Investigation of morphology and structure of drug-loaded PLA-b-PEO-b-PLA polymeric micelle: A dissipative particle dynamics simulations study.

The dissipative particle dynamics (DPD) simulation was used to study the morphologies and structures of the paclitaxel-loaded PLA-b-PEO-b-PLA polymeric micelle. We focused on the influences of PLA block length, PLA-b-PEO-b-PLA copolymer concentration, paclitaxel drug content on morphologies and structures of the micelle. Our simulations show that: (i) with the PLA block length increase, the self-assemble structure of PLA-b-PEO-b-PLA copolymers with paclitaxel vary between onion-like structure (core-middle layer-shell) to spherical core-shell structure. The PEO shell thins and the size of the PLA core increases. The onionlike structures are comprised of the PEO hydrophilic core, the PLA hydrophobic middle layer, and the PEO hydrophilic shell, the distribution of the paclitaxel drug predominantly occurs within the hydrophobic intermediate layer; (ii) The system forms a spherical core-shell structure when a small amount of the drug is added, and within a certain range, the size of the spherical structure increases as the drug amount increases. When the drug contents (volume fraction) cdrug = 10%, it can be observed that the PLA4-b-PEO19-b-PLA4 spherical structures connect to form rod-shaped structures. With the length of PLA block NPLA = 8, as the paclitaxel drug concentrations cdrug = 4%, PEO has been insufficient to completely encapsulate the PLA and paclitaxel drug beads. To enhance drug loading capacity while maintaining stability of the system in aqueous solution, the optimal composition for loading paclitaxel is PLA4-b-PEO19-b-PLA4; the drug content is not higher than 4%; (iii) The paclitaxel-loaded PLA4-b-PEO19-b-PLA4 micelle undergo the transition from onionlike (core-middle layer-shell) to spherical (core-shell) to rod-shaped and lamellar structure as the PLA4-b-PEO19-b-PLA4 copolymer concentration increases from ccp = 10% to 40%.

Deleted in liver cancer 1 suppresses the growth of prostate cancer cells through inhibiting Rho-associated protein kinase pathway.

Objective: Deleted in liver cancer 1 (DLC1) is a GTPase-activating protein that is reported as a suppressor in certain human cancers. However, the detailed biological function of DLC1 is still unclear in human prostate cancer (PCa). In the present study, we aimed to explore the function of DLC1 in PCa cells. Methods: Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line (LNCaP) using RNA interference and lentiviral vector transduction. The Cell Counting Kit-8 assay was performed to determine cell proliferation. The cell cycle was examined by performing a propidium iodide staining assay. Results: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells. Moreover, DLC1 expression was negatively correlated with Rho-associated protein kinase (ROCK) expression in LNCaP cells. Importantly, this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo. Conclusion: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.

Diet-induced microbial adaptation process of red deer (Cervus elaphus) under different introduced periods.

Insufficient prey density is a major factor hindering the recovery of the Amur tiger (Panthera tigris altaica), and to effectively restore the Amur tiger, red deer (Cervus elaphus) was released into the Huangnihe National Nature Reserve of Northeast China as the main reinforcement. Differences in feeding and synergistic changes caused by the intestinal microbial communities could impact the adaptation of wildlife following reintroductions into field environments. We analyzed the foraging changes in shaping the intestinal microbial community of the red deer after being released to the Huangnihe National Nature Reserve and screened the key microbial flora of the red deer when processing complex food resources. The feeding and intestinal microbial communities of the red deer were analyzed by plant Deoxyribonucleic acid (DNA) barcoding sequencing and 16S rRNA high-throughput sequencing, respectively. The results showed that there were significant differences in food composition between wild and released groups [released in 2019 (R2): n = 5; released in 2021 (R0): n = 6]; the wild group fed mainly on Acer (31.8%) and Abies (25.6%), R2 fed mainly on Betula (44.6%), R0 had not formed a clear preferred feeding pattern but had certain abilities to process and adapt to natural foods. Firmicutes (77.47%) and Bacteroides (14.16%) constituted the main bacterial phylum of red deer, of which, the phylum Firmicutes was the key species of the introduced red deer for processing complex food resources (p < 0.05). The wild release process significantly changed the intestinal microbial structure of the red deer, making it integrate into the wild red deer. The period since release into the wild may be a key factor in reshaping the structure of the microbial community. This study suggested that the intestinal microbial structure of red deer was significantly different depending on how long since captive deer has been translocated. Individuals that have lived in similar environments for a long time will have similar gut microbes. This is the adaption process of the wildlife to natural environment after wild release, taking into account the gut microbes, and the feeding changes in shaping microbial communities can help introduced red deer match complex food resources and novel field environments.

4-bit DAC based 6.9Gb/s PAM-8 UOWC system using single-pixel mini-LED and digital pre-compensation.

