PROVEN-DIA group exhibited significantly greater improvements in diet quality, with a 2.8-point increase in the BALANCE Index (vs. 0.5 in the control, p = 0.03), and a significant improvement in the DQIR (p < 0.001). No significant differences between groups were observed in MVPA, HbA1C, glycaemia, or body weight. Conclusions: The PROVEN-DIA intervention proved feasible within the Brazilian public health context, resulting in significant improvements in dietary quality among individuals at high risk for T2D. A larger trial with longer follow-up is warranted to evaluate its effectiveness in preventing the progression to diabetes. However, to enhance physical activity outcomes, specific adaptations and targeted strategies may be required to better support participant engagement in exercise. Full article

In response to the dual challenges of the mechanical behavior of steel sheet pile cofferdam and sediment control in urban water intake projects, a multi-method integrated study was conducted based on the Nenjiang Project. The results show that the peak stress of FSP-IV steel sheet piles (64.3 MPa) is located at a depth of 5.5–8.0 m in the center of the foundation pit, and that the maximum horizontal displacement (6.96 mm) occurs at the middle of the side span of the F pile. The internal support stress increases with depth, reaching 87.2 MPa at the bottom, with significant stress concentration at the connection of the surrounding girder. The lack of support or excessively large spacing leads to insufficient stiffness at the side span (5.3 mm displacement at the F point) and right-angle area (B/H point). The simultaneously developed sediment control integrated system, through double-line water intake, layered placement of the geotextile filter, and the collaborative construction of the water intake hole–filter layer system, achieves a 75% reduction in sediment content and a decrease in standard deviation. This approach ensures stable water quality and continuous water supply, ultimately forming a systematic solution for water intake in high-sediment rivers. Full article

Manufacturing processes are inherently complex, multi-objective in nature, and highly sensitive to process parameter settings. This paper presents two simple and efficient optimization algorithms—Best–Worst–Random (BWR) and Best–Mean–Random (BMR)—developed to solve both constrained and unconstrained optimization problems of manufacturing processes involving single, multi-, and many-objectives. These algorithms are free from metaphorical inspirations and require no algorithm-specific control parameters, which often complicate other metaheuristics. Extensive testing reveals that BWR and BMR consistently deliver competitive, and often superior, performance compared to established methods. Their multi- and many-objective extensions, named MO-BWR and MO-BMR, respectively, have been successfully applied to tackle 2-, 3-, and 9-objective optimization problems in advanced manufacturing processes such as friction stir processing (FSP), ultra-precision turning (UPT), laser powder bed fusion (LPBF), and wire arc additive manufacturing (WAAM). To aid in decision-making, the proposed BHARAT can be integrated with MO-BWR and MO-BMR to identify the most suitable compromise solution from among a set of Pareto-optimal alternatives. The results demonstrate the strong potential of the proposed algorithms as practical tools for intelligent decision-making in real-world manufacturing applications. Full article

Understanding the foot strike pattern (FSP) and impact force of running-related injuries is crucial for athletes and researchers. This study investigated a novel method for detecting FSP using the loadsol^® sensor insole during treadmill running. Twelve collegiate athletes ran at three different speeds (12, 15, and 20 km/h), with their FSP determined using both the kinematic method based on the foot strike angle and the loadsol^® method based on the plantar force applied to the rear-, mid-, and forefoot sensor areas. This study provides significant insights into FSP detection. Comparing the kinematic method to the loadsol^® method, the rearfoot, midfoot, and forefoot strike detection rates were 94.7%, 37.1%, and 81.8%, respectively. Moreover, the FSP was not uniform, even during treadmill running at a constant speed, with most participants exhibiting mixed patterns across different speeds. The loadsol^® sensor insole could offer a promising device for in-field measurement of FSP and impact forces, potentially helping researchers and athletes better understand and predict the potential running-related injury risks by monitoring step-to-step variations in running biomechanics. Full article

The large-scale disposal of loquat (Eriobotrya japonica Lindl.) flowers during fruit thinning represents a significant waste of bioactive resources. This study systematically evaluated how three processing methods—fresh (FS), heat-dried (HD), and freeze-dried (FD) treatments—affect the flavonoid composition and antioxidant capacity of loquat flower extracts, with the aim of developing value-added, sugar-free functional tea ingredients. Using UPLC-MS/MS and DPPH assays, we analyzed both pre-(FS/HD/FD) and post-extraction samples (FSP/HDP/FDP) to assess processing-specific metabolic signatures and extraction efficiency. The results revealed that heat-dried powder (HDP) exhibited the highest total flavonoid content and DPPH scavenging capacity (615.24 µg Trolox/g), attributed to enhanced release of stable compounds like quercetin. Freeze-dried powder (FDP) better preserved heat-sensitive flavonoids, such as catechin-(4α→8)-gallocatechin and naringenin, but showed lower overall antioxidant activity. Multivariate analysis confirmed distinct clustering patterns, with heat-drying favoring flavonoid extractability while freeze-drying maintained metabolic diversity. These findings demonstrate that processing methods significantly influence bioactive compound retention and functionality, with heat-drying offering optimal balance between yield and practicality for industrial applications. This work provides a scientific foundation for upcycling loquat flowers into standardized nutraceutical ingredients, addressing both agricultural waste reduction and the growing demand for natural functional foods. Full article

