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Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia–reperfusion (I/R) injury. However, the precise mechanism underlying myocardial ferroptosis remains less known. In this study, we investigated the pathophysiological mechanisms of methylmalonic acid (MMA) associated with ferroptosis activation in cardiomyocytes after I/R. We found an increase level of MMA in patients with acute myocardial injury after reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. MMA treatment was found to be associated with excessive oxidative stress in cardiomyocytes, leading to ferroptosis-related myocardial injury. In mice with I/R injury, MMA treatment aggravated myocardial oxidative stress and ferroptosis, which amplified the myocardial infarct size and cardiac dysfunction. Mechanistically, MMA promoted NOX2/4 expression to increase reactive oxygen species (ROS) production in cardiomyocytes, aggravating myocardial injury. Notably, the increased ROS further activated ferroptosis by inhibiting solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. In addition, MMA decreased the ectopic nuclear distribution of nuclear factor E2-related factor 2 (NRF2) by increasing the interaction between NRF2 and kelch-like ECH-associated protein 1 (KEAP1). This impeded the activation of GPX4/SLC7A11, downstream of NRF2, activating ferroptosis and aggravating myocardial cell injury. Collectively, our study indicates that MMA activates oxidative stress and ROS generation, which induces ferroptosis to exacerbate cardiomyocyte injury in an I/R model. These findings may provide a new perspective for the clinical treatment of I/R injury and warrant further investigation. Associated Products

The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance. Associated Products

Clinical treatment for osteosarcoma (OS) is still lacking effective means, and no significant progress in OS treatment have been made in recent years. Single chemotherapy has serious side effects and can produce drug resistance easily, resulting poor therapeutic effect. As a modern and non-invasive treatment form, photodynamic therapy (PDT) is widely used to treat diverse cancers. Chemotherapy in combination with PDT is a particularly efficient antitumor method that could overcome the defects of monotherapies. Since mitochondria is a key subcellular organelle involved in cell apoptosis regulation, targeting tumor cells mitochondria for drug delivery has become an important entry point for anti-tumor therapy. Herein, we rationally designed a core-shell structured biomimetic nanoplatform, i.e., D@SLNP@OSM-IR780, to achieve tumor homologous targeting and mitochondria targeted drug release for chemotherapy combined with PDT against OS. Upon 808 nm laser irradiation, D@SLNP@OSM-IR780 exhibited excellent photo-cytotoxicity in vitro . The excellent targeting effect of D@SLNP@OSM-IR780 in tumor tissues produced a tumor inhibition rate of 98.9% in vivo . We further indicated that synergistic chemo-photodynamic effect induced by D@SLNP@OSM-IR780 could activate mitochondria-mediated apoptosis pathway, along with host immune response and potential photothermal effect. On the whole, D@SLNP@OSM-IR780 is revealed to be a promising platform for OS targeted combination therapeutics. Associated Products

Flotation of goethite, a representative mineral of laterite ore, which is essential source of nickel used in secondary batteries, was conducted using salicylhydroxamic acid as the collector. The presence of ferric ions derived from goethite in the pulp resulted in an increased consumption of the collector during flotation. Following three washing stages, the maximum recovery of 98.5 wt% was achieved with a collector dosage of only 60 % in the absence of a washing stage. The oxalic acid is employed to eliminate ferric ions via precipitation without the requirement for supplementary water, energy, and time-consuming washing stages. The utilization of 40 g⋅t −1 of oxalic acid yielded comparable recovery outcomes to those observed in the three washing stages. Furthermore, theoretical investigations were conducted to determine the collector species influencing goethite flotation with density functional theory. It was observed that compared with that of goethite with non-ionized salicylhydroxamic acid complex, the complexation energy for goethite with ionized salicylhydroxamic acid was lower by 113.9 kJ⋅mol −1 , indicating that the optimum adsorption onto the mineral surface strongly depends on ionized salicylhydroxamic acid species. This study presents a potential method for reduction of reagent consumption in the flotation of future complex laterite ore, an acidic soil in which metal ions might be present. Additionally, the theoretical framework elucidates the complexation of collectors to minerals that are challenging to quantify experimentally. Associated Products

