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Abstract Demyelination occurs widely in the central nervous system (CNS) neurodegenerative diseases, especially the multiple sclerosis (MS), which with a complex and inflammatory lesion microenvironment inhibiting remyelination. Sirtuin6 (SIRT6), a histone/protein deacetylase is of interest for its promising effect in transcriptional regulation, cell cycling, inflammation, metabolism and longevity. Here we show that SIRT6 participates in the remyelination process in mice subjected to LPC-induced demyelination. Using pharmacological SIRT6 inhibitor or activator, we found that SIRT6 modulated LPC-induced damage in motor or cognitive function. Inhibition of SIRT6 impaired myelin regeneration, exacerbated neurological deficits, and decreased oligodendrocyte precursor cells (OPCs) proliferation and differentiation, whereas activation of SIRT6 reversed behavioral performance in mice, demonstrating a beneficial effect of SIRT6. Importantly, based on RNA sequencing analysis of the corpus callosum tissues, it was further revealed that SIRT6 took charge in regulation of glial activation during remyelination, and significant alterations in CHI3L1 were obtained, a glycoprotein specifically secreted by astrocytes. Impaired proliferation and differentiation of OPCs could be induced in vitro using supernatants from reactive astrocyte, especially when SIRT6 was inhibited. Mechanistically, SIRT6 regulates the secretion of CHI3L1 from reactive astrocytes by histone-H3-lysine-9 acetylation (H3K9Ac). Adeno-associated virus-overexpression of SIRT6 (AAV-SIRT6-OE) in astrocytes improved remyelination and functional recovery after LPC-induced demyelination, whereas together with AAV-CHI3L1-OE inhibits this therapeutic effect. Collectively, our data elucidate the role of SIRT6 in remyelination and further reveal astrocytic SIRT6/CHI3L1 as the key regulator for improving the remyelination environment, which may be a potential target for MS therapy.

This study reports the preparation of two single-phase high-entropy rare-earth niobates (RE1/5Ho1/5Er1/5Y1/5Yb1/5)3NbO7, (RE = Ce, Lu), and two composite-phase high-entropy rare-earth niobates (RE1/5Ho1/5Er1/5Y1/5Yb1/5)3NbO7:(RE1/5Ho1/5Er1/5Y1/5Yb1/5)NbO4 = 1:2, (RE = Ce, Lu) via solid-phase synthesis. The interactions of these samples with molten calcium-magnesium-aluminum-silicates (CMAS) were studied at 1300 °C to explore their performance and mechanism in CMAS corrosion. The results indicate that the corrosion process involves the phase transformation of RE3NbO7 and the formation of apatite products. The Ce-composition sample exhibits superior performance in terms of reaction layer thickness, remaining CMAS thickness, and RE3+ content in the remaining CMAS. These findings underscore the potential application of high-entropy rare-earth niobates in thermal barrier coatings (TBCs) and contribute to understanding niobate system resistance to CMAS corrosion.

BackgroundWhite matter injury is a predominant form of brain injury in preterm infants. However, effective drugs for its treatment are currently lacking. Previous studies have shown the neuroprotective effects of Isoliquiritigenin (ISL), but its impact on white matter injury in preterm infants remains poorly understood.AimsThis study aimed to investigate the protective effects of ISL against white matter injury caused by infection in preterm infants using a mouse model of lipopolysaccharide-induced white matter injury, integrating network pharmacology as well as in vivo and in vitro experiments.MethodsThis study explores the potential mechanisms of ISL on white matter injury by integrating network pharmacology. Core pathways and biological processes affected by ISL were verified through experiments, and motor coordination, anxiety-like, and depression-like behaviors of mice were evaluated using behavioral experiments. White matter injury was observed using hematoxylin-eosin staining, Luxol Fast Blue staining, and electron microscopy. The development of oligodendrocytes and the activation of microglia in mice were assessed by immunofluorescence. The expression of related proteins was detected by Western blot.ResultsWe constructed a drug-target network, including 336 targets associated with ISL treatment of white matter injury. The biological process of ISL treatment of white matter injury mainly involves microglial inflammation regulation and myelination. Our findings revealed that ISL reduced early nerve reflex barriers and white matter manifestations in mice, leading to decreased activation of microglia and release of proinflammatory cytokines. Additionally, ISL demonstrated the ability to mitigate impairment in oligodendrocyte development and myelination, ultimately improving behavior disorders in adult mice. Mechanistically, we observed that ISL downregulated HDAC3 expression, promoted histone acetylation, enhanced the expression of H3K27ac, and regulated oligodendrocyte pro-differentiation factors.ConclusionThese findings suggest that ISL can have beneficial effects on white matter injury in preterm infants by alleviating inflammation and promoting oligodendrocyte differentiation.

