A pioneering epidemic study has revealed a strong association between obesity and the risk of colitis. In this study, a high fat diet was found to significantly aggravate colitis induced by dextran sulfate sodium (DSS). Meanwhile, a high fat diet changed the miRNA profile of the visceral adipose exosomes, switching the exosomes from anti-inflammatory to a pro-inflammatory phenotype. Strikingly, these inflammatory exosomes efficiently circulated into the lamina propria of the intestine, while these exosomes predisposed the intestine to inflammation via promoting macrophage M1 polarization. Mechanistically, the exosomes promoted M1 differentiation at least partially via transferring pro-inflammatory miRNAs, such as miR-155. Moreover, exosome-mediated miR-155 inhibitor delivery significantly prevented DSS-induced colitis. Together, the study has revealed an exosomal pathway of how obesity aggravates colitis and proposes an exosome-based intervention strategy for colitis management.

Hepatic progenitor cells (HPC) play important roles in both liver regeneration and carcinogenesis. Combined hepatocellular‐cholangiocarcinoma (CHC), a malignant primary liver tumor with poor prognosis, is thought to be of HPC origin. However, the prognostic significance of this etiology is not well defined. Therefore, we retrospectively investigated the relationship of HPC‐related pathological features and long‐term outcome in patients with CHC in our department. In a cohort of 80 patients identified between 1997 and 2003, including 70 patients who underwent resection with curative intent, overall survival (OS) and disease‐free survival (DFS) were correlated with the proliferative activity of nontumor ductular reaction (DR) and the expression levels of HPC and biliary markers including α‐fetoprotein (AFP), keratin 7 (K7), keratin 19 (K19), oval cell (OV)‐6, epithelial cell adhesion molecule (EpCAM), and c‐Kit in both tumor and nontumor liver. We found that nontumor ductular reactions (DRs), specifically the proliferating cell nuclear antigen (PCNA) labeling index of the ductular reaction (PI‐DR), a surrogate for transit‐amplifying compartments, was an independent prognostic factor for both OS and DFS. By contrast, intratumoral expression of only one marker, absence of AFP, was associated with OS. PI‐DR was also independently associated with synchronous “multicentric occurrence” in hepatocellular carcinoma components, a feature of CHC that may predispose to metachronous multifocal tumorigenesis. Conclusion: Proliferative ductular reaction related to HPC activation is associated with recurrence of CHC. Background HPC activation is strongly associated with multifocal occurrence and related tumor recurrence, highlighting the critical role of background liver disease, a “field effect,” in the recurrence of CHC. (Hepatology 2012;56:1804–1816)

Rationale: Reciprocal interactions between leukemic cells and bone marrow mesenchymal stromal cells (BMMSC) remodel the normal niche into a malignant niche, leading to leukemia progression. Exosomes have emerged as an essential mediator of cell-cell communication. Whether leukemic exosomes involved in bone marrow niche remodeling remains unknown.Methods: We investigated the role of leukemic exosomes in molecular and functional changes of BMMSC in vitro and in vivo. RNA sequencing and bioinformatics were employed to screen for miRNAs that are selectively sorted into leukemic exosomes and the corresponding RNA binding proteins.Results: We demonstrated that leukemia cells significantly inhibited osteogenesis by BMMSC both in vivo and in vitro. Some tumor suppressive miRNAs, especially miR-320, were enriched in exosomes and thus secreted by leukemic cells, resulting in increased proliferation of the donor cells. In turn, the secreted exosomes were significantly endocytosed by adjacent BMMSC and thus inhibited osteogenesis at least partially via β-catenin inhibition. Mechanistically, miR-320 and some other miRNAs were sorted out into the exosomes by RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), as these miRNAs harbor the recognition site for HNRNPA1.Conclusion: HNRNPA1-mediated exosomal transfer of miR-320 from leukemia cells to BMMSC is an important mediator of leukemia progression and is a potential therapeutic target for CML.

