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Abstract Background Luteolin is an active ingredient in various traditional Chinese medicines for the treatment of multiple tumors. However, the mechanisms of its inhibitory effect on osteosarcoma proliferation and metastasis remain unclear. Purpose To elucidate the anti-osteosarcoma mechanisms of luteolin based on network pharmacology and experimental verification. Study Design Integrate network pharmacology predictions, scRNA-seq analysis, molecular docking, and experimental validation. Methods Luteolin-related targets and osteosarcoma-associated targets were collected from several public databases. The luteolin against osteosarcoma targets were screened and a PPI network was constructed to identify the hub targets. The GO and KEGG enrichment of osteosarcoma-associated targets and luteolin against osteosarcoma targets were performed. And scRNA-seq analysis was performed to determine the distribution of the core target expression in OS tissues. Molecular docking, cell biological assays, and osteosarcoma orthotopic mouse model was performed to validate the inhibitory effect and mechanisms of luteolin on osteosarcoma proliferation and metastasis. Results Network pharmacology showed that 251 luteolin against osteosarcoma targets and 8 hub targets including AKT1, ALB, CASP3, IL6, JUN, STAT3, TNF, and VEGFA, and the PI3K-AKT signaling pathway might play an important role in anti-osteosarcoma of luteolin. Analysis of public data revealed that AKT1, IL6, JUN, STAT3, TNF, and VEGFA expression in OS tissue was significantly higher than that in normal bones, and the diagnostic value of VEGFA for overall survival and metastasis was increased over time. scRNA-seq analysis revealed significantly higher expression of AKT1, STAT3, and VEGFA in MYC+ osteoblastic OS cells, especially in primary samples. Moreover, the docking activity between luteolin and the hub targets was excellent, as verified by molecular docking. Experimental results showed that luteolin could inhibit cell viability and significantly decrease the expression of AKT1, STAT3, IL6, TNF, and VEGFA, and luteolin could also inhibit osteosarcoma proliferation and metastasis in osteosarcoma orthotopic mouse model. Conclusion This study shows that luteolin may regulate multiple signaling pathways by targeting various genes like AKT1, STAT3, IL6, TNF, and VEGFA to inhibit osteosarcoma proliferation and metastasis. Graphical abstract

Coal is the main energy source in China, which is also an important guarantee for the safety and stability of the national power supply as well as economic development. However, the coal combustion process for power generation will produce a large amount of fly ash, and the long-term piling of fly ash solid waste will seriously pollute the soil, water, atmosphere, and ecological environment, on the contrary, the fly ash can be used as a raw material for the prevention and control of coal spontaneous combustion disasters in mines. However, the current application of fly ash in the field of mine fire prevention was certainly limited, such as small amount of scattered utilization, low technical content, low added value, etc. The current scale of harmless pre-treatment and fire prevention and utilization of fly ash is still unable to meet the requirements of the national “carbon peaking and carbon neutrality” target for solid waste resource utilization and green mine construction. For further promote the efficient, high-value, and large-scale utilization of fly ash to realize the rapid development of fly ash-based fire prevention materials and technologies, this paper summarizes the principle, classification, latest development, and application effects of fly ash slurry, fly ash gel, fly ash foam and other fire prevention technologies. Based on the above analysis, this paper condenses three key problems that need to be solved, such as the separation of hazardous substances and valuable components in fly ash solid waste, the precipitation and plugging of pipes during long-distance transportation of highly concentrated fly ash slurry, and the law of seepage and accumulation of fly ash-based fire prevention materials in the goaf. In order to improve the effectiveness of fly ash solid waste in preventing spontaneous combustion of coal and to meet the national requirements for green mines as well as intelligent mine construction under the “carbon neutrality and emission peak” target, this paper proposes the development direction of “Long-lasting for fire prevention-Synergistic carbon sequestration – Intelligent control” for fly ash solid waste in the field of fire prevention technology. Future research will focus on the low-cost and long-lasting fire prevention fly ash solid waste-based materials, integrated fly ash fire prevention technology with mineralized CO2 sequestration and fire prevention, and intelligent fly ash fire prevention material application systems, which will promote the high-value and large-scale reuse of fly ash waste in the field of fire prevention, finally improving the efficiency of preventing and controlling of spontaneous combustion disasters in coal mines, and ensuring the safe and efficient mining.

