Folate modified dual pH/reduction-responsive mixed micelles assembled using FA-PEG-PDEAEMA and PEG-SS-PCL for doxorubicin delivery.

Aiming at achieving the concurrent performances of high loading, well controlled release and active targeted delivery, folate (FA) modified dual pH/reduction-responsive mixed polymeric micelles were rationally assembled using FA-PEG-PDEAEMA and PEG-SS-PCL by dissipative particle dynamics (DPD) simulations. The optimized polymers PEG112-PDEAEMA40, FA-PEG112-PDEAEMA40, and PEG112-SS-PCL70 were synthesized and characterized using 1H NMR, FT-IR and GPC, and their mixed micelles were applied for doxorubicin (DOX) delivery. The drug loading capacity (LC) and encapsulation efficiency (EE) values of the MIX1 (FA-PEG112-PDEAEMA40/PEG112-SS-PCL70) at a DOX/polymer feeding ratio of 15 mg/30 mg were 20.22% and 50.69%, which were higher than those of single polymer micelles and MIX2 (PEG112-PDEAEMA40/PEG112-SS-PCL70). Particle size distributions, mesoscopic morphologies, DPD simulations and in vitro drug release profiles all confirmed the well-controlled release performance of the DOX-loaded micelles formed by MIX1: slow DOX release with a cumulative release of 20.46% in the neutral environment and accelerated release with a cumulative release of 74.20% at pH 5.0 + 10 mM DTT within 120 h, which were similar to those of MIX2. Cytotoxicity assay found that both MIX1 and MIX2 blank micelles were biocompatible, and a superior inhibitory effect of the FA-modified DOX-loaded micelles MIX1 on HepG2 cells was found compared to that of free DOX and non-FA-modified DOX-loaded micelles MIX2. All of these confirmed the superiority of MIX1 micelles with high loading capacity, well controlled release, and enhanced inhibitory effects on HepG2 cells, which might be a prospective candidate for anticancer drug delivery.

The construction and analysis of ceRNA network and patterns of immune infiltration in lung adenocarcinoma.

BACKGROUND: Competitive Endogenous RNA (ceRNA) may be closely associated with tumor progression. However, studies on ceRNAs and immune cells in LUAD are scarce. METHOD: The profiles of gene expression and clinical data of LUAD patients were extracted from the TCGA database. Bioinformatics methods were used to evaluate differentially-expressed genes (DEGs) and to form a ceRNA network. Preliminary verification of clinical specimens was utilized to detect the expressions of key biomarkers at the tissues. Cox and Lasso regressions were used to identify key genes, and prognosis prediction nomograms were formed. The mRNA levels of 9 genes in the risk score model in independent clinical LUAD samples were detected by qRT-PCR. The interconnection between the risk of cancer and immune cells was evaluated using the CIBERSORT algorithm, while the conformation of notable tumor-infiltrating immune cells (TIICs) in the LUAD tissues of the high and low risk groups was assessed using the RNA transcript subgroup in order to identify tissue types. Finally, co-expression study was used to examine the interconnection between the key genes in the ceRNA networks and the immune cells. RESULT: A ceRNA network of 115 RNAs was established, and nine key genes were identified to construct a Cox proportional-hazard model and create a prognostic nomogram. This risk-assessment model might serve as an independent factor to forecast the prognosis of LUAD, and it was consistent with the preliminary verification of clinical specimens. Survival analysis of clinical samples further validated the potential value of high risk groups in predicting LUAD prognosis. Five immune cells were identified with significant differences in the LUAD tissues of the high and low risk groups. Besides, two pairs of biomarkers associated with the growth of LUAD were found, i.e., E2F7 and macrophage M1 (R = 0.419, p = 1.4e- 08) and DBF4 and macrophage M1 (R = 0.282, p < 2.2 e- 16). CONCLUSION: This study identified several important ceRNAs, i.e. (E2F7 and BNF4) and TIICs (macrophage M1), which might be related to the development and prognosis of LUAD. The established risk-assessment model might be a potential tool in predicting LUAD of prognosis.

DPD simulations and experimental study on reduction-sensitive polymeric micelles self-assembled from PCL-SS-PPEGMA for doxorubicin controlled release.