The cold plasma (CP) technique was applied to alleviate the contamination of polycyclic aromatic hydrocarbon (PAH) in this investigation. Two different CP treatments methods were implemented in the production of beef patties, to investigate their inhibition and degradation capacity on PAHs. With 5 different cooking oils and fats addition, the inhibition mechanism of in-package cold plasma (ICP) pretreatment was explored from the aspect of raw patties fatty acids composition variation. The results of principal component analysis showed that the first two principal components accounted for more than 80 % of the total variation in the original data, indicating that the content of saturated fatty acids was significantly positively correlated with the formation of PAHs. ICP pretreatment inhibited the formation of PAHs by changing the composition of fatty acids, which showed that the total amount of polyunsaturated fatty acids decreased and the total amount of monounsaturated fatty acids increased. Sensory discrimination tests demonstrated there were discernable differences between 2 CP treated samples and the controls, utilization of the ICP pretreatment in meat products processing was expected to achieve satisfying eating quality. In conclusion, CP treatment degraded PAHs through stepwise ring-opening oxidation in 2 reported pathways, the toxicity of PAHs contaminated products was alleviated after CP treatment. Associated Products

Membrane fouling is one of the issues that hinder the widespread application of electrified membranes. This study focuses on mitigating membrane fouling caused by natural organic matter (NOM) through pre-coagulation techniques. The effectiveness of pre-coagulation was evaluated based on the flux and removal efficiency of electrified membranes. Pre-coagulation can remove a portion of NOM and reduce the negative surface charge of residual NOM, thereby reducing the attachment of NOM to the surface of electrified membranes. As a result, pre-coagulation effectively increased the flux of electrified membranes for treating water samples containing NOM. Additionally, pre-coagulation alleviated the decrease in surface current density of electrified membranes caused by NOM pollution, leading to improved bisphenol A (BPA) removal performance. The effectiveness of pre-coagulation in enhancing membrane performance depends on the choice of coagulant. Compared to polyferric chloride (PFC), PFC-cationic polyacrylamide composite coagulants (PFC-CPAM) facilitated the aggregation of NOM into larger flocs with a branched structure, demonstrating a stronger capability to mitigate membrane fouling. However, it should be noted that the presence of CPAM may result in irreversible internal fouling due to the polarization effect induced by the electric field. Moreover, when the weight ratio of PFC to CPAM was 1:1, the flocs became overly dense, resulting in reduced flux. This study provides valuable insights for the application of pre-coagulation techniques in mitigating fouling issues in electrified membranes. Associated Products

In order to investigate the effects of multi-frequency ultrasound-assisted immersion freezing (MUIF) on the meat quality of Macrobrachium rosenbergii , tail meat was subjected to different MUIF treatments respectively, namely 20 + 40 kHz (MUIF-20 + 40), 20 + 60 kHz (MUIF-20 + 60), 40 + 60 kHz (MUIF-40 + 60) and 20 + 40 + 60 kHz (MUIF-20 + 40 + 60), and the immersion freezing (IF) as control. Results showed that average diameter of ice crystals was 28 μm in IF, and that was only 8 μm in MUIF-20 + 40 + 60. When compared to IF, MUIF alleviated oxidative deterioration of lipids and proteins, but only at higher ultrasound frequency (MUIF-40 + 60; MUIF-20 + 40 + 60). Carbonyl content of MUIF-20 + 40 + 60 was only 40% of that in IF. Similarly, protein denaturation was inhibited in MUIF (except for MUIF-20 + 40). Transmission electron microscopy showed greater distortion of the ultrastructural components in IF, MUIF-40 + 60, and MUIF-20 + 40 + 60, suggested by bended Z -line. In conclusion, MUIF can be an effective strategy to mitigate mechanical damage and protein deterioration in the meat of Macrobrachium rosenbergii . Associated Products

