Transmembrane routes of cationic liposome-mediated gene delivery using human throat epidermis cancer cells

For studying the mechanism of cationic liposome-mediated transmembrane routes for gene delivery, various inhibitors of endocytosis were used to treat human throat epidermis cancer cells, Hep-2, before transfection with Lipofectamine 2000/pGFP-N2 or Lipofectamine 2000/pGL3. To eliminate the effect of inhibitor toxicity on transfection, the RLU/survival rate was used to represent the transfection efficiency. Chlorpromazine and wortmannin, clathrin inhibitors, decreased transfection efficiency by 44 % (100 μM) and 31 % (100 nM), respectively. At the same time, genistein, a caveolin inhibitor, decreased it by 30 % (200 μM). Thus combined transmembrane routes through the clathrin and caveolae-mediated pathways were major mechanisms of cell uptake for the cationic liposome-mediated gene delivery. After entering the cells, microtubules played an important role on gene delivery as vinblastine, a microtubulin inhibitor, could reduce transfection efficiency by 41 % (200 nM)

Intracavity generated visible self-reconstructing Bessel-like laser beams by thermal effect

Abstract(#br)In this paper we report the intracavity realization of visible reconstructing Bessel-like beams when a thin Nd:YVO 4 crystal is inserted in a diode-pumped Pr:YLF laser at 639.5 nm. The position of the thin crystal and the intracavity power determine the Bessel-like mode generated. The self-reconstructing characteristic of the obtained Bessel-like beam is also demonstrated

Assessment of the influence on Hypsizygus marmoreus stem waste as a sustainable alternative to corn in Holdobagy geese dietary

The processing of edible mushrooms generates a large amount of mushroom residue. How to handle this mushroom residue in a way that avoids environmental pollution and maximizes effective utilization is a current issue that needs to be explored. This study aimed to investigate the effects of substituting dietary corn with Hypsizygus marmoreus mushroom stem waste (HSW) in the diet of geese. The control group was fed with a basal diet (BD), and the other groups were fed the basal diet to which 12% (HSW12 group), 24% (HSW24 group), or 32% (HSW32 group) of HSW were added to replace the equivalent proportion of corn. The test lasted 28 days. The results showed that the average daily feed intake (ADFI) of the HSW12 and HSW24 groups at 35–49 d, and the HSW12 and HSW32 groups at 35–63 d, was significantly higher compared to the BD group (p<0.05). The average daily gain (ADG) of the HSW12 group was significantly higher than BD at 35–49 d (p<0.05), but there was no significant difference in the feed/gain (F/G) among the groups. The levels of serum total protein (TP), albumin (ALB), globulin (GLOB), glutathione peroxidase (GSH-Px), and catalase (CAT) in HSW24 group were significantly higher than those in the BD group (p<0.05). Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) decreased significantly, and there were no significant differences in carcass traits and meat quality. As 24% HSW supplementation had the best overall effect on the growth performance, serum biochemical indicators, meat quality, and carcass traits of geese, gut microbiota analysis was only performed on this group. The microbiota α-diversity of the cecum and ileum did not differ significantly between the BD and HSW24 groups. Principal coordinate analysis (PCoA) indicated that the difference in the cecum was significant in the β-diversity (p<0.05). Short chain fatty acid-producing bacteria and decomposing protein and carbohydrate bacteria (Prevotella) were enriched in the cecum in the HSW24 group. Gut immune regulating and nutritional bacteria, Lactococcus and Bacillus, respectively, were enriched in the ileum in HSW24 group. Spearman’s analysis indicated that Bacillus, Prevotella, and Clostridium were positively associated with serum protein and lipid metabolism. These results indicate that 24% HSW substitution of corn could improve goose serum ALB and fat metabolism, and increase serum antioxidant capacity, which may becaused by the improvement of goose cecal microbiota

Anti-angiogenesis therapy in the Vx2 rabbit cancer model with a lipase-cleavable Sn 2 taxane phospholipid prodrug using αvβ3-targeted theranostic nanoparticles

In nanomedicine, the hydrophobic nature of paclitaxel has favored its incorporation into many nanoparticle formulations for anti-cancer chemotherapy. At lower doses taxanes are reported to elicit anti-angiogenic responses. In the present study, the facile synthesis, development and characterization of a new lipase-labile docetaxel prodrug is reported and shown to be an effective anti-angiogenic agent in vitro and in vivo. The Sn 2 phosphatidylcholine prodrug was stably incorporated into the lipid membrane of α(v)β(3)-integrin targeted perfluorocarbon (PFC) nanoparticles (α(v)β(3)-Dxtl-PD NP) and did not appreciably release during dissolution against PBS buffer or plasma over three days. Overnight exposure of α(v)β(3)-Dxtl-PD NP to plasma spiked with phospholipase enzyme failed to liberate the taxane from the membrane until the nanoparticle integrity was compromised with alcohol. The bioactivity and efficacy of α(v)β(3)-Dxtl-PD NP in endothelial cell culture was as effective as Taxol(®) or free docetaxel in methanol at equimolar doses over 96 hours. The anti-angiogenesis effectiveness of α(v)β(3)-Dxtl-PD NP was demonstrated in the Vx2 rabbit model using MR imaging of angiogenesis with the same α(v)β(3)-PFC nanoparticle platform. Nontargeted Dxtl-PD NP had a similar MR anti-angiogenesis response as the integrin-targeted agent, but microscopically measured decreases in tumor cell proliferation and increased apoptosis were detected only for the targeted drug. Equivalent dosages of Abraxane(®) given over the same treatment schedule had no effect on angiogenesis when compared to control rabbits receiving saline only. These data demonstrate that α(v)β(3)-Dxtl-PD NP can reduce MR detectable angiogenesis and slow tumor progression in the Vx2 model, whereas equivalent systemic treatment with free taxane had no benefit

