Evolutionary analysis of a complete chicken genome.

Microchromosomes are prevalent in nonmammalian vertebrates [P. D. Waters et al., Proc. Natl. Acad. Sci. U.S.A. 118 (2021)], but a few of them are missing in bird genome assemblies. Here, we present a new chicken reference genome containing all autosomes, a Z and a W chromosome, with all gaps closed except for the W. We identified ten small microchromosomes (termed dot chromosomes) with distinct sequence and epigenetic features, among which six were newly assembled. Those dot chromosomes exhibit extremely high GC content and a high level of DNA methylation and are enriched for housekeeping genes. The pericentromeric heterochromatin of dot chromosomes is disproportionately large and continues to expand with the proliferation of satellite DNA and testis-expressed genes. Our analyses revealed that the 41-bp CNM repeat frequently forms higher-order repeats (HORs) at the centromeres of acrocentric chromosomes. The centromere core regions where the kinetochore attaches often encompass telomeric sequence (TTAGGG)n, and in a one of the dot chromosomes, the centromere core recruits an endogenous retrovirus (ERV). We further demonstrate that the W chromosome shares some common features with dot chromosomes, having large arrays of hypermethylated tandem repeats. Finally, using the complete chicken chromosome models, we reconstructed a fine picture of chordate karyotype evolution, revealing frequent chromosomal fusions before and after vertebrate whole-genome duplications. Our sequence and epigenetic characterization of chicken chromosomes shed insights into the understanding of vertebrate genome evolution and chromosome biology.

Synergistic Modulation of Mass Transfer and Parasitic Reactions of Zn Metal Anode via Bioinspired Artificial Protection Layer.

Rechargeable aqueous zinc-ion batteries are regarded as promising energy storage devices due to their attractive economic benefits and extraordinary electrochemical performance. However, the sluggish Zn2+ mass transfer behavior and water-induced parasitic reactions that occurred on the anode-electrode interface inevitably restrain their applications. Herein, inspired by the selective permeability and superior stability of plasma membrane, a thin UiO-66 metal-organic framework layer with smart aperture size is ex-situ decorated onto the Zn anode. Experimental characterizations in conjunction with theoretical calculations demonstrate that this bio-inspired layer promotes the de-solvation process of hydrated Zn2+ and reduces the effective contact between the anode and H2 O molecules, thereby boosting Zn2+ deposition kinetics and restraining interfacial parasitic reactions. Hence, the Zn||Zn cells could sustain a long lifespan of 1680 h and the Zn||Cu cells yielded a stable coulombic efficiency of over 99.3% throughout 600 cycles under the assistance of the bio-inspired layer. Moreover, pairing with δ-MnO2 cathode, the full cells also demonstrate prominent cycling stability and rate performance. From the bio-inspired design philosophy, this work provides a novel insight into the development of aqueous batteries.

TEMINET: A Co-Informative and Trustworthy Multi-Omics Integration Network for Diagnostic Prediction.

Advancing the domain of biomedical investigation, integrated multi-omics data have shown exceptional performance in elucidating complex human diseases. However, as the variety of omics information expands, precisely perceiving the informativeness of intra- and inter-omics becomes challenging due to the intricate interrelations, thus presenting significant challenges in the integration of multi-omics data. To address this, we introduce a novel multi-omics integration approach, referred to as TEMINET. This approach enhances diagnostic prediction by leveraging an intra-omics co-informative representation module and a trustworthy learning strategy used to address inter-omics fusion. Considering the multifactorial nature of complex diseases, TEMINET utilizes intra-omics features to construct disease-specific networks; then, it applies graph attention networks and a multi-level framework to capture more collective informativeness than pairwise relations. To perceive the contribution of co-informative representations within intra-omics, we designed a trustworthy learning strategy to identify the reliability of each omics in integration. To integrate inter-omics information, a combined-beliefs fusion approach is deployed to harmonize the trustworthy representations of different omics types effectively. Our experiments across four different diseases using mRNA, methylation, and miRNA data demonstrate that TEMINET achieves advanced performance and robustness in classification tasks.

Modulating Surface Electron Density of Heterointerface with Bio-Inspired Light-Trapping Nano-Structure to Boost Kinetics of Overall Water Splitting.

