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Background Colorectal cancer (CRC) is one of the most malignant cancer worldwide, and the limited efficacy of existing treatments is the leading cause of death in patients with CRC. Thus, novel drugs for CRC treatment are urgently needed. Methods We screened an FDA-approved small-molecule library upon HCT116 cells, and identified lomitapide as a novel CRC anticancer compound. Then we confirmed the activities of lomitapide on CRC cells by WST-1 assay, colony formation, and flow cytometry. RNA sequencing and GO analysis were used to investigate the mechanisms underlying the anticancer effects of lomitapide. LiP-SMap was introduced to search for the potential targets of lomitapide. The in vivo experiment was conducted to confirm the therapeutic efficiency and safety of lomitapide as an anticancer agent. Results Lomitapide exhibited remarkable antitumor properties in vitro and in vivo, while activated autophagy is characterized by GO analysis as a key biological process in lomitapide-induced CRC repression. Moreover, lomitapide stimulated mitochondrial dysfunction-mediated AMPK activation, resulting in increased AMPK phosphorylation and enhanced Beclin1/Atg14/Vps34 interactions, provoking autophagy induction. LiP-SMap analysis showed that PP2A was the direct target of lomitapide, and the bioactivity of lomitapide was attenuated in PP2A-deficient cells, suggesting that the anticancer effect of lomitapide occurs in a PP2A-dependent manner. Conclusions Our results indicate that lomitapide activates AMPK-regulated autophagy to inhibit the proliferation and tumorigenesis of CRC cells by directly targeting PP2A, and can be a novel therapeutic agent for the treatment of CRC patients.

Treatment of neuropathic pain (NP) resulting from nerve injury is one of the most complicated and challenging in modern practice. Pharmacological treatments for NP are not fully effectively and novel approaches are requisite. Recently, transplantation of bone mesenchymal stem cells (BMSCs) has represented a promising approach for pain relief and neural repair, but how it produces beneficial effects on resiniferatoxin (RTX) induced nerve injury is still unclear. Here, we identified the BMSCs' analgesic effects and their potential mechanisms of microglial cells activation on RTX induced neuralgia. Immunostaining, biochemical studies demonstrated that microglia rather than astrocyte cells activation involved in RTX induced mechanical hyperalgesia, whereas the GFP-labeled BMSCs alleviated this mechanical hyperalgesia. Moreover, pain-related TRPA1, PKCδ, CaMKIIɑ (Calcium/calmodulin dependent protein kinase II), P38/MAPK (mitogen-activated protein kinase), p-P65 activation and expression in the spinal cord were significantly inhibited after BMSC administration. In addition, BMSCs treated RTX mice displayed a lower density of mushroom dendritic spines. Our research suggested that activation of PKCδ-CaMKIIɑ-P38/MAPK-p-P65 pathway and mushroom dendritic spines abnormal increase in the spinal cord is the main mechanism of RTX induced neuropathic pain, and transplant of BMSCs to the damaged nerve may offer promising approach for neuropathic pain.

Four potent native human mAbs targeting distinct epitopes on TeNT were isolated with neutralization potency ranging from approximately 17 mg to 6 mg each equivalent to 250IU of human anti-TeNT immunoglobulin. TT0170 binds fragment B, TT0069 and TT0155 bind fragment AB. MAb TT0067 binds fragment C and blocks the binding of TeNT to gangliosides, Co-crystal structure of TT0067 with fragment C of TeNT at 2.01 A resolution demonstrated that mAb TT0067 directly occupies the W pocket of one of the receptor binding sites on TeNT, resulting in blocking the binding of TeNT to ganglioside on the surface of host cells to neutralize TeNT, and revealed at the first time at atomic level the mechanism of action by TeNT neutralizing antibody and the key neutralization epitope on the fragment C of TeNT, and provided the critical information for development of fragment C of TeNT as a better and safer tetanus vaccine.

Currently, air pollution from vessel exhaust emission is increasingly prominent. In particular, Jiangsu province, as a large inland waterway transportation province, has a large amount of ship emissions; however, the amount of such emissions remains unidentified. Considering the importance of the Beijing-Hangzhou Grand Canal for Jiangsu province and for the country, the inland vessel emission inventory of the Beijing-Hangzhou Grand Canal in Jiangsu province in 2014 was established using activity-based approach, the total annual emissions of particulate and gaseous pollutants were quantified, and the emission characteristics of vessels were also discussed. Dry cargo ships are the largest source of air pollutants, with ships whose gross tonnage is between 200 and 600 tons having the greatest contribution to exhaust emission. The order of the emission contribution for each vessel operation condition was as follows: normal navigation > passing through the shipping-lockage > berthing > mooring. Vessels running on the fairway made the greatest contribution in the aspect of the spatial distribution. Except in February, the monthly emissions not from ships presented a relatively steady trend.

Electrochromic devices are emerging as a futuristic technology for flexible electronics with the practical application values in energy-saving, displaying and military camouflage, however, the limitations in the optical, electrical and mechanical properties of the existing transparent conducting electrodes (TCEs) appear as a major obstacle for realizing high performance flexible electrochromic devices. In this work, we have proposed and demonstrated a fast-response and bendable polymer poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT: PSS) electrochromic device based on the embedded nickel (Ni) grid electrode. The Ni grid electrode, fabricated though patterned electroplating, has low sheet resistance (~1.3 Ω/sq), high transparency (~80%), excellent mechanical reliability and long-term chemical stability, exhibiting a figure of merit of 1250, surpassing the most existing TCEs. In addition, we have proposed a compact electrochromic architecture with the electrochromic PEDOT: PSS layer and solid polymer electrolyte being sandwiched between two embedded Ni grid electrodes. The device shows a short coloration and bleaching time (~1 s for 90% optical contrast), a high coloration efficiency (325 cm2/C) and excellent mechanical reliability (optical contrast retention ~80% after 1000 bending circles), paving a way for high performance flexible electronics.

The cell wall structure of mushroom sclerotium was investigated by a fractionation of its soluble cell wall polysaccharides followed by chemical, physico-chemical and microscopic analyses. The present results suggest that cell wall structure of Pleurotus tuber regium sclerotium contains three main layers: an outer layer of glycoproteins, a middle layer of hyper-branched glucans and an inner layer of complex between hyper-branched glucan and chitin. The structure of the hyper-branched glucans were elucidated by the methylation analysis to be composed of →1)-Glcp-(4→ linkages as the backbone with some →1)-Glcp-(6→ linkages existed in the side chains, while some →1)-Glcp-(3→ linkages might exist in the backbone or side chains. SEC-MALLS analysis revealed that hyper-branched β-glucans had a Mw ranging from 1.4 to 5.2 × 106 g/mol and R.M.S. radius ranging from 26 nm to 38.5 nm. SEM and AFM further showed that hyper-branched β-glucans were spherical in shape when dispersed in water.

Films of anatase were prepared on silicon and silica supports by ultrasonic nebulization of an ethanol solution of titanium acetylacetonate followed by pyrolysis and annealing in oxygen at 380°C. The transformation to rutile occurred in the temperature range 800–950°C without degradation of the film quality. TiO 2 films could be slightly reduced to TiO 2−x at 500°C in an atmosphere of pure hydrogen and further reduction, giving increased conductivity, occurs at elevated temperature. These films were comparable in quality to those prepared by more elaborate techniques.