miR-377-5p inhibits lung cancer cell proliferation,invasion, and cell cycle progression by targeting AKT1 signaling

Lung carcinoma is the most common type of malignant tumors globally, and its molecular mechanisms remained unclear. With the aim to investigate the effects of microRNA (miR)-377-5p on the cell development, invasion, metastasis, and cycle of lung carcinoma, this study was performed. We evaluated miR-377-5p expression levels in lung cancer tissues and cell models. Cell viability, proliferation, migration, invasion abilities, and cell cycle distribution were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, crystal violet, transwell, and flow cytometry assay. Furthermore, expression levels of protein kinase B α subunit (AKT1) and proteins related to cell cycle and epithelial-mesenchymal transition (EMT) were assessed using Western blot analysis and quantitative real-time polymerase chain reaction. These results suggested that miR-377-5p was downregulated in vivo and in cell models, and miR-377-5p overexpression inhibited cell viability, proliferation, migration, invasion, and induced cell-cycle arrest. In addition, as a target of miR-377-5p, AKT1 alleviated the decreases of cell viability, proliferation, migration, invasion, the S-phase cells, the expression of cyclin D1, fibronectin, and vimentin, as well as the increases of the G0/G1-phase cells, the expression of Foxo1, p27 ^kip1, p21 ^Cip1 and E-cadherin when miR-377-5p overexpressed. In conclusion, miR-377-5p inhibited cell development and regulated cell cycle distribution and EMT by targeting AKT1, which provided a theoretical basis for further study of lung carcinoma therapeutics.     

Retracted: miR-145 modulates epithelial-mesenchymal transition and invasion by targeting ZEB2 in non–small cell lung cancer cell lines

Lung cancer is the leading cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a major event that drives cancer progression. Here we aim to investigate the role of microRNA, miR-145, in regulating EMT of the highly invasive non–small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction analysis indicated that miR-145 was downregulated in cancer tissue compared with that in adjacent normal tissue. NSCLC cell lines, namely H1299, PC7, and SPCA-1, also demonstrated miR-145 downregulation, which is correlated well with their invasive ability, assessed by the Matrigel invasion assay. miR-145 overexpression resulted in downregulation of N-cadherin, and downregulation of vimentin and E-cadherin, suggesting a decreased EMT activity. TargetScan analysis predicted that a binding site exists between miR-145 and an oncogene, ZEB2, which was verified using the dual-luciferase assay. Alteration of miR-145 expression also induced inverse effects on ZEB2 expression, and a negative correlation exists between ZEB2 and miR-145 in human tissues. ZEB2 and miR-145 also exerted antagonizing effects on the invasion of NSCLC cells. Therefore, miR-145 is an important molecule in NSCLC that regulates cancer EMT through targeting ZEB2.     

Local Application of Ibandronate/Gelatin Sponge Improves Osteotomy Healing in Rabbits

Delayed healing or non-union of skeletal fractures are common clinical complications. Ibandronate is a highly potent anti-catabolic reagent used for treatment of osteopenia and fracture prevention. We hypothesized that local application of ibandronate after fracture fixation may improve and sustain callus formation and therefore prevent delayed healing or non-union. This study tested the effect of local application of an ibandronate/gelatin sponge composite on osteotomy healing. A right-side distal-femoral osteotomy was created surgically, with fixation using a k-wire, in forty adult male rabbits. The animals were divided into four groups of ten animals and treated by: (i) intravenous injection of normal saline (Control); (ii) local implantation of absorbable gelatin sponge (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS), and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks the affected femora were harvested for X-ray photography, computed tomography (CT), biomechanical testing and histopathology. At both time-points the results showed that the calluses in both the ibandronate-treated groups, but especially in the IB+GS group, were significantly larger than in the control and GS groups. At four weeks the cross sectional area (CSA) and mechanical test results of ultimate load and energy in the IB+GS group were significantly higher than in other groups. Histological procedures showed a significant reduction in osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results indicate that local application of an ibandronate/gelatin sponge biomaterial improved early osteotomy healing after surgical fixation and suggest that such treatment may be a valuable local therapy to enhance fracture repair and potentially prevent delayed or non-union.     

Comprehensive metabolomic,proteomic and physiological analyses of grain yield reduction in rice under abrupt drought–flood alternation stress

Abrupt drought–flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought–flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought–flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought–flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought–flood alteration stress, which are factors that leads to the rice grain yield reduction.     

