Search

During the aerial spraying of pesticides by plant protection UAVs (unmanned aerial vehicles), droplets are deposited below the aircraft under the influence of rotor airflow. The existence of a downwash airflow can improve the deposition of spray on target crops. However, during operation, variations in flight altitude and the gradual decrease in the payload of pesticide solution in the tank leads to changes in the flow field below the UAV which affects droplets distribution. In order to study this, the downwash airflow speed and droplet distributions below a UAV under different flight altitudes (1.5–3 m) and payloads (0-10 kg) were measured and analysed. The results indicated that the changes in operational parameters normally found during operation can change distribution of downwash airflow in all directions but particularly vertical and this can affect the distribution of spray below the UAV. Through correlation analysis, it was shown that the vertical component of airflow (downwash) had a significant positive correlation with spray deposition and penetration (P < 0.05, B = 0.082, B = 0.029), and a negative correlation with droplet deposition uniformity (coefficient of variation) and drift (P < 0.05, B = −3.818, B = −0.042). Thus, it can be seen that downwash is conducive to spray deposition and penetration, which can improve the droplet distribution uniformity and reduce drift. Thus, the influence mechanism of UAV airflow on droplet distribution was explored and shown to strongly influence have the quality of spraying by plant protection UAVs. • Wireless wind speed sensors used to test the downwash airflow UAV. • Reduction in payload affects the downwash airflow of UAV. • Downwash airflow of UAV in turn affects spray distribution. • Vertical downwash airflow has a significant correlation with droplet distribution. [ABSTRACT FROM AUTHOR]

A regorafenib nanodrug is prepared by self-assembly using regorafenib and clinically approved indocyanine green, which sufficiently delivers regorafenib into colorectal tumor and liver metastasis, markedly enhances regorafenib's therapeutic efficacy. [Display omitted] • A regorafenib nanodrug (nanoRF) was fabricated by self-assembly. • NanoRF encapsulated regorafenib with a high loading content of 96%. • NanoRF exhibited excellent reproducibility and colloidal stability. • NanoRF effectively delivered regorafenib into tumor local and liver. • NanoRF enhanced regorafenib's antitumor efficacy in advanced colorectal cancers. Distant metastases and chemotherapy repellency are the key causes of colorectal cancer (CRC)-related mortality. Regorafenib, an oral multi-kinase inhibitor approved for treating advanced CRC with distant metastases and/or chemo-resistance, however only improves median overall survival by 1.4 months. Such limited therapeutic effect is likely due to the low bioavailability of orally administered hydrophobic regorafenib. A regorafenib nanodrug is fabricated by one-step self-assembly with a clinically often-used fluorescent agent (indocyanine green) for overcoming regorafenib's limitations, towards improving regorafenib's therapeutic efficacy in advanced CRC. This nanodrug (nanoRF) was characterized, and its antitumor effects were assessed in three preclinical CRC models. NanoRF converts regorafenib's delivery approach from oral to intravenous with a significantly high encapsulation efficacy of regorafenib (96%) and a long-time colloidal stability. Nanodrug (nanoRF) markedly prolongs regorafenib's blood circulation by halving clearance rate, and enhances regorafenib's tumor accumulation. Across three preclinical CRC models (xenografted tumor, chemodrug-resistant xenografted tumor, and liver metastasis), nanoRF drastically enhances regorafenib's tumor inhibiting efficacy by 0.5–4 folds and effectively extends survival by 0.5–5 folds. This regorafenib nanodrug is a simple, safe, and efficient therapeutic nanodrug for treating advanced CRC with a ready-to-be-clinically-translated potential. [ABSTRACT FROM AUTHOR]