Delivery of anticancer drugs by amphiphilic polymeric micelles with disulfide bonds as the reduction-responsive groups has potential application in the field of drug-controlled release. In this study, three disulfide-linked polycaprolactone-b-polyethylene glycol methyl ether methacrylate (PCL-SS-PPEGMA) were synthesized and confirmed by 1H NMR and GPC, and then used for doxorubicin (DOX) delivery. The CMC values of the three PCL-SS-PPEGMA micelles were low (0.71-4.56 mg/L), indicative of the good stability of micelles in aqueous solution. The drug loading content (LC) and encapsulation efficiency (EE), together with the DOX accelerated release profiles were determined, with good drug loading capacity and well drug-controlled release performance. And to explore the mesoscopic behavior of reduction-responsive drug-loaded polymeric micelles, by using a dedicated disulfide bond-breaking model and script, dissipative particle dynamics (DPD) simulations were carried out on the three PCL-SS-PPEGMA polymers. Their self-assembled behavior, formation of DOX-loaded micelles, the disulfide bond-breaking process, as well as the DOX reduction-responsive release process were simulated and assessed. Comparing the DPD simulation results with the experimental data, we found that they were in good agreement, effectively demonstrating that the DPD simulation method developed can provide a practical mesoscopic approach for the reduction-responsive drug-loaded polymeric micelles that involved the cleavage of dynamic covalent bonds.

Observation of magnetic adatom-induced Majorana vortex and its hybridization with field-induced Majorana vortex in an iron-based superconductor.

Braiding Majorana zero modes is essential for fault-tolerant topological quantum computing. Iron-based superconductors with nontrivial band topology have recently emerged as a surprisingly promising platform for creating distinct Majorana zero modes in magnetic vortices in a single material and at relatively high temperatures. The magnetic field-induced Abrikosov vortex lattice makes it difficult to braid a set of Majorana zero modes or to study the coupling of a Majorana doublet due to overlapping wave functions. Here we report the observation of the proposed quantum anomalous vortex with integer quantized vortex core states and the Majorana zero mode induced by magnetic Fe adatoms deposited on the surface. We observe its hybridization with a nearby field-induced Majorana vortex in iron-based superconductor FeTe0.55Se0.45. We also observe vortex-free Yu-Shiba-Rusinov bound states at the Fe adatoms with a weaker coupling to the substrate, and discover a reversible transition between Yu-Shiba-Rusinov states and Majorana zero mode by manipulating the exchange coupling strength. The dual origin of the Majorana zero modes, from magnetic adatoms and external magnetic field, provides a new single-material platform for studying their interactions and braiding in superconductors bearing topological band structures.

pH-Sensitive Mixed Micelles Assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for Doxorubicin Delivery: Experimental and DPD Simulations Study.

To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (N,N-diethylaminoethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and polycaprolactone-b-poly (poly(ethylene glycol) methyl ether methacrylate) (PCL-PPEGMA), which were synthesized and confirmed by 1H NMR and gel permeation chromatographic (GPC). The critical micelle concentration (CMC) values of the prepared mixed micelles were low, and the micellar sizes and zeta potentials of the blank mixed micelles demonstrated good pH-responsive behavior. Combined experimental techniques with dissipative particle dynamics (DPD) simulation, the particle sizes, zeta potentials, drug loading content (LC), encapsulation efficiency (EE), aggregation morphologies, and doxorubicin (DOX) distribution of the mixed micelles were investigated, and the high DOX-loading capacity of the mixed micelles was found. Both in vitro DOX release profiles and DPD simulations of the DOX dynamics release process exhibited less leakage and good stability in neutral conditions and accelerated drug release behavior with a little initial burst in slightly acidic conditions. Cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles had good biocompatibility, and DOX-loaded mixed micelles revealed certain cytotoxicity. These results suggest that the drug-loaded mixed micelles that consisted of the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA can be new types of pH-responsive well-controlled release anticancer drug delivery mixed micelles.

Nearly quantized conductance plateau of vortex zero mode in an iron-based superconductor.