Superplastic forming is considered a highly efficient technique for shaping intricate components from titanium matrix composites (TMCs). In this work, high-temperature TMCs with 5 vol% (TiBw + TiCp) reinforcements underwent superplastic tensile tests at various temperatures and strain rates. The results demonstrated that at all deformation temperatures (900 °C–1050 °C) and strain rates (5 × 10−3 s−1 to 10−4 s−1), the elongation of composite sheets surpassed 100%. The strain rate of 10−3 s−1 and a temperature of 1000 °C were found to yield the maximum elongation of 328.1%. At 900 °C, the matrix grains maintain a lamellar morphology during the main stage of deformation, and dynamic recovery (DRV) is the primary mechanism of matrix softening. At 1000 °C, wide-range dynamic recrystallization (DRX) takes place, and grain boundary slip coordinated by grain rotation is the main mechanism of deformation. At 1050 °C, the matrix grains undergo DRX and grow rapidly by migration, and the number of grain boundaries decreases dramatically, resulting in poor superplastic qualities. In the early stages of superplastic deformation, micropores sprout at the triple grain boundaries and at the interfaces between the reinforcements and the matrix. As the deformation proceeds, the micropores extend along the tensile direction and connect with each other to form cavity stringers (CS). The distance between the CS rapidly narrows as the stretching process continues, and eventually the CS links horizontally to form cavity coalescence (CC). Micropore dilatation around the reinforcements causes debonding and cavitation, leading to material failure.

Abstract It is difficult to obtain a single-phase environmental barrier coating material that simultaneously offers the advantages of low thermal conductivity, a suitable coefficient of thermal expansion, and excellent corrosion resistance. Herein, to synthesize the advantages of single-phase materials, we have developed an effective approach for the design of high-entropy multiphase ceramics of rare earth oxides and silicates. Such a specific design approach is capable of making high-entropy RE2SiO5/RE2O3 and RE2SiO5/RE2Si2O7 (RE = Lu, Yb, Tm, Er, Ho, and Y) multiphase ceramics as two types of potential environmental barrier coating materials for Al2O3f/Al2O3 and SiCf/SiC ceramic matrix composites.

Esophageal squamous cell carcinoma (ESCC), a highly aggressive subtype of esophageal cancer, is characterized by late-stage diagnosis and limited treatment options. Recent advancements in transcriptome sequencing technologies have illuminated the molecular intricacies of ESCC tumors, revealing metabolic reprogramming as a prominent feature. Specifically, the Warburg effect, marked by enhanced glycolysis, has emerged as a hallmark of cancer, offering potential therapeutic targets. In this study, we comprehensively analyzed bulk RNA-seq data from ESCC patients, uncovering elevated SRA1 expression in ESCC development and a poorer prognosis. Silencing of SRA1 led to a modulation of glycolysis-related products and a shift in PKM2 expression. Our findings shed light on the intricate molecular landscape of ESCC, highlighting SRA1 as a potential therapeutic target to disrupt glycolysis-dependent energy production. This metabolic reprogramming may hold the key to innovative treatment strategies for ESCC, ultimately improving patient outcomes.

Abstract For decreasing the global cost of corrosion, it is essential to understand the intricate mechanisms of corrosion and enhance the corrosion resistance of materials. However, the ambiguity surrounding the dominant mechanism of calcium‐magnesium aluminosilicate (CMAS) molten salt corrosion in extreme environments hinders the mix‐and‐matching of the key rare earth elements for increasing the resistance of monosilicates against corrosion of CMAS. Herein, an approach based on correlated electron microscopy techniques combined with density functional theory calculations is presented to elucidate the complex interplay of competing mechanisms that control the corrosion of CMAS of monosilicates. These findings reveal a competition between thermodynamics and kinetics that relies on the temperatures and corrosion processes. Innovative medium‐entropy monosilicates with exceptional corrosion resistance even at 1500 °C are developed. This is achieved by precisely modulating the radii of rare earth ions in monosilicates to strike a delicate balance between the competition in thermodynamics and kinetics. After 50 and 100 h of corrosion, the thinnest reactive layers are measured to be only 28.8 and 35.4 µm, respectively.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

Abstract Background Mitochondrial genome abnormalities can lead to mitochondrial dysfunction, which in turn affects cellular biology and is closely associated with the development of various diseases. The demand for mitochondrial DNA (mtDNA) sequencing has been increasing, and Illumina and MGI are two commonly used sequencing platforms for capture-based mtDNA sequencing. However, there is currently no systematic comparison of mtDNA sequencing performance between these two platforms. To address this gap, we compared the performance of capture-based mtDNA sequencing between Illumina's NovaSeq 6000 and MGI's DNBSEQ-T7 using tissue, peripheral blood mononuclear cell (PBMC), formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and urine samples. Results Our analysis indicated a high degree of consistency between the two platforms in terms of sequencing quality, GC content, and coverage. In terms of data output, DNBSEQ-T7 showed higher rates of clean data and duplication compared to NovaSeq 6000. Conversely, the amount of mtDNA data obtained by per gigabyte sequencing data was significantly lower in DNBSEQ-T7 compared to NovaSeq 6000. In terms of detection mtDNA copy number, both platforms exhibited good consistency in all sample types. When it comes to detection of mtDNA mutations in tissue, FFPE, and PBMC samples, the two platforms also showed good consistency. However, when detecting mtDNA mutations in plasma and urine samples, significant differenceof themutation number detected was observed between the two platforms. For mtDNA sequencing of plasma and urine samples, a wider range of DNA fragment size distribution was found in NovaSeq 6000 when compared to DNBSEQ-T7. Additionally, two platforms exhibited different characteristics of mtDNA fragment end preference. Conclusions In summary, the two platforms generally showed good consistency in capture-based mtDNA sequencing. However, it is necessary to consider the data preferences generated by two sequencing platforms when plasma and urine samples were analyzed.