Summary: Human trophoblast development study has long been limited by the lack of suitable materials. Here we present a detailed protocol for the differentiation of human expanded potential stem cells (hEPSCs) into human trophoblast stem cells (TSCs) and for the subsequent establishment of TSC lines. The hEPSC-derived TSC lines can be continuously passaged and are functional in further differentiation into syncytiotrophoblasts and extravillous trophoblasts. The hEPSC-TSC system offers a valuable cell source for studying human trophoblast development in pregnancy.For complete details on the use and execution of this protocol, please refer to Gao et al. (2019)1 and Ruan et al. (2022).2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract High‐grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single‐cell RNA sequencing (scRNA‐Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA‐Seq is used to identify a unique initiating cell subpopulation (SULT1E1+) in high‐grade meningiomas. This subpopulation modulates the polarization of M2‐type macrophages and promotes meningioma progression and recurrence. A novel patient‐derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1+ and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1+ in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high‐grade meningiomas and provide a novel therapeutic target for refractory high‐grade meningioma.

Background: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. Methods: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. Results: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. Limitations: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. Conclusion: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine., Introduction Although ketamine--a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist--is valued for its clinical applications in anesthesia and pain management, and esketamine (the S-enantiomer of ketamine) has begun to be used for [...]

Alzheimers disease (AD) is a common neurodegenerative disease that brings about enormous economic pressure to families and society. Inhibiting abnormal aggregation of Aβ and accelerating the dissociation of aggregates is treated as an effective method to prevent and treat AD. Recently, nanomaterials have been applied in AD treatment due to their excellent physicochemical properties and drug activity. As a drug delivery platform or inhibitor, various excellent nanomaterials have exhibited potential in inhibiting Aβ fibrillation, disaggregating, and clearing mature amyloid plaques by enhancing the performance of drugs. This review comprehensively summarizes the advantages and disadvantages of nanomaterials in modulating amyloid aggregation and AD treatment. The design of various functional nanomaterials is discussed, and the strategies for improved properties toward AD treatment are analyzed. Finally, the challenges faced by nanomaterials with different dimensions in AD-related amyloid aggregate modulation are expounded, and the prospects of nanomaterials are proposed.

Nightmares influence the mental health of university students, but the prevalence of nightmare and nightmare disorder requires additional documentation. The data of detailed nightmare experience of nightmare disorder and related depressive mood in this population are also scarce. First, a total of 1,451 students in a comprehensive Chinese university were invited to report their nightmare frequency. Sixty-eight patients with nightmare disorder were diagnosed using a semi-structured clinical interview according to the "Diagnostic and Statistical Manual of Mental Disorders" (5th ed.; DSM-5; American Psychiatric Association, 2013). Second, 60 patients with nightmare disorder (8 of 68 patients were dismissed due to data incompletion) and 124 gender-matched, healthy students were invited to answer the Nightmare Experience Questionnaire (NEQ) and the Plutchik-van Praag Depression Inventory (PVP). Of 1,451 students, 923 reported nightmares (its annual prevalence was 63.61%), and 68 were diagnosed with nightmare disorder (its prevalence was 4.69%), with a female preponderance. The mean PVP and four NEQ scale scores in patients were higher than those in healthy students. The PVP scores were correlated with NEQ Physical Effect in patients, and with Negative Emotion in healthy students. This is the first report regarding nightmare disorder prevalence and detailed nightmare experience in university students. The findings of a high prevalence of nightmare disorder in women and elevated scores of nightmare experience among patients in the university population might help address the mechanisms and the management of patients with nightmare disorder.

Truscott (1996) questions the practicability of grammar correction, and he believes that written corrective feedback (WCF) is not only a waste of time, but even harmful to the students as well. This has led to a great deal of discussion and research on WCF in second-language (L2) writing. Ferris (1999) is the representative opponent of Truscott's point of view, who argues that WCF should not be abandoned in that it can improve the accuracy of L2 learners' writing. Many empirical studies have been conducted and the results support Ferris' view that WCF is useful in promoting the development of L2 writing. This paper gives a literature review from a dichotomy perspective of WCF.