Benefitting from the antenna effect and localized surface plasmon resonance (LSPR), a metal nanoparticle with a designed morphology has the amazing ability to confine light energy into the required extremely small volume, whose refractive index largely affects the optical properties of the whole metal nanoparticle. In this work, the optical spectra and near-field distribution of a gold nanocrescent array were investigated both experimentally and theoretically. To find out the LSPR wavelength and the enhancement using different morphologies of sharp tips, the spectra of gold nanocrescent arrays with different waist widths (d) were first measured, which were then confirmed and analyzed using the finite difference time-domain method and the hybridization theory. At last, the LSPR of this array with 100 nm diameter dielectric nanodisks was studied for sensing in subwavelength areas. Our results showed that because of its giant nanoantenna-enhanced electromagnetic field at the two tips, this gold nanocrescent array could be a suitable local senor to sense the variation of a local medium in a subwavelength area.
A series of novel zinc oxide-silica composites with three-dimensionally ordered macropores (3DOM) structure were synthesized via colloidal crystal template method and used as sorbents for hydrogen sulfide (H2S) removal at room temperature for the first time. The performances of the prepared sorbents were evaluated by dynamic breakthrough testing. The materials were characterized before and after adsorption using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). It was found that the composite with 3DOM structure exhibited remarkable desulfurization performance at room temperature and the enhancement of reactive adsorption of hydrogen sulfide was attributed to the unique structure features of 3DOM composites; high surface areas, nano-crystalline ZnO and the well-ordered interconnected macroporous with abundant mesopores. The introduction of silica could be conducive to support the 3DOM structure and the high dispersion of zinc oxide. Moisture in the H2S stream plays a crucial role in the removal process. The effects of Zn/Si ratio and the calcination temperature of 3DOM composites on H2S removal were studied. It demonstrated that the highest content of ZnO could reach up to 73 wt% and the optimum calcination temperature was 500C. The multiple adsorption/regeneration cycles showed that the 3DOM ZnO-SiO2 sorbent is stable and the sulfur capacity can still reach 67.4% of that of the fresh sorbent at the 5th cycle. These results indicate that 3DOM ZnO-SiO2 composites will be a promising sorbent for H2S removal at room temperature.
Matrine has been used in anti-inflammatory and anti-cancer therapies for a long time. However, the anti-metastatic effect and related mechanism(s) in colorectal cancer (CRC) are still unclear. In this study, we investigated whether the administration of matrine could inhibit the proliferation, motility, and invasion of human CRC cells via regulating p38 signaling pathway. Results showed that matrine inhibited migration and invasion of CRC cells in vitro and in vivo. Additionally, after being treated with matrine for 24 h, the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 as well as proteinase activity in CRC cells were reduced in a dose-dependent manner. Moreover, matrine reduced the phosphorylation level of p38 obviously. Combined treatment with p38 inhibitor (SB203580) and matrine resulted in a synergistic reduction of invasion as well as MMP-2/-9 expression in CRC cells. It was also found that matrine inhibited the proliferation and metastasis of CRC tumor in vivo. In conclusion, p38 signaling pathway may involve in matrine's inhibitory effects on migration and invasion of CRC cells by reducing the expression of MMP-2/-9, suggesting that matrine may be a potential therapeutic agent for CRC.
We report a novel strategy for the fabrication of nanoporous gold (NPG) films. The fabrication process involves the electrodeposition of a gold-tin alloy, followed by subsequent chemical dealloying of tin. Scanning electron microscopy (SEM) images show a bicontinuous nanoporous structure formed on the substrates after chemical dealloying. Energy dispersive x-ray (EDX) analysis indicates that there are no impurities in the Au-Sn alloy film with an average composition of 58 at. % Au and 42 at. % Sn. After dealloying, only gold remains in the NPG film indicating the effectiveness of this technique. X-ray diffraction (XRD) results reveal that the as-prepared Au-Sn alloy film is composed of two phases (Au5Sn and AuSn), while the NPG film is composed of a single phase (Au). We demonstrate that this approach enables the fabrication of NPG films, either freestanding or supported on various conductive substrates such as copper foil, stainless steel sheet and nickel foam. The resulting NPG electrode exhibits enhanced electrocatalytic activity toward both H2O2 reduction and methanol oxidation compared to the polished Au disc electrode. Our strategy provides a general method to fabricate high quality NPG films on conductive substrates, which will broaden the application potential of NPG or NPG-based materials in various fields such as catalysis, optics and sensor technology.