Tri-peptide cationic lipids for gene delivery

A novel tri-peptide cationic lipid can efficiently transfer DNA and siRNA into tumor cells and tumors of mice with little in vitro and in vivo toxicity

Observation of Rydberg moir\'e excitons

Rydberg excitons, the solid-state counterparts of Rydberg atoms, have sparked considerable interest in harnessing their quantum application potentials, whereas a major challenge is realizing their spatial confinement and manipulation. Lately, the rise of two-dimensional moir\'e superlattices with highly tunable periodic potentials provides a possible pathway. Here, we experimentally demonstrate this capability through the observation of Rydberg moir\'e excitons (XRM), which are moir\'e trapped Rydberg excitons in monolayer semiconductor WSe2 adjacent to twisted bilayer graphene. In the strong coupling regime, the XRM manifest as multiple energy splittings, pronounced redshift, and narrowed linewidth in the reflectance spectra, highlighting their charge-transfer character where electron-hole separation is enforced by the strongly asymmetric interlayer Coulomb interactions. Our findings pave the way for pursuing novel physics and quantum technology exploitation based on the excitonic Rydberg states.Comment: 24 pages, including 4 figures and 6 supplementary figure

Anti-angiogenic nanotherapy inhibits airway remodeling and hyper-responsiveness of dust mite triggered asthma in the Brown Norway rat

Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via α(v)β(3)-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of α(v)β(3)-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0.01) in the upper airways/bronchi of HDM rats using simultaneous (19)F/(1)H MR neovascular imaging, which was corroborated by adjunctive fluorescent microscopy. Micelles without a drug payload (α(v)β(3)-No-Drug) served as a carrier-only control. Morphometric measurements of HDM rat airway size (perimeter) and vessel number at 21d revealed classic vascular expansion in control rats but less vascularity (p<0.001) after the anti-angiogenic nanotherapies. CD31 RNA expression independently corroborated the decrease in airway microvasculature. Methacholine (MCh) induced respiratory system resistance (Rrs) was high in the HDM rats receiving α(v)β(3)-No-Drug micelles while α(v)β(3)-Dxtl-PD or α(v)β(3)-Fum-PD micelles markedly and equivalently attenuated airway hyper-responsiveness and improved airway compliance. Total inflammatory BAL cells among HDM challenged rats did not differ with treatment, but α(v)β(3)(+ )macrophages/monocytes were significantly reduced by both nanotherapies (p<0.001), most notably by the α(v)β(3)-Dxtl-PD micelles. Additionally, α(v)β(3)-Dxtl-PD decreased BAL eosinophil and α(v)β(3)(+ )CD45(+) leukocytes relative to α(v)β(3)-No-Drug micelles, whereas α(v)β(3)-Fum-PD micelles did not. Conclusion: These results demonstrate the potential of targeted anti-angiogenesis nanotherapy to ameliorate the inflammatory hallmarks of asthma in a clinically relevant rodent model

Genomic prediction of drought tolerance during seedling stage in maize using low-cost molecular markers

Drought tolerance in maize is a complex and polygenic trait, especially in the seedling stage. In plant breeding, complex genetic traits can be improved by genomic selection (GS), which has become a practical and effective breeding tool. In the present study, a natural maize population named Northeast China core population (NCCP) consisting of 379 inbred lines were genotyped with diversity arrays technology (DArT) and genotyping-by-sequencing (GBS) platforms. Target traits of seedling emergence rate (ER), seedling plant height (SPH), and grain yield (GY) were evaluated under two natural drought stress environments in northeast China. Adequate genetic variations were observed for all the target traits, but they were divergent across environments. Similarly, the heritability of the target trait also varied across years and environments, the heritabilities in 2019 (0.88, 0.82, 0.85 for ER, SPH, GY) were higher than those in 2020 (0.65, 0.53, 0.33) and cross-2-years (0.32, 0.26, 0.33). In total, three marker datasets, 11,865 SilicoDArT markers obtained from the DArT-seq platform, 7837 SNPs obtained from the DArT-seq platform, and 91,003 SNPs obtained from the GBS platform, were used for GS analysis after quality control. The results of phylogenetic trees showed that broad genetic diversity existed in the NCCP population. Genomic prediction results showed that the average prediction accuracies estimated using the DArT SNP dataset under the two-fold cross-validation scheme were 0.27, 0.19, and 0.33, for ER, SPH, and GY, respectively. The result of SilicoDArT is close to the SNPs from DArT-seq, those were 0.26, 0.22, and 0.33. For the trait with lower heritability, the prediction accuracy can be improved using the dataset filtered by linkage disequilibrium. For the same trait, the prediction accuracies estimated with two DArT marker datasets were consistently higher than that estimated with the GBS SNP dataset under the same genotyping cost. The prediction accuracy was improved by controlling population structure and marker quality, even though the marker density was reduced. The prediction accuracies were improved by more than 30% using the significant-associated SNPs. Due to the complexity of drought tolerance under the natural stress environments, multiple years of data need to be accumulated to improve prediction accuracy by reducing genotype-by-environment interaction. Modeling genotype-by-environment interaction into genomic prediction needs to be further developed for improving drought tolerance in maize. The results obtained from the present study provides valuable pathway for improving drought tolerance in maize using GS