Herein, inspired by natural sunflower heads' properties increasing the temperature of dish-shaped flowers by tracking the sun, a novel hybrid heterostructure (MoS2 /Ni3 S2 @CA, CA means carbon nanowire arrays) with the sunflower-like structure to boost the kinetics of water splitting is proposed. Density functional theory (DFT) reveals that it can modulate the active electronic states of NiMo atoms around the Fermi-level through the charge transfer between the metallic atoms of Ni3 S2 and MoMo bonds of MoS2 to boost overall water splitting. Most importantly, the finite difference time domain (FDTD) could find that its unique bio-inspired micro-nano light-trapping structure has high solar photothermal conversion efficiency. With the assistance of the photothermal field, the kinetics of water-splitting is improved, affording low overpotentials of 96 and 229 mV at 10 mA cm-2 for HER and OER, respectively. Moreover, the Sun-MoS2 /Ni3 S2 @CA enables the overall alkaline water splitting at a low cell voltage of 1.48 and 1.64 V to achieve 10 and 100 mA cm-2 with outstanding catalytic durability. This study may open up a new route for rationally constructing bionic sunflower micro-nano light-trapping structure to maximize their photothermal conversion and electrochemical performances, and accelerate the development of nonprecious electrocatalysts for overall water splitting.

Electrolyte Regulation of Bio-Inspired Zincophilic Additive toward High-Performance Dendrite-Free Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries hold attractive potential for large-scale energy storage devices owing to their prominent electrochemical performance and high security. Nevertheless, the applications of aqueous electrolytes have generated various challenges, including uncontrolled dendrite growth and parasitic reactions, thereby deteriorating the Zn anode's stability. Herein, inspired by the superior affinity between Zn2+ and amino acid chains in the zinc finger protein, a cost-effective and green glycine additive is incorporated into aqueous electrolytes to stabilize the Zn anode. As confirmed by experimental characterizations and theoretical calculations, the glycine additives can not only reorganize the solvation sheaths of hydrated Zn2+ via partial substitution of coordinated H2 O but also preferentially adsorb onto the Zn anode, thereby significantly restraining dendrite growth and interfacial side reactions. Accordingly, the Zn anode could realize a long lifespan of over 2000 h and enhanced reversibility (98.8%) in the glycine-containing electrolyte. Furthermore, the assembled Zn||α-MnO2 full cells with glycine-modified electrolyte also delivers substantial capacity retention (82.3% after 1000 cycles at 2 A g-1 ), showing promising application prospects. This innovative bio-inspired design concept would inject new vitality into the development of aqueous electrolytes.

Genomic insight into the nocturnal adaptation of the black-crowned night heron (Nycticorax nycticorax).

BACKGROUND: The black-crowned night heron (Nycticorax nycticorax) is an ardeid bird successfully adapted to the nocturnal environment. Previous studies had indicated that the eyes of the night herons have evolved several specialized morphological traits favoring nocturnal vision. However, the molecular mechanisms of the nocturnal vision adaptation of night herons remained inattentions. In this study, the whole genome of N. nycticorax was sequenced and comparative analyses were performed on the vision-related and olfactory receptor (OR) genes to understand the molecular mechanisms of the visual and olfactory adaptation of night herons. RESULTS: The results indicated that a number of vision genes were under positive or relaxed selection in N. nycticorax, whereas a number of other vision genes were under relaxed or intensified selection in the boat-billed heron (Cochlearius cochlearius), which suggested that the two species adapt to nocturnality with different genetic mechanisms. The different selections acting on vision genes are probably associated with the enlargement of eye size and the enhancement of visual sensitivity in night herons. The analyses on olfactory receptor (OR) genes indicated that the total number of OR genes in the genomes of N. nycticorax and C. cochlearius were about half those in the little egret (Egretta garzetta), whereas the diversity of their OR genes was not remarkably different. Additionally, the number of expressed OR genes in the transcriptomes of N. nycticorax was also fewer than that in E. garzetta. These results suggest a reduced olfactory capability in night herons compared with E. garzetta. CONCLUSIONS: Our results provided evidence that several vision genes of the night herons were subjected to different natural selections, which can contribute to a better understanding of the genetic mechanisms of visual adaptions of the night heron. In addition, the finding of the reduced number of total and expressed OR genes in night herons may reflect a trade-off between olfaction and vision.