The Fano resonance induced by symmetry breaking could improve the sensitivity of localized surface plasmon resonance sensors. In this work, the spectra of gold nanocrescent arrays are measured and confirmed by simulation results through the finite element method (FEM). The Fano resonance presented in the spectra could be modulated by the symmetry breaking with different waist widths, which are understood through plasmonic hybridization theory with the help of surface charge distribution. Our results indicate the Fano lineshape is generated by the coherent coupling of the quadrupole plasmon mode QH of nanohole and the antibonding plasmon mode DAB of nanocrescent. Finally, the high figure of merit (FoM=1.6-3.5) of the Q mode in the visible region illustrates this nanocrescent Fano sensor is of great value in the biological and chemical scientific fields.
We propose and demonstrate a fiber Bragg grating sensor interrogator based on a 2D imaging system using a virtually imaged phased array (VIPA) and infrared camera. There are no moving parts, and the interrogator has good stability and reliability. The absolute wavelength accuracy of the interrogator is better than that of traditional diffraction grating and a 1D-imaging-system-based method, thanks to the VIPA's high spectral resolution and large angular dispersion. The wavelength resolution of the interrogator is about 7 pm, and the spectral range of this interrogator is more than 30 nm. The optimum setup for the best wavelength resolution is analyzed.
Peptide-based nanomaterials are widely used as nanocarriers for catalysis, drug delivery, and gene delivery. In this paper, we designed and synthesized the amphiphilic tripeptides through solution phase synthesis. The tripeptides were purified by column chromatography and the molecular structures were confirmed by (1)H NMR and TOF-MS. The tripeptides could self-assemble into spherical nanoparticles in aqueous media with a low critical aggregation concentration. The size and morphology of the nanoparticles were performed by dynamic light scattering, scanning electron microscopy and transmission electron microscope. The peptide-based nanoparticles were used as biocompatible nanocarriers for encapsulating hydrophobic doxorubicin (DOX) to achieve controlled release. The CCK-8 assay indicated that the peptide-based nanocarriers could enhance cellular uptake and drug efficacy of DOX to A549 tumor cell line. These results showed that the self-assembly of amphiphilic tripeptides provided a facile strategy to fabricate nanoparticles for anti-tumor drug delivery.
In order to improve the transfection efficiency (TE) and biocompatibility, we synthesized a series of hyperbranched cationic polymers by ring-opening polymerization between diepoxide and several polyamines. These materials can condense plasmid DNA efficiently into nanoparticles that have much lower cytotoxicity than those derived from bPEI. In vitro transfection experiments showed that polymers prepared from branched or cyclic polyamine (P1 and P5) exhibited TE several times higher than 25KDa bPEI. More significantly, serum seemed to have no negative effect on P1-P5 mediated transfection. On the contrary, the TE of P1 improved, even when the serum concentration reached 70%. Several assays demonstrated the excellent serum tolerance of such polycationic vectors: bovine serum albumin (BSA) adsorption assay revealed considerably lower protein adsorption of P1-P5 than PEI; P1 showed better DNA protection ability from degradation by DNase I than PEI; flow cytometry results suggested that any concentration of serum may not decrease the cellular uptake of P1/DNA polyplex; and confocal laser scanning microscopy also found that serum has little effect on the transfection. By using specific cellular uptake inhibitors, we found that the polyplexes enter the cells mainly via caveolae and microtubule-mediated pathways. We believe that this ring-opening polymerization may be an effective synthetic approach toward gene delivery materials with high biological activity.
