Genome sequence analysis reveals potential for virulence genes and multi-drug resistance in an Enterococcus faecalis 2A (XJ05) strain that causes lamb encephalitis.

BACKGROUND: Enterococcus is an important component of normal flora in human and animals, but in recent years, the pathogenicity of Enterococcus has been confirmed in clinical medicine. More and more animal infections have been reported in veterinary clinics. For the last decades, outbreaks of encephalitis in lambs have become much more common in Northern Xinjiang, China. Consequent studies have confirmed that these affected lambs had been commonly infected with E. faecalis. More than 60 E. faecalis were isolated from the brain of infected lambs, A highly virulent strain entitled E. faecalis 2A (XJ05) were selected, sequenced and analyzed. RESULT: Using whole genome sequence and de novo assembly, 18 contigs with NGS and annotation were obtained. It is confirmed that the genome has a size of 2.9 Mb containing 2783 protein-coding genes, as well as 54 tRNA genes and 4 rRNA genes. Some key features of this strain were identified, which included 7 predicted antibiotic resistance genes and 18 candidate virulence factor genes. CONCLUSION: The E. faecalis 2A (XJ05) genome is conspicuous smaller than E.faecalis V583, but not significantly different from other non-pathogenic E. faecalis. It carried 7 resistance genes including 4 kind of antibiotics which were consistent with the results of extensive drug resistance phenotypic, including aminoglycoside, macrolide, phenicol, and tetracycline. 2A (XJ05) also carried 18 new virulence factor genes related to virulence, hemolysin genes (cylA, cylB, cylM, cylL) may play an important role in lamb encephalitis by E. faecalis 2A (XJ05).

Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis.

Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women associated with the metastasis of tuberin-null cells with hyperactive mammalian target of rapamycin complex 1 (mTORC1) activity. Clinical trials with the mTORC1 inhibitor rapamycin have revealed partial efficacy but are not curative. Pregnancy appears to exacerbate LAM, suggesting that estrogen (E2) may play a role in the unique features of LAM. Using a LAM patient-derived cell line (bearing biallelic Tuberin inactivation), we demonstrate that E2 stimulates a robust and biphasic activation of ERK2 and transcription of the late response-gene Fra1 associated with epithelial-to-mesenchymal transition. In a carefully orchestrated collaboration, activated mTORC1/S6K1 signaling enhances the efficiency of Fra1 translation of Fra1 mRNA transcribed by the E2-ERK2 pathway, through the phosphorylation of the S6K1-dependent eukaryotic translation initiation factor 4B. Our results indicate that targeting the E2-ERK pathway in combination with the mTORC1 pathway may be an effective combination therapy for LAM.

Stabilized, superparamagnetic functionalized graphene/Fe3O4@Au nanocomposites for a magnetically-controlled solid-state electrochemiluminescence biosensing application.

Herein, a multifunctional nanoarchitecture has been developed by integrating the branched poly(ethylenimine) functionalized graphene/iron oxide hybrids (BGNs/Fe3O4) and luminol capped gold nanoparticles (luminol-AuNPs). The luminescent luminol-AuNPs as an electrochemiluminescence marker can be assembled on the nanocarrier of BGNs/Fe3O4 hybrids efficiently via the Au-N chemical bonds and electrostatic adsorption. Meanwhile, the multifunctional nanoarchitecture has been proved with excellent electron transfer, good stability, high emission intensity, etc. Furthermore, we successfully developed an ultrasensitive magnetically-controlled solid-state electrochemiluminescence (ECL) platform for label-free determination of HeLa cells using this multifunctional nanocomposite. Excellent performance of the magnetically-controlled ECL biosensing platform has been achieved including a high sensitivity for HeLa cells with a linear range from 20 to 1 × 10(4) cells/mL, good stability, and reproducibility.

Anionic Lipid, pH-Sensitive Liposome-Gold Nanoparticle Hybrids for Gene Delivery - Quantitative Research of the Mechanism.

Gene therapy is a potential method for treating a large range of diseases. Gene vectors are widely used in gene therapy for promoting the gene delivery efficiency to the target cells. Here, gold nanoparticles (AuNPs) coated with dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) are synthesized using a facile method for a new gene vector (DODAB/DOPE-AuNPs), which possess 3- and 1.5-fold higher transfection efficiency than those of DODAB-AuNPs and a commercial transfection agent, respectively. Meanwhile, it is nontoxic with concentrations required for effective gene delivery. Imaging and quantification studies of cellular uptake reveal that DOPE increases gene copies in cells, which may be attributed to the smaller size of AuNPs/DNA complexes. The dissociation efficiency of DNA from the endocytic pathway is quantified by incubating with different buffers and investigated directly in the cells. The results suggest that DOPE increases the internalization of AuNPs/DNA complexes and promotes DNA release from early endosomes for the vector is sensitive to the anionic lipid membrane and the decreasing pH along the endocytic pathway. The new vector contains the potential to be the new alternative as gene delivery vector for biomedical applications.

Network-based pharmacology-based research on the effect and mechanism of the Hedyotis diffusa-Scutellaria Barbata pair in the treatment of hepatocellular carcinoma.

The Hedyotis diffusa-Scutellaria officinalis pair (HD-SB) has therapeutic effects on a variety of cancers. Our study was to explore the mechanism of HD-SB in the treatment of hepatocellular carcinoma (HCC). A total of 217 active ingredients of HD-SB and 1196 HCC-related targets were reserved from the TCMSP and the SwissTarget Prediction database, and we got 63 intersection targets from GeneCards. We used a Venn diagram, and Cytoscape found that the three core ingredients were quercetin, luteolin, and baicalein. The PPI analysis showed that the core targets were TP53, CDK2, XPO1, and APP. Molecular docking results showed that these core ingredients had good binding potential with the core targets. HD-SB acts simultaneously on various HCC-related signaling pathways, including proteoglycans in cancer and the P53 signaling pathway. In vitro experiments confirmed that HD-SB can inhibit HepG2 cell proliferation by increasing TP53 and APP levels and decreasing XPO1 and CDK2 levels. This study analyzed active ingredients, core targets, and central mechanisms of HD-SB in the treatment of HCC. It reveals the role of HD-SB in targeting the P53 signaling pathway in the treatment of HCC. We hope that our research could provide a new perspective to the therapy of HCC and find new anticancer drugs.

Sophorolipid-toluidine blue conjugates for improved antibacterial photodynamic therapy through high accumulation.

Anti-bacterial photodynamic therapy is the most promising treatment protocol for bacterial infection, but low accumulation of photosensitizers has seriously hindered their development in clinical application. Here, with inherent outstanding affinity to bacterial cell envelope, sophorolipid produced from Candida bombicola has been conjugated to toluidine blue (SL-TB) through amidation reaction. The structure of SL-TB conjugates was identified by 1H-NMR, FT-IR and ESI-HRMS. The interfacial assembly and photophysical properties of SL-TB conjugates have been disclosed through surface tension, micro-polarity, electronic and fluorescence spectra. After light irradiation, the log10 (reduced CFU) of free toluidine blue to P. aeruginosa and S. aureus were 4.5 and 7.9, respectively. In contrast, SL-TB conjugates showed a higher bactericidal activity, with a reduction of 6.3 and 9.7 log10 units of CFU against P. aeruginosa and S. aureus, respectively. The fluorescence quantitative results showed that SL-TB could accumulate 2850 nmol/1011 cells and 4360 nmol/1011 cells by P. aeruginosa and S. aureus, which was much higher than the accumulation of 462 nmol/1011 cells and 827 nmol/1011 cells of free toluidine blue. Through the cooperation of triple factors, including sophorose affinity to bacterial cells, hydrophobic association with plasma membrane, and electrostatic attraction, higher SL-TB accumulation was acquired, which has enhanced antibacterial photodynamic efficiencies.

Design and synthesis of hederagenin derivatives modulating STING/NF-κB signaling for the relief of acute liver injury in septic mice.

Systemic inflammatory responses often result in sepsis and inhibition of inflammation is one strategy for sepsis treatment. In this study, we designed and synthesized 32 novel hederagenin (HD) derivatives with modifications at the A-ring, C-28, and C-23 positions and screened their anti-inflammatory activities in vitro, finding multiple compounds with potential anti-inflammatory activity. Of these, compound 1 was the most effective and was used for subsequent investigations into its mechanism of action and in vivo activity. In vivo assessments of anti-inflammatory activity showed that compound 1 reduced inflammation in a mouse model of sepsis with acute liver injury caused by lipopolysaccharide (LPS). Compound 1 also inhibited STING, p-IRF3, p-TBK1, p-p65, and p-IκB proteins in cGAS-STING-associated signaling. These findings indicated that compound 1 reduced inflammation through inhibition of STING expression and hence reducing activation of STING and nuclear factor-κB (NF-κB) signaling. Our work demonstrated that compound 1 is a promising lead compound for designing and developing anti-sepsis drugs.

Detection of emerging HoBi-like Pestivirus (BVD-3) during an epidemiological investigation of bovine viral diarrhea virus in Xinjiang: a first-of-its-kind report.

Xinjiang pastoral area is the second largest pastoral area in China, accounting for 26.8% of the available grassland area in the country, and the geographical advantage of cattle breeding industry is very obvious. Bovine viral diarrhea virus (BVDV) has always been one of the important viral diseases that have plagued the development of cattle farming industry in the world. As one of the main pastoral areas of China's cattle farming industry, the Xinjiang pastoral area has also been deeply affected. In this study, 6,153 bovine serum samples were collected from 18 large-scale cattle farms in 13 cities in Xinjiang. The antibodies and antigens of 6,153 and 588 serum samples were detected by serological detection methods, respectively. Ten serum samples, which were antigen-positive by ELISA, were randomly selected for RT-PCR detection, sequencing, and phylogenetic analysis of suspected HoBi-like Pestivirus (HoBiPeV) strains. The results showed that the positive rates of BVDV antibodies and antigens were 53.68% (3,303/6,153) and 6.12% (36/588), respectively. One of the 10 randomly selected seropositive samples was infected with the HoBiPeV strain. HoBiPeV, also referred to as BVDV-3, is an emerging atypical Pestivirus that occurs in cattle and small ruminants, and its clinical signs are similar to those of BVDV infection. Based on the whole genome of the BVDV-3 reference strain (JS12/01) on the GenBank, the homology of the detected strain was 96.02%. The whole genome nucleotide sequence was submitted to the GenBank database, and the gene accession number was obtained: OP210314. The whole genome of isolate OP210314 was 12.239 nucleotides and contained a 5'-UTR of 340 nucleotides, a 3'-UTR of 199 nucleotides, and a large open reading frame (ORF) encoding a polyprotein consisting of 3,899 amino acids. In conclusion, the prevalence rate of BVDV infection in Xinjiang dairy cows is high, and the genetic diversity is increasing. This study successfully identified and isolated HoBiPeV in Xinjiang for the first time, posing a potential threat to the cattle industry in Xinjiang.

Isolation, identification, molecular typing, and drug resistance of Escherichia coli from infected cattle and sheep in Xinjiang, China.

BACKGROUND: Escherichia coli infections are common in Xinjiang, a major region of cattle and sheep breeding in China. Therefore, strategies are required to control E. coli. The aim of this study was to investigate the phylogenetic groups, virulence genes, and antibiotic resistance characteristics of E. coli isolates. METHODS: In this study, 116 tissue samples were collected from the organs of cattle and sheep that were suspected of having E. coli infections between 2015 and 2019. Bacteria in the samples were identified using a biochemical identification system and amplification of 16S rRNA, and the phylogenetic groupings of E. coli isolates were determined by multiplex polymerase chain reactions. In addition, PCR detection and analysis of virulence factors, antibiotic resistance genes, and drug-resistant phenotypes of E. coli isolates were performed. RESULTS: A total of 116 pathogenic E. coli strains belonging to seven phylogenetic groups were isolated, with the majority of isolates in groups A and B1. Among the virulence genes, curli-encoding crl had the highest detection rate of 97.4%, followed by hemolysin-encoding hlyE with the detection rate of 94.82%. Antimicrobial susceptibility test results indicated that the isolates had the highest rates of resistance against streptomycin (81.9%). CONCLUSION: These characteristics complicate the prevention and treatment of E. coli-related diseases in Xinjiang.

Amphiphilic di-cationic methylene blue for improving antibacterial photodynamic efficiency through high accumulation and low aggregation on bacterial cell surfaces.

The aggregation state of photosensitizers on the surface of bacterial cells is an important scientific problem for antibacterial photodynamic therapy (APDT). High accumulation and high photoactive state maintenance of photosensitizers are the prerequisite of high APDT efficiency. In this study, an amphiphilic di-cationic methylene blue photosensitizer (C12-MB) was synthesized through quaternization, and its structure, interface properties, photophysical properties and antibacterial photodynamic properties were studied. The results showed that C12-MB could reduce 4.27 log10 CFU and 4.8 log10 CFU for P. aeruginosa and S. aureus under irradiation of light at 660 nm, higher than the parent methylene blue. Through a spectroscopic study on photosensitizer adsorption over the bacterial surface, C12-MB can be accumulated with higher concentration, and the photo-active monomer content is 73% and 70% over P. aeruginosa and S. aureus, higher than those of methylene blue: 25% and 49%, respectively. The higher content of non-aggregated photo-active monomer could contribute to higher antibacterial photodynamic efficiency. For C12-MB adsorbed over bacterial surfaces, planar packing inhibition and electrostatic repulsion could contribute to lower C12-MB aggregation, which provides an useful reference for the structural design of high-efficiency photosensitizers.

Role of the Rho pathway in regulating valvular interstitial cell phenotype and nodule formation.

The differentiation of valvular interstitial cells (VICs) to a myofibroblastic or osteoblast-like phenotype is commonly found in calcific valvular stenosis, although the molecular-level mechanisms of this process remain poorly understood. Due to the role of the Rho pathway in various vascular diseases and in the expression of a myofibroblast phenotype, the present study was inspired by the hypothesis that Rho activation is involved in regulating cellular processes related to valve calcification. It was found that increased RhoA and Rho kinase (ROCK) activity was associated with increased nodule formation in VIC cultures in vitro, and intentional induction of RhoA activity led to a further increase in nodules and expression of α-smooth muscle actin. VICs treated with ROCK inhibitors were also examined for nodule formation, proliferation, apoptosis, and expression of myofibroblastic or osteoblastic markers. ROCK inhibition dramatically reduced myofibroblast-regulated nodule formation in VIC cultures, as evidenced by a decrease in nodule number, total nodule area, α-smooth muscle actin-positive stress fibers, apoptosis, and gene expression of myofibroblast-related phenotypic markers. Meanwhile, ROCK inhibition was less effective at reducing nodule formation associated with osteogenic activity. In fact, ROCK inhibition increased the expression of alkaline phosphatase and effected only a modest decrease in nodule number when applied to VIC cultures with higher osteogenic activity. Thus, the Rho pathway possesses a complex role in regulating the VIC phenotype and nodule formation, and it is hoped that further elucidation of these molecular-level events will lead to an improved understanding of valvular disease and identification of potential treatments.

Efficacy of simvastatin treatment of valvular interstitial cells varies with the extracellular environment.

OBJECTIVE: The lack of therapies that inhibit valvular calcification and the conflicting outcomes of clinical studies regarding the impact of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors on valve disease highlight the need for controlled investigations to characterize the interactions between HMG-CoA reductase inhibitors and valve tissue. Thus, we applied multiple in vitro disease stimuli to valvular interstitial cell (VIC) cultures and examined the impact of simvastatin treatment on VIC function. METHODS AND RESULTS: VICs were cultured on 3 different substrates that supported various levels of nodule formation. Transforming growth factor (TGF)-beta1 was also applied as a disease stimulus to VICs on 2-D surfaces or encapsulated in 3-D collagen gels and combined with different temporal applications of simvastatin. Simvastatin inhibited calcific nodule formation in a dose-dependent manner on all materials, although the level of statin efficacy was highly substrate-dependent. Simvastatin treatment significantly altered nodule morphology, resulting in dramatic nodule dissipation over time, also in a substrate-dependent manner. These effects were mimicked in 3-D cultures, wherein simvastatin reversed TGF-beta1-induced contraction. Decreases in nodule formation were not achieved via the HMG-CoA reductase pathway, but were correlated with decreases in ROCK activity. CONCLUSIONS: These studies represent a significant contribution to understanding how simvastatin may impact heart valve calcification.

Study on Flow Characteristics of Working Medium in Microchannel Simulated by Porous Media Model.

As a phase change evaporator, a microchannel array heat exchanger is of great significance in the field of microscale heat dissipation. The performance of which strongly depends on the flow resistance, capillary force, and other factors. In order to improve the heat dissipation efficiency, it is necessary to perform an in-depth study of the characteristics of microchannel flow using numerical simulation. However, the current simulation model requires high computational cost and long simulation time. To solve this problem, this paper simplifies the numerical simulation of the rectangular parallel array microchannels by building the basic flow model based on the concept of porous media. In addition, we explore the effect of aspect-ratio (AR), hydraulic diameter, inlet velocity, and other parameters of fluid flow behavior inside the microchannels. Meanwhile, a user-defined function (UDF) is formulated to add the capillary force into the model to introduce capillary force into the porous media model. Through the above research, the paper establishes the porous media model for single-phase and gas-liquid two-phase flow, which acts as a simplification of microchannel array simulation without grossly affecting the results obtained. In addition, we designed and manufactured experiments using silicon-based microchannel heat exchangers with different-ratios, and combined with the visualization method to measure the performance of the device and compared them with simulation results. The theoretical model is verified through the suction experiment of array microchannel evaporator capillary core. The simplified model of microchannel array significantly saves the computational cost and time, and provides guidance for the related experimental researches.

[Role of mitochondrial-mediated cardiomyocytes injury in acute myocardial infarction with cardiogenic shock].

Acute myocardial infarction with cardiogenic shock (AMI-CS) refers to the rapid decrease in cardiac output in a short period of time, and it leads to severe insufficient perfusion of various organs and causes systemic microcirculatory dysfunction, which is the most common cause of the death of patients with acute myocardial infarction (AMI). At present, the main strategy for clinical treatment of AMI-CS is revascularization, which reduces the mortality of AMI-CS. However, myocardial ischemia and reperfusion can cause ischemia/reperfusion (I/R) injury, induce myocardial mitochondrial dysfunction, and a large amount of reactive oxygen species (ROS) accumulation. Mitochondrial-mediated apoptosis of cardiomyocytes is the main reason of cardiomyocyte death during reperfusion injury. This article summarizes the role of mitochondrial in AMI-CS, which focus on three aspects of mitochondrial permeability transition pore (mPTP) opening, mitochondrial autophagy and mitochondrial fusion/division. It is expected to provide new ideas for clinical AMI-CS and identify potential complications targets.

Effect of the immobilized microcystin-LR-degrading enzyme MlrA on nodularin degradation and its immunotoxicity study.

In freshwater ecosystems with frequent cyanobacterial blooms, the cyanobacteria toxin pollution is becoming increasingly serious. Nodularin (NOD), which has strong biological toxicity, has emerged as a new pollutant and affects the normal growth, development and reproduction of aquatic organisms. However, little information is available regarding this toxin. In this study, a graphene oxide material modified by L-cysteine was synthesized and used to immobilize microcystin-LR (MC-LR)-degrading enzyme (MlrA) to form an immobilized enzyme nanocomposite, CysGO-MlrA. Free-MlrA was used as a control. The efficiency of NOD removal by CysGO-MlrA was investigated. Additionally, the effects of CysGO-MlrA and the NOD degradation product on zebrafish lymphocytes were detected to determine the biological toxicity of these two substances. The results showed the following: (1) There was no significant difference in the degradation efficiency of NOD between CysGO-MlrA and free-MlrA; the degradation rate of both was greater than 80% at 1 h (2) The degradation efficiency of the enzyme could retain greater than 81% of the initial degradation efficiency after the CysGO-MlrA had been reused 7 times. (3) CysGO-MlrA retained greater than 50% of its activity on the 8th day when preserved at 0 °C, while free-MlrA lost 50% of its activity on the 4th day. (4) CysGO-MlrA and the degradation product of NOD showed no obvious cytotoxicity to zebrafish lymphocytes. Therefore, CysGO-MlrA might be used as an efficient and ecologically safe degradation material for NOD.

Effects of Bacillus cereus PAS38 on Immune-Related Differentially Expressed Genes of Spleen in Broilers.

This study mainly explored the immunomodulatory mechanisms of the probiotic Bacillus cereus PAS38 (PB) on broiler spleen. A total of 120 avian white feather broilers were randomly divided into 4 groups (N = 30), as follows: control (CNTL, fed with basal diet), PB (fed with diet supplemented with probiotic B. cereus PAS38), vaccine (VAC, fed with basal diet and injected with Newcastle disease virus vaccine), and vaccine + PB group (PBVAC, fed with basal diet supplemented with B. cereus PAS38 and injected with NDV vaccine). The experiment was conducted for 42 days. Twelve spleens were collected from four different groups, weighed, and cut into histological sections, and transcriptome analysis was performed using RNA-seq. Results of the spleen and histological section relative weights showed that feeding with probiotic B. cereus PAS38 and vaccination had a similar tendency to promote spleen development. Compared with the CNTL group, 21 immune-related genes were significantly downregulated in the PB and PBVAC groups. These genes were mainly involved in attenuating inflammatory response. The upregulated antimicrobial peptide NK-lysin and guanylate-binding protein 1 expression levels indicated that this strain enhanced the body's antimicrobial capacity. B. cereus PAS38 also amplified the broilers' immune response to the vaccine, which mainly reflected on nonspecific immunity. Hence, probiotic B. cereus PAS38 can regulate and promote the immune function of broilers.

Biomagnification characteristics and health risk assessment of the neurotoxin BMAA in freshwater aquaculture products of Taihu Lake Basin, China.

In freshwater aquaculture ecosystems with high-frequency occurrences of cyanobacteria blooms, a chronic neurotoxic cyanobacteria toxin, ß-N-methylamino-l-alanine (BMAA), is a new pollutant that affects the normal growth, development, and reproduction of aquaculture organisms. BMAA poses a great threat to the food quality and food safety of aquatic products. In this paper, high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) was used to detect the contents of BMAA in the edible portions of six representative freshwater aquaculture products (Corbicula fluminea, Anodonta arcaeformis, Macrobrachium nipponense, Eriocheir sinensis, Ctenopharyngodon idella, and Mylopharyngodon piceus) from Taihu Lake Basin in China. Noncarcinogenic health risks were assessed with reference to the model recommended by the International Environmental Modelling and Software Society and based on the biomagnification characteristics of BMAA in the various aquaculture products investigated by the stable nitrogen isotope technique. The average BMAA concentrations in the edible portions of the six freshwater culture products were from 2.05 ±â€¯1.40 to 4.21 ±â€¯1.26 µg g-1 dry weight (DW), and the difference was significant (p < 0.05), such a difference increased with the increase in the trophic level in the aquaculture products. Although a biomagnification indication was observed, the trophic magnification factor (TMF) was only 1.20 which exhibited a relatively low biomagnification efficiency. The annual health risk values of BMAA in all the measured aquatic products were within the maximum tolerable range (<1 × 10-6 a-1), and the health risk increased with the increase in the trophic level. The risk values of BMAA in the six freshwater aquaculture products for children was slightly higher than the negligible level (<1 × 10-7 a-1), thus there might have potential health risks for children's long-term consumption. Considering China's national conditions, the guidance values of BMAA based on the quality and safety of freshwater aquaculture products were proposed to be 7.2 µg g-1 DW for adults and 1.8 µg g-1 DW for children.

Mesoporous Colloidal Photonic Crystal Particles for Intelligent Drug Delivery.

Particle-based delivery systems demonstrate a pregnant value in the fields of drug research and development. Efforts to advance this technology focus on the fabrication of functional particles with enhanced efficiency and performance for drug delivery. Here, we present a new type of mesoporous colloidal photonic crystal particle (MCPCP)-based drug-delivery system with distinct features. As the MCPCPs were constructed by self-assembling monodisperse mesoporous nanoparticles in microfluidic droplet templates, they were composed of hierarchical macro- and mesoporous structures and could provide plenty of nanopores and interconnected nanochannels for synergistic loading of both micro- and macromolecule drugs with large quantity and sustained release. In addition, by integrating the stimuli-responsive poly( N-isopropylacrylamide) hydrogel into the MCPCPs and employing it as a "gating" to control the opening of the macro- and mesopores, the MCPCP delivery systems were imparted with the function of controllable release. More attractively, as the average refractive index of the MCPCPs was decreased during the release of the loaded actives, the photonic band gaps of the MCPCPs blue-shifted correspondingly; this provided a novel stratagem for real-time self-reporting of the therapeutic agent release process of the MCPCPs. Hence, the MCPCPs are ideal for intelligent drug delivery because of these dramatical features.

Lipid-Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in†vitro and in†vivo.

Lipid-based nanoparticles as gene vectors have attracted considerable attention for their high gene transfection efficiency and low cytotoxicity. In our previous work, we synthesized gold nanoparticles/dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) (GDD) as anionic lipid- and pH-sensitive gene vectors. To further realize targeted gene transfection, a series of gold nanoparticles/DODAB/DOPE/DOPE-folic acid (DOPE-FA) with various ratios of DOPE-FA were prepared and termed as GFn (for which n=1.0, 2.5, 5.0, 7.5, or 10.0 %). The gene transfection efficiency mediated by GF2.5 can reach about 85 % for MCF-7 (FA-receptor-positive cells), higher than those of the negative control (GDD, 35 %) and positive control (Lipofectamine 2000, 65 %). However, GF2.5 does not further promote gene transfection into A549 (FA-receptor-negative cells). The higher gene transfection efficiency for MCF-7 cells can be attributed to enhanced cellular uptake efficiency mediated by the FA targeting ability. Furthermore, GF2.5 was also found to accumulate at the specific tumor site and showed enhanced in vivo gene delivery ability. In addition, no significant harm was observed for the main tissues of the mice after treatment with GF2.5. Therefore, GF2.5, with the targeting ability and improved transfection efficiency, shows promise for its utility in gene therapy for tumor cells that overexpress FA receptors. We believe the results of this study will find more broad applications in gene therapy.