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EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. Previously, we showed that EZH2 downregulation enhances neuron differentiation of human mesenchymal stem cells (hMSCs); however, the underlying mechanisms of EZH2‐regulated neuron differentiation are still unclear. Here, we identify Smurf2 as the E3 ubiquitin ligase responsible for the polyubiquitination and proteasome‐mediated degradation of EZH2, which is required for neuron differentiation. A ChIP‐on‐chip screen combined with gene microarray analysis revealed that PPARγ was the only gene involved in neuron differentiation with significant changes in both its modification and expression status during differentiation. Moreover, knocking down PPARγ prevented cells from undergoing efficient neuron differentiation. In animal model, rats implanted with intracerebral EZH2‐knocked‐down hMSCs or hMSCs plus treatment with PPARγ agonist (rosiglitazone) showed better improvement than those without EZH2 knockdown or rosiglitazone treatment after a stroke. Together, our results support Smurf2 as a regulator of EZH2 turnover to facilitate PPARγ expression, which is specifically required for neuron differentiation, providing a molecular mechanism for clinical applications in the neurodegenerative diseases. Graphical Abstract Smurf2‐mediated degradation of EZH2 enhances neuronal differentiation of human mesenchymal stem cells (hMSCs). This enables expression of PPARgamma in hMSCs, which when implanted improve recovery in a rat model of stroke.

This study aimed to investigate the heterogeneity of academic resilience among nursing students using latent profile analysis and its associated influencing factors. Nursing students experience higher levels of stress compared to their peers in other professions, and the cultivation of academic resilience plays a pivotal role in their ability to effectively cope with this stress. Academic resilience not only facilitates success in the face of academic adversity but also contributes to the promotion of mental well-being among nursing students. However, the current research on the academic resilience of nursing students has predominantly focused on a scale-centered total score approach, disregarding individual variability, and hindering the development to inform personalized interventions for enhancing academic resilience. A cross-sectional study. A convenience sampling method was used to collect a total of 644 nursing students from two medical schools in Guangzhou City. The participants were recruited through an online survey conducted from January to March 2023. The questionnaires consisted of a general information form, the Chinese version of the Academic Resilience Scale-30 (C-ARS-30), the 10-item Connor Davidson Resilience Scale (CD-RISC-10), and the General Self-Efficacy Scale (GSES). Latent profile analysis was used to identify distinct categories of academic resilience among nursing students, and influencing factors were examined through ordinal logistic regression analysis. The academic resilience levels of nursing students can be divided into three potential categories: 'low academic resilience' (13.0%), 'moderate academic resilience' (70.0%), and 'high academic resilience' (17.0%). Level of grade, GPA, self-reported physical health level, resilience and self-efficacy were significantly influenced the different categories of academic resilience of nursing students (P<0.05). The majority of undergraduate nursing students were placed in the moderate academic resilience group, however, educational institutions should pay special attention to nursing students demonstrating low levels. Regular assessments of academic resilience are recommended, and personalized interventions should be tailored to address specific academic resilience characteristics across different grades of nursing students. Strategies aimed at enhancing academic resilience among nursing students may include improvements in GPA performance, attention to physical health, and the reinforcement of resilience and self-efficacy.

Glioblastoma (GBM) is the most common primary brain tumor in adults. Tumor invasion is the major reason for treatment failure and poor prognosis in GBM. Inhibiting migration and invasion has become an important therapeutic strategy for GBM treatment. Enhancer of zeste homolog 2 (EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. In this study, we report that EZH2 and CXCR4 were overexpressed in glioma patients. Furthermore, elevated EZH2 and CXCR4 were correlated with shorter disease-free survival. In three human GBM cell lines, EZH2 modulated the expression of miR-9, which directly targeted the oncogenic signaling of CXCR4 in GBM. The ectopic expression of miR-9 dramatically inhibited the migratory capacity of GBM cells in vitro. Taken together, our results indicate that miR-9, functioning as a tumor-suppressive miRNA in GBM, is suppressed through epigenetic silencing by EZH2. Thus, miR-9 may be an attractive target for therapeutic intervention in GBM.

Phosphorus-rich olivine (P2O5>1 wt%) is a mineral that has been reported only in a few terrestrial and extraterrestrial occurrences. Previous investigations suggest that P-rich olivine mainly forms through rapid crystallization from high-temperature P-rich melts. Here, we report a new occurrence of P-rich olivine in an ungrouped carbonaceous chondrite Dar al Gani (DaG) 978. The P-rich olivine in DaG 978 occurs as lath-shaped grains surrounding low-Ca pyroxene and olivine grains. The lath-shaped olivine shows a large variation in P2O5 (0-5.5 wt%). The P-rich olivine grains occur in a chondrule fragment and is closely associated with chlorapatite, merrillite, FeNi metal, and troilite. Tiny Cr-rich hercynite is present as inclusions within the P-rich olivine. The lath-shaped texture and the association with Cr-rich hercynite indicates that the P-rich olivine in DaG 978 formed by replacing low-Ca pyroxene precursor by a P-rich fluid during a thermal event, rather than by crystallization from a high-temperature melt. The large variation of P2O5 within olivine grains on micrometer-scale indicates a disequilibrium formation process of the P-rich olivine. The occurrence of P-rich olivine in DaG 978 reveals a new formation mechanism of P-rich olivine.

