Submerged plant-biochar composite system exhibits effective control over residual organic pollutants in the benthic organisms of aquaculture ponds.

As of now, submerged plants and biochar have demonstrated significant benefits in aquaculture pond sediment remediation. However, there is limited research on the synergistic effects of biochar and submerged plants in mitigating hydrophobic organic contaminant (HOC) accumulation in aquaculture benthic organisms and in controlling the nutrient (nitrogen and phosphorus) levels in aquaculture water. This study assesses a submerged plant-biochar system's efficacy in removing HOCs from simulated freshwater aquaculture ponds. Vallisneria natans was planted in sediment with varying levels of wheat straw biochar, while Corbicula fluminea served as the targeted benthic organism. The bioaccumulation experiment identified the optimal biochar ratio for the Vallisneria natans-biochar system in controlling HOCs in aquaculture products. Analyses included final accumulation concentrations in benthic organisms, changes in freely-dissolved concentrations in aquaculture sediment, and a mass balance calculation to explore key factors in their removal from the system. Results indicated that the Vallisneria natans-1.5% biochar composite system achieved optimal control of HOCs in sediment and aquaculture products. Biochar addition to the sediment in the composite system demonstrated a "promotion with low addition, inhibition with high addition" effect on Vallisneria natans growth. Notably, the addition of 1.5% biochar (VN1.5 group) significantly promoted the growth of Vallisneria natans leaves and roots. Comparing the final pollutant proportions in different environmental media, concentrations in water (0.20%-1.8%), clam accumulation (0.032%-0.11%), and plant absorption (0.10%-0.44%) constituted a minimal portion of the overall pollutant load in the system. The majority of pollutants (24%-65%) were degraded in the aquaculture environment, with microbial degradation likely playing a predominant role. Bacterial phyla, particularly Proteobacteria and Firmicutes, were identified as potential direct contributors to pollutant degradation in the Vallisneria natans-biochar system.

Pushing the thinness limit of silver films for flexible optoelectronic devices via ion-beam thinning-back process.

Reducing the silver film to 10 nm theoretically allows higher transparency but in practice leads to degraded transparency and electrical conductivity because the ultrathin film tends to be discontinuous. Herein, we developed a thinning-back process to address this dilemma, in which silver film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the shallow implantation of silver atoms into the substrate during deposition, the thinness of silver films down to 4.5 nm can be obtained, thinner than ever before. The atomic-level surface smooth permits excellent visible transparency, electrical conductivity, and the lowest haze among all existing transparent conductors. Moreover, the ultrathin silver film exhibits the unique robustness of mechanical flexibility. Therefore, the ion-beam thinning-back process presents a promising solution towards the excellent transparent conductor for flexible optoelectronic devices.

L-Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload.

SCOPE: Oxidative stress caused by iron overload tends to result in intestinal mucosal barrier dysfunction and intestinal microbiota imbalance. As a neutral and nonprotein amino acid, L-Citrulline (L-cit) has been implicated in antioxidant and mitochondrial amelioration properties. This study investigates whether L-cit can alleviate iron overload-induced intestinal injury and explores the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are intraperitoneally injected with iron dextran, then gavaged with different dose of L-cit for 2 weeks. L-cit treatment significantly alleviates intestine pathological injury, oxidative stress, ATP level, and mitochondrial respiratory chain complex activities, accompanied by ameliorating mitochondrial quality control. L-cit-mediated protection is associated with the upregulation of Glutathione Peroxidase 4 (GPX4) expression, inhibition Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy and ferroptosis, and improvement of gut microbiota. To investigate the underlying molecular mechanisms, Intestinal Porcine Epithelial Cell line-J2 (IPEC-J2) cells are treated with L-cit or AMP-activated Protein Kinase (AMPK) inhibitor. AMPK signaling has been activated by L-cit. Notably, Compound C abolishes L-cit's protection on intestinal barrier, mitochondrial function, and antioxidative capacity in IPEC-J2 cells. CONCLUSION: L-cit may restrain ferritinophagy and ferroptosis to regulate iron metabolism, and induce AMPK pathway activation, which contributes to exert antioxidation, ameliorate iron metabolism and mitochondrial quality control, and improve intestinal microbiota. L-cit is a promising therapeutic strategy for iron overload-induced intestinal injury.

Status and developmental trends in recombinant collagen preparation technology.

Recombinant collagen is a pivotal topic in foundational biological research and epitomizes the application of critical bioengineering technologies. These technological advancements have profound implications across diverse areas such as regenerative medicine, organ replacement, tissue engineering, cosmetics and more. Thus, recombinant collagen and its preparation methodologies rooted in genetically engineered cells mark pivotal milestones in medical product research. This article provides a comprehensive overview of the current genetic engineering technologies and methods used in the production of recombinant collagen, as well as the conventional production process and quality control detection methods for this material. Furthermore, the discussion extends to foresee the strides in physical transfection and magnetic control sorting studies, envisioning an enhanced preparation of recombinant collagen-seeded cells to further fuel recombinant collagen production.

Characteristics and driving factors of antibiotic resistance genes in aquaculture products from freshwater ponds in China Yangtze River Delta.

Antibiotic resistance genes (ARGs) are widespread in aquaculture and pose a huge threat to aquaculture organisms and human health. In this study, occurrences and relative abundances of ARGs were analysed in the guts of products cultured in freshwater ponds in the Yangtze River Delta region in China. A total of 29 ARGs were found in the gut samples, with detection frequencies ranging from 4.8% to 81%, and the relative abundances (ARGs/16S rRNA) ranging from 10-7 to 1. In addition, the human dietary intake of ARGs via aquaculture products was assessed, where the daily intake of most ARGs via aquaculture products was higher than those via PM2.5 and drinking water, but lower than that via vegetables. The relative abundances of MGE (IS613, Tp614, tnpA and int1) were significantly correlated with those of multiple ARGs, indicating the horizontal gene transfer (HGT) of ARGs among gut microorganisms. Proteobacteria, Firmicutes and Actinobacteria were the dominated microbial communities found in the guts of aquaculture products. In addition, significant correlations were found between Cyanobacteria and int1, between Nitrospira and tetE, and between sul2 and aadA2, indicating potential same hosts of these genes. In addition, results from co-correlation indicated both HGT (dominated by MGEs) of ARGs and the enrichment of ARGs in bacteria. MGEs, mostly int1, were more effective than bacteria in increasing the ARG abundance. This study could provide a better understanding of the transmission of ARGs in the aquaculture environment and improve the quality of aquaculture products and the ecology.

Effects of exposure to the explosive and environmental pollutant 2,4,6-trinitrotoluene on ovarian follicle development in rats.

Although 2,4,6-trinitrotoluene (TNT) is a dangerous carcinogen in environmental pollution, information on the reproductive effects of TNT explosive contamination is limited. To explore the possible ovarian effects, TNT explosive-exposed rat models were established, and Wistar female rats were exposed to low and high TNT (40 g and 80 g, air and internal) explosives. After a month of exposure, the estrous cycle, ovarian histopathology, and follicle counting were conducted. Serum hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), progesterone, testosterone, and estradiol were detected, and the mRNA and protein expression of steroidogenic enzymes were measured. The results showed that the diestrus phase duration was significantly (P < 0.05) increased in the high TNT-exposed groups. In addition, the proportions of preantral follicles were significantly (P < 0.05) decreased in the high TNT-exposed groups, as well as the proportions of atretic follicles. The serum estradiol levels were significantly (P < 0.05) increased, and the follicle-stimulating hormone and luteinizing hormone levels were significantly (P < 0.05) decreased in the high TNT-exposed groups. The mRNA levels of steroidogenic acute regulatory protein (Star), cytochrome P450 cholesterol side chain cleavage (Cyp11a1, Cyp17a1 and Cyp19a1), hydroxysteroid dehydrogenase 3b (Hsd3b) and steroidogenic factor-1 (SF-1) were significantly (P < 0.05) increased in the TNT-exposed groups. The protein levels of Star, Cyp11a1 and Hsd3b were increased (P < 0.05) in the TNT-exposed groups. These results indicate that the exposure of rats to TNT explosive can subsequently affect ovarian follicle development, suggesting that the mechanism may involve disrupting steroidogenesis.

Flavonoid metabolites in tea plant (Camellia sinensis) stress response: Insights from bibliometric analysis.

In the context of global climate change, tea plants are at risk from elevating environmental stress factors. Coping with this problem relies upon the understanding of tea plant stress response and its underlying mechanisms. Over the past two decades, research in this field has prospered with the contributions of scientists worldwide. Aiming in providing a comprehensive perspective of the research field related to tea plant stress response, we present a bibliometric analysis of the this area. Our results demonstrate the most studied stresses, global contribution, authorship and collaboration, and trending research topics. We highlight the importance of flavonoid metabolites in tea plant stress response, particularly their role in maintaining redox homeostasis, yield, and adjusting tea quality under stress conditions. Further research on the flavonoid response under various stress conditions can promote the development of cultivation measures, thereby improving stress resistance and tea quality.