Low-cost underwater wireless optical communication (UOWC) systems are attractive for high-speed connections among unmanned vehicles or devices in various underwater applications. Here we demonstrate a high-speed and low-cost UOWC system using a low-resolution digital to analog converter (DAC), a single-pixel mini-sized light-emitting diode (mini-LED), and digital pre-compensation (DPC). The enabled DPC scheme comprises digital pre-distortion (DPD), digital pre-emphasis (DPE), and digital resolution enhancer (DRE), which pre-compensate for mini-LED nonlinearity, the bandwidth limitation of the mini-LED and avalanche photodiode detector, and DAC resolution limitation, respectively. The simulation results show that the in-band signal-to-quantization noise ratio can be increased by 6.8 dB using DRE based on a 4-bit DAC. To further improve the system capacity, we tune the level of DPE in order to optimize the trade-off between the residual inter-symbol interference and signal-to-noise ratio. With the combination of optimized DPE and DRE, we obtain a 21.1% higher data rate compared with full DPE only and demonstrate the transmission of 6.9 Gb/s PAM-8 signal over a 2-m distance underwater based on a single-pixel mini-LED and 4-bit DAC. This paper reports a cost-effective UOWC system first using a low-resolution DAC and DPC, which offers a promising path toward low-cost underwater optical wireless networks.

Integrative genomics analysis of the ever-shrinking pectin methylesterase (PME) gene family in foxtail millet (Setaria italica).

Pectin methylesterase (PME) plays a vital role in the growth and development of plants. Their genes can be classified into two types, with Type-1 having an extra domain, PMEI. PME genes in foxtail millet (Setaria italica L.) have not been identified, and their sequence features and evolution have not been explored. Here, we identified 41 foxtail millet PME genes. Decoding the pro-region, containing the PMEI domain, revealed its more active nature than the DNA encoding PME domain, easier to be lost to produce Type-2 PME genes. We inferred that the active nature of the pro-region could be related to its harbouring more repetitive DNA sequences. Further, we revealed that though whole-genome duplication and tandem duplication contributed to producing new copies of PME genes, phylogenetic analysis provided clear evidence of ever-shrinking gene family size in foxtail millet and the other grasses in the past 100 million years. Phylogenetic analysis also supports the existence of two gene groups, Group I and Group II, with genes in Group II being more conservative. Our research contributes to understanding how DNA sequence structure affects the functional innovation and evolution of PME genes.

Selenium nanoparticles derived from Proteus mirabilis YC801 alleviate oxidative stress and inflammatory response to promote nerve repair in rats with spinal cord injury.

Microbial biotransformation and detoxification of biotoxic selenite into selenium nanoparticles (SeNPs) has emerged as an efficient technique for the utilization of selenium. SeNPs are characterized by high bioavailability and have several therapeutic effects owing to their antioxidant, anti-inflammatory and neuroprotective activities. However, their influence on microenvironment disturbances and neuroprotection after spinal cord injury (SCI) is yet to be elucidated. This study aimed to assess the influence of SeNPs on SCI and explore the underlying protective mechanisms. Overall, the proliferation and differentiation of neural stem cells were facilitated by SeNPs derived from Proteus mirabilis YC801 via the Wnt/ß-catenin signaling pathway. The SeNPs increased the number of neurons to a greater extent than astrocytes after differentiation and improved nerve regeneration. A therapeutic dose of SeNPs remarkably protected the integrity of the spinal cord to improve the motor function of the hind limbs after SCI and decreased the expression of several inflammatory factors such as tumor necrosis factor-α and interleukin-6 in vivo and enhanced the production of M2-type macrophages by regulating their polarization, indicating the suppressed inflammatory response. Besides, SeNPs reversed the SCI-mediated production of reactive oxygen species. In conclusion, SeNPs treatment holds the potential to improve the disturbed microenvironment and promote nerve regeneration, representing a promising therapeutic approach for SCI.

Effects of concentration and chain length of the sequence copolymer on interfacial properties of homopolymers/sequence copolymers ternary blends: A DPD simulation study.

The effect of the concentration and chain length of the copolymer AB with sequence length τ = 8 on the interfacial properties of the ternary mixtures A10/AB/B10 are investigated by the dissipative particle dynamics (DPD) simulations. It is found that: i) As the copolymer concentration varies from 0.05 to 0.15, increasing the copolymer enrichment at the center of the interface enlarges the interface width ω and reduces the interfacial tension. However, as the concentration of the sequence copolymers further increases to 0.2, because the interface has formed micelles and the micellization could lower the efficiency of copolymers as a compatibilizer, the interfacial tension exhibits a slightly increase; ii) elevating the copolymer chain length, the copolymer volumes vary from a cylinder shape to a pancake shape. The blends of the copolymer with chain length Ncp = 24 exhibit a wider interfacial width w and a lower interfacial tension γ, which indicates that the sequenced copolymer Ncp = 24 exhibits a better performance as the compatibilizers. This study illustrates the correlations between the reduction in interfacial tension produced by the sequence copolymers and their molecular parameters, which guide a rational design of an efficient compatibilizer.

Multi-Scale Spatial Prediction of Wild Boar Damage Risk in Hunchun: A Key Tiger Range in China.