Currently, supramolecular self-assembly of dendrons and dendrimers emerges as a powerful and challenging strategy for developing sophisticated nanostructures with excellent performances. Here we report a supramolecular hybrid strategy to fabricate a bio-inspired dendritic system as a versatile delivery nanoplatform. With a rational design, dual-functionalized low-generation peptide dendrons (PDs) self-assemble onto inorganic nanoparticles via coordination interactions to generate multifunctional supramolecular hybrid dendrimers (SHDs). These SHDs exhibit well-defined nanostructure, arginine-rich peptide corona, and fluorescent signaling properties. As expected, our bio-inspired supramolecular hybrid strategy largely enhances the gene transfection efficiency of SHDs approximately 50?000-fold as compared to single PDs at the same R/P ratio. Meanwhile the bio-inspired SHDs also (i) provide low cytotoxicity and serum resistance in gene delivery; (ii) provide inherent fluorescence for tracking intracellular pathways including cellular uptake, endosomal escape, and gene release; and (iii) work as an alternative reference for monitoring desired protein expression. More importantly, in vivo animal experiments demonstrate that SHDs offer considerable gene transfection efficiency (in muscular tissue and in HepG2 tumor xenografts) and real-time bioimaging capabilities. These SHDs will likely stimulate studies on bio-inspired supramolecular hybrid dendritic systems for biomedical applications both in vitro and in vivo.
To observe the effects of electrical hippocampal stimulation of ?? subunit of extrasynaptic GABA(A) receptor in kainic acid-induced epileptic rats, explore the optimal therapeutic parameters and elucidate the possible mechanism of electrical stimulation for hippocampal epilepsy.
The increased number of CD4(+)CD25(+)Treg cells in tumor local and peripheral splenic tissues is related to the low immune function as well as to tumor recurrence and metastasis. Our pre-clinical studies showed that low-dose radiation (LDR) of the spleen in liver cancer patients significantly improves immune functions. However, the molecular mechanisms of such radiation remained ill defined. This study explores the role of CD4(+)CD25(+)Treg cells in radiation-induced immunomodulatory effects. Using the diethylnitrosamine (DEN)-induced rat liver tumor model and in vitro cell experiments, the percentage of CD4(+)CD25(+)Treg/CD4(+) cells in the blood and the expressions of Foxp3(+), IL-10, TGF-?, and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) in spleen and liver tumors significantly decreased after LDR of the spleen in rats with liver cancer. The tumors became smaller than those in the non-radiated group, with both showing a parallel relation. Flow cytometry and MTT results revealed that LDR failed to inhibit CD4(+)CD25(+)Treg cell proliferation. Conversely, apoptosis was reduced and proliferation was stimulated. This process also changed CTLA-4 molecule expression on the surfaces of CD4(+)CD25(+)Treg cells and reduced their inhibitory function against CD4(+)CD25(-)T cell proliferation, and the suppression function of CD4(+)CD25(+)Treg cells was further weakened with the introduction of the CTLA-4 inhibitor. Findings demonstrate that the reduction of CTLA-4 expression on the CD4(+)CD25(+)Treg cell surface and the further inhibition of cell function may be considered as important regulators of LDR-induced immunomodulatory effects. This study provides experimental evidence to elucidate the immune enhancement induced by this process and presents a novel method for liver cancer immunotherapy.