Stereo Lithography Apparatus (SLA) has demonstrated improvements on surface-roughness and dimensional-accuracy of the precision casting prototypes in recent years, which however is still far from being satisfactory in industrial. One primary problem is the easy crack of the ceramic shell at sintering process originated from the high thermal expansion coefficient of the photosensitive resin. Herein, this paper aims to find a solution for the cracking problem of the SLA-prototyped ceramic shells. This paper introduces recent studies mainly focusing on the aspect of photosensitive resin modification, the hollow structure improvement inside the photosensitive resin prototype, the wax sheet pasting method on the weak part of ceramic shells, and the sintering process design of the photosensitive resin in ceramic shells. The performance of ceramic shells through these studies are evaluated, and a fundamental solution to the cracking problem of ceramic shells is thereafter prospected.

The study examines the corrosion behavior of the (NdSmEuGd)(1-x)/2Dy2xZr2O7 series in 1300 °C molten salt CMAS, demonstrating that the dense layer formed by ZrO2 and apatite could effectively inhibit the penetration of CMAS. Smaller rare-earth ion radii tend to form larger-sized ZrO2, while larger rare-earth ion radii favor apatite formation. Therefore, by carefully balancing the rare earth ion radii in the composition design of high-entropy samples, the levels of ZrO2 and apatite formation can be adjusted to prevent CMAS infiltration. This approach helps identify high-entropy zirconate samples with superior corrosion resistance to CMAS.

Accurate traffic flow prediction in road networks is essential for intelligent transportation systems (ITS). Since traffic data are collected from the road network with spatial topological and time series sequences, the traffic flow prediction is regarded as a spatial–temporal prediction task. With the powerful ability to model the non-Euclidean data, the graph convolutional network (GCN)-based models have become the mainstream framework for traffic forecasting. However, existing GCN-based models either use the manually predefined graph structure to capture the spatial features, ignoring the heterogeneity of road networks, or simply perform 1-D convolution with fixed kernel to capture the temporal dependencies of traffic data, resulting in insufficient long-term temporal feature extraction. To solve those issues, a spatial–temporal correlation constrained dynamic graph convolutional network (STC-DGCN) is proposed for traffic flow forecasting. In STC-DGCN, a spatial–temporal embedding encoder module (STEM) is first constructed to encode the dynamic spatial relationships for road networks at different time steps. Then, a temporal feature encoder module with heterogeneous time series correlation modeling (TFE-HCM) and a spatial feature encoder module with dynamic multi-graph modeling (SFE-DCM) are designed to generate dynamic graph structures for effectively capturing the dynamic spatial and temporal correlations. Finally, a spatial–temporal feature fusion module based on a gating fusion mechanism (STM-GM) is proposed to effectively learn and leverage the inherent spatial–temporal relationships for traffic flow forecasting. Experimental results from three real-world traffic flow datasets demonstrate the superior performance of the proposed STC-DGCN compared with state-of-the-art traffic flow forecasting models.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

As the demand for aero-engines with a high thrust-to-weight ratio has increased, the comprehensive performance requirements for thermal barrier coatings (TBCs) have become extremely challenging. Among them, the indicator that measures the service life of TBCs not only requires a high coefficient of thermal expansion (CTE) but also strong resistance to molten calcium-magnesium-aluminum-silicate (CMAS) corrosion. In this study, we used the solid-state method to prepare (La0.2Nd0.2Sm0.2Eu0.2Lu0.2)2Ce2O7 (5RLC), (La0.25Nd0.25Sm0.25Eu0.25)2Ce2O7 (4RLC), and Sm2Ce2O7 (SC) by sintering at 1700 °C for 10 h. By regulating the average radius and the variation of rare-earth ions through high-entropy designing, the lattice structure, micromorphology, element composition, CTE, and resistance to CMAS corrosion were systematically studied. The results showed that the bulk samples had defective fluorite structures, dense microstructures, and a uniform distribution of elements. At 1400 °C, the CTEs of 5RLC and 4RLC were 12.14 × 10−6 K−1 and 12.45 × 10−6 K−1, respectively. After 20 h of CMAS corrosion at 1300 °C, the thickness of the product layers was only 9.73 μm and 10.80 μm for 5RLC and 4RLC, respectively. In this study, we combined the high coefficient of thermal expansion and excellent CMAS corrosion resistance of 5RLC and 4RLC and found that they can maintain a good service life.

Through the incorporation of phosphorus (P) as a third component, an in-situ formation of a magnetic phase with a nanotwin structure was achieved. The utilization of selective laser melting (SLM) enabled the synthesis of a Cu–Fe–P immiscible alloy that exhibits an integrated structure and function. The microstructure predominantly consists of a magnetic heterogeneous Fe–P-rich phase, comprising a mixture of Fe2P and a small quantity of Fe3P, which is distributed within the ε-Cu Cu-rich matrix in alternating “fiber-layer” and “particle-shape” forms. Additionally, the fibrous Fe2P phase exhibited precipitation of α-Fe, while the Fe–P-rich phase experienced the precipitation of high-density nanotwinned Cu (nt-Cu) particles. The microstructure density and structural characteristics of Cu–Fe–P immiscible alloys were enhanced through the adjustment of laser energy density, leading to improvements in their mechanical and magnetic properties. It was observed that the microstructure density initially increased and then decreased with increasing laser energy density. The highest relative density of the Cu–Fe–P immiscible alloy microstructure (98%) was achieved at a laser energy density of 53 J/mm3. Furthermore, the influence of laser energy density on the mechanical and soft magnetic properties of Cu–Fe–P immiscible alloys was examined. The findings indicate that the mechanical and soft magnetic properties of these alloys are affected by the laser energy density. The findings indicate that the compact Cu–Fe–P immiscible alloys exhibit favorable compression mechanical properties and soft magnetic properties. Specifically, the ultimate compressive stress can reach 890.5 ± 20 MPa, while the failure strain can reach 20.5 ± 2%. Additionally, the coercivity is observed to be as low as 20.0 Oe, the magnetic saturation strength as high as 93.5 emu/g, and the residual magnetization at 1.1 emu/g.

