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Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high social burden and limited treatments. Hypoxic condition of the brain is considered an important pathological mechanism of ASD. HIF1A is a key participant in brain hypoxia, but its contribution to the pathophysiological landscape of ASD remains unclear. Methods: ASD-related datasets were obtained from GEO database, and HIF1A-related genes from GeneCards. Co-expression module analysis identified module genes, which were intersected with HIF1A-related genes to identify common genes. Machine learning identified hub genes from intersection genes and PPI networks were constructed to explore relationships among hub and HIF1A. Single-cell RNA sequencing analyzed hub gene distribution across cell clusters. ASD mouse model was created by inducing maternal immune activation (MIA) with poly(I:C) injections, verified through behavioral tests. Validation of HIF1A pathway and hub genes was confirmed through Western Blot, qPCR, and immunofluorescence in ASD mice and microglia BV-2 cells. Results: Using CEMiTool and GeneCards, 45 genes associated with ASD and HIF1A pathway were identified. Machine learning identified CDKN1A, ETS2, LYN, and SLC16A3 as potential ASD diagnostic markers. Single-cell sequencing pinpointed activated microglia as key immune cells. Behavioral tests showed MIA offspring mice exhibited typical ASD-like behaviors. Immunofluorescence confirmed the activation of microglia and HIF1A pathway in frontal cortex of ASD mice. Additionally, IL-6 contributed to ASD by activating JUN/HIF1A pathway, affecting CDKN1A, LYN, and SLC16A3 expression in microglia. Conclusions: HIF1A-related genes CDKN1A, ETS2, LYN, and SLC16A3 are strong diagnostic markers for ASD and the activation of IL-6/JUN/HIF1A pathway in microglia contributes to the pathogenesis of ASD.

The utilization of high-strength and tough petroleum casing steel has become the focus of various research groups worldwide, particularly in the past decade. However, defining its forming behavior presents several challenges, stemming from the complexity of enhancing strength and toughness on the steel's characteristics. To address this issue, this study employed a low-carbon microalloyed steel and introduced V and Nb elements sequentially, resulting in three groups of steels under investigation. Subsequently, mechanical properties and microstructure characteristics were examined. Interestingly, the addition of V and Nb elements resulted in both tensile and yield strengths above 1200 MPa and 1173 MPa, respectively, satisfying the criteria for the V170 oil casing. Furthermore, after adding V, V(C,N) precipitates uniformly in the steel. Still, the Nb element is not completely precipitated as there is a significant amount of Nb in solid solution. The effective grain size of the investigated steel increases from 0.92 μm to 0.98 μm after adding V and Nb elements, accompanied by a reduction in the fraction of HAGB from 47.4 % to 42.4 %. Therefore, V element plays a vital and positive role in improving the mechanical properties of the experimental steel, while Nb element has only a minor effect.

Medium Mn steels are the primary candidates in the fields of automobile, construction machinery et al. due to the advantages of high strength-ductility combination, and low costs. By now, the balance of good performance and high preparation efficiency is still a critical issue to be unsolved, which restricts their further applications. This work designs a novel Al-contained medium Mn low-density steel and explores the effect of a short intercritical-annealing process. The microstructure evolution of multi-scales, especially the austenite characteristics and Mn partitioning behaviors is analyzed, and the relationship between austenite and tensile properties is discussed. The results indicate Al can broaden the annealing processing window and improve the annealing temperature. When annealed at 780 °C, the austenite reverted transformation happens quickly and after annealing for 3 min, the austenite volume fraction maintains stable in the range of 52.4–56.7 vol%, but the morphology and Mn concentration are very different. A large amount of blocky austenite with a coarse size of more than 1 μm and a low Mn concentration of 8–9 wt% forms at the longer annealing time of 20 min, while the austenite almost presents a lath-like shape with a high Mn concentration exceeding 10 wt% at annealing time of 4 min. The tensile properties are closely related to the volume fraction and mechanical stability of austenite, and the sample annealed for 4 min exhibited the best performance with tensile strength of 1192 MPa and total elongation of 33 %, due to its slow TRIP effect.

Moyamoya disease (MMD) is an idiopathic and chronic steno-occlusive cerebrovascular disease. Genetic studies identified RNF213 as a principal susceptibility gene of MMD. In this study, peripheral blood mononuclear cells (PBMCs) were obtained from an MMD patient with RNF213 p. R4810K mutations, and the PBMCs were then reprogrammed to induced pluripotent stem cells (iPSCs) by the transfection of non-integrated episomal vectors. The iPSC line shows pluripotency markers and has the potential for in vitro differentiation into three germ layers, and will be valuable for elucidating the underlying cellular mechanisms of MMD, selecting therapeutic targets, and developing drugs.

We describe a unique case in which a patient was initially diagnosed with meningoencephalitis and then detected anti-myelin oligodendrocyte glycoprotein (MOG) antibody and demyelinating brain lesions. A 43-year-old Chinese man who complained of headache and fever, was diagnosed with meningoencephalitis after cerebrospinal fluid (CSF) analysis. One month after onset, brain imaging revealed multiple lesions in bilateral white matter, and the anti-MOG antibody was detected in his serum and CSF (titer is 1:32 and 1:10, respectively). After a 3-month glucocorticoid therapy, repeated brain imaging and serological analysis for anti-MOG antibodies showed significant improvement. Multiple intracranial demyelinating lesions secondary to meningoencephalitis may be accompanied by anti-MOG antibody positivity, which can be reversed by hormone therapy.

The placenta, as a “transit station” between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6–72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Summary: In animal cells, the dysregulation of centrosome duplication and cohesion maintenance leads to abnormal spindle assembly and chromosomal instability, contributing to developmental disorders and tumorigenesis. However, the molecular mechanisms involved in maintaining accurate centrosome number control and tethering are not fully understood. Here, we identified coiled-coil domain-containing 102A (CCDC102A) as a centrosomal protein exhibiting a barrel-like structure in the proximal regions of parent centrioles, where it prevents centrosome overduplication by restricting interactions between Cep192 and Cep152 on centrosomes, thereby ensuring bipolar spindle formation. Additionally, CCDC102A regulates the centrosome linker by recruiting and binding C-Nap1; it is removed from the centrosome after Nek2A-mediated phosphorylation at the onset of mitosis. Overall, our results indicate that CCDC102A participates in controlling centrosome number and maintaining centrosome cohesion, suggesting that a well-tuned system regulates centrosome structure and function throughout the cell cycle.

Visualization techniques are effective tools in diagnosis and therapy for biomedical applications. Due to the unavoidable shortcomings of single optical or magnetic resonance imaging, the introduction of dual functional imaging system is of great significance. Herein a new Gd1-xNdx(CO3)OH@SiO2 core–shell nanostructure were developed to fulfill the corresponding demands. Uniform nanospheres were acquired with surface modification and coated with thickness tunable silica shells. The samples presented strong luminescence penetrating biological tissue, due to the wide spectral region covering NIR I & II window of Nd3+ under 808 nm laser excitation. On the other hand, distinct contrast enhancement could be viewed for in vitro and in vivo MRI trials, which generates from high paramagnetic relaxation of Gd3+ and well dispersibility caused by silica shells. Along with the non-toxicity proved by the low concentration of leaching Gd3+ and nice biocompatibility of silica coated nanospheres, it is a superior candidate for NIR and MRI dual functional imaging platform in biological applications.

A nanoscale stretching-induced one-dimensional (1D) nanofiller orientation in a three-dimensional (3D) film (the films form cell walls of foamed materials) is beneficial for improving the dielectric and electromagnetic interference (EMI) shielding properties of composite systems. However, nanoscale stretching may cause nanofiller separation, negatively impacting their properties. In this study, a two-dimensional (2D) nanofiller was introduced into a carbon nanofibre/poly(vinylidene fluoride) (CNF/PVDF) nanocomposite system to improve the nanoscale confined-space stretching effect. As a result, the degree of in-film orientation of the CNFs was significantly improved. Based on this effect, boron nitride was used as a 2D dielectric nanofiller to improve the degree of in-plane orientation of CNFs and to prepare 3D nanocomposite films with improved dielectric properties (improved by 54.3 %). Furthermore, 2D conductive nanofiller graphene nanoplatelets (GNPs) were employed to improve the degree of in-film orientation of CNFs for the preparation of CNF/GNP/PVDF nanocomposite foams with improved electrical conductivity and EMI shielding performance (increased by 89.4 %, from 18.8 to 35.6 dB·g−1·cm3 at 10 GHz). A Monte Carlo simulation was used to verify that the 2D nanofiller improved the 1D nanofiller orientation in the 3D nanocomposite film. This study provides a guide for the design of high-performance foamed nanocomposite materials.