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Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

In this paper, the spectral element differential method (SEDM) is improved to solve the nonlinear thermoelastic coupling problems with interface thermal resistance and interface gap in composite structures. The utilization of both Lobatto and Chebyshev node sets in SEDM significantly enhances solution efficiency by replacing integration with direct differential. Moreover, for strongly nonlinear problems caused by thermal radiation, unknown terms are incorporated into the stiffness matrix, and the relaxation iteration technique is also employed, the convergence has been improved compared to traditional methods. Importantly, the element format of the SEDM for 3D problems with discontinuous interfaces is given specifically in this paper, and element‐by‐element loop assembly of stiffness matrices is realized. Numerical examples confirm the effectiveness of the present method in efficiently and accurately solving 2D and 3D problems with discontinuous interfaces. The present method not only achieves faster convergence than the traditional finite element method, but also attains higher accuracy with fewer degrees of freedom and shorter computational time. Compared to the spectral element method (SEM), the proposed method significantly reduces the computation time of the stiffness matrix. Furthermore, by employing the coupled SEM‐SEDM approach, computational efficiency is enhanced while maintaining high precision in sensitive regions. [ABSTRACT FROM AUTHOR]

Microplastic (MP) pollution, a global environmental problem, has been recently studied in marine and freshwater environments. However, our understanding of MP effect on terrestrial ecosystems, especially carbon (C) and nitrogen (N) turnover remains poor. This review summarizes the sources and distribution characteristics of MPs in terrestrial ecosystems and explores their effects on soil properties, plant growth, C and N turnover. Once entering the terrestrial ecosystem, MPs could involve in sequestrating carbon and nitrogen by changing soil properties (e.g., pH, soil aggregate stability, and soil porosity). MPs could exert direct influences on plants or on soil physical environment and microbial metabolic environment to indirectly affect plant growth, thus altering the quantity and quality of soil C and N inputs by shifts in plant litter and roots. The changes of the dominant bacteria phyla, related functional genes, and enzymes caused by MP pollution could affect C and N cycles. Additionally, the MP effect varies with its properties (e.g., types, shapes, elemental composition, functional groups, released additives). Future researches should unify the standard system of MP separation, detection, and reveal the ecological effects of MPs, especially their impacts on terrestrial carbon and nitrogen cycles in the context of climate changes.

Brain metastasis in osteosarcoma (BMO) is rare and its clinical characteristics are often buried among studies on brain metastasis of bone and soft tissue sarcomas. The aim of the present study was to summarize the incidence, clinical characteristics, treatment and outcomes of patients with BMO. This retrospective study included 7 patients with BMO who received treatment in our center between 2005 and 2019. The clinical medical records of the 7 patients, together with data of 70 BMO patients published in 33 articles and retrieved by means of PubMed and Medline, were analyzed, retrospectively. Data analysis of the 97 BMO patients showed a high correlation between the interval from the primary diagnosis to BMO occurrence and the interval from the primary diagnosis to prior metastases. Multivariate analysis showed that chemotherapy, radiotherapy and surgery were three main factors affecting the overall survival of BMO patients (HR = 0.427; HR = 0.372; HR = 0.296). Surgery combined with chemotherapy or radiotherapy offered a better overall survival than surgery alone. Patients with BMO may obtain survival benefits from regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy. This is a retrospective study describing the characteristics of metastasic intervals, locations, clinical features and prognosis in 97 patients with brain metastasis of osteosarcoma (BMO). Multivariate analysis showed that chemotherapy was effective as surgery and radiotherapy for the treatment of BMO. Our findings emphasize the importance of regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Microbial communities regulating multiple ecosystem functions in agricultural ecosystems remain unclear, limiting our ability to predict how agricultural systems will respond to nutrient management. Here, we assessed the effects of 5‐year different fertilization treatments (CK, no‐fertilization; M, organic fertilization; MNPK, combined inorganic and organic fertilization; NPK, inorganic fertilization) on the bacterial and fungal composition, co‐occurrence networks complexity and the relationship of keystone taxa with soil multifunctionality. Our results showed that fertilization shifted the bacterial and fungal community composition. The increased nodes of degree and decreased average path length with the application of organic fertilizer suggested a more stable network. The improved soil multifunctionality was also observed in combined organic and inorganic fertilization treatment, which positively correlated with the fungal community composition rather than bacterial, indicating that fungi are important in driving soil functions. Notably, the keystone taxa fOTU3995 and fOTU2868 belong to Sordariomycetes and were correlated with soil organic carbon, total nitrogen, total phosphorus, and alkaline phosphatase. These indicated that the keystone taxa play an important role in increasing in soil nutrient, C cycling, and P cycling. Together, our findings highlight that combined organic and inorganic fertilization increases the network complexity and soil multifunctionality, further confirming the role of keystone taxa Sordariomycetes in driving soil multifunctionality. This suggested that combined organic and inorganic have the potential to preserve agroecosystem sustainability and strengthen the role of microorganisms in ecosystem functions. [ABSTRACT FROM AUTHOR]