Background: The epidermal growth factor receptor (EGFR) has played an important role in the growth and apoptosis of colon cancer. The RNA interference (RNAi) technique can suppress gene expression, but the effects of double combining sites RNAi targeting EGFR have not been well understood. Methods: pU6-EGFR-shRNA-1 and pU6-EGFR-shRNA-2 expressive vectors were transfected to the LoVo cells. Five groups were selected for the study: Group 1, the control cells; group 2, the negative control plasmid vector HK; group 3, pU6-EGFR-shRNA-1; group 4, pU6-EGFR-shRNA-2; group 5, pU6-EGFR-shRNA-1 and pU6-EGFR-shRNA-2, half for each. The mRNA and protein expression were assessed by Real Time quantitative PCR and Western blot. Apoptosis was determined via flow cytometry. IC50 and the inhibition ratio of 5-fluorouracil (5-FU) were carried out by CCK-8. Results: In groups 3, 4, and 5, the mRNA expression was decreased by (80.22 ± 3.42)%, (81.30 ± 2.83)%, and (90.58 ± 2.76)%, respectively, and the protein expression was decreased by (74.11 ± 4.02)%, (73.39 ± 2.30)%, and (90.39 ± 3.34)%, respectively. Meanwhile, the cell apoptosis increased by (10.43 ± 0.49)%, (10.13 ± 0.39)%, and (14.17 ± 0.53)%, respectively. The IC50 of 5-FU and cell inhibition ratio analysis demonstrated that there were significant differences between the following three: group 5, groups 3 and 4, and groups 1 and 2. Conclusions: Both pU6-EGFR-shRNA-1 and pU6-EGFR-shRNA-2 are capable of suppressing EGFR expression of the LoVo cell and can promote apoptosis and increase the cell toxicity of 5-FU. The double combining sites RNAi technique is significantly better than a single site. [Copyright &y& Elsevier]

Human anterior gradient-2 (AGR2), a member of protein disulfide isomerase (PDI) family, is present in both intracellular and extracellular compartments. Although AGR2 is overexpressed in various human cancers and reported to promote aggressive tumor features, little is known regarding AGR2′s extracellular functions during tumorigenesis. Here, we demonstrate that secreted AGR2 promotes cell migration and metastasis of colorectal cancer (CRC) in vitro and in vivo . Mechanistically, secreted AGR2 elevated Wnt11 expression, triggering non-canonical Wnt signaling: the Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII) and c-jun amino-terminal kinase (JNK) pathways. Knockdown of Wnt11 or pretreatment with CaMKII and JNK inhibitors reversed the secreted AGR2′s migration-promoting effect. Further studies revealed that AGR2 antagonized canonical Wnt/β-catenin signaling via activating CaMKII. Collectively, our study uncovers a critical role of Wnt11-mediated non-canonical Wnt signaling (CaMKII and JNK pathways) in secreted AGR2′s promoted migration of CRC cells. These results raise the possibility that secreted AGR2 may be a potential therapeutic target towards inhibiting CRC metastasis. [ABSTRACT FROM AUTHOR]

Highlights: [•] HMGB1 in the peritoneal cavity of mice after surgical trauma was detected. [•] HMGB1 in the peritoneal cavity recruited myeloid derived suppressor cells. [•] Blocking HMGB1 reduced the recruitment of myeloid derived suppressor cells. [•] The recruited MDSCs favor postoperative peritoneal metastasis of colon cancer. [ABSTRACT FROM AUTHOR]

Human anterior gradient-2 (AGR2), a member of protein disulfide isomerase (PDI) family, is upregulated in various human cancers and reportedly has oncogenic activities. However, the functional roles of AGR2 and its regulation in colorectal cancer (CRC) remain unclear. Here, we showed that AGR2 promoted CRC tumorigenesis and progression in vitro and in vivo and acted as an independent prognostic factor of poor outcome. AGR2 was negatively regulated by DNA methyltransferase 3a (DNMT3a) through directly methylating AGR2 promoter and by a DNMT3a–SPRY2–miR-194 axis. Moreover, AGR2 mediated the resistance to 5-Aza-2′-deoxycytidine (5-Aza) treatment. Knockdown of AGR2 improved the therapeutic effect of 5-Aza in human CRC xenograft tumor model. Thus, our work supports AGR2's oncogenic role in CRC, reveals DNMT3a-mediated epigenetic modulation on AGR2 promoter, and uncovers a new DNMT3a signaling module controlling expression of AGR2. Upregulated AGR2 offset 5-Aza mediated epigenetic therapy. This work might provide potential targets for clinical anti-cancer therapy. • AGR2 acted as an oncogene in CRC. • AGR2 was downregulated by DNMT3a in a dual manner: AGR2 promoter methylation and a DNMT3a–SPRY2–miR-194 signaling axis. • AGR2 mediated the drug resistance of 5-Aza in CRC. AGR2 knockdown could improve the therapeutic effect of 5-Aza in CRC. [ABSTRACT FROM AUTHOR]