Aberrant METTL14 gene expression contributes to malignant transformation of benzene-exposed myeloid cells.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Transmission of Oyster Mushroom Spherical Virus to Progeny via Basidiospores and Horizontally to a New Host Pleurotus floridanus.

Mycoviruses are usually transmitted horizontally via hyphal anastomosis and vertically through sporulation in natural settings. Oyster mushroom spherical virus (OMSV) is a mycovirus that infects Pleurotus ostreatus, with horizontal transmission via hyphal anastomosis. However, whether OMSV can be vertically transmitted is unclear. This study aimed to investigate the transmission characteristics of OMSV to progeny via basidiospores and horizontally to a new host. A total of 37 single-basidiospore offspring were obtained from OMSV-infected P. ostreatus and Pleurotus pulmonarius for Western blot detection of OMSV. The OMSV-carrying rate among monokaryotic isolates was 19% in P. ostreatus and 44% in P. pulmonarius. Then, OMSV-free and OMSV-infected monokaryotic isolates were selected for hybridization with harvested dikaryotic progeny strains. Western blot analyses of the offspring revealed that the OMSV transmission efficiency was 50% in P. ostreatus and 75% in P. pulmonarius, indicating vertical transmission via sexual basidiospores. Furthermore, we observed the horizontal transfer of OMSV from P. pulmonarius to Pleurotus floridanus. OMSV infection in P. floridanus resulted in significant inhibition of mycelial growth and yield loss. This study was novel in reporting the vertical transmission of OMSV through basidiospores, and its infection and pathogenicity in a new host P. floridanus.

Two-dimensional antiferromagnetic topological insulators in KCuSe/NaMnBi van der Waals heterobilayers.

The interplay between band topology and magnetism plays a central role in achieving exotic physical phenomena and innovative spintronics applications. While prior works have mainly focused on ferromagnetic matter, little is known about the manipulation of band topology in antiferromagnets. Here, we report the emergence of a two-dimensional (2D) antiferromagnetic topological insulator (AFM TIs) by proximity coupling a 2D TI and a normal AFM insulator, and remarkably realize it in a concrete example of the KCuSe/NaMnBi heterobilayer. The first-principles calculations show that a band gap as large as 63.8 meV can be opened up by spin-orbit coupling, revealing the possible application even at room temperature. The size of the band gap depends on the separation between KCuSe and NaMnBi QLs, which can be switched experimentally by applying external strain. Moreover, the heterobilayer presents an integer topological invariant with a value of Z2 = 1 and a pair of gapless edge states. The findings not only broaden the range of 2D AFM topological quantum materials, but could also inspire more research in van der Waals heterobilayers for topological spintronics.

Boys, Girls, and Grandparents: The Impact of the Sex of Preschool-Aged Children on Family Living Arrangements and Maternal Labor Supply.

In this study, we consider household decision-making on living arrangements and maternal labor supply in extended families with young children. In such a context, decision-making is driven by the concerns that the companionship of children is a household public good and that family members share childcare and related domestic duties. The incentive to share children's companionship is affected by son preference, whereas the economic motive of labor division hinges on the potential wage rate of the mother. Both channels play important roles in households with mothers whose wage rates are high, while sharing the companionship of (grand) sons is the main driving force in households with mothers whose wage rates are low. Using China Health and Nutrition Survey (CHNS) data, we find that among less-educated mothers, the incidence of a family coresiding with the paternal grandmother is at least 8.6 percentage points higher if the firstborn is a boy. At the same time, maternal labor supply increases by 2.9 days per month. By contrast, for educated mothers, the propensity for coresidence is higher, the working hours are longer, and the impact of the child's sex is not significant. Our study not only provides a better understanding of the demographic and economic factors determining coresidence and intrahousehold time allocations but also lends empirical support to policies aiming to increase female labor supply and improve the well-being of girls.

Overlooked Role of Electrostatic Interactions in HER Kinetics on MXenes: Beyond the Conventional Descriptor ΔG ∼ 0 to Identify the Real Active Site.