We previously found that endoplasmic reticulum (ER) stress was involved in ventricular arrhythmias in diabetic cardiomyopathy. The present study was aimed to investigate the possible mechanism. In the in vivo study, diabetes cardiomyopathy (DCM) was induced by streptozotocin (STZ) injection. Hemodynamic and plasma brain natriuretic peptide (BNP) detections were used to evaluate cardiac functions; ECG was used to assess the vulnerability to arrhythmias by recording ventricular arrhythmia events (VAEs). In the in vitro study, high-glucose incubation was employed to mimic the diabetic environment of myocytes. Immunofluorescent staining was used to investigate the nuclear factor of activated T cells (NFAT) nuclear translocation and (FK506-binding protein 12.6) FKBP12.6 disassociation. [(3)H]-ryanodine binding assay was implemented to assess the channel activity of ryanodine receptor. In both in vivo and in vitro studies, activity of calcineurin was determined by colorimetric method, and western blotting was used to detect protein expression levels. In the in vivo study, we found that inhibition of both of ER stress and PERK activation decreased the VAEs in DCM rats, accompanied by reduced activity of calcineurin in myocardial tissue. In the in vitro study, in high-glucose incubated myocytes, the depletion of PERK reduced activity of calcineurin, decreased NFAT translocation and FKBP12.6 disassociation from ryanodine receptor 2 (RyR2). Furthermore, PERK deletion also reduced RyR2 channel activity and consequently impaired intracellular calcium accumulation. We concluded that PERK/calcineurin-pathway was involved in intracellular calcium regulation in myocytes in diabetic heart, which might be the mechanism inducing arrhythmias in DCM.
Hydrophilic-hydrophobic-hydrophilic triblock copolymers, such as Pluronic L64, P85, and P105, have attracted more attention due to their enhancement in muscular gene delivery. In the present study, a new kind of electroneutralized triblock copolymer, LPL, dendron G2(L-lysine-Boc)-PEG2k-dendron G2(L-lysine-Boc), was designed and investigated. This hydrophobic-hydrophilic-hydrophobic copolymer is composed of a structure reverse to that of L64, one of the most effective materials for intramuscular gene delivery so far. Our results showed that LPL exhibited good in vivo biocompatibility after intramuscular and intravenous administration. LPL mediated higher reporter gene expression than L64 in assays of ?-galactosidase (LacZ), luciferase, and fluorescent protein E2-Crimson. Furthermore, LPL-mediated mouse growth hormone expression significantly accelerated mouse growth within the first 10 days. Altogether, LPL-mediated gene expression in skeletal muscle exhibits the potential of successful gene therapy. The current study also presented an innovative way to design and construct new electroneutralized triblock copolymers for safe and effective intramuscular gene delivery.
An ABC transporter gene ( OsABCG15 ) was proven to be involved in pollen development in rice. The corresponding protein was localized on the plasma membrane using subcellular localization. Wax, cutin, and sporopollenin are important for normal development of the anther cuticle and pollen exine, respectively. Their lipid soluble precursors, which are produced in the tapetum, are then secreted and transferred to the anther and microspore surface for polymerization. However, little is known about the mechanisms underlying the transport of these precursors. Here, we identified and characterized a member of the G subfamily of ATP-binding cassette (ABC) transporters, OsABCG15, which is required for the secretion of these lipid-soluble precursors in rice. Using map-based cloning, we found a spontaneous A-to-C transition in the fourth exon of OsABCG15 that caused an amino acid substitution of Thr-to-Pro in the predicted ATP-binding domain of the protein sequence. This osabcg15 mutant failed to produce any viable pollen and was completely male sterile. Histological analysis indicated that osabcg15 exhibited an undeveloped anther cuticle, enlarged middle layer, abnormal Ubisch body development, tapetum degeneration with a falling apart style, and collapsed pollen grains without detectable exine. OsABCG15 was expressed preferentially in the tapetum, and the fused GFP-OsABCG15 protein was localized to the plasma membrane. Our results suggested that OsABCG15 played an essential role in the formation of the rice anther cuticle and pollen exine. This role may include the secretion of the lipid precursors from the tapetum to facilitate the transfer of precursors to the surface of the anther epidermis as well as to microspores.