Construction of Bio-inspired Film with Engineered Hydrophobicity to Boost Interfacial Reaction Kinetics of Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries typically suffer from sluggish interfacial reaction kinetics and drastic cathode dissolution owing to the desolvation process of hydrated Zn2+ and continual adsorption/desorption behavior of water molecules, respectively. To address these obstacles, a bio-inspired approach, which exploits the moderate metabolic energy of cell systems and the amphiphilic nature of plasma membranes, is employed to construct a bio-inspired hydrophobic conductive poly(3,4-ethylenedioxythiophene) film decorating α-MnO2 cathode. Like plasma membranes, the bio-inspired film can "selectively" boost Zn2+ migration with a lower energy barrier and maintain the integrity of the entire cathode. Electrochemical reaction kinetics analysis and theoretical calculations reveal that the bio-inspired film can significantly improve the electrical conductivity of the electrode, endow the cathode-electrolyte interface with engineered hydrophobicity, and enhance the desolvation behavior of hydrated Zn2+ . This results in an enhanced ion diffusion rate and minimized cathode dissolution, thereby boosting the overall interfacial reaction kinetics and cathode stability. Owing to these intriguing merits, the composite cathode can demonstrate remarkable cycling stability and rate performance in comparison with the pristine MnO2 cathode. Based on the bio-inspired design philosophy, this work can provide a novel insight for future research on promoting the interfacial reaction kinetics and electrode stability for various battery systems.

Genome-wide variant-based study of genetic effects with the largest neuroanatomic coverage.

BACKGROUND: Brain image genetics provides enormous opportunities for examining the effects of genetic variations on the brain. Many studies have shown that the structure, function, and abnormality (e.g., those related to Alzheimer's disease) of the brain are heritable. However, which genetic variations contribute to these phenotypic changes is not completely clear. Advances in neuroimaging and genetics have led us to obtain detailed brain anatomy and genome-wide information. These data offer us new opportunities to identify genetic variations such as single nucleotide polymorphisms (SNPs) that affect brain structure. In this paper, we perform a genome-wide variant-based study, and aim to identify top SNPs or SNP sets which have genetic effects with the largest neuroanotomic coverage at both voxel and region-of-interest (ROI) levels. Based on the voxelwise genome-wide association study (GWAS) results, we used the exhaustive search to find the top SNPs or SNP sets that have the largest voxel-based or ROI-based neuroanatomic coverage. For SNP sets with >2 SNPs, we proposed an efficient genetic algorithm to identify top SNP sets that can cover all ROIs or a specific ROI. RESULTS: We identified an ensemble of top SNPs, SNP-pairs and SNP-sets, whose effects have the largest neuroanatomic coverage. Experimental results on real imaging genetics data show that the proposed genetic algorithm is superior to the exhaustive search in terms of computational time for identifying top SNP-sets. CONCLUSIONS: We proposed and applied an informatics strategy to identify top SNPs, SNP-pairs and SNP-sets that have genetic effects with the largest neuroanatomic coverage. The proposed genetic algorithm offers an efficient solution to accomplish the task, especially for identifying top SNP-sets.

Effect of APOE ε4 on multimodal brain connectomic traits: a persistent homology study.

BACKGROUND: Although genetic risk factors and network-level neuroimaging abnormalities have shown effects on cognitive performance and brain atrophy in Alzheimer's disease (AD), little is understood about how apolipoprotein E (APOE) ε4 allele, the best-known genetic risk for AD, affect brain connectivity before the onset of symptomatic AD. This study aims to investigate APOE ε4 effects on brain connectivity from the perspective of multimodal connectome. RESULTS: Here, we propose a novel multimodal brain network modeling framework and a network quantification method based on persistent homology for identifying APOE ε4-related network differences. Specifically, we employ sparse representation to integrate multimodal brain network information derived from both the resting state functional magnetic resonance imaging (rs-fMRI) data and the diffusion-weighted magnetic resonance imaging (dw-MRI) data. Moreover, persistent homology is proposed to avoid the ad hoc selection of a specific regularization parameter and to capture valuable brain connectivity patterns from the topological perspective. The experimental results demonstrate that our method outperforms the competing methods, and reasonably yields connectomic patterns specific to APOE ε4 carriers and non-carriers. CONCLUSIONS: We have proposed a multimodal framework that integrates structural and functional connectivity information for constructing a fused brain network with greater discriminative power. Using persistent homology to extract topological features from the fused brain network, our method can effectively identify APOE ε4-related brain connectomic biomarkers.