Abstract In this study, a compound control strategy for motor side and quasi‐Z source side is proposed to improve the robustness of the quasi‐Z source permanent magnet synchronous motor drive system subjected to external disturbance. In this method, the complementary sliding mode control and sliding mode control as feedback controllers are combined with the disturbance observer technology as a feed‐forward compensator to achieve fast tracking and disturbance suppression for the PMSM drive system. Firstly, the signal models of quasi‐Z source inverters and motors are established. Secondly, by introducing state variables, the composite sliding mode controller is designed with strong robustness based on matched disturbances. Then, in order to further improve the disturbance suppression performance, a disturbance observer based on a feed‐forward compensator is designed to estimate the mismatched external disturbances in the motor drive system. Finally, the global asymptotic stability based on Lyapunov criterion is proved. The simulation and experimental results show that the proposed compound control strategy has the advantages of fast convergence, small motor speed pulsation and strong robustness to external disturbances.

ObjectiveThe purpose of this study was to explain the internal mechanism of attention focus affecting performance of countermovement jump based on muscle synergy theory.MethodsParticipants involved untrained group(N = 10) and high-level group(N = 11). Subjects performed countermovement jump with internal attention focus instruction (IF), external distal attention focus instruction (EDF), and external proximal attention focus instruction (EPF). The electromyography (EMG) signals of the dominant vastus lateralis muscle (VL), semitendinosus muscle (ST), tibial anterior muscle (TA), rectus femoris muscle (RF), and medial gastrocnemius (MG) were recorded. The non-negative matrix factorization was used to extract muscle synergy.Results1) Attention focus did not affect countermovement jump performance and the number of muscle synergy in the high-level group (P>0.05). 2) Attention focus instructions affected the untrained group countermovement jump (PConclusionFor the untrained people, the improved motor performance caused by attention focus resembled the adaptive changes that occur with long-term training. The reason why an EDF is superior to EPF is that the former produces more thorough changes in muscle synergy.

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood–testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.

In aluminum alloys, the most often utilized cast Al–Si alloy system, the microstructure often needs to be improved by modification and inoculation treatment. This study comprehensively examines the impact of nanocrystals produced by Fe–B–Si amorphous alloys on the solidification behavior and microstructure of hypoeutectic Al–Si7 alloy and hypereutectic Al–Si17 alloy. The nucleation temperature of α-Al is increased and the nucleation of α-Al is easier as well as crystallization platform becomes shorter. For primary Si, the nucleation temperature is decreased and the nucleation is inhibited. The eutectic transformation is promoted and the reaction time is shortened. For α-Al, in situ nano-Fe2B can act as its heterogeneous nucleation sites and promote its nucleation. Meanwhile, the growth of α-Al dendrites is constrained by nearby grains and nanocrystals that do not participate in nucleation, therefore refining the dendrites. Furthermore, nano-Fe2B promotes the eutectic transformation and refines the eutectic microstructure. At the same time, the microstructure of the eutectic groups is refined and the distribution is more dispersed due to the confinement of finer adjacent grains and the hindrance of nanocrystals that do not participate in nucleation.

Abstract Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.

Abstract Background Elevated intraocular pressure (IOP) is the main risk factor for glaucoma, which might cause the activation of astrocytes in optic nerve head. To determine the effect of mechanical stretch on the astrocytes, we investigated the changes in cell phenotype, proteins of interest and signaling pathways under biaxial stretch. Method The cultured astrocytes in rat optic nerve head were stretched biaxially by 10 and 17% for 24 h, respectively. Then, we detected the morphology, proliferation and apoptosis of the stretched cells, and performed proteomics analysis. Protein expression was analyzed by Isobaric tags for relative and absolute quantification (iTRAQ) mass spectrometry. Proteins of interest and signaling pathways were screened using Gene Ontology enrichment analysis and pathway enrichment analysis, and the results were verified by western blot and the gene-chip data from Gene Expression Omnibus (GEO) database. Result The results showed that rearrangement of the actin cytoskeleton in response to stimulation by mechanical stress and proliferation rate of astrocytes decreased under 10 and 17% stretch condition, while there was no significant difference on the apoptosis rate of astrocytes in both groups. In the iTRAQ quantitative experiment, there were 141 differential proteins in the 10% stretch group and 140 differential proteins in the 17% stretch group. These proteins include low-density lipoprotein receptor-related protein (LRP6), caspase recruitment domain family, member 10 (CARD10), thrombospondin 1 (THBS1) and tetraspanin (CD81). The western blot results of LRP6, THBS1 and CD81 were consistent with that of iTRAQ experiment. ANTXR2 and CARD10 were both differentially expressed in the mass spectrometry results and GEO database. We also screened out the signaling pathways associated with astrocyte activation, including Wnt/β–catenin pathway, NF-κB signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, ECM-receptor interaction, and transforming growth factor-β (TGF-β) signaling pathway. Conclusion Mechanical stimulation can induce changes in cell phenotype, some proteins and signaling pathways, which might be associated with astrocyte activation. These proteins and signaling pathways may help us have a better understanding on the activation of astrocytes and the role astrocyte activation played in glaucomatous optic neuropathy.

Studies have demonstrated that physical activity (PA) is negatively associated with academic procrastination. However, there is limited research on the mechanism underlying this relationship. This study aims to explore the relationship between PA and academic procrastination by investigating the roles of physical self-perceptions and self-esteem. 916 college students (650 females; Mean age = 19.11, SD age = 1.04) participated in the study. Participants completed the Physical Activity Rating Scale-3, the Physical Self-Perceptions Profile, the Rosenberg Self-Esteem Scale, and the Academic Procrastination Questionnaires. Descriptive statistics, Pearson’s correlation, and mediating effect analysis were carried out using SPSS 25.0. The results showed that (a) PA, physical self-perceptions, and self-esteem were negatively correlated with academic procrastination, (b) self-esteem mediated the association between PA and academic procrastination, and (c) physical self-perceptions and self-esteem sequentially mediated the association between PA and academic procrastination. These findings have deepened our understanding on the relationship between PA and academic procrastination, highlighting important approaches to deal with academic procrastination.

Postnatal immune activation (PIA) often induces neuroinflammation and disrupts neural functions, ultimately causing cognitive impairment. Among them, neuronal dysfunction is one of the key causes of many neurological diseases. It is particularly important to develop effective neuroprotectants to prevent inflammatory brain diseases. Recently, the protective effect of astilbin (ASB) on nervous system diseases has attracted much attention. However, whether ASB can resolve neuronal dysfunction and cognitive decline triggered by PIA remains unclear. In this study, we used the lipopolysaccharide (LPS)-induced PIA model and found that ASB improved PIA-induced cognitive impairment and neuronal dysfunction in adult mice. Moreover, ASB inhibited PIA-induced neurogenesis deficits and synaptic damage. Finally, we found that ASB treatment inhibited the levels of EZH2/H3K27me3 and decreased the enrichment level of H3K27me3 at the promoter of BCL2 and BDNF. Together, our results demonstrated that ASB may protect against PIA-induced cognitive impairment through EZH2-mediated histone methylation. This study established the role of ASB and epigenetic factor EZH2 regulatory network on the PIA model, which provided new clues and theoretical guidance for the clinical treatment of PIA-induced cognitive impairment.

Dynamic metal nanoclusters have garnered widespread attention due to their unique properties and potential applications in various fields. Researchers have been dedicated to developing new synthesis methods and strategies to control the morphologies, compositions, and structures of metal nanoclusters. Through optimized synthesis methods, it is possible to prepare clusters with precise sizes and shapes, providing a solid foundation for subsequent research. Accurate determination of their crystal structures is crucial for understanding their behavior and designing custom functional materials. Dynamic metal nanoclusters also demonstrate potential applications in catalysis and optoelectronics. By manipulating the sizes, compositions, and surface structures of the clusters, efficient catalysts and optoelectronic materials can be designed and synthesized for various chemical reactions and energy conversion processes. This review summarizes the research progress in the synthesis methods, crystal structure characterization, and potential applications of dynamic metal nanoclusters. Various nanoclusters composed of different metal elements are introduced, and their potential applications in catalysis, optics, electronics, and energy storage are discussed. Additionally, the important role of dynamic metal nanoclusters in materials science and nanotechnology is explored, along with an overview of the future directions and challenges in this field.

Most methods used to synthesize and prepare NiAl intermetallics and their alloys have the disadvantages of complexity and high cost. In this paper, the NiAl alloy was prepared by a Combustion Synthesis and Hot Pressing (CSHP) technique under rapid solidification. The grain size of the NiAl alloy is significantly refined to 60–80 μm, which reduces the stress concentration during deformation and improves the fracture strength and fracture hardness. Moreover, the large internal stress and greater amount of dislocations in the as-cast microstructure are produced by their formation under pressure due to the fast cooling rate in the solidification process. The high dislocation density strengthens the NiAl alloy, giving it higher strength, hardness, and work-hardening ability. The high compression properties are also present in the NiAl intermetallics at room temperature, in which the fracture strength is around 1005 MPa and the fracture strain reaches 21.6%. The compressive fracture strength at room temperature is higher than that of the pure NiAl alloy prepared by the Hot-Pressing-Aided Exothermic Synthesis (HPES, about 632 MPa), while it is slightly lower than that of pure NiAl alloy treated by HPES and Hot Isostatic Pressing (HIP, 1050 MPa). The fracture strain is significantly higher than that of the NiAl alloy prepared by other methods. This study can provide guidance for the successful preparation of the NiAl alloy with high strength and toughness.

To study the effectiveness of filled cracks as a means of anti-blasting and wave-elimination for underground protective structures, 36 one-dimensional impact tests were carried out on the intact rock specimens and rock specimens with filled cracks using the SHPB apparatus. The transmittance, stress wave velocity and peak stress value of the specimen under different working conditions were obtained. The impacts of confining pressure level, filling thickness and filling material types on stress wave attenuation were analyzed. The results show that, with the increase of the thickness of the filled cracks, the transmittance of the specimen, stress wave velocity, and stress wave peak stress attenuate clearly. The greater the thickness of the filled crack, the smaller the transmission energy of the stress wave during the propagation process. With the increase of confining pressure, the wave- eliminating effect of filled cracks is reduced due to the closure of pores, but still demonstrate stress wave attenuation effect to some extent. Therefore, using particles with higher compressive strength as crack-filling material and increasing filling thickness can effectively improve the wave-eliminating effect in engineering protection.

The precision and consistency of the microdroplet jetting procedure are crucial for the casting sand mold’s performance during binder injection. The generation and jetting of microdroplets in piezoelectric printheads were examined in this study in relation to changes in specific jetting process parameters. Using finite element analysis and a simplified physical model of a microdroplet jetting device, an electromechanically coupled model of a microdroplet jetting device was created in order to study the characteristics of microdroplet jetting. A volume-of-fluid model was also created in order to study the microdroplet jetting process and perform repeatability tests. The effects of altering nozzle radius, actuation pulse width, intake velocity, and fluid viscosity on microdroplet jetting properties were then investigated using the models. We were able to control the development of satellite droplets thanks to the knowledge we gained about how each process parameter affected droplet status. This study demonstrates how the radius of the nozzle and the pulse width of the piezoelectric actuation signal have a significant impact on the jetting properties of piezoelectric printheads and the production of microdroplets. The quantitative correlations between process factors and jetting characteristics can be used to optimize microdroplet production and reduce droplet size. Finally, this study will help create control systems for microdroplet jetting operations and enhance the precision of 3D printed casting sand molds.

The cooling control of the melt during the casting process is of great significance. A comprehensive closed-loop cooling control of castings by adopting a skeletal sand mold design was proposed. The skeletal sand mold consisting of an adaptive shell, functional cavities and a support was designed and created based on the finite difference meshes of a casting. It was applied to a round wall test casting. Two kinds of skeletal sand molds, one with lattice support and the other with enforcing ribs for this casting were designed and printed out by the 3D printing (3DP) method. Aluminum alloy A356 was cast by using these two sand molds. The first mold was cooled by natural convection, the other one by water spray cooling. Two sound castings were obtained. The sand mold temperature, cooling curves, microstructures, mechanical properties, residual stress and deformation were measured, compared and discussed. Water spray cooling hastened the cooling rate by 62%, increased the content of Mg and Cu in the α-Al matrix, improved the mechanical properties, and altered the surface residual stress state.

Growing evidence indicates that postnatal immune activation (PIA) can adversely increase the lifetime risk for several neuropsychiatric disorders, including anxiety and depression, which involve the activation of glial cells and early neural developmental events. Several glia-targeted agents are required to protect neonates. Folic acid (FA), a clinical medication used during pregnancy, has been reported to have neuroprotective properties. However, the effects and mechanisms of FA in PIA-induced neonatal encephalitis and mood disorders remain unclear. Here, we investigated the roles of FA in a mouse model of PIA, and found that FA treatment improved depressive- and anxiety-like behaviors in adults, accompanied by a decrease in the number of activated microglia and astrocytes, as well as a reduction in the inflammatory response in the cortex and hippocampus of neonatal mice. Furthermore, we offer new evidence describing the functional differences in FA between microglia and astrocytes. Our data show that epigenetic regulation plays an essential role in FA-treated glial cells following PIA stimulation. In astrocytes, FA promoted the expression of IL-10 by decreasing the level of EZH2-mediated H3K27me3 at its promoter, whereas FA promoted the expression of IL-13 by reducing the promoter binding of H3K9me3 mediated by KDM4A in microglia. Importantly, FA specifically regulated the expression level of BDNF in astrocytes through H3K27me3. Overall, our data supported that FA may be an effective treatment for reducing mood disorders induced by PIA, and we also demonstrated significant functional differences in FA between the two cell types following PIA stimulation.

Cicada flower, scientifically named Cordyceps chanhua, is an important and well-known Chinese cordycipitoid medicinal mushroom. Although most mycoviruses seem to induce latent infections, some mycoviruses cause host effects. However, the effects of mycovirus on the fungal development and stress tolerance of C. chanhua remain unknown. In this study, we report a novel mycovirus designated Cordyceps chanhua partitivirus 1 (CchPV1) from C. chanhua isolate RCEF5997. The CchPV1 genome comprises dsRNA 1 and dsRNA 2, 1784 and 1563 bp in length, respectively. Phylogenetic analysis using the aa sequences of RdRp revealed that CchPV1 grouped with members of the genus Gammapartitivirus in the family Partitiviridae. We further co-cultivated on PDA donor strain RCEF5997 and recipient C. chanhua strain RCEF5833 (Vf) for 7 days, and we successfully obtained an isogenic line of strain RCEF5833 with CchPV1 (Vi) through single-spore isolation, along with ISSR marker and dsRNA extraction. The biological comparison revealed that CchPV1 infection slows the growth rate of the host, but increases the conidiation and formation of fruiting bodies of the host. Furthermore, the assessment of fungal tolerance demonstrated that CchPV1 weakens the multi-stress tolerance of the host. Thus, CchPV1 infection cause changes in fungal development and multi-stress tolerance of the host C. chanhua. The findings of this study elucidate the effects of gammapartitivirus on host entomogenous fungi and provide a novel strategy for producing high-quality fruiting bodies of C. chanhua.

