The contribution of the Beijing, Tianjin and Hebei region's iron and steel industry to local air pollution in winter.

The Beijing, Tianjin and Hebei region (BTH) in China is a highly populated area that has recently experienced frequent haze episodes in winter. With high production capacities, the iron and steel industry (ISI) has long been a key source of air pollutants in BTH and is thus considered responsible for the degradation of local air quality. Here, we conducted a cross-disciplinary research combining the Weather Research and Forecasting with Chemistry (WRF/Chem) model, the multiregional input-output model (MRIO) and the health assessment model to explore the impacts of the ISI on air pollution in the BTH region in January 2012. Our results show large increases in air pollution due to direct ISI emissions, with up to a 90 µg/m3 monthly average of fine particulate matter (PM2.5) and sulfur dioxide (SO2) in eastern Tangshan and western Handan. In addition to direct emissions, the ISI has induced large quantities of indirect emissions from upstream sectors (e.g., the electricity and transportation sectors), leading to PM2.5, SO2 and NOx increases of 2-10 µg/m3 in BTH. Considering the direct and indirect emissions, we estimated that 275 (233-313) PM2.5-related mortalities occurred in January, and approximately 42% of these premature deaths occurred in Tangshan. A high rate of premature deaths also occurred in urban Beijing due to its high population density. Revealing the great health burden caused by the ISI, our results underscore the necessity for the Chinese government to reduce air pollutant emissions from the ISI and its upstream industries in BTH.

Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing anti-glioma efficacy by modulating glioma microenvironment.

Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood-brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms in vivo and in vitro. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.

Enhanced antitumor and anti-metastasis efficacy against aggressive breast cancer with a fibronectin-targeting liposomal doxorubicin.

The chemotherapy of aggressive breast tumor is usually accompanied by a poor prognosis because of the metastasis of tumor cells. Thus, it is important to simultaneously enhance antitumor and anti-metastasis efficacy. Fibronectin and its complexes are expressed on the walls of tumor vessels and in tumor stroma. Moreover, the expression of fibronectin in metastatic sites is even higher than that in primary tumors. Herein, we designed a fibronectin-targeting CREKA-modified liposomal doxorubicin (CREKA-Lipo-Dox) for the therapy of metastatic breast tumor. CREKA-Lipo was uniformly formed with high entrapment efficiency. It exhibited longer blood circulation time compared with free Dox, and there was no significant change compared with PEG-Lipo-Dox. Immunofluorescence results revealed that the CREKA-Lipo-Dox could specifically bind to fibronectin in the tumor vessels and tumor stroma. The antitumor and anti-metastasis efficacy of CREKA-loaded liposome was more obvious than that of free Dox or unmodified Dox-Lipo. Taken together, binding fibronectin by CREKA could be an attractive therapeutic strategy for metastatic breast cancer in the future.

Development of a multi-target peptide for potentiating chemotherapy by modulating tumor microenvironment.

Finding effective cures against aggressive malignancy remains a major challenge in cancer chemotherapy. Here, we report a "tadpole"-like peptide by covalently conjugating the alanine-alanine-asparagine "tail" residual to the cyclic tumor homing peptide iRGD (CCRGDKGPDC) to afford nRGD, which significantly enhanced tumoricidal effects of doxorubicin, by either co-administered as a physical mixture or as a targeting ligand covalently conjugated to the liposomal carrier. Given twice at an equivalent dose of 5 mg/kg, doxorubicin loaded liposomes modified with nRGD (nRGD-Lipo-Dox) showed excellent antitumor efficacy in 4T1 breast cancer mice, of which 44.4% remained alive for over 90 days without recurrence during the period of investigation. The dramatic improvement in antitumor efficacy was attributed to nRGD-Lipo-Dox which appeared to specifically interact with tumor vascular endothelial cells to achieve efficient tumor penetration, and modulate tumor microenvironment with depletion of tumor associated macrophages.