Biochemical characterization of caffeoyl coenzyme A 3-O-methyltransferase from wheat.

MAIN CONCLUSION: TaCCoAOMT1 is located in wheat chromosome 7A and highly expressed in stem and root. It is important for lignin biosynthesis, and associated with stem maturity but not lodging resistance. Caffeoyl coenzyme A 3-O-methyltransferases (CCoAOMTs) are one important class of enzymes to carry out the transfer of the methyl group from S-adenosylmethionine to the hydroxyl group, and play important roles in lignin and flavonoids biosynthesis. In the present study, sequences for CCoAOMT from the wheat genome were analyzed. One wheat CCoAOMT that belonged to bona fide subclade involved in lignin biosynthesis, namely TaCCoAOMT1, was obtained by the prokaryotic expression in E. coli. The three-dimensional structure prediction showed a highly similar structure of TaCCoAOMT1 with MsCCoAOMT. Recombinant TaCCoAOMT1 protein could only use caffeoyl CoA and 5-hydroxyferuloyl CoA as effective substrates and caffeoyl CoA as the best substrate. TaCCoAOMT1 had a narrow optimal pH and thermal stability. The TaCCoAOMT1 gene was highly expressed in wheat stem and root tissues, paralleled CCoAOMT enzyme activity. TaCCoAOMT1 mRNA abundance and enzyme activity increased linearly with stem maturity, but showed little difference between wheat lodging-resistant (H4546) and lodging-sensitive (C6001) cultivars in elongation, heading and milky stages. These data suggest that TaCCoAOMT1 is an important CCoAOMT for lignin biosynthesis that is critical for stem development, but not directly associated with lodging-resistant trait in wheat.

Dearomative Intramolecular Diels-Alder/Sulfur Extrusion Reaction of Thiophenes with Alkynes Using peri-Substituted Naphthalene as a Tether.

Dearomative intramolecular Diels-Alder/sulfur extrusion reaction of thiophenes with alkynes successfully afforded fluoranthenes in moderate to excellent yields. The proximity of both reactive sites fixed at the peri-position of naphthalene would play an important role in the progress of this reaction. Tri(o-tolyl)phosphine effectively suppressed the side reactions as a sulfur scavenger.

Genomic insights into the endangered white-eared night heron (Gorsachius magnificus).

OBJECTIVES: A genome sequence of a threatened species can provide valuable genetic information that is important for improving the conservation strategies. The white-eared night heron (Gorsachius magnificus) is an endangered and poorly known ardeid bird. In order to support future studies on conservation genetics and evolutionary adaptation of this species, we have reported a de novo assembled and annotated whole-genome sequence of the G. magnificus. DATA DESCRIPTION: The final draft genome assembly of the G. magnificus was 1.19 Gb in size, with a contig N50 of 187.69 kb and a scaffold N50 of 7,338.28 kb. According to BUSCO analysis, the genome assembly contained 97.49% of the 8,338 genes in the Aves (odb10) dataset. Approximately 10.52% of the genome assembly was composed of repetitive sequences. A total of 14,613 protein-coding genes were predicted in the genome assembly, with functional annotations available for 14,611 genes. The genome assembly exhibited a heterozygosity rate of 0.49 heterozygosity per kilobase pair. This draft genome of G. magnificus provides valuable genomic resources for future studies on conservation and evolution.

MOCAT: multi-omics integration with auxiliary classifiers enhanced autoencoder.

