Rationale: Extracellular vesicles (EVs) have emerged as novel mediators of cell-to-cell communication that are capable of the stable transfer of therapeutic microRNAs (miRNAs), and thus, EVs hold immense promise as a miRNA delivery system for cancer therapy. Additionally, as miRNA-containing EVs are secreted into circulation, miRNAs contained within plasma EVs may represent ideal biomarkers for diseases. The objective of this study was to characterize a potential tumor suppressor miRNA, miR-101, and explore the potential of miR-101 delivery via EVs for in vivo therapy of metastatic osteosarcoma as well as the potential value of plasma EV-packaged miR-101 (EV-miR-101) level for predicting osteosarcoma metastasis.Methods: The relationship of miR-101 expression and osteosarcoma progression was investigated in osteosarcoma specimens by in situ hybridization (ISH), and the potential inhibitory effect of miR-101 was further investigated using in vivo models. Using prediction software analysis, the mechanism of action of miR-101 in osteosarcoma was explored using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting and dual-luciferase assay. Adipose tissue-derived mesenchymal stromal cells (AD-MSCs) were transduced with lentiviral particles to obtain miR-101-enriched EVs. A Transwell assay and lung metastasis models of osteosarcoma were used to observe the effect of miR-101-enriched EVs on osteosarcoma invasiveness and metastasis. Detection of plasma EV-miR-101 levels was carried out in osteosarcoma patients and healthy controls by qRT-PCR.Results: miR-101 expression was markedly lower in metastatic osteosarcoma specimens compared to non-metastatic specimens. Significantly fewer metastatic lung nodules were formed by Saos-2 cells overexpressing miR-101 and SOSP-9607 cells overexpressing miR-101 injected into mice. With increased miR-101 expression, B cell lymphoma 6 (BCL6) mRNA and protein expression levels were reduced, and miR-101 was found to exert its effects by directly targeting BCL6. AD-MSCs were successfully engineered to secrete miR-101-enriched EVs. Once taken up by osteosarcoma cells, these EVs showed suppressive effects on cell invasion and migration in vitro, and systemic administration of these EVs effectively suppressed metastasis in vivo with no significant side effects. Finally, the EV-miR-101 level was lower in osteosarcoma patients than in healthy controls and even lower in osteosarcoma patients with metastasis than in those without metastasis.Conclusion: Our data support the function of miR-101 as a tumor suppressor in osteosarcoma via downregulation of BCL6. AD-MSC derived miR-101-enriched EVs represent a potential innovative therapy for metastatic osteosarcoma. EV-miR-101 also represents a promising circulating biomarker of osteosarcoma metastasis.

Marxist as well as classical and neo-liberal theories expect that the development of capitalist agriculture will be accompanied by the spread of an agricultural proletariat. That was what happened in eighteenth-century England; it is also what is happening in contemporary India. This article asks, first of all: just what is the size of China's present agricultural proletariat? And how do we understand and explain those dimensions? Our finding is that, contrary to our own initial expectations, hired agricultural year-workers in China today total only 3 percent of all labor input in agriculture (and short-term workers another 0.4 percent), in sharp contrast to India's 45 percent, this even while the past two decades have seen very substantial "capitalization" (i.e., increased capital input per unit of land) in agriculture. We term the phenomenon "capitalization without proletarianization," perhaps the most distinctive characteristic of recent Chinese agricultural development.

This article emphasizes the urgent demand for measurements of university internationalization and proposes a new approach to develop a set of internationally applicable indicators for measuring university internationalization performance. The article looks into existing instruments developed for assessing university internationalization, particularly focusing on the methodological aspects. By examining the weaknesses of current instruments, a new approach for developing indicators for university internationalization has been proposed in the study. The new approach highlights the method for developing indicators, people who should be engaged in the process and the steps should be followed in indicator development.The study also provides a conceptual framework of university internationalization for developing the indicator set. Suggestions for further work are made at the end of the article.

The aim of the present study was to describe the expression and distribution of bone morphogenetic protein (BMP) in odontogenic tumors by immunohistochemistry using monoclonal antibody against bovine BMP (BMPMcAb). Eight types of odontogenic tumors (44 cases), including ameloblastoma (20 cases), cementifying fibroma (8 cases), benign cementoblastoma (5 cases), dentinoma (3 cases), compound odontoma (2 cases), adenomatoid odontogenic tumor (2 cases), calcifying epithelial odontogenic tumor (2 cases) and odontogenic fibroma (2 cases), were studied. The results showed that, according to the immunostaining pattern of BMPMcAb, tumors could be classified into two types: all cementifying fibromas, benign cementoblastomas, dentinomas, odontogenic fibromas, and compound odontomas demonstrated a positive reaction, whereas all ameloblastomas, adenomatoid odontogenic tumors, and calcifying epithelial odontogenic tumors were negative. BMPMcAb-positive odontogenic tumors were those tumors with formation of enamel, dentin, cementum or bone. Therefore, BMP might play an important role in the formation of calcified dental tissues and the development of odontogenic tumors contaning such tissues.

Background Idiopathic pulmonary fibrosis is characterized by loss of lung epithelial cells and inexorable progression of fibrosis with no effective and approved treatments. The distal airway stem/progenitor cells (DASCs) have been shown to have potent regenerative capacity after lung injury. In this work, we aimed to define the role of mouse DASCs (mDASCs) in response to bleomycin-induced lung fibrosis in mice. Methods The mDASCs were isolated, expanded in vitro, and labeled with GFP by lentiviral infection. The labeled mDASCs were intratracheally instilled into bleomycin-induced pulmonary fibrosis mice on day 7. Pathological change, collagen content, α-SMA expression, lung function, and mortality rate were assessed at 7, 14, and 21 days after bleomycin administration. Tissue section and direct fluorescence staining was used to show the distribution and differentiation of mDASCs in lung. Results The transplanted mDASCs could incorporate, proliferate, and differentiate into type I pneumocytes in bleomycin-injured lung. They also inhibited fibrogenesis by attenuating the deposition of collagen and expression of α-SMA. In addition, mDASCs improved pulmonary function and reduce mortality in bleomycin-induced pulmonary fibrosis mice. Conclusions The data strongly suggest that mDASCs could ameliorate bleomycin-induced pulmonary fibrosis by promotion of lung regeneration and inhibition of lung fibrogenesis. Electronic supplementary material The online version of this article (10.1186/s13287-019-1257-2) contains supplementary material, which is available to authorized users.