Copper exposure induces ovarian granulosa cell apoptosis by activating the caspase-dependent apoptosis signaling pathway and corresponding changes in microRNA patterns.

Environmental copper (Cu) contamination is a complex worldwide public health problem. However, information on the effects of Cu pollution on human reproduction is limited. Although our previous studies have indicated that Cu exposure disrupts ovarian folliculogenesis, the underlying mechanism needs to be further explored. In this study, human luteinized ovarian granulosa cells and a rat animal model were used to investigate whether Cu exposure affects ovarian follicle development by inducing apoptosis and to elucidate the possible mechanisms. The results showed that Cu exposure from weaning to sexual maturity significantly decreased the proportion of preantral follicles but increased the proportion of atretic follicles (P < 0.05). In addition, 6 mg/kg Cu increased the proportion of antral follicles, while 12 and 25 mg/kg Cu decreased it (P < 0.05). We also found that 6 mg/kg Cu exposure inhibited apoptosis of ovarian granulosa cells, while 12 and 25 mg/kg Cu promoted apoptosis (P < 0.05). Experiments on primary human luteinized ovarian granulosa cells suggested that higher levels of Cu exposure induced a significant increase in the mRNA levels of Bcl2 Bax , Fas, Caspase8, and Caspase3 (P < 0.05), and the protein levels of BAX, BCL2, CASPASE3, CASPASE8, CLE-CASPASE3, CLE-CASPASE8 and BAX/BCL2 were also increased (P < 0.05). miRNA chip analyses identified a total of 95 upregulated and 10 downregulated miRNAs in human luteinized granulosa cells exposed to Cu. Hsa-miR-19b-3p, hsa-miR-19a-3p, miR-548ar-3p, hsa-miR-652-5p, and hsa-miR-29b-5p were decreased after Cu exposure (P < 0.05). Additionally, the level of hsa-miR-144-5p was increased (P < 0.05). Together, our results reveal that Cu exposure induces abnormal ovarian folliculogenesis by inducing ovarian granulosa cell apoptosis, which is triggered by the caspase-dependent apoptosis signaling pathway, and that miRNAs may be involved in this process.

5.7 GHz Ultrasensitive Shear Horizontal-Surface Acoustic Wave Humidity Sensor Based on LiNbO3/SiO2/SiC Heterostructures with a Sensitive Layer of Polyethyleneimine-SiO2 Nanocomposites.

Humidity sensing and water molecule monitoring have become hot research topics attributed to their potential applications in monitoring breathing/physiological conditions of humans, air conditioning in greenhouses, and soil moisture in agriculture. However, there is a huge challenge for highly sensitive and precision humidity detection with wireless and fast responsive capabilities. In this work, a hybrid/synergistic strategy was proposed using a LiNbO3/SiO2/SiC heterostructure to generate shear-horizontal (SH) surface acoustic waves (SAWs) and using a nanocomposite of polyethylenimine-silicon dioxide nanoparticles (PEI-SiO2 NPs) to form a sensitive layer, thus achieving an ultrahigh sensitivity of SAW humidity sensors. Ultrahigh frequencies (1∼15 GHz) of SAW devices were obtained on a high-velocity heterostructure of LiNbO3/SiO2/SiC. Among the multimodal wave modes, we selected SH waves for humidity sensing and achieved a high mass-sensitivity of 5383 MHz · mm2 · µg-1. With the PEI-SiO2 NP composite as the sensitive layer, an ultrahigh sensitivity of 2.02 MHz/% RH was obtained, which is two orders of magnitude higher than those of the conventional SAW humidity sensors (∼202.5 MHz frequency) within a humidity range of 20-80% RH.

Dry-Transferable Photoresist Enabled Reliable Conformal Patterning for Ultrathin Flexible Electronics.

Photolithographic techniques, which are widely used in the silicon-based semiconductor industry, enable the manufacture of high-yield and high-resolution features at the micrometer and nanometer scales. However, conventional photolithographic processes cannot accommodate the micro/nanofabrication of flexible and stretchable electronics. In this study, a microfabrication approach that uses a synthesized, environmentally friendly, and dry-transferable photoresist to enable the reliable conformal manufacturing of thin-film electronics is reported, which is also compatible with the existing cleanroom processes. Photoresists with high-resolution, high-density, and multiscale patterns can be transferred onto various substrates in a defect-free and conformal-contact manner, thus enabling multiple wafer reuses. Theoretical studies are conducted to investigate the damage-free peel-off mechanism of the proposed approach. The in situ fabrication of various electrical components, including ultralight and ultrathin biopotential electrodes, has been demonstrated, which offer lower interfacial impedance, durability, and stability, and the components are applied to collect electromyography signals with superior signal-to-noise ratio (SNR) and quality. Additionally, an exemplary demonstration of a human-machine interface indicates the potential of these electrodes in many emerging applications, including healthcare, sensing, and artificial intelligence.

Programmable Nanoscale Crack Lithography for Multiscale PMMA Patterns.

Crack lithography is important for preparing microstructured materials. This strategic use of cracking breaks with the traditional idea that cracks are unwanted and has great potential for high-resolution and high-throughput production. However, the ability to control nanoscale crack patterning is still insufficient. Here, we present a nanoscale, programmable angle-dependent technique to control crack generation that relies on standard electron-beam lithography. Multiscale patterns of poly(methyl methacrylate) of arbitrary shape, geometric size, and large area were obtained, greatly expanding the processing capacity of electron-beam lithography. In addition, we observed the interaction between adjacent structures and cracks, which resulted in crack suppression or second-order cracks. We also demonstrated that angle-dependent nanoscale cracks can be used in physical unclonable functions and have great application prospects in the field of information security. We believe that our strategy for programmable nanoscale crack patterning provides new opportunities and perspectives for nanofabrication.

Topics and trends in fresh tea (Camellia sinensis) leaf research: A comprehensive bibliometric study.

Tea plant (Camellia sinensis) is a widely cultivated cash crop and tea is a favorite functional food in the world. Fresh tea leaves (FTLs) play a critical role in bridging the two fields closely related to tea cultivation and tea processing, those are, tea plant biology and tea biochemistry. To provide a comprehensive overview of the development stages, authorship collaboration, research topics, and hotspots and their temporal evolution trends in the field of FTLs research, we conducted a bibliometric analysis, based on 971 publications on FTLs-related research published during 2001-2021 from Web of Science Core Collection. CiteSpace, R package Bibliometrix, and VOSviewer were employed in this research. The results revealed that the development history can be roughly divided into three stages, namely initial stage, slow development stage and rapid development stage. Journal of Agricultural & Food Chemistry published most articles in this field, while Frontiers in Plant Science held the highest total citations and h-index. The most influential country, institution, and author in this field was identified as China, the Chinese Academy of Agricultural Sciences, and Xiaochun Wan, respectively. FTLs-related research can be categorized into three main topics: the regulation mechanism of key genes, the metabolism and features of essential compounds, and tea plants' growth and stress responses. The most concerning hotspots are the application of advanced technologies, essential metabolites, leaf color variants, and effective cultivation treatments. There has been a shift from basic biochemical and enzymatic studies to studies of molecular mechanisms that depend on multi-omics technologies. We also discussed the future development in this field. This study provides a comprehensive summary of the research field, making it easier for researchers to be informed about its development history, status, and trends.

High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development.

Increasing evidence has shown that gut microbes play an important role in the reproductive endocrine system and the development of polycystic ovary syndrome (PCOS). However, whether environmental factors are involved in these gut microbiota alterations has seldom been studied. In this study, we aimed to explore the crucial role of an imbalanced gut microbiota on abnormal ovarian follicle development induced by Cu. A 1:1 matched case-control study with 181 PCOS patients and 181 controls was conducted using a propensity score matching protocol. Information regarding dietary Cu intake was obtained from a face-to-face dietary intake interview. Alterations in the gut microbiota were detected by high-throughput 16 S rDNA sequencing. The results showed that dietary Cu intake was positively correlated with the risk of PCOS, and the risk threshold was approximately 1.992 mg/d. Compared with those with dietary Cu intakes lower than 1.992 mg/d, those who had a higher dietary Cu intake had a 1.813-fold increased risk of PCOS (OR=1.813, 95% CI: 1.150-2.857). PCOS patients had a lower relative abundance of Bacteroides than controls (P = 0.003), and Bacteroides played a partial mediating role between dietary Cu exposure and PCOS (Pindirect effect=0.026, 95% CI: 0.002-0.072). In addition, an animal model of Cu exposure through the diet showed that Cu can induce gut microbiota disorder; increase serum levels of LPS, MDA, and IL-6; and alter host ovarian steroidogenesis to affect ovarian follicle development. Staphylococcus played a partial mediating role between Cu exposure and CYP17A1 (Pg_Staphylococcus=0.083, 95% CI: 0.001-0.228). Overall, this study shows that long-term exposure to high dietary Cu levels can affect the composition of the gut microbiota, cause inflammation and oxidative stress, and then interfere with hormone signaling, ultimately affecting ovarian follicle development.

