Boosting Checkpoint Immunotherapy with Biomimetic Nanodrug Delivery Systems.

Immune checkpoint blockade (ICB) has achieved unprecedented progress in tumor immunotherapy by blocking specific immune checkpoint molecules. However, the high biodistribution of the drug prevents it from specifically targeting tumor tissues, leading to immune-related adverse events. Biomimetic nanodrug delivery systems (BNDSs) readily applicable to ICB therapy have been widely developed at the preclinical stage to avoid immune-related adverse events. By exploiting or mimicking complex biological structures, the constructed BNDS as a novel drug delivery system has good biocompatibility and certain tumor-targeting properties. Herein, the latest findings regarding the aforementioned therapies associated with ICB therapy are highlighted. Simultaneously, prospective bioinspired engineering strategies can be designed to overcome the four-level barriers to drug entry into lesion sites. In future clinical translation, BNDS-based ICB combination therapy represents a promising avenue for cancer treatment.

GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26-bearing mice model was established to examine GRIK5-induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.

Occurrence patterns of black water and its impact on fish in cutover areas of Eucalyptus plantations.

Black runoff occasionally flows from cutover areas of Eucalyptus plantations, polluting rivers and ponds, and resulting in fish death in severe cases. However, the occurrence patterns and environmental impacts of this black water remain unclear. Herein, we analyzed the major characteristics of black water at the occurrence sites, tested the complexation reaction of ground eucalyptus leaves with a solution of Fe3+, and determined the color and absorbance of the complex solution. The results showed that the water was dark blue, with weak acidity and strong light absorbance. The water contained a high level of dissolved organic matter content, while its chemical oxygen demand, total N, total P, NO3--N, and NH4+-N concentrations were significantly higher than those in the stream water from Eucalyptus, Pinus massoniana Lamb., and Cunninghamia lanceolata stands during the growth period. Additionally, the tannic acid concentration in the black water was 1.0 mg L-1 higher than that in the stream water from the Eucalyptus stand. The input of black water increases the concentration of tannic acid and NH4+-N, and the degradation of organic matter consumes dissolved oxygen in downstream ponds, leading to fish deaths. The presence of fresh logging residues and hot, humid weather also enable black water formation. Field investigations and simulation experiments revealed fresh Eucalyptus residues decompose rapidly under high-temperature and rainfall conditions, releasing large amounts of tannic acid, which reacts with Fe3+ to form a dark blue tannic acid­iron complex and results in black water. These results indicate that the rich Fe3+ in runoff may be a key factor in the occurrence of black water. The logging of Eucalyptus plantations during the dry season or on non-rainy days and a reduction in the logging area could prevent the occurrence of black water or mitigate the extent of its environmental hazards.

Minimally Invasive versus Open Simultaneous Resections of Colorectal Cancer and Synchronous Liver Metastases: A Meta-Analysis.

The aim of this meta-analysis was to compare the efficacy and safety of simultaneous resections between the minimally invasive approach (MIA) and the open approach (OA) for patients with colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). A systematic search was conducted in the Cochrane Library, PubMed, EMBASE and Ovid databases (until May 5, 2016). Studies comparing the perioperative results and long-term outcomes for patients undergoing simultaneous CRC and SCRLM resections between the two approaches were evaluated. Six studies were identified, which included 164 minimally invasive and 213 open simultaneous resections of CRC and SCRLM. MIA was associated with lesser surgical blood loss (mean difference = -155.85 mL; 95% confidence interval: -305.64 to -6.06, P = 0.04) and shorter length of postoperative stay (mean difference = -3.16 days; 95% confidence interval: -4.00 to -2.31, P < 0.00001.). The other perioperative results, including operating time, operative blood transfusion, intestinal function recovery time, and postoperative complications, did not differ significantly. No significant difference in the disease-free survival and overall survival rates between the two approaches was observed. In conclusion, compared with the OA, the MIA for simultaneous CRC and SCRLM resections is safe and effective for the treatment of SCRLM with lesser surgical blood loss and shorter length of postoperative stay. The MIA may be an alternative to the OA for simultaneous CRC and SCRLM resections for appropriately selected patients with resectable SCRLM.

Laparoscopic resections of colorectal cancer and synchronous liver metastases: a case controlled study.

PURPOSE: To investigate the efficacy and safety of laparoscopic simultaneous resections of colorectal cancer and synchronous colorectal liver metastases (SCRLM), relative to open surgery. METHODS: Between 1 January 2009 and 20 April 2014, 20 of 25 patients who underwent laparoscopic simultaneous colorectal cancer and SCRLM resections were matched with 20 of 29 patients who underwent an open approach, based on prognostic propensity scores. Perioperative results and survival outcomes were compared. RESULTS: The laparoscopic and open groups were comparable in demographics, cancer characteristics, surgery characteristics, and chemotherapy treatment. No postoperative mortality occurred in either group. The estimated blood loss and postoperative stay were significantly greater in the open group than in the laparoscopic group (all, p < .05). All other perioperative results and postoperative complications were similar between the two groups, as well as three-year overall and disease-free survival rates. CONCLUSIONS: The postoperative complications and survival rates of patients given laparoscopic simultaneous colorectal cancer and SCRLM resections were similar to those treated with an open approach, but with greater short-term benefits. Laparoscopy in this setting by an experienced surgical team appears safe and effective, and is a feasible alternative to an open approach for selected patients.

miR-361-5p inhibits hepatocellular carcinoma cell proliferation and invasion by targeting VEGFA.

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we found that miR-361-5p is down-regulated in 135 patients with HCV-related hepatocellular carcinoma (HCC). Moreover, the expressions of miR-361-5p were highly correlated with VEGFA in these HCC patients. Further, CCK-8 proliferation assay indicated that miR-361-5p mimics inhibited the cell proliferation of HepG2 and SNU-398 HCC cells. Transwell assay showed that miR-361-5p mimics inhibited the invasion and migration of HepG2 and SNU-398 HCC cells. Luciferase assays revealed that miR-361-5p directly bound to the 3'untranslated region of VEGFA, and western blotting showed that miR-361-5p inhibited the expression of VEGFA. Generally, this study indicated that miR-361-5p is down-regulated in HCC and inhibits proliferation and invasion of HCC cell lines via VEGFA. In future, miR-361-5p will be a potential therapeutic agent for HCC.

[Nutrient concentration and storage in different organs of Eucalyptus under effects of nitrogen topdressing].

A field experiment was conducted to study the effects of nitrogen (N) topdressing on the biomass accumulation and nutrient concentration and storage in different organs of two-year-old eucalyptus. Comparing with the control, N topdressing increased the eucalyptus biomass by 24.2%. Branch had the highest increment (38.2%), while leaf had the lowest one. The nutrient uptake under N topdressing was improved significantly, with the order of P > K > N > Mg > Ca > Si. Leaf had the highest contents of N, P, Mg, and Si; trunk had the highest storage of K; while branch had the most significant increase of nutrient concentration and storage. The N, P, and K were recycled mainly through internal flux, with 73.8% of N, 79.1% of P, and 72.9% of K in leaf transferred back to the plant before leaf fallen, and the external flux of these three nutrients only occupied 14.8%, 7.7%, and 8.6% of their total storage in the tree, respectively. The Ca, Mg and Si were the external flux elements, especially for Ca. 89.2% of Ca in leaf was cycled in external flux, accounting for 25.9% of its total storage in the tree.