Chickpea is a legume that grows in most parts of the world. It is negatively affected by abiotic and biotic factors like drought and fungal diseases, respectively. One of the most important soil-borne pathogens affecting chickpeas is Fusarium oxysporum f.sp. ciceris (Foc). Its population dynamics in the soil are affected by fluctuations in soil water content and host characteristics. For the last three decades, drought has been common in most areas of the world due to global warming. Drought stress decreases the quality and quantity of the chickpeas, particularly where soil-borne pathogens are the main stress factor for plants. The use of both drought-tolerant and disease-resistant cultivars may be the only option for cost-effective yield production. In this study, we screened the seeds of twelve chickpea genotypes WR-315, JG-62, C-104, JG-74, CPS-1, BG-212, ANNIGERI, CHAFFA, BG-215, UC-27, ILC-82, and K-850 for drought tolerance at increasing polyethylene glycol (PEG) concentrations (0-, 5-, 7.5-, 10-, 15-, 20-, 25-, 30- and 50%) to create drought stress conditions at different severities. The performances of genotypes that were previously tested in Foc resistance/susceptibility studies were assessed in terms of percentage of germination, radicle and hypocotyl length, germination energy, germination rate index, mean germination time, and vigor index in drought conditions. We determined the genotypes of C-104, CPS-1, and WR-315 as drought-susceptible, moderately drought-tolerant, and drought-tolerant, respectively. We then elucidated the stress levels of selected genotypes (20-day-old seedlings) at 0–15% PEG conditions via measuring proline and malondialdehyde (MDA) contents. Our findings showed that genotypes that were resistant to Foc also exhibited drought tolerance. The responses of chickpea genotypes infected with Foc under drought conditions are the next step to assess the combined stress on chickpea genotypes. Full article

One major challenge of friction stir processing (FSP) is its sensitivity to parameters like advancing and rotational speeds. This study examined the effect of tool travel speed on the microstructural evolution and mechanical properties of a new-generation Al-6Mg alloy. Optical and electron microscopy, EBSD, and shear-punch testing (SPT) were used. Two travel speeds, 50 and 120 mm/min, revealed significant differences in microstructure and properties at ambient temperature. EBSD provided misorientation maps and boundary fraction data. Microstructure analysis showed continuous dynamic recrystallization in the nugget zone, with finer grains observed at the higher speed. Microhardness was greater on both sides at 120 mm/min. The TMAZ showed elongated grains at 120 mm/min, while recrystallized grains were more prominent at 50 mm/min. In the HAZ, partial recrystallization occurred at 120 mm/min, whereas extensive recrystallization was observed at 50 mm/min. The SPT results indicated variations in stiffness between advancing and retreating sides, especially 2 mm from the nugget center. At 10 and 20 mm from the center, higher stiffness and strength were recorded at 120 mm/min. This study established correlations between joint stiffness, grain misorientation, and travel speed. Full article

This study’s novelty lies in providing first-time insights into the isolated role of Friction Stir Processing (FSP) travel speed on microstructure evolution and mechanical performance (micro-hardness, tensile properties, impact energy, and wear behavior) specifically in hypoeutectic as-cast Al-5 wt.% Si alloys, addressing a critical unaddressed gap in previous works (typically on near-eutectic compositions of Si > 6.5 wt.%). FSP, a solid-state technique, is highly effective for enhancing the properties of cast materials. The FSP was conducted at a fixed rotational speed of 1330 rpm and various travel speeds (26, 33, 42, and 52 mm/min). The FSP improves the mechanical properties of as-cast Al-5Si alloy by refining its grain structure. This leads to higher hardness, ultimate tensile strength (UTS), yield strength (YS), and strain at fracture and toughness compared to the as-cast condition. The specimen processed at 26 mm/min achieved the highest values of YS, UTS, toughness, and wear resistance. The fracture surfaces of the tensile and impact test specimens were examined using scanning electron microscopy (SEM) and discussed. Results indicated that the fracture surfaces revealed a transition from predominantly brittle fracture in the as-cast alloy to ductile fracture at 26 mm/min, changing to a mixed fracture mode at 52 mm/min. These findings underscore the critical importance of optimizing FSP travel speed to significantly tailor and enhance the mechanical performance of as-cast hypoeutectic Al-5Si alloys for industrial applications. Full article

The increase in chronic diseases and climate change in recent decades has been driven by food systems that affect both human health and the environment. This study investigated the interrelation between food consumption, obesity, undernutrition, and climate change, aiming to understand how these factors connect within the global syndemic. The methodology used was a scoping review, in which 12 articles were analyzed after an initial search that resulted in 11,208 references. The references were screened using the Rayyan software (Rayyan Systems Inc. (Doha, Qatar), version 1.6.1 and web-based version), removing duplicates and assessing the studies based on eligibility criteria. The articles addressed different aspects, such as the relationship between food consumption, obesity, undernutrition, and climate change, providing data on how food insecurity and socioeconomic conditions influence these conditions. In sequence, we developed a conceptual model to offer a detailed view of the factors affecting the global syndemic, considering the availability of food, its accessibility, stability in supply, and its use in the diet. The model recognizes that climate change affects food consumption both directly and indirectly. Direct effects include the impact of extreme weather events—such as floods and droughts—on the availability, access, quantity, and quality of food. Indirectly, climate change exacerbates socioeconomic vulnerabilities and disrupts food systems in more structural ways, contributing to increased food insecurity. The findings revealed that food insecurity, in turn, can lead to both obesity and undernutrition, particularly among vulnerable populations. There was a scarcity of studies that integrated the relationship between undernutrition, climate change, and food consumption, especially in certain regional contexts such as Latin America. The evidence gathered in the literature and the conceptual model provide a foundation for future research and the development of more effective public policies that integrate food issues, public health, and climate change in a more holistic and interconnected approach. Full article

Background: Adverse cardiac remodeling drives heart failure progression, but the role of hyaluronan-binding protein (HYBID) in this process remains unclear. This study investigated the role of HYBID as a key profibrotic factor in the progression of adverse cardiac remodeling with a focus on its functional impact on cardiac fibroblasts and underlying molecular mechanisms. Methods: RNA sequencing analysis was employed to identify differentially expressed genes in mouse ventricular tissue post-myocardial infarction (MI). Fibroblast-specific genetically modified mouse models (knockdown and overexpression) were generated using FSP1 promoter-driven adeno-associated viruses. Comprehensive histological and biochemical assessments were conducted both in vivo and in vitro to evaluate the effects of HYBID modulation on cardiac remodeling. Molecular docking and immunoprecipitation assays were utilized to elucidate the mechanistic interactions between HYBID and its downstream targets. Results: RNA sequencing revealed HYBID as a fibroblast-enriched protein significantly upregulated in myocardial tissue of MI mice. Fibroblast-specific knockdown of HYBID attenuated MI-induced fibroblast activation, improved cardiac function, and mitigated adverse cardiac remodeling. Conversely, HYBID overexpression exacerbated fibroblast activation and promoted cardiac remodeling. Mechanistically, HYBID was found to competitively bind to STAT5A, thereby inhibiting the anti-fibrotic effects of MMP13 and driving fibroblast activation and adverse remodeling post-MI. Conclusions: Our findings establish HYBID as a novel fibroblast-enriched regulator that exacerbates fibrosis and adverse cardiac remodeling following MI. By uncovering the HYBID–STAT5A–MMP13 axis as a critical signaling pathway, this study provides new insights into the molecular mechanisms underlying heart failure progression. Full article

Wastes resulting from the depulping of tropical fruits such as siriguela (Spondias purpurea), umbu (Spondias tuberosa), and juçara (Euterpe edulis) can be used as a source of bioactive compounds and nutrients. Therefore, the aim of this work was to chemically characterize the flours of siriguela seeds and peels (FSSs and FSPs), umbu seeds and peels (FUSs and FUPs), umbu pulp refine cake (FUC), and defatted juçara pulp refine cake (FJC) based on their proximate composition and mineral content, fatty acids, total phenolic content (TPC) and antioxidant capacity (ABTS^•+, DPPH^•, and FRAP). The results were expressed on a dry basis. The FJC had the highest lipid and protein percentage (10% and 31%, respectively), while for carbohydrates; FUS samples had the highest value (80%). FSSs presented the highest levels of Ca (239.7 mg 100 g⁻¹), Mg (183.3 mg 100 g⁻¹), and FSP of K (1403.9 mg 100 g⁻¹). Regarding the fatty acid profiles, palmitic acid (C16:0) was found as the main fatty acid in FSSs (28.87%), FSPs (69.31%), and FUC (45.68%), while oleic acid (C18:1) was found as the main fatty acid in FUSs (32.63%), FUPs (48.24%), and FJC (61.58%). The FUP sample exhibited the highest antioxidant potential (1852.81 mg GAE 100 g⁻¹, 130 µmol Trolox g⁻¹, 131 µmol Trolox g⁻¹, and 590 µmol Fe²⁺ g⁻¹ by TPC, ABTS^•+, DPPH^•, and FRAP, respectively). As the first comparative study of these specific fruits wastes, the results showed that their flours are promising sources of nutrients and bioactive compounds. In addition, their use can contribute to the circular economy and Sustainable Development Goals (SDGs) 2 and 12 of the 2030 Agenda. Full article