Majorana zero modes (MZMs) are spatially localized, zero-energy fractional quasiparticles with non-Abelian braiding statistics that hold promise for topological quantum computing. Owing to the particle-antiparticle equivalence, MZMs exhibit quantized conductance at low temperature. By using variable-tunnel-coupled scanning tunneling spectroscopy, we studied tunneling conductance of vortex bound states on FeTe0.55Se0.45 superconductors. We report observations of conductance plateaus as a function of tunnel coupling for zero-energy vortex bound states with values close to or even reaching the 2e 2/h quantum conductance (where e is the electron charge and h is Planck's constant). By contrast, no plateaus were observed on either finite energy vortex bound states or in the continuum of electronic states outside the superconducting gap. This behavior of the zero-mode conductance supports the existence of MZMs in FeTe0.55Se0.45.

Evidence for Majorana bound states in an iron-based superconductor.

The search for Majorana bound states (MBSs) has been fueled by the prospect of using their non-Abelian statistics for robust quantum computation. Two-dimensional superconducting topological materials have been predicted to host MBSs as zero-energy modes in vortex cores. By using scanning tunneling spectroscopy on the superconducting Dirac surface state of the iron-based superconductor FeTe0.55Se0.45, we observed a sharp zero-bias peak inside a vortex core that does not split when moving away from the vortex center. The evolution of the peak under varying magnetic field, temperature, and tunneling barrier is consistent with the tunneling to a nearly pure MBS, separated from nontopological bound states. This observation offers a potential platform for realizing and manipulating MBSs at a relatively high temperature.

Survival and Growth of Epiphytic Ferns Depend on Resource Sharing.

Locally available resources can be shared within clonal plant systems through physiological integration, thus enhancing their survival and growth. Most epiphytes exhibit clonal growth habit, but few studies have tested effects of physiological integration (resource sharing) on survival and growth of epiphytes and whether such effects vary with species. We conducted two experiments, one on individuals (single ramets) and another on groups (several ramets within a plot), with severed and intact rhizome treatments (without and with physiological integration) on two dominant epiphytic ferns (Polypodiodes subamoena and Lepisorus scolopendrium) in a subtropical montane moist forest in Southwest China. Rhizome severing (preventing integration) significantly reduced ramet survival in the individual experiment and number of surviving ramets in the group experiment, and it also decreased biomass of both species in both experiments. However, the magnitude of such integration effects did not vary significantly between the two species. We conclude that resource sharing may be a general strategy for clonal epiphytes to adapt to forest canopies where resources are limited and heterogeneously distributed in space and time.

Higher clonal integration in the facultative epiphytic fern Selliguea griffithiana growing in the forest canopy compared with the forest understorey.

BACKGROUND AND AIMS: The advantage of clonal integration (resource sharing between connected ramets of clonal plants) varies and a higher degree of integration is expected in more stressful and/or more heterogeneous habitats. Clonal facultative epiphytes occur in both forest canopies (epiphytic habitats) and forest understories (terrestrial habitats). Because environmental conditions, especially water and nutrients, are more stressful and heterogeneous in the canopy than in the understorey, this study hypothesizes that clonal integration is more important for facultative epiphytes in epiphytic habitats than in terrestrial habitats. METHODS: In a field experiment, an examination was made of the effects of rhizome connection (connected vs. disconnected, i.e. with vs. without clonal integration) on survival and growth of single ramets, both young and old, of the facultative epiphytic rhizomatous fern Selliguea griffithiana (Polypodiaceae) in both epiphytic and terrestrial habitats. In another field experiment, the effects of rhizome connection on performance of ramets were tested in small (10 × 10 cm(2)) and large (20 × 20 cm(2)) plots in both epiphytic and terrestrial habitats. KEY RESULTS: Rhizome disconnection significantly decreased survival and growth of S. griffithiana in both experiments. The effects of rhizome disconnection on survival of single ramets and on ramet number and growth in plots were greater in epiphytic habitats than in terrestrial habitats. CONCLUSIONS: Clonal integration contributes greatly to performance of facultative epiphytic ferns, and the effects were more important in forest canopies than in forest understories. The results therefore support the hypothesis that natural selection favours genotypes with a higher degree of integration in more stressful and heterogeneous environments.

Water relations and gas exchange of fan bryophytes and their adaptations to microhabitats in an Asian subtropical montane cloud forest.

