Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding. The resulted trastuzumab-polymersome-DM1 (Tra-PS-DM1) exhibits a mean size of 95.3 nm and remarkable drug loading efficiency % of 99.3%. In addition to its superior stability, we observed the rapid release of DM1 in a controlled manner under reductive conditions. Compared to the native polymersomes, Tra-PS-DM1 has shown greatly improved cellular uptake and significantly reduced IC50 up to 17-fold among HER-2-positive cancer cells. Moreover, Tra-PS-DM1 demonstrated superb growth inhibition of HER-2-positive tumoroids; specifically, BT474 tumoroids shrunk up to 62% after 12 h treatment. With exceptional stability and targetability, the PG-shelled Tra-PS-DM1 appears as an attractive approach for HER-2-positive tumor treatment

Molecular Mechanism of Overcoming Host Resistance by the Target of Rapamycin Gene in Leptographium qinlingensis

Leptographium qinlingensis is a fungal symbiont of the Chinese white pine beetle (Dendroctonus armandi) and a pathogen of the Chinese white pine (Pinus armandii) that must overcome the terpenoid oleoresin defenses of host trees to invade and colonize. L. qinlingensis responds to monoterpene flow with abundant mechanisms that include the decomposing and use of these compounds as a nitrogen source. Target of Rapamycin (TOR) is an evolutionarily conserved protein kinase that plays a central role in both plants and animals through integration of nutrients, energies, hormones, growth factors and environmental inputs to control proliferation, growth and metabolism in diverse multicellular organisms. In this study, in order to explore the relationship between TOR gene and carbon sources, nitrogen sources, host nutrients and host volatiles (monoterpenoids) in L. qinlingensis, we set up eight carbon source treatments, ten nitrogen source treatments, two host nutrients and six monoterpenoids (5%, 10% and 20%) treatments, and prepared different media conditions. By measuring the biomass and growth rate of mycelium, the results revealed that, on the whole, the response of L. qinlingensis to nitrogen sources was better than carbon sources, and the fungus grew well in maltose (carbon source), (NH4)2C2O4 (inorganic nitrogen source), asparagine (organic nitrogen source) and P. armandii (host nutrient) versus other treatments. Then, by analyzing the relationship between TOR expression and different nutrients, the data showed that: (i) TOR expression exhibited negative regulation in response to carbon sources and host nutrition. (ii) The treatments of nitrogen sources and terpenoids had positively regulatory effects on TOR gene; moreover, the fungus was most sensitive to β-pinene and 3-carene. In conclusion, our findings reveal that TOR in L. qinlingensis plays a key role in the utilization of host volatiles as nutrient intake, overcoming the physical and chemical host resistances and successful colonization

A Multi-Objective Optimization Approach Based on an Enhanced Particle Swarm Optimization Algorithm With Evolutionary Game Theory

Due to conflicts among objectives of multi-objective optimization (MO) problems, it remains challenging to gain high-quality Pareto fronts for different MO issues. Attempt to handle this challenge and obtain high-performance Pareto fronts, this paper proposes a novel MO optimizer via leveraging particle swarm optimization (PSO) with evolutionary game theory (EGT). Firstly, a modified self-adaptive PSO (MSAPSO) adopting a novel self-adaptive parameter adaption rule determined by the evolutionary strategy of EGT to tune the three key parameters of each particle is proposed in order to well balance the exploration and exploitation abilities of MSAPSO. Then, a parameter selection principle is provided to sufficiently guarantee convergence of MSAPSO followed after the analytical convergence investigation of this optimizer so as to assure convergence of the searched Pareto front toward the true Pareto front as far as possible. Subsequently, a MSAPSO-based MO optimizer is developed, in which an external archive is applied to preserve the searched non-dominated solutions and a circular sorting method is amalgamated with the elitist-saving method to update the external archive. Lastly, the performance of the proposed method is examined by 16 benchmark test functions against 4 well-known MOO methods. The simulation results reveal that the proposed method dominates its peers regarding the quality of the Pareto fronts for most of the studied benchmarks. Furthermore, the results of the non-parametric analysis confirm that the proposed method significantly outperforms its contenders at the confidential level of 95% over the 16 benchmarks

The complete chloroplast genome of Tilia endochrysea Handel-Mazzetti 1926 (Malvaceae)