BACKGROUND: Integrating multi-omics data is emerging as a critical approach in enhancing our understanding of complex diseases. Innovative computational methods capable of managing high-dimensional and heterogeneous datasets are required to unlock the full potential of such rich and diverse data. METHODS: We propose a Multi-Omics integration framework with auxiliary Classifiers-enhanced AuToencoders (MOCAT) to utilize intra- and inter-omics information comprehensively. Additionally, attention mechanisms with confidence learning are incorporated for enhanced feature representation and trustworthy prediction. RESULTS: Extensive experiments were conducted on four benchmark datasets to evaluate the effectiveness of our proposed model, including BRCA, ROSMAP, LGG, and KIPAN. Our model significantly improved most evaluation measurements and consistently surpassed the state-of-the-art methods. Ablation studies showed that the auxiliary classifiers significantly boosted classification accuracy in the ROSMAP and LGG datasets. Moreover, the attention mechanisms and confidence evaluation block contributed to improvements in the predictive accuracy and generalizability of our model. CONCLUSIONS: The proposed framework exhibits superior performance in disease classification and biomarker discovery, establishing itself as a robust and versatile tool for analyzing multi-layer biological data. This study highlights the significance of elaborated designed deep learning methodologies in dissecting complex disease phenotypes and improving the accuracy of disease predictions.

Identifying potential genetic epistasis implicated in Alzheimer's disease via detection of SNP-SNP interaction on quantitative trait CSF Aß42.

Although genome-wide association studies have identified multiple Alzheimer's disease (AD)-associated loci by selecting the main effects of individual single-nucleotide polymorphisms (SNPs), the interpretation of genetic variance in AD is limited. Based on the linear regression method, we performed genome-wide SNP-SNP interaction on cerebrospinal fluid Aß42 to identify potential genetic epistasis implicated in AD, with age, gender, and diagnosis as covariates. A GPU-based method was used to address the computational challenges posed by the analysis of epistasis. We found 368 SNP pairs to be statistically significant, and highly significant SNP-SNP interactions were identified between the marginal main effects of SNP pairs, which explained a relatively high variance at the Aß42 level. Our results replicated 100 previously reported AD-related genes and 5 gene-gene interaction pairs of the protein-protein interaction network. Our bioinformatics analyses provided preliminary evidence that the 5-overlapping gene-gene interaction pairs play critical roles in inducing synaptic loss and dysfunction, thereby leading to memory decline and cognitive impairment in AD-affected brains.

Comparative genomics illuminates karyotype and sex chromosome evolution of sharks.

Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.

Genome-Wide Epistasis Study of Cerebrospinal Fluid Hyperphosphorylated Tau in ADNI Cohort.

Alzheimer's disease (AD) is the main cause of dementia worldwide, and the genetic mechanism of which is not yet fully understood. Much evidence has accumulated over the past decade to suggest that after the first large-scale genome-wide association studies (GWAS) were conducted, the problem of "missing heritability" in AD is still a great challenge. Epistasis has been considered as one of the main causes of "missing heritability" in AD, which has been largely ignored in human genetics. The focus of current genome-wide epistasis studies is usually on single nucleotide polymorphisms (SNPs) that have significant individual effects, and the amount of heritability explained by which was very low. Moreover, AD is characterized by progressive cognitive decline and neuronal damage, and some studies have suggested that hyperphosphorylated tau (P-tau) mediates neuronal death by inducing necroptosis and inflammation in AD. Therefore, this study focused on identifying epistasis between two-marker interactions at marginal main effects across the whole genome using cerebrospinal fluid (CSF) P-tau as quantitative trait (QT). We sought to detect interactions between SNPs in a multi-GPU based linear regression method by using age, gender, and clinical diagnostic status (cds) as covariates. We then used the STRING online tool to perform the PPI network and identify two-marker epistasis at the level of gene-gene interaction. A total of 758 SNP pairs were found to be statistically significant. Particularly, between the marginal main effect SNP pairs, highly significant SNP-SNP interactions were identified, which explained a relatively high variance at the P-tau level. In addition, 331 AD-related genes were identified, 10 gene-gene interaction pairs were replicated in the PPI network. The identified gene-gene interactions and genes showed associations with AD in terms of neuroinflammation and neurodegeneration, neuronal cells activation and brain development, thereby leading to cognitive decline in AD, which is indirectly associated with the P-tau pathological feature of AD and in turn supports the results of this study. Thus, the results of our study might be beneficial for explaining part of the "missing heritability" of AD.

A high-quality genome assembly highlights the evolutionary history of the great bustard (Otis tarda, Otidiformes).