Hunchun, a typical area suffering wild boar (Sus scrofa) damage, is an important region for the Siberian Tiger (Panthera tigris) in China. By incorporating the maximum entropy model with 22 variables in the home range scale (12 variables) and in the feeding site scale (10 variables), we predicted wild boar damage risks in this area of China and analyzed how spatial factors influence damage risk. Damage risk was found to be high in areas close to the forest edge, areas with a higher forest cover and lower to medium deciduous forest proportion, low road density, and a medium river density and farmland proportion. The proportion of farmland which was identified as being in the high damage risk zone was 23.55%, of which 38.68% was within the habitat area of the Siberian Tiger. Finally, we propose wild boar damage prevention based on different management goals.

The long noncoding RNA ZFAS1 facilitates bladder cancer tumorigenesis by sponging miR-329.

The incidence and mortality rate of bladder cancer have dramatically expanded, so it's urgent to discover new biomarker and therapeutic target for bladder cancer. Recently, lncRNA has been identified as oncogene or tumor suppressor to regulate the tumorigenesis. LncRNA ZFAS1 has been confirmed as oncogene in various tumors. However, the expression, function, and underlying mechanism of ZFAS1 in bladder carcinogenesis have yet to be totally clarified. In the current study, our data demonstrated that ZFAS1 expression was significantly upregulated in bladder cancer tissues and cell lines. Furthermore, Kaplan-Meier analysis revealed that high ZFAS1 expression was significantly associated with unfavorable progression free survival (PFS) (P = 0.0034 < 0.01) and overall survival (OS) (P = 0.0041 < 0.01) of bladder cancer patients. Moreover, silencing of ZFAS1 expression could markedly suppress bladder cancer cells proliferation and colony formation, arrest cell cycle, promote cell apoptosis and inhibit cell migration in vitro. In addition, bioinformatics analysis, luciferase reporter assay, and pull down assay revealed that ZFAS1 straightly interacted with miR-329. Lastly, rescue experiments confirmed that miR-329 inhibitor reversed the tumor suppressing roles of ZFAS1 knockdown on bladder cancer cells. Collectively, our results illuminated that ZFAS1 could serve as an oncogene in the tumorigenesis of bladder cancer, and discovered the functional regulatory network of ZFAS1 sponging miR-329.

Regulation of growth of human bladder cancer by miR-192.

The regulation of microRNA-192 (miR-192) is impaired in many cancers. Here, we investigated the role of miR-192 in the proliferation, cell cycle progression, and apoptosis of bladder cancer cells. Human bladder cancer cells were transfected with human miR-192 precursor or non-specific control miRNA. The effect of miR-192 on cell proliferation was assessed by a MTT assay. The effects of miR-192 on cell cycle regulation and apoptosis were evaluated by flow cytometry. Western blot was used to analyze the protein levels of cyclin D1, p21, p27, Bcl-2, Bax, and Mcl-1. We found that overexpression of miR-192 significantly decreased the proliferation of bladder cancer cells by 22 and 54 % at 48 and 72 h, respectively. MiR-192-overexpressing cells exhibited a significant increase in G0/G1 phase and a significant decrease in S phase compared to the control miRNA-transfected cells. Moreover, overexpression of miR-192 significantly induced apoptotic death in bladder cancer cells, increased the levels of p21, p27, and Bax, and decreased the levels of cyclin D1, Bcl-2, and Mcl-1. Taken together, these data suggest that miR-192 may be a suppressor for bladder cancer cells by cell cycle regulation.

Dysregulation of cell cycle related genes and microRNAs distinguish the low- from high-risk of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a biologically heterogeneous disease with considerable variation in clinical aggressiveness. In this study, bioinformatics was used to detect the patterns of gene expression alterations of PCa patients. METHODS: The gene expression profile GSE21034 and GSE21036 were downloaded from Gene Expression Omnibus (GEO) database. Significantly changed mRNA transcripts and microRNAs were identified between subtypes with favorable (cluster 2) and unfavorable (cluster 5) prognosis by two-side unequal variances t test. MicroRNAs and their potential target genes were identified by TargetScan and miRTarBase, respectively. Besides, the overlapped genes between the target genes of microRNAs and mRNA transcripts were assessed by Fisher' exact test (one side). The functional annotation was performed by DAVID, followed by construction of protein-protein interaction (PPI) network. RESULTS: Compared to cluster 2, 1556 up-regulated and 1288 down-regulated transcripts were identified in cluster 5. Total 28 microRNAs were up-regulated and 30 microRNAs were down-regulated in cluster 5. Besides, 12 microRNAs target transcripts were significantly overlapped with down-regulated transcripts in cluster 5 with none of them was found overlapped with up-regulated transcripts. Functional annotation showed that cell cycle was the most significant function. In the PPI network, BRCA1, CDK1, TK1 and TRAF2 were hub protein of signature genes in cluster 5, and TGFBR1, SMAD2 and SMAD4 were hub proteins of signature gnens in cluster 2. CONCLUSIONS: Our findings raise the possibility that genes related with cell cycle and dysregulated miRNA at diagnosis might have clinical utility in distinguishing low- from high-risk PCa patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_156.

Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis.

The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. T­tests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.