Tilia endochrysea Handel-Mazzetti 1926, distributed in the southern margin of Chinese Subtropical Zone, is the only one species in genus Tilia has dehiscent fruit. The whole chloroplast genome of T. endochrysea was 162,838 bp with 36.46% GC content, including a large single-copy (LSC) region of 91,264 bp, a small single-copy (SSC) region of 20,414 bp, and a pair of inverted repeats (IRs) of 51,160 bp. The chloroplast genome encodes 130 genes, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree shows T. endochrysea was the basal taxon in Tilia and closely related to Craigia yunnanensis (Smith et Evans 1921)

Establishment of RNA Interference Genetic Transformation System and Functional Analysis of FlbA Gene in <i>Leptographium qinlingensis</i>

Leptographium qinlingensis is a pathogenic fungus of Pinus armandii that is epidemic in the Qinling Mountains. However, an effective gene interference strategy is needed to characterize the pathogenic genes in this fungus on a functional level. Using the RNA silencing vector pSilent-1 as a template, we established an RNA interference genetic transformation system mediated by Agrobacterium tumefaciens GV3101, which is suitable for the gene study for Leptographium qinlingensis by homologous recombination and strain interference system screening. The LqFlbA gene was silenced using the RNA interference approach described above, and the resulting transformants displayed various levels of silencing with a gene silencing effectiveness ranging from 41.8% to 91.4%. The LqFlbA-RNAi mutant displayed altered colony morphology, sluggish mycelium growth, and diminished pathogenicity toward the host P. armandii in comparison to the wild type. The results indicate that this method provides a useful reverse genetic system for studying the gene function of L. qinlingensis, and that LqFlbA plays a crucial role in the growth, development, and pathogenicity of L. qinlingensis

Phylogeny of Regulators of G-Protein Signaling Genes in Leptographium qinlingensis and Expression Levels of Three RGSs in Response to Different Terpenoids

Leptographium qinlingensis is a bark beetle-vectored pine pathogen in the Chinese white pine beetle (Dendroctonus armandi) epidemic in Northwest China. L. qinlingensis colonizes pines despite the trees&rsquo; massive oleoresin terpenoid defenses. Regulators of G-protein signaling (RGS) proteins modulate heterotrimeric G-protein signaling negatively and play multiple roles in the growth, asexual development, and pathogenicity of fungi. In this study, we have identified three L. qinlingensis RGS genes, and the phylogenetic analysis shows the highest homology with the regulators of G-protein signaling proteins sequence from Ophiostoma piceae and Grosmannia clavigera. The expression profiles of three RGSs in the mycelium of L. qinlingensis treated with six different terpenoids were detected, as well as their growth rates. Under six terpenoid treatments, the growth and reproduction in L. qinlingensis were significantly inhibited, and the growth inflection day was delayed from 8 days to 12&ndash;13 days. By analyzing the expression level of three RGS genes of L. qinlingensis with different treatments, results indicate that LqFlbA plays a crucial role in controlling fungal growth, and both LqRax1 and LqRgsA are involved in overcoming the host chemical resistances and successful colonization

Analyzing Trends of Dike-Ponds between 1978 and 2016 Using Multi-Source Remote Sensing Images in Shunde District of South China

Dike-ponds have experienced significant changes in the Pearl River Delta region over the past several decades, especially since China&rsquo;s economic reform, which has seriously affected the construction of ecological environments. In order to monitor the evolution of dike-ponds, in this study we use multi-source remote sensing images from 1978 to 2016 to extract dike-ponds in several periods using the nearest neighbor classification method. A corresponding area weighted dike-pond invasion index (AWDII) is proposed to describe the spatial evolution of dike-ponds, both qualitatively and quantitatively. Furthermore, the evolution mechanisms of dike-ponds are determined, which can be attributed to both natural conditions and human factors. Our results show that the total area of dike-ponds in 2016 was significantly reduced and fragmentation had increased compared with the situation in 1978. The AWDII reveals that Shunde District has experienced three main phases, including steady development, rapid invasion and a reduction of invasion by other land use types. Most dike-ponds have now converted into built-up areas, followed by cultivated lands, mainly due to government policies, rural area depopulation, and river networks within Shunde. Our study indicates that the AWDII is applicable towards the evaluation of the dynamic changes of dike-ponds. The rational development, and careful protection, of dike-ponds should be implemented for better land and water resource management