Understanding the atomic-level mechanism of the hydrogen evolution reaction (HER) on MXene materials is crucial for developing affordable HER catalysts, while their complex surface terminations present a substantial challenge. Herein, employing constant-potential grand canonical density functional theory calculations, we elucidate the reaction kinetics of the HER on MXenes with various surface terminations by taking experimentally reported Mo2C as a prototype. We observe a contradictory scenario on Mo2C MXene when using conventional thermodynamic descriptor ΔGH* (hydrogen binding energy). Both competing surface phases that emerge close to the equilibrium potential meet the ΔGH* ∼ 0 criterion, while they exhibit distinctly different reaction kinetics. Contrary to previous studies that identified surface *O species as active sites, our research reveals that these *O sites are kinetically inert for producing H2 but are easily reduced to H2O. Consequently, the surface Mo atoms, exposed from the rapid reduction of the surface *O species, serve as the actual active sites catalyzing the HER via the Volmer-Heyrovsky mechanism, as confirmed by experimental studies. Our findings highlight the overlooked role of electrostatic repulsion in HER kinetics, a factor not captured by thermodynamic descriptor ΔGH*. This work provides new insights into the HER mechanism and emphasizes the importance of kinetic investigations for a comprehensive understanding of the HER.

Role of FMRP in AKT/mTOR pathway-mediated hippocampal autophagy in fragile X syndrome.

Fragile X syndrome (FXS) is caused by epigenetic silencing of the Fmr1 gene, leading to the deletion of the coding protein FMRP. FXS induces abnormal hippocampal autophagy and mTOR overactivation. However, it remains unclear whether FMRP regulates hippocampal autophagy through the AKT/mTOR pathway, which influences the neural behavior of FXS. Our study revealed that FMRP deficiency increased the protein levels of p-ULK-1 and p62 and decreased LC3II/LC3I level in Fmr1 knockout (KO) mice. The mouse hippocampal neuronal cell line HT22 with knockdown of Fmr1 by lentivirus showed that the protein levels of p-ULK-1 and p62 were increased, whereas LC3II/LC3I was unchanged. Further observations revealed that FMRP deficiency obstructed autophagic flow in HT22 cells. Therefore, FMRP deficiency inhibited autophagy in the mouse hippocampus and HT22 cells. Moreover, FMRP deficiency increased reactive oxygen species (ROS) level, decreased the co-localization between the mitochondrial outer membrane proteins TOM20 and LC3 in HT22 cells, and caused a decrease in the mitochondrial autophagy protein PINK1 in HT22 cells and Fmr1 KO mice, indicating that FMRP deficiency caused mitochondrial autophagy disorder in HT22 cells and Fmr1 KO mice. To explore the mechanism by which FMRP deficiency inhibits autophagy, we examined the AKT/mTOR signaling pathway in the hippocampus of Fmr1 KO mice, found that FMRP deficiency caused overactivation of the AKT/mTOR pathway. Rapamycin-mediated mTOR inhibition activated and enhanced mitochondrial autophagy. Finally, we examined whether rapamycin affected the neurobehavior of Fmr1 KO mice. The Fmr1 KO mice exhibited stereotypical behavior, impaired social ability, and learning and memory impairment, while rapamycin treatment improved behavioral disorders in Fmr1 KO mice. Thus, our study revealed the molecular mechanism by which FMRP regulates autophagy function, clarifying the role of hippocampal neuron mitochondrial autophagy in the pathogenesis of FXS, and providing novel insights into potential therapeutic targets of FXS.

Effects of Fmr1 Gene Mutations on Sex Differences in Autism-Like Behavior and Dendritic Spine Development in Mice and Transcriptomic Studies.

Fragile X syndrome (FXS) is the most common single gene disorder contributing to autism spectrum disorder (ASD). Although significant sex differences are observed in FXS, few studies have focused on the phenotypic characteristics as well as the differences in brain pathological changes and gene expression in FXS by sex. Therefore, we analyzed sex differences in autism-like behavior and dendritic spine development in two-month-old male and female Fmr1 KO and C57 mice and evaluated the mechanisms at transcriptome level. Results suggest that Fmr1 KO mice display sex differences in autism-like behavior and dendritic spine density. Compared to females, male had more severe effects on anxiety, repetitive stereotype-like behaviors, and socializing, with higher dendritic spine density. Furthermore, two male-biased and five female-biased expressed genes were screened based on KEGG pathway enrichment and protein-protein interaction (PPI) analyses. In conclusion, our findings show mutations in the Fmr1 gene lead to aberrant expression of related genes and affect the sex-differentiated behavioral phenotypes of Fmr1 KO mice by affecting brain development and functional architecture, and suggest future studies should focus on including female subjects to comprehensively reflect the differentiation of FXS in both sexes and develop more precise and effective therapeutic strategies.