Excessive rainfall leads to maize yield loss of a comparable magnitude to extreme drought in the United States

Increasing drought and extreme rainfall are major threats to maize production in the United States. However, compared to drought impact, the impact of excessive rainfall on crop yield remains unresolved. Here, we present observational evidence from crop yield and insurance data that excessive rainfall can reduce maize yield up to ?34% (?17 ± 3% on average) in the United States relative to the expected yield from the long‐term trend, comparable to the up to ?37% loss by extreme drought (?32 ± 2% on average) from 1981 to 2016. Drought consistently decreases maize yield due to water deficiency and concurrent heat, with greater yield loss for rainfed maize in wetter areas. Excessive rainfall can have either negative or positive impact on crop yield, and its sign varies regionally. Excessive rainfall decreases maize yield significantly in cooler areas in conjunction with poorly drained soils, and such yield loss gets exacerbated under the condition of high preseason soil water storage. Current process‐based crop models cannot capture the yield loss from excessive rainfall and overestimate yield under wet conditions. Our results highlight the need for improved understanding and modeling of the excessive rainfall impact on crop yield.     

Identification of proteins capable of metal reduction from the proteome of the Gram‐positive bacterium Desulfotomaculum reducens MI‐1 using an NADH‐based activity assay

Understanding of microbial metal reduction is based almost solely on studies of Gram‐negative organisms. In this study, we focus on Desulfotomaculum reducens MI‐1, a Gram‐positive metal reducer whose genome lacks genes with similarity to any characterized metal reductase. Using non‐denaturing separations and mass spectrometry identification, in combination with a colorimetric screen for chelated Fe(III)‐NTA reduction with NADH as electron donor, we have identified proteins from the D. reducens proteome not previously characterized as iron reductases. Their function was confirmed by heterologous expression in Escherichia coli. Furthermore, we show that these proteins have the capability to reduce soluble Cr(VI) and U(VI) with NADH as electron donor. The proteins identified are NADH : flavin oxidoreductase (Dred_2421) and a protein complex composed of oxidoreductase flavin adenine dinucleotide/NAD(P)‐binding subunit (Dred_1685) and dihydroorotate dehydrogenase 1B (Dred_1686). Dred_2421 was identified in the soluble proteome and is predicted to be a cytoplasmic protein. Dred_1685 and Dred_1686 were identified in both the soluble as well as the insoluble protein fraction, suggesting a type of membrane association, although PSORTb predicts both proteins are cytoplasmic. This study is the first functional proteomic analysis of D. reducens and one of the first analyses of metal and radionuclide reduction in an environmentally relevant Gram‐positive bacterium.     

Molecular phylogeny of Macrolycus (Coleoptera: Lycidae) with description of new species from China

Macrolycus is a genus of net‐winged beetles with 69 species distributed in the eastern Palearctic and northernmost part of the Oriental region. The first molecular phylogeny of Macrolycus was produced using an rrnL + tRNA‐Leu + nad1 mtDNA fragment. The major lineages and species limits were identified with morphology and molecular data. We propose that Cerceros is a subgenus of Macrolycus to enable identification of all adult specimens in the genus without DNA sequencing. Two species groups are proposed in Macrolycus s. str. and six in Cerceros. Additionally, twelve Macrolycus species are newly described from China: M. aquilinus, M. baihualingensis, M. bicolor, M. guangxiensis, M. jianfenglingensis, M. kuatunensis, M. lizipingensis, M. parvus, M. phoeniceus, M. rhodoneurus, M. rosaceus and M. sichuanensis. Macrolycus holzschuhi is proposed to be a junior subjective synonym of M. jeanvoinei. The highest diversity of Macrolycus is found in southern China. The species from the main islands of Japan are placed in two species groups: M. excellens is a sister to remaining species of the M. murzini group and the M. flabellatus group is a monophylum of closely related species in a sister position to the M. bicolor group.     

Relationships of diversity,disparity, and their evolutionary rates in squirrels (Sciuridae)

Several theories predict that rapidly diversifying clades will also rapidly diverge phenotypically; yet, there are also reasons for suspecting that diversification and divergence might not be correlated. In the widely distributed squirrel clade (Sciuridae), we test for correlations between per lineage speciation rates, species richness, disparity, and a time‐invariant measure of disparity that allows for comparing rates when evolutionary modes differ, as they do in squirrels. We find that species richness and speciation rates are not correlated with clade age or with each other. Disparity appears to be positively correlated with clade age because young, rapidly diversifying Nearctic grassland clades are strongly pulled to a single stable optimum but older, slowly diversifying Paleotropical forest clades contain lineages that diverge along multiple ecological and morphological lines. That contrast is likely due to both the environments they inhabit and their phylogenetic community structure. Our results argue against a shared explanation for diversity and disparity in favor of geographically mediated modes of speciation and ecologically mediated modes of phenotypic evolution.