Conservation genomics often relies on non-invasive methods to obtain DNA fragments which limit the power of multi-omic analyses for threatened species. Here, we report multi-omic analyses based on a well-preserved great bustard individual (Otis tarda, Otidiformes) that was found dead in the mountainous region in Gansu, China. We generate a near-complete genome assembly containing only 18 gaps scattering in 8 out of the 40 assembled chromosomes. We characterize the DNA methylation landscape which is correlated with GC content and gene expression. Our phylogenomic analysis suggests Otidiformes and Musophagiformes are sister groups that diverged from each other 46.3 million years ago. The genetic diversity of great bustard is found the lowest among the four available Otidiformes genomes, possibly due to population declines during past glacial periods. As one of the heaviest migratory birds, great bustard possesses several expanded gene families related to cardiac contraction, actin contraction, calcium ion signaling transduction, as well as positively selected genes enriched for metabolism. Finally, we identify an extremely young evolutionary stratum on the sex chromosome, a rare case among birds. Together, our study provides insights into the conservation genomics, adaption and chromosome evolution of the great bustard.

Electrolyte Modulation of Biological Chelation Additives toward a Dendrite-Free Zn Metal Anode.

Aqueous zinc-ion batteries are considered promising energy storage devices due to their superior electrochemical performance. Nevertheless, the uncontrolled dendrites and parasitic side reactions adversely affect the stability and durability of the Zn anode. To cope with these issues, inspired by the chelation behavior between metal ions and amino acids in the biological system, glutamic acid and aspartic acid are selected as electrolyte additives to stabilize the Zn anode. Experimental characterizations in conjunction with theoretical calculation results indicate that these additives can simultaneously modify the solvation structure of hydrated Zn2+ and preferentially adsorb onto the Zn anode, thereby restricting the occurrence of interfacial side reactions and enhancing the performance of the Zn anode. Benefiting from these synergistic effects, the as-assembled Zn-based batteries containing additive electrolytes achieved admirable electrochemical performance. From the viewpoint of electrolyte regulation, this work provides a bright direction toward the development of aqueous batteries.

Development and evaluation of neutralizing antibodies for cross-protection against West Nile virus and Japanese encephalitis virus.

Background: West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus. Methods: Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application. Results: In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans. Conclusion: This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

Arctiin attenuates iron overload­induced osteoporosis by regulating the PI3K/Akt pathway.

Iron overload is a prevalent pathological factor observed among elderly individuals and those with specific hematological disorders, and is frequently associated with an elevated incidence of osteoporosis. Although arctiin (ARC) has been shown to possess antioxidant properties and the ability to mitigate bone degeneration, its mechanism of action in the treatment of iron overload­induced osteoporosis (IOOP) remains incompletely understood. To explore the potential molecular mechanisms underlying the effects of ARC, the MC3T3­E1 cell osteoblast cell line was used. Cell Counting Kit was used to assess MC3T3­E1 cell viability. Alkaline phosphatase staining and alizarin red staining were assessed for osteogenic differentiation. Calcein AM assay was used to assess intracellular iron concentration. In addition, intracellular levels of reactive oxygen species (ROS), lipid peroxides, mitochondrial ROS, apoptosis rate and mitochondrial membrane potential changes in MC3T3­E1 cells were examined using flow cytometry and corresponding fluorescent dyes. The relationship between ARC and the PI3K/Akt pathway was then explored by western blotting and immunofluorescence. In addition, the effects of ARC on IOOP was verified using an iron overload mouse model. Immunohistochemistry was performed to evaluate expression of osteogenesis­related proteins. Micro-CT and H&E were used to analyze bone microstructural parameters and histomorphometric indices in the bone tissue. Notably, ARC treatment reversed the decreased viability and increased apoptosis in MC3T3­E1 cells originally induced by ferric ammonium citrate, whilst promoting the formation of mineralized bone nodules in MC3T3­E1 cells. Furthermore, iron overload induced a decrease in the mitochondrial membrane potential, augmented lipid peroxidation and increased the accumulation of ROS in MC3T3­E1 cells. ARC not only positively regulated the anti­apoptotic and osteogenic capabilities of these cells via modulation of the PI3K/Akt pathway, but also exhibited antioxidant properties by reducing oxidative stress. In vivo experiments confirmed that ARC improved bone microarchitecture and biochemical parameters in a mouse model of iron overload. In conclusion, ARC exhibits potential as a therapeutic agent for IOOP by modulating the PI3K/Akt pathway, and via its anti­apoptotic, antioxidant and osteogenic properties.