The purpose of this study was to examine the moderating effects of goal orientations and self-efficacy between competitive cognitive anxiety and motor performance under conditions featuring different levels of ego-threat. Eighty-one (40 females) collegiate-level basketball players (M age = 20.26 years and SD = 2.68) completed Sport Competitive Anxiety Test, Ego Orientation in Sport Questionnaire, and General Self-Efficacy Scale prior to the experiment. Athletes participated in two sessions of free-throw tasks. After the first session, which was under a control condition, participants performed in a free-throw competitive session while being provided opponents’ scores that induced different levels of competitive cognitive anxiety. Performance is defined as the accuracy (%) in two free-throw sessions. A hierarchical multiple regression showed that high level of task-orientation and low level of ego-orientation can buffer the impairment of competitive cognitive anxiety on motor performance. The relationship between competitive cognitive anxiety and motor performance did not vary with self-efficacy. An a repeated-measured analysis of covariance after cluster analysis revealed that a high-task/low-ego profile benefited athletes the most regarding the impairment of competitive cognitive anxiety. Together, ego- and task-orientations and “goal profile” moderate the relationship between competitive cognitive anxiety and motor performance; however, self-efficacy may not serve as a moderator variable in between.

A super-multivariate optimization algorithm is proposed to suppress the grating lobes (GLs) of non-uniform arrays. For position-only variable cases of any huge array, it is always difficult to deal with by using clustering algorithm because of thousands of variables. The proposed method achieves grating lobe suppression (GLS) by taking position gradient of dynamic maximum GL and obtaining phase difference by comparing with every element, which requires only precious few extra computations. When gradient function varying with each element position is established, an appropriate sigmoid function will be introduced and used to control the magnitude of small element displacement. After each generation of element-movement operation, electric field of all elements are superimposed and partially cancelled out each other in the target direction. In addition, the gradient computing does not significantly increase the cost of total computation under multi-variable conditions, which avoids the unacceptable cost of conventional clustering optimization algorithm. In this paper, a 16×16-element array is optimized, and a result comparison with random optimization (RO), particle swarm optimization (PSO), and gradient algorithm (GA) is present. The validity of the proposed algorithm for GLS is verified through using a 100×100-element array. In the final, a large array antenna based on subarrays is optimized for a low sidelobe level (SLL) below -20dB using the proposed algorithm. The results meet the requirements and show the effectiveness of the proposed algorithm.

Sex-determining region Y-related high mobility group-box 10 (SOX10), a member of the SOX family, has recently been highlighted as an essential transcriptional factor involved in developmental biology. Recently, the functionality of SOX 10 has been increasingly revealed by researchers worldwide. It has been reported that SOX10 significantly regulates the proliferation, migration, and apoptosis of tumors and is closely associated with the progression of cancer. In this review, we first introduce the basic background of the SOX family and SOX10 and then discuss the pathophysiological roles of SOX10 in cancer. Besides, we enumerate the application of SOX10 in the pathological diagnosis and therapeutic potential of cancer. Eventually, we summarize the potential directions and perspectives of SOX10 in neoplastic theranostics. The information compiled herein may assist in additional studies and increase the potential of SOX10 as a therapeutic target for cancer.

Cordyceps chanhua is an important cordycipitoid mushroom widely used in Asia and beyond. Beauvericin (BEA), one of the bioactive compounds of C. chanhua, has attracted much attention because of its medicinal value and food safety risk. In order to clear up the relationship between oxidative stress and BEA synthesis, we investigated the impact of H2O2-induced oxidative stress on the secondary metabolism of C. chanhua using untargeted metabolomics and a transcript profiling approach. Metabolic profiling of C. chanhua mycelia found that in total, 73 differential metabolites were identified, including organic acids, phospholipids, and non-ribosomal peptides (NRPs), especially the content of BEA, increasing 13-fold under oxidative stress treatment. Combining transcriptomic and metabolomic analyses, we found that the genes and metabolites associated with the NRP metabolism, especially the BEA biosynthesis, were highly significantly enriched under H2O2-induced stress, which indicated that the BEA metabolism might be positive in the resistance of C. chanhua to oxidative stress. These results not only aid in better understanding of the resistance mechanisms of C. chanhua against oxidative stress but also might be helpful for molecular breeding of C. chanhua with low BEA content.

When performing fluorescent magnetic particle testing in steel welding-repaired zones, as traditional viewpoint usually ascribes magnetic particle indications to discontinuous welding defects such as cracks, incomplete fusion, etc., welding-repaired zones showing indications of these defects are always judged to be unqualified. In this study, a novel reticular phase was identified on the weld fusion line of 06Cr13Ni4Mo. By selected area electron diffraction, it was proved to be an austenite. By roasting test, it was proved to be induced by the thermal effect of welding. Non-ferromagnetic reticular austenite reduces the overall magnetic permeability, leading to the presence of fluorescent magnetic particle indication. Though the mechanical properties of the welding repaired zone are changed by the reticular austenite with the yield strength, tensile strength, and microhardness decreasing to 571 MPa, 752 MPa, and 279, respectively, they still exceed the required values of standard specifications. 06Cr13Ni4Mo welding-repaired zones showing magnetic particle indications induced by reticular austenite are qualified and should be accepted.

The aerial refueling is a kind of complex system engineering, and the influencing factors are closely related to the tanker and the receiver. Due to the special layout of single wing, large wingspan, high vertical tail and large landing gear fairing on the large tanker(soft refueling), the aerodynamic interference among the tanker, hose cone sleeve and receiver becomes very complicated during the process of refueling docking in air formation flight. By analyzing the main characteristics of domestic and foreign large-scale tanker and advanced reciever aircraft, the aerodynamic interference between tanker and receiver aircraft in the process of air refueling docking is summarized, the typical system of air refueling and refueling formation flight and the procedures of air refueling are studied, and the verification elements possibly influencing the safety docking control for air refueling are put forward and analyzed. The analysis of safety control verification elements can provide the theoretical guidance for the determination of the procedure of the soft air refueling and receiving docking, and basis for the selection of the air refueling and receiving docking speed.

Achieving an optimal configuration of the diffuser is indispensable for high pump performances. In this work, a numerical study on diffuser configuration is conducted for a high pump performance using a computational fluid dynamics code, and the effects of the wrap angle and the relative position of the diffuser vane to the impeller on pump performances are included. The results indicate that the modified diffuser with a suitable wrap angle may improve the pump hydraulic efficiency and the head by approximately 4% and 8%, respectively, while a suitable position of the diffuser vane can enhance the pump head by more than 4%. Meanwhile, the pressure recovery coefficient and the local Euler head of the diffuser are adopted to evaluate the diffuser performance. For a high pump performance, the local Euler head of the diffuser has a peak value at the leading edge with the change rate of zero along the meridian streamline, meaning that no blade loading at the leading edge of the diffuser guarantees a better match between the impeller and the diffuser.

Increasing evidence has demonstrated that hypoxia was an aggressive feature in endometrial cancer (EC), which is significantly associated with the tumor grade, lymph node metastasis, and tumor resistance to chemotherapy. However, the relationship between hypoxia and the immune microenvironment in EC is not very clear. Exosomes are small membrane vesicles secreted from a variety of cell types which mediate cell-to-cell communication through transported biomolecules. Here, we investigated whether exosomes can play an immunomodulatory role in intercellular communication between EC cells and macrophages. EC KEL cells were cultured under hypoxia or normoxic condition to collect exosomes. After identification, the exosomes derived from hypoxic or normoxic KEL cells were cultured with the monocyte cell line THP-1 to study the immunoregulation function of KEL cells. The results showed that the total number of exosomes produced by hypoxic KEL cells was significantly higher than that in normoxic condition. In addition, hypoxia markedly stimulated the increase in miRNA-21 expression in the exosomes. After coculture, we found that exosomal miRNA-21 could be horizontally transferred into THP-1 cells. And then, the notably enhanced mRNA expression levels of IL-10 and CD206 in THP-1 cells were observed, suggestive of M2 polarization. To further study the effect of miRNA-21-containing exosomes, we transfected miRNA-21 mimics or inhibitor into THP-1 cells. The results showed that miRNA-21 mimics promoted IL-10 and CD206 mRNA expression levels, and the miRNA-21 inhibitor significantly prevented the alteration induced by intake of hypoxic KEL cell-derived exosomes. In summary, we found that endometrial cancer KEL cells in hypoxic condition promoted monocyte THP-1 cell transformation to M2-like polarization macrophages through delivering exosomal miRNA-21, which may be a potential mechanism of the formation of the immune microenvironment in EC progression.

A hybrid linear ion trap-quadrupole-Orbitrap high-resolution mass spectrometry (LTQ-Orbitrap-HRMS) was used to qualitatively and quantitatively analyse the myriocin in Isaria cicadae and its allies. The samples were prepared with 95% methanol for 30 min by ultrasonic-assisted extraction. The target compound was purified by ODS solid-phase extraction (SPE) column. The enriched samples were identified by mass spectrometry. The results showed that the contents of myriocin in both wild and artificial Isaria cicadae were below the detection limit, while a strain of Ophiocordyceps longissima and Cordyceps cicadae Shing (Dujiaolong), both closely related to the Isaria cicadae, and its asexual mycelia are rich in myriocin. It suggests that it may be wrong to consider C. cicadae as I. cicadae’s teleomorph in Genbank or Mycobank in many published reports based on chemical classification, and the species rich in myriocin is probably not Isaria cicadae.

Phase evolution and microwave dielectric properties of Ca0.61Nd0.26Ti1-x(Al1/2Nb1/2)xO₃ ceramic in the range of 0 ≤ x ≤ 0.2 have been determined in this paper. For 0 ≤ x ≤ 0.1, X-ray diffraction results showed a single perovskite phase. Dielectric constant (ε r) and quality factor (Qxf) kept high values and temperature coefficient of resonant frequency (τf) decreased by 32.4% from 247 ppm/°C to 167 ppm/°C. When 0.15 ≤ x ≤ 0.2, extra peaks with peak positions coincidental with Ca₂Nb₂O₇ phase appeared. Typically, high relative permittivity (≥ 90) and quality factor (≥ 6,400 GHz) could be obtained when sintered at 1400 °C for 2h.

In this paper, a Taguchi method based on fitting and prediction is proposed to accelerate the optimization process in antenna array synthesis. The implementation procedure combines the normal Taguchi method and the curve fitting technique. A possible solution is determined by prediction based on fitting curves. Specifically, the fitting curves are obtained by using the dynamic points calculated and updated as the Taguchi method progress and recorded in the response table necessarily produced in the procedure. Test functions are used for conducting some confirmation experiments, and the results verify the validity of the proposed method. In order to illustrate its good practicability, two linear antenna arrays with a null controlled pattern and a flat top pattern, respectively, are successfully optimized by using both of the normal Taguchi method and the proposed one. Some comparisons and discussions of their results are given in the paper, which proves that the proposed method has a better practicability, not only because it inherits the global optimization characteristics of the normal Taguchi method but also because it accelerates the convergence process.