Crystallization is one of the most fundamental processes for both solid inorganic and organic materials in nature. The classical crystallization model mainly involves the monomer-by-monomer addition of simple chemical species. Recently, nanoparticle attachment has been realized as an important mechanism of crystallization in comparatively low-temperature aqueous natural and synthetic systems. However, no evidence of crystallization by particle attachment has been reported in petrologically important melts. In this study, we described spherical (Mg,Fe)-oxides with a protrusion surface in a shock-induced melt pocket from the martian meteorite Northwest Africa 7755. Transmission electron microscopic observations demonstrate that the (Mg,Fe)-oxides are structure-coherent intergrowth of ferropericlase and magnesioferrite. The magnesioferrite is mainly present adjacent to the interface between (Mg,Fe)-oxides spherules and surrounding silicate glass, but not in direct contact with the silicate glass. Thermodynamic and kinetic considerations suggest that development of the spherical (Mg,Fe)-oxides can be best interpreted with crystallization by particle attachment and subsequent Ostwald ripening. This indicates that crystallization by particle attachment can also take place in high-temperature melts and has potential implications for understanding the nucleation and growth of early-stage crystals in high-temperature melts, such as chondrules in the solar nebula, erupted volcanic melts, and probably even intrusive magmas.

Background T-2 toxin poses a great threat to human health because it has the highest toxicity of the currently known trichothecene mycotoxins. To understand the in vivo toxicity and transformation mechanism of T-2 toxin, we investigated the role of one kind of principal phase I drug-metabolizing enzymes (cytochrome P450 [CYP450] enzymes) on the metabolism of T-2 toxin, which are crucial to the metabolism of endogenous substances and xenobiotics. We also investigated carboxylesterase, which also plays an important role in the metabolism of toxic substances. Methods A chemical inhibition method and a recombinant method were employed to investigate the metabolism of the T-2 toxin by the CYP450 enzymes, and a chemical inhibition method was used to study carboxylesterase metabolism. Samples incubated with human liver microsomes were analyzed by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC- QqQ MS) after a simple pretreatment. Results In the presence of a carboxylesterase inhibitor, only 20 % T-2 toxin was metabolized. When CYP enzyme inhibitors and a carboxylesterase inhibitor were both present, only 3 % of the T-2 toxin was metabolized. The contributions of the CYP450 enzyme family to T-2 toxin metabolism followed the descending order CYP3A4, CYP2E1, CYP1A2, CYP2B6 or CYP2D6 or CYP2C19. Conclusion Carboxylesterase and CYP450 enzymes are of great importance in T-2 toxin metabolism, in which carboxylesterase is predominant and CYP450 has a subordinate role. CYP3A4 is the principal member of the CYP450 enzyme family responsible for T-2 toxin metabolism. The primary metabolite produced by carboxylesterase is HT-2, and the main metabolite produced by CYP 3A4 is 3′-OH T-2. The different metabolites show different toxicities. Our results will provide useful data concerning the toxic mechanism, the safety evaluation, and the health risk assessment of T-2 toxin.

Chinese time adverbs play an important role in the development direction and state of the event (Guo., 1984； Zhang Y. S., 2000). Among them, the diversity of time adverbs can be based on the tense, observe the sequence of time development from the perspective of a bystander, and express the relative time concept of time flow. The common classifications are past, present, and future; it can also be tense, observing events from the perspective of the parties to the event Time and state in development (Lv Shuxiang, 1942), indicating that time adverbs not only cover the concept of time, highlight the characteristics of action state to improve comprehension, but also increase the integrity of language (Lu. & Ma. 1989; Zhang. Y., 2000 ). After exploring the past studies of time adverbs, there are not many studies that mainly focus on semantics, and consider the importance of vocabulary learning (Milton, 2009), so this study focuses on 52 adverbs of time that appear in textbooks. Based on the concept of aspect, it i

Aim： The aim of this study was to determine the therapeutic effect of Periplocoside A （PSA）, a natural product isolated from the traditional Chinese herbal medicine Periploca sepium Bge, in MOG35- 55（myelin oligodendrocyte glycoprotein 35-55）-induced experimental autoimmune encephalomyelitis （EAE）. Methods： Female C57BL/6 mice immunized with MOG35-55 were treated with （50 mg/kg or 25 mg/kg） or without PSA following immunization and continuously throughout the study. The degree of CNS inflammation was evaluated by H＆E staining. Anti-MOG-specific recall responses were analyzed by [^3H]-Thymidine incorporation, ELISA, and RT-PCR. The proportion of IL-17-producing T cells was measured by flow cytometry. Results： Oral administration of PSA significantly reduced the incidence and severity of EAE, which closely paralleled the inhibition of MOG35-55-specific IL-17 production. Importantly, PSA inhibited the transcription of IL-17 mRNA and RORyt. Further studies examining intracellular staining and adoptive transfer EAE validated the direct suppressive effect of PSA on Th17 cells. In vitro studies also showed that PSA significantly inhibited the differentiation of Th17 cells from murine purified CD4 T cells in a dose-dependent manner. Conclusion： PSA ameliorated EAE by suppressing IL-17 production and inhibited the differentiation of Th17 cells in vitro. Our results provide new insight into the potential mechanisms underlying the immunosuppressive and anti-inflammatory effects of PSA.