Background Periodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive. Results Exosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway. Conclusion In conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos. Graphical Abstract

Cancer-associated cachexia (CAC) has tremendous effects on the patient's tolerance to chemotherapy and the quality of life, especially in the advanced stages, such as the acute and terminal stages of chronic myeloid leukemia (CML). However, the underlying mechanisms and mediators remain unclear. Here, we showed that mice injected with CML-derived exosomes had significant weight loss and great drop of body fat rate. In the meanwhile, we found that CML-derived exosomes could be taken up by adipose tissue, and, in turn, suppressed the adipogenic ability of adiposederived mesenchymal stem cells (ADSCs). By RNA sequencing, miR-92a-3p was found highly expressed in both CML cells and the derivative exosomes. Mechanistically, miR-92a-3p inhibited adipogenesis of ADSCs via posttranscriptionally decreasing C/EBPα expression when transferred into the ADSCs with the exosomes, and encapsulating miR-92a-3p inhibitor into CML exosomes blocked the antiadipogenic effects of CML exosomes. In addition, we also found that miR-92a-3p was highly expressed in exosomes from some other types of cancers that cause cachexia. These results demonstrate that adipogenesis inhibition by tumor-derived exosomes, mainly exosomal microRNAs like miR-92a-3p, are the main mediators for CAC.

Reliability assessment is a critical consideration in equipment engineering project. Successful reliability assessment, which is dependent on selecting features that accurately reflect performance degradation as the inputs of the assessment model, allows for the proactive maintenance of equipment. In this paper, a novel method based on kernel principal component analysis (KPCA) and Weibull proportional hazards model (WPHM) is proposed to assess the reliability of rolling bearings. A high relative feature set is constructed by selecting the effective features through extracting the time domain, frequency domain, and time-frequency domain features over the bearing’s life cycle data. The kernel principal components which can accurately reflect the performance degradation process are obtained by KPCA and then input as the covariates of WPHM to assess the reliability. An example was conducted to validate the proposed method. The differences in manufacturing, installation, and working conditions of the same type of bearings during reliability assessment are reduced after extracting relative features, which enhances the practicability and stability of the proposed method.

it is challenging to develop a low-cost household water treatment (HWt) that simultaneously deliver an effective and robust way for safe and reliable water supply. Here, we report a simple flow-through filter made by zeolite-cotton packing in a tube (Zct) as low-cost HWt device to remove heavy metal ions from contaminated water. The zeolite-cotton is fabricated by an on-site template-free growth route that tightly binds mesoporous single-crystal chabazite zeolite onto the surface of cotton fibers. As a result, the ZCT set-up with optimized diameter achieves both high adsorption efficiency, proper flow rate, reliable supply and strong stability at the same time. After flowed through the set up packed with 10 g of zeolite-cotton, 65 mL 1000 ppm Cu 2+ solution was purified down to its safety limit (<1 ppm). Notably, their efficiency remains unaltered when filtering several ions simultaneously. In a simulated purification process, 8 L of water contaminated by Cu 2+ , cd 2+ and pb 2+ could be transformed into drinking water and it enables the removal of heavy metals to concentrations of below 5 ppb (μg L −1 ). We also show that the Zct can be used for disinfection by introducing Ag-exchanged zeolite-cotton without contaminating the water with Ag ions (<0.05 ppm).Drinking water safety is one of the most serious health problems throughout the world, especially for those people in relatively undeveloped districts. Health risks may arise from consumption of water contaminated with numerous pollutants such as heavy metal ions, persistent organic pollutants, pharmaceutical waste, virus and microbial pathegens 1 . As reported by World Health Organization (WHO), nearly 2 billion people are using either un-improved drinking water source or faecally-contaminated water. Close to half a million diarrheal deaths in low-and middle-income countries are attributed to unsafe drinking-water, and the vast majority of these deaths occur among children under five 2 . Household water treatment (HWT) is an important public health intervention to improve the quality of drinking-water, particularly among those who rely on water from unimproved sources. Further, safe drinking-water is an immediate priority in most emergencies, and HWT can be an effective emergency response intervention 3,4 , for example, the project solar disinfection (SODIS) of drinking water 5-8 , which is awarded the 2020 UNESCO Prizes, is an important HWT technique approved by WHO.Unlike organic pollutants, heavy metal ions in water is hard to notice and avoid but pose a long-term threat to human. Heavy metal contaminated water usually has no visible difference as compared to safe drinking water, however, every little intake will not degrade but accumulate in human body. Even if the heavy metal-polluted water is not directly taken by human, it can also accumulate in algae, shellfish and fish, then concentrate through food chain and finally result in serious disease such as encephalopathy, hemolytic anemia or even cancer 9-11 . Those global issues have reminded people to se...

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