Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4+ macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3+ T cells with high proportion of TIGIT+ cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.
The fruit of Chaenomeles speciosa is a traditional Chinese medicine used for the treatment of dyspepsia and various inflammatory diseases. In the present study, we evaluated the potential radical scavenging capacity, and activity against nitrous oxide, inflammatory cytokines production and neuramindase (NA) of its isolates. The results showed that 3,4-dihydroxybenzoic acid (1) displayed higher inhibitory activities on DPPH and NA with IC50 values of 1.02 μg/mL and 1.27 μg/mL respectively, and quercetin (2) also showed significant inhibitory action on DPPH and NA, with IC50 values of 3.82 μg/mL and 1.90 μg/mL. Compounds 1, 2 and methyl 3-hydroxybutanedioic ester (3) could inhibit the production of TNF-α by 22.73%, 33.14% and 37.19% at 5 μg/mL (P < 0.05) compared with the control. In addition, compound 2 was found to be active on the release of IL-6 in RAW264.7 macrophage cells, with an inhibitory rate of 39.79% (P < 0.05). The anti-inflammatory effect of compound 3 is disclosed for the first time in this study. Avian influenza is usually accompanied by virus invasion followed by the occurrence of oxidative stress and serious inflammation, so the multiple effects of the isolates may play a cocktail-like role in the treatment of avian influenza, and C. speciosa components, especially quercetin, might be a potent source for anti-viral and anti-inflammatory agents.
Objectives Coronavirus disease 2019 (COVID-19) has become a serious threat to people's health worldwide. As the world's largest healthcare workforce and the core forces fighting against the epidemic, nurses are on the frontline of this battle. A number of ethical issues have given rise to numerous concerns that have largely affected nurses in different ways as they respond to the epidemic. In addition, excessive expectations from people can exert undue pressure, which can easily lead to burnout in nurses. Methods In this consensus, the expert panel method was used to develop and reach a consensus. The members involved in the formation of the consensus included an expert discussion panel and a consensus writing expert group, a methodologist, and four secretaries. After 16 rounds of online expert consultation and two rounds of expert panel meetings, the writing team analyzed and reviewed the 78 amendments suggested by the experts to develop a consensus on nursing ethics for prevention and control of major infectious disease outbreaks based on the ethical vision of life care. Results This expert consensus focuses on five essential domains: the responsibilities and rights of nurses, the nurse-patient relationship, the doctor-nurse relationship, and the relationship between society and nurses throughout the epidemic. Conclusions We hope this consensus can help nurses better understand and respond to the ethical issues and challenges in public health emergencies such as the COVID-19 outbreak, and raise reasonable public expectations of the roles and responsibilities of nurses in these situations.
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