Environmentally responsive peptide dendrimers loaded with drugs are suitable candidates for cancer therapy. In this study, we report the preparation and characterization of mPEGylated peptide dendrimer-linked diaminocyclohexyl platinum (II) (dendrimer-DACHPt) conjugates as pH-responsive drug delivery vehicles for tumor suppression in mice. The DACHPt has a molecular structure, is and activity closely related to oxaliplatin and was linked to dendrimer via N,O-chelate coordination. The products were pH-responsive and released drug significantly faster in acidic environments (pH 5.0) than pH 7.4. Consequently, the conjugates suppressed tumor growth better than clinical oxaliplatin(®) without inducing toxicity in an SKOV-3 human ovarian cancer xenograft. Through the systemic delivery of conjugates, 25-fold higher tumor platinum uptake at 36 h post-injection was seen observed due to the enhanced permeability and retention (EPR) effect thereby remarkably enhancing the therapeutic indexes of this small-molecule drug. Thus, the mPEGylated peptide dendrimer-linked DACH-platinum conjugates are novel potential drug delivery systems with implications in future ovarian cancer therapy.
Peptide dendrimer drug conjugate based nanoparticles are recently developed as a potential candidate for drug delivery vehicle. In this study, we prepared and characterized the enzyme-sensitive amphiphilc mPEGylated dendron-GFLG-DOX conjugate via two-step highly efficient click reaction. Dynamic light scattering (DLS) and transmission electron microscope (TEM) studies demonstrated the mPEGylated dendron-GFLG-DOX conjugate self-assembled into compact nanoparticles with negatively charged surface. The nanoparticles with 9.62 wt% (weight percent) of DOX showed enzyme-sensitive property by drug release tests. The nanoparticles were shown to effectively kill cancer cells in vitro. The fluorescent image indicated that the nanoparticles could accumulate and retain within tumor for a long time. Moreover, the nanoparticles substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis of the 4T1 murine breast cancer model confirmed as the evidences from tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The nanoparticles reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shifts and histological analysis. Therefore, the mPEGylated dendron-GFLG-DOX conjugate based nanoparticle serves as a potential drug delivery vehicle for breast cancer therapy.
Viral nanoparticles have attracted extensive research interests in diverse applications of diagnosis and therapy. In particular, filamentous M13 bacteriophages have shown great potential in biomedical applications. However, its pathways entering into cells still remain unclear, and this greatly hinders its further use as a drug or gene carrier. Here, a ratiometric M13 pH probe is designed by conjugating two fluorescent dyes onto the surface of M13. Since the intensity ratio is not influenced by probe concentration, ion strength, temperature, photobleaching, and optical path length, this ratiometric probe can be used to investigate the intracellular pH map of M13. More importantly, the internalization mechanism of M13 can be elucidated. It is found that this filamentous phage shows great cell-type dependence in interaction with cells and internalization mechanism. The phage tends to be bounded on the cell membrane of only epithelial cells, not endothelial cells. Furthermore, the M13 phage enters into cells through endocytosis with specific mechanism: clathrin-mediated endocytosis and macropinocytosis for HeLa; vesicular transport, clathrin-mediated endocytosis, and macropinocytosis for MCF-7; caveolae-mediated endocytosis for human dermal microvascular endothelial cell (HDMEC). This work provides key notes for cancer diagnosis and therapy based on filamentous bacteriophage, especially for design of pH-sensitive drug delivery systems.
DNA sequence-dependent photoluminescence enhancement is found for a cationic polyelectrolyte complexed with single stranded DNA and described as a result of an interplay between electrostatic attraction and the ?-? stacking between the polyelectrolyte's backbone and DNA's bases.