CXCR3 Inhibition Blocks the NF-κB Signaling Pathway by Elevating Autophagy to Ameliorate Lipopolysaccharide-Induced Intestinal Dysfunction in Mice.

Autophagy is a cellular catabolic process in the evolutionarily conservative turnover of intracellular substances in eukaryotes, which is involved in both immune homeostasis and injury repairment. CXCR3 is an interferon-induced chemokine receptor that participates in immune regulation and inflammatory responses. However, CXCR3 regulating intestine injury via autophagy along with the precise underlying mechanism have yet to be elucidated. In the current study, we employed an LPS-induced inflammatory mouse model and confirmed that CXCR3 knockout significantly attenuates intestinal mucosal structural damage and increases tight junction protein expression. CXCR3 knockout alleviated the LPS-induced increase in the expression of inflammatory factors including TNF-α, IL-6, p-65, and JNK-1 and enhanced autophagy by elevating LC3II, ATG12, and PINK1/Parkin expression. Mechanistically, the function of CXCR3 regarding autophagy and immunity was investigated in IPEC-J2 cells. CXCR3 inhibition by AMG487 enhanced autophagy and reduced the inflammatory response, as well as blocked the NF-κB signaling pathway and elevated the expression of the tight junction protein marker Claudin-1. Correspondingly, these effects were abolished by autophagy inhibition with the selective blocker, 3-MA. Moreover, the immunofluorescence assay results further demonstrated that CXCR3 inhibition-mediated autophagy blocked p65 nuclear translocation, and the majority of Claudin-1 was located at the tight junctions. In conclusion, CXCR3 inhibition reversed LPS-induced intestinal barrier damage and alleviated the NF-κB signaling pathway via enhancing autophagy. These data provided a theoretical basis for elucidating the immunoregulatory mechanism by targeting CXCR3 to prevent intestinal dysfunction.

An application of waste algae biochar in aquaculture water to remove co-existed cadmium and PAHs and the corresponding mechanism.

Water quality in aquaculture farms is highly related to the quality of aquaculture products and the connected environment. Cadmium (Cd2+) and polycyclic aromatic hydrocarbons (PAHs) are two of the most common pollutants in the aquaculture water, while biochar derived from waste algae (Enteromorpha prolifera), namely BE, was applied in farms ponds to improve water quality. Firstly, the adverse environmental impact of BE was minor, while the concentrations of the heavy metal (Cd2+ in the present study) and PAHs (FLU, PHE, FLT and PYR) were removed with efficiencies of 49%, 88%, 90%, 91% and 88%, respectively. The ecological risk values (RQs) were reduced subsequently with a rate of 58 ± 11%. After dosing BE, the ecological risk values in all the studied ponds were lower than 1, indicating no ecological risk in the corresponding aquaculture environment. The sorption capacities (qm) of BE were 15, 12, 6.3, 0.41, 0.29 and 0.56 mg·g-1 for Cd2+, FLU, PHE, FLT, PYR and BaP, respectively. The sorption capacities were acceptable compared with those derived from other types of biomass. The removal mechanisms were partition (PAHs), complexation (Cd2+), π-π interaction (Cd2+ and PAHs), precipitation (Cd2+) and ion-exchange (Cd2+). Practically and theoretically, the algae biochar is applicable in the aquaculture environment, where Cd2+ and PAHs co-exist.

Resist nanokirigami for multipurpose patterning.

Resist-based patterning solutions play essential roles in modern micro- and nanoscale science and technology. The commonly used 'resist' patterning strategy depends on selective-area scission or cross-linking of resist molecules under the action of an energy beam. In this work, we propose and demonstrate a different resist-patterning strategy, termed 'resist nanokirigami', in which the resist structures are defined by their outlines and revealed by selective mechanical peeling of the unwanted resist film. Unlike conventional resist-based patterning processes, the final resist-nanokirigami structures do not undergo exposure and the exposure area is dramatically reduced. With these two advantages, a variety of functional structures that are difficult or impossible to fabricate by conventional processes, such as inverse nanostructures and their oligomers, multi-scale electrodes and freestanding plasmonic nanogaps, can be easily achieved with much higher efficiency. Thus, with its unique and complementary capabilities, the resist-nanokirigami process provides a new patterning solution that expands the family of lithography techniques and will play a significant role in fabricating multi-scale functional structures.

Solar Light Management Enabled by Dual-Responsive Smart Window.

Smart windows with tunable optical properties for energy-saving and privacy protection applications are receiving increasing attention. However, current studies of smart windows either involve the use of complex material preparation processes and complex device systems for window switching or continue to face several challenges, including low luminous transmittance, low luminous and solar modulation, and narrow wavelength range management problems. Here, we report a dual-responsive smart window that achieves solar light management in the range of 200-2500 nm. This smart window is fabricated by combining a reversible thermoresponsive hydrogel that acts as a thermochromic material with a ZnO/Ag/ZnO multilayer film that acts as a transparent heater. The as-prepared smart window can modulate solar light over a range from ultraviolet to infrared and achieves active responses to high-temperature weather, with passive responses being produced through electrical heating. The smart window shows high luminous transmittance (81.7%) and high luminous modulation (81.6%), together with an outstanding solar modulation performance (62.9%). In outdoor demonstrations, the as-prepared smart window exhibited a promising temperature regulation ability under strong solar irradiation. Therefore, the proposed smart window promises to provide a simple and effective energy management technology for buildings.

Suspended 3D metallic dimers with sub-10 nm gap for high-sensitive SERS detection.

The suspended metallic nanostructures with tiny gaps have certain advantages in surface-enhanced Raman scattering (SERS) due to the coaction of the tiny metallic nanogaps and the substrate-decoupled electromagnetism resonant modes. In this study, we used the lithographic HSQ/PMMA electron-beam bilayer resist exposure combined with a deposition-induced nanogap-narrowing process to define elevated suspended metallic nanodimers with tiny gaps for surface-enhanced Raman spectroscopy detection. By adjusting the deposited metal thickness, the metallic dimers with sub-10 nm gaps can be reliably obtained. These dimers with tunable nanogaps successfully served as excellent SERS substrates, exhibiting remarkable high-sensitivity detection ability for crystal violet molecules. Systematic experiments and simulations were conducted to explain the origin of the improved SERS performance. The results showed that the 3D elevated suspended metallic dimers could achieve a higher SERS enhancement factor than the metallic dimers on HSQ pillars and a common Si substrate, demonstrating that this kind of suspended metallic dimer is a promising route for high-sensitive SERS detection and other plasmonic applications.

L-Citrulline Supplementation Restrains Ferritinophagy-Mediated Ferroptosis to Alleviate Iron Overload-Induced Thymus Oxidative Damage and Immune Dysfunction.

L-citrulline (L-cit) is a key intermediate in the urea cycle and is known to possess antioxidant and anti-inflammation characteristics. However, the role of L-cit in ameliorating oxidative damage and immune dysfunction against iron overload in the thymus remains unclear. This study explored the underlying mechanism of the antioxidant and anti-inflammation qualities of L-cit on iron overload induced in the thymus. We reported that L-cit administration could robustly alleviate thymus histological damage and reduce iron deposition, as evidenced by the elevation of the CD8+ T lymphocyte number and antioxidative capacity. Moreover, the NF-κB pathway, NCOA4-mediated ferritinophagy, and ferroptosis were attenuated. We further demonstrated that L-cit supplementation significantly elevated the mTEC1 cells' viability and reversed LDH activity, iron levels, and lipid peroxidation caused by FAC. Importantly, NCOA4 knockdown could reduce the intracellular cytoplasmic ROS, which probably relied on the Nfr2 activation. The results subsequently indicated that NCOA4-mediated ferritinophagy was required for ferroptosis by showing that NCOA4 knockdown reduced ferroptosis and lipid ROS, accompanied with mitochondrial membrane potential elevation. Intriguingly, L-cit treatment significantly inhibited the NF-κB pathway, which might depend on restraining ferritinophagy-mediated ferroptosis. Overall, this study indicated that L-cit might target ferritinophagy-mediated ferroptosis to exert antioxidant and anti-inflammation capacities, which could be a therapeutic strategy against iron overload-induced thymus oxidative damage and immune dysfunction.