Preparation, structural analysis and physicochemical properties of the Cordyceps cicadae exopolysaccharide iron complex.

In this study, EPS-Fe(III) complexes were synthesized, and their structural characteristics, thermal stability, antioxidant activity and digestive properties were evaluated. The content of iron in the EPS-Fe(III) complex was 6.34 ± 1.43 %. The absorbance bands of EPS and EPS-Fe(III) complexes were easily changed, indicating that iron ions can interact with the hydroxyl or carboxyl groups of EPS. Energy spectrometric analysis showed that a strong iron signal was observed in the EPS-Fe(III) complex. The IC50 values of the EPS-Fe(III) complex for DPPH, hydroxyl radical and ABTS were 1.52 mg/mL, 2.63 mg/mL and 1.20 mg/mL, respectively. Under oxidative stress, EPS-Fe(III) can prolong the lifespan of nematodes through the DAF-16 and SKN-1 pathways. Under the condition of gastric juice and intestinal juice, the iron content released from artificial intestinal juice reached 66 %. In addition, the negative effect of trypsin or polyphenols on the solubility of iron in EPS-Fe(III) digestive solution was lower than that in ferric chloride digestive solution. In conclusion, the EPS-Fe(III) complex can be used as a new type of iron supplement, which has good antioxidant activity, high stability and good water solubility.

CaMKII is a modulator in neurodegenerative diseases and mediates the effect of androgen on synaptic protein PSD95.

Androgens rapidly regulate synaptic plasticity in hippocampal neurones, but the underlying mechanisms remain unclear. In this study, we carried out a comprehensive bioinformatics analysis of functional similarities between androgen receptor (AR) and the synaptic protein postsynaptic density 95 (PSD95) to evaluate the effect. Using different measurements and thresholds, we obtained consistent results illustrating that the two proteins were significantly involved in similar pathways. We further identified CaMKII plays a critical role in mediating the rapid effect of androgen and promoting the expression of PSD95. We used mouse hippocampal neurone HT22 cells as a cell model to investigate the effect of testosterone (T) on intracellular Ca2+ levels and the mechanism. Calcium imaging experiments showed that intracellular Ca2+ increased to a peak due to calcium influx in the extracellular fluid through L-type and N-type voltage-gated calcium channels when HT22 cells were treated with 100 nM T for 20 min. Subsequently, we investigated whether the Ca2+/CaMKII signaling pathway mediates the rapid effect of T, promoting the expression of the synaptic protein PSD95. Immunofluorescence cytochemical staining and western blotting results showed that T promoted CaMKII phosphorylation by rapidly increasing extracellular Ca2+ influx, thus increasing PSD95 expression. This study demonstrated that CaMKII acts as a mediator assisting androgen which regulates the synaptic protein PSD95Also, it provides evidence for the neuroprotective mechanisms of androgens in synaptic plasticity and reveals the gated and pharmacological mechanisms of the voltage-gated Ca2+ channel family for androgen replacement therapy.

A magnetic topological insulator in two-dimensional EuCd2Bi2: giant gap with robust topology against magnetic transitions.

Magnetic topological states open up exciting opportunities for exploring fundamental topological quantum physics and innovative design of topological spintronics devices. However, the nontrivial topologies, for most known magnetic topological states, are usually associated with and may be heavily deformed by fragile magnetism. Here, using a tight-binding model and first-principles calculations, we demonstrate that a highly robust magnetic topological insulator phase, which remains intact under both ferromagnetic and antiferromagnetic configurations, can emerge in two-dimensional EuCd2Bi2 quintuple layers. Because of spin-orbital coupling, an inverted gap with intrinsic band inversions occuring simultaneously for up and down spin channels is obtained, accompanied by a nonzero spin Chern number and a pair of gapless edge states, and remarkably the magnitude of the nontrivial band gap for EuCd2Bi2 reaches as much as 750 meV. Moreover, the robustness of the magnetic TI phase is further confirmed by rotating the magnetization directions, indicating that EuCd2Bi2 represents a promising material for understanding and utilizing the topological insulating states in two-dimensional spin-orbit magnets.