Amphidiploid species in the Brassicaceae family, such as Brassica napus, are more tolerant to environmental stress than their diploid ancestors.A relatively salt tolerant B. napus line, N119, identified in our previous study, was used. N119 maintained lower Na(+) content, and Na(+)/K(+) and Na(+)/Ca(2+) ratios in the leaves than a susceptible line. The transcriptome profiles of both the leaves and the roots 1?h and 12?h after stress were investigated. De novo assembly of individual transcriptome followed by sequence clustering yielded 161,537 nonredundant sequences. A total of 14,719 transcripts were differentially expressed in either organs at either time points. GO and KO enrichment analyses indicated that the same 49 GO terms and seven KO terms were, respectively, overrepresented in upregulated transcripts in both organs at 1?h after stress. Certain overrepresented GO term of genes upregulated at 1?h after stress in the leaves became overrepresented in genes downregulated at 12?h. A total of 582 transcription factors and 438 transporter genes were differentially regulated in both organs in response to salt shock. The transcriptome depicting gene network in the leaves and the roots regulated by salt shock provides valuable information on salt resistance genes for future application to crop improvement.
A novel one-pot synthesis for the subeutectic growth of (111) oriented Si nanowires on an in situ formed nickel nanoparticle catalyst prepared from an inexpensive nickel nitrate precursor is developed. Additionally, anchoring the nickel nanoparticles to a simultaneously reduced graphene oxide support created synergy between the individual components of the c-SiNW-G composite, which greatly improved the reversible charge capacity and it is retention at high current density when applied as an anode for a Li-ion battery. The c-SiNW-G electrodes for Li-ion battery achieved excellent high-rate performance, producing a stable reversible capacity of 550 mAh g(-1) after 100 cycles at 6.8 A g(-1) (78% of that at 0.1 A g(-1)). Thus, with further development this process creates an important building block for a new wave of low-cost silicon nanowire materials and a promising avenue for high rate Li-ion batteries.
Selenium deficiency is a causative factor in heart failure and microRNAs (known as miRNAs or miRs) play an important role in numerous cardiovascular diseases. However, the changes of miRNA expression during selenium deficiency and whether selenium deficiency is involved in cardiac dysfunction remain unclear. In the present study, miRNA expression profiling was carried out in normal rats, selenium?deficient rats and selenium?supplemented rats by miRNA microarray. Cardiac function was evaluated by analyzing the plasma brain natriuretic peptide level, echocardiographic parameters and hemodynamic parameters. Cardiac glutathione peroxidase activity was assessed by spectrophotometry. The histological changes were examined by hematoxylin and eosin staining. Electrocardiograph was used to test the arrhythmia. The differentially expressed miRNAs were verified by reverse transcription?polymerase chain reaction. Additionally, the underlying mechanism associated with the Wnt/??catenin signaling pathway was further explored. The cardiac dysfunction of the rat with selenium deficiency was mainly associated with five upregulated miRNAs, which were miR?374, miR?16, miR?199a?5p, miR?195 and miR?30e*, and three downregulated miRNAs, which were miR?3571, miR?675 and miR?450a*. Among these, the expression of miR?374 was the highest, which may be of vital importance in rats with selenium deficiency. In conclusion, the possible mechanism of selenium deficiency?induced cardiac dysfunction was associated with the Wnt/??catenin signaling pathway.
Mechanical properties are among the most concerned issues for artificial bone grafting materials. The scaffolds used for bone grafts are either too brittle (glass) or too weak (polymer), and therefore composite scaffolds are naturally expected as the solution. However, despite the intensive studies on composite bone grafting materials, there still lacks a material that could be matched to the natural cancellous bones. In this study, nanosized bioactive particles (BP) with controllable size and good colloidal stability were used to composite with gelatin, forming macroporous scaffolds. It was found that the mechanical properties of obtained composite scaffolds, in terms of elastic modulus, compressive strength, and strain at failure, could match to that of natural cancellous bones. This is ascribed to the good distribution of particle in matrix and strong interaction between particle and gelatin. Furthermore, the incorporation of BPs endues the composite scaffolds with bioactivity, forming HA upon reacting with simulated body fluid (SBF) within days, thus stimulating preosteoblasts attachment, growth, and proliferation in these scaffolds. Together with their good mechanical properties, these composite scaffolds are promising artificial bone grating materials.