Fan life forms are bryophytes with shoots rising from vertical substratum that branch repeatedly in the horizontal plane to form flattened photosynthetic surfaces, which are well suited for intercepting water from moving air. However, detailed water relations, gas exchange characteristics of fan bryophytes and their adaptations to particular microhabitats remain poorly understood. In this study, we measured and analyzed microclimatic data, as well as water release curves, pressure-volume relationships and photosynthetic water and light response curves for three common fan bryophytes in an Asian subtropical montane cloud forest (SMCF). Results demonstrate high relative humidity but low light levels and temperatures in the understory, and a strong effect of fog on water availability for bryophytes in the SMCF. The facts that fan bryophytes in dry air lose most of their free water within 1 h, and a strong dependence of net photosynthesis rates on water content, imply that the transition from a hydrated, photosynthetically active state to a dry, inactive state is rapid. In addition, fan bryophytes developed relatively high cell wall elasticity and the osmoregulatory capacity to tolerate desiccation. These fan bryophytes had low light saturation and compensation point of photosynthesis, indicating shade tolerance. It is likely that fan bryophytes can flourish on tree trunks in the SMCF because of substantial annual precipitation, average relative humidity, and frequent and persistent fog, which can provide continual water sources for them to intercept. Nevertheless, the low water retention capacity and strong dependence of net photosynthesis on water content of fan bryophytes indicate a high risk of unbalanced carbon budget if the frequency and severity of drought increase in the future as predicted.

[Ecological adaptability of different provenance Eupatorium adenophorum Spreng].

By using reciprocal transplant method, Eupatorium adenophorum Spreng. seedlings of five different provenances were reciprocally transplanted into six different sites in Yunnan Province, with the survival rate, plant height, branch number, biomass, flower number per plant, and seed production measured during the period from April 2007 to May 2008. The seedlings growth and reproductive traits of different provenance E. adenophorum all showed strong plasticity to environmental conditions. With increasing latitude and altitude of transplant site, plant height, branch number, biomass, flower number per plant, and seed production of different provenance E. adenophorum decreased, and the differences in these growth and reproductive traits were significant among the transplant sites. However, there were no significant differences in these traits among different provenance E. adenophorum. Provenance and transplant site had no significant interactive effects on the above-mentioned traits except seed production. At each site, the survival rate, growth potential, and reproductive capability of local provenance E. adenophorum didn't have any superiority, illustrating that the success in the invasion of E. adenophorum in Yunnan Province was mainly due to the phenotypic plasticity of the plant, while local adaptability only played lesser important role.

[Plant diversity of different replaced communities after Eupatorium adenophorum removal].

Plant diversity of different replaced communities after Eupatorium adenophorum removal. WANG In this paper, an investigation on the structure, species composition and plant diversity of replaced communities after the removal of invasive E. adenophorum at the beginning of 1980s was made in the Shuangbo County of Yunnan Province, with local aged Pinus yunnanensis and unmanaged E. adenophorum forests as the reference. The results showed that in replaced communities, the richness, Shannon-Wiener, Simpson, and Pielou evenness indices values of woody species were 25 to approximately 28, 1.06 to approximately 2.34, 0.36 to approximately 0.86 and 0.32 to approximately 0.73, and those of herb species were 6 to approximately 8, 1.51 to approximately 1.97, 0.74 to approximately 0.84 and 0.84 to approximately 0.90, respectively. In unmanaged E. adenophorum community, the corresponding indices values of woody species were 3, 0.14, 0.10 and 0.13, and those of herb species were 3, 0.09, 0.03 and 0.08, respectively, being much lower than those of the replaced communities. The replaced communities dominated by fast-growing tree species in E. adenophorum forest developed through a 20 years rehabilitation period, under which, there was a clear understory layer dominated by native species. The density and growth rate of E. adenophorum was inhibited in the replaced communities. In comparison with the E. adenophorum community, the plant diversity of replaced communities was greatly increased. Among the replaced communities, P. yunnanensis + Schima wallichii + Eucalyptus globules community had the greatest plant diversity, but the replaced communities had lower plant diversity than the aged P. yunnanensis, with 42, 2.88, 0.92 and 0.77 for woody species, and 8, 2.08, 0.86 and 0.90 for herb species, respectively. It was suggested that more attention should be paid to conserve the rehabilitated communities, especially the P. yunnanensis plantation built on the degraded lands invaded by E. adenophorum. In addition, the introduction of local broad-leaved species and some shade-loving herb plants into these plantations and its follow-up management were also important for the sustainable development of the revegetation.