Understanding the irreversible fouling mitigation performance of conductive membranes is crucial for engineering applications. In this study, the effectiveness of conductive membranes in mitigating the irreversible fouling caused by typical membrane pollutants and actual surface water was investigated. The results indicated that the conductive membranes had the greatest mitigating effect on irreversible fouling caused by humic substances and the weakest mitigating effect on that caused by proteins. The growth rates of irreversible membrane fouling over five-cycle filtration with conductive membranes were reduced by 58.6 % (humic acid), 42.3 % (sodium alginate), and 30 % (bovine serum albumin) compared to those without power. Moreover, conductive membranes exhibited a commendable irreversible fouling mitigation effect when treating real surface water. The irreversible fouling growth rate and resistance decreased by 41.6 % and 49.9 %, respectively, compared to those without power. Although the increase in the ionic strength of the feed water weakened the effectiveness of the conductive membranes in irreversible fouling mitigation, it was still significantly better than that without power. Associated Products

Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease. Associated Products

Chilling injury (CI) is a bottleneck factor constraining the refrigeration and cold chain logistics of mango fruit. Methyl jasmonate (MeJA) is an important phytohormone that can regulate multiple abiotic stresses. This study evaluated the potential effects of MeJA on CI in ‘Guifei’ mango fruit stored at 4 °C and its underlying mechanisms involved in the regulation of antioxidation and energy status. The application of 50 µM MeJA mitigated CI symptoms and improved ripening-related quality during refrigeration, as indicated by a lowered CI index, retarded declines in chlorophyll fluorescence ( Fv/Fm ) and chromaticity L * and advanced color transformation (from green to yellow), softening and accumulation of soluble solids. MeJA treatment repressed the increases in relative conductivity (RC), malondialdehyde (MDA) content and reactive oxygen species (ROS) (O 2 -. and H 2 O 2 ). Reduced ROS generation in MeJA-treated fruit was a consequence of the enhancement of antioxidant enzyme activities , including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR). Ultrastructural observation revealed that MeJA treatment protected mitochondrial structure. MeJA treatment promoted intracellular energy synthesis and utilization, as indicated by increments in intracellular adenosine triphosphate (iATP) level, activities of isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH), cytochrome C oxidase (CCO), H + -ATPase and Ca 2+ -ATPase as well as contents of reduced coenzymes (NADH and FADH 2 ). In addition, the expression levels of genes ( MiAPYs , MiENTs , MiPUPs and MiAPRTs ) related to extracellular ATP (eATP) hydrolysis, eATP transport and iATP regeneration were upregulated in response to MeJA, contributing to maintenance of eATP/iATP homeostasis . These findings suggest that MeJA could reinforce cold tolerance in mango fruit by inhibiting oxidative stress and promoting energy metabolism. Associated Products

Background Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed "Mixture") containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma. Associated Products

The accumulation of volatile fatty acids (VFAs) during anaerobic digestion of leachate from waste transfer stations can destabilize the system. Zero-valent iron (ZVI), with its strong reducing properties, has the significant potential to enhance anaerobic digestion by optimizing the microenvironment for anaerobic microorganisms, enriching microbial communities and promoting direct interspecies electron transfer (DIET). This study examined three continuous-flow scenarios: a control without ZVI (0 # ), initial ZVI addition (1 # ), and ZVI addition during significant VFAs accumulation (2 # ). Both ZVI-supplemented systems outperformed the control, with 2 # demonstrating superior performance. Compared to the control, 2 # reduced VFAs accumulation by 82.45 %, increased pH by 2.51 units, improved COD removal by 67.03 %, enhanced methane production by 0.41 L/gCOD, and increased methane concentration by 32.41 %. ZVI addition reduced the oxidation-reduction potential (ORP) by 131–183 mV in 2 # , facilitating anaerobic conditions conducive to methanogenic activity. Microbial sequencing revealed that VFAs-oxidizing bacteria and methanogens in 2 # were 6.28–14.64 % and 40.80–69.98 % more abundant, respectively, than in 0 # , significantly enhancing VFAs degradation. The enrichment of DIET-related microorganisms, such as Methanobacterium and Syntrophomonas , was also higher in 2 # . ZVI addition during VFAs accumulation stabilizes the anaerobic process, offering a cost-effective and eco-friendly solution for treating leachate and other high-strength organic wastewaters. Associated Products