On the basis of terminal group electrostatic interactions (TGEI), a supra-amphiphile is formed between a homopolymer of polylactic acid with carboxyl group at one end (PLA-COOH) and hepta-6-hydrazyl-?-cyclodextrin (HH-CD). The amphiphile can self-assemble into a micellar structure in aqueous solution. The outer surface of the micelle, which is composed of cyclodextrins, can be further modified via host-guest interactions. Considering the biocompatibility of the building blocks, the application of the micelles in a nanocarrier of anticancer drugs is further explored.
Hawk tea (Litsea coreana var. lanuginose) is a very popular herbal tea in the southwest of China. According to the maturity degree of raw materials, Hawk tea can usually be divided into three types: Hawk bud tea (HB), Hawk primary leaf tea (HP), and Hawk mature leaf tea (HM). In this study, some of the bioactive constituents and antioxidant properties of the three kinds of Hawk tea infusions were comparatively investigated. The results showed that the contents of total flavonoids, vitamin C, and carbohydrates in Hawk bud tea infusion (HBI) were higher than those in Hawk primary leaf tea infusion (HPI) and Hawk mature leaf tea infusion (HMI). HPI had higher contents of total polyphenols and exhibited better DPPH radical scavenging activity and ferric reducing activity power. HBI could provide more effective protection against erythrocyte hemolysis. As age is going from bud to mature leaf, the ability to inhibit the formation of low density lipoprotein (LDL) conjugated diene and the loss of tryptophan fluorescence decreased. The bioactive constituents and antioxidant activities of Hawk tea infusions were significantly affected by the maturity degree of the raw material.
Background. Controversy remains for the association between hepatocyte nuclear factor 4? (HNF-4?) P2 promoter polymorphism rs1884613 and type 2 diabetes (T2D). There was no association test of this polymorphism with prediabetes and T2D in the Chinese population. Moreover, an updated meta-analysis in various ethnic groups is needed to establish the contribution of rs1884613 to T2D risk. Methods. Using the Sequenom MassARRAY platform approach, we genotyped rs1884613 of HNF-4? in the P2 promoter region among 490 T2D patients, 471 individuals with prediabetes, and 575 healthy controls. All the individuals were recruited from 16 community health service centers in Nanshan district in Shenzhen province. Using STATA 11.0 software, meta-analysis was performed to summarize the overall contribution of rs1884613 to T2D risk. Results. Polymorphism rs1884613 was associated with genetic susceptibility to prediabetes in the whole samples (OR = 1.40, 95% CI = 1.16-1.68, P = 0.0001) and the female subgrouped samples (OR = 1.48, 95% CI = 1.14-1.92, P = 0.003) after adjusting for age and body mass index (BMI). In contrast, there was no association of rs1884613 with T2D in the whole samples and male in our case-control study and meta-analysis. Conclusions. Our results suggest that rs1884613 contributes to susceptibility to prediabetes, whereas this polymorphism may not play an important role in the development of T2D.
It is critical for the clinical success to take the biological function into consideration when integrating the antibacterial function into the implanted biomaterials. To this aim, we prepared gentamycin sulfate (GS)-loaded carboxymethyl-chitosan (CM-chitosan) hydrogel cross-linked by genipin. The prepared hydrogels not only achieved superb inhibition on bacteria growth and biofilm formation of Staphylococcus aureus but also significantly enhanced the adhesion, proliferation, and differentiation of MC3T3-E1 cells. The observed dual functions were likely based on the intrinsic property of the positive charged chitosan-based hydrogel, which could be modified to selectively disrupt the bacteria wall/membrane and promote cell adhesion and proliferation, as suggested by the membrane permeability study. The genipin concentration played an important role in controlling the degradation time of the chitosan hydrogel and the MC3T3-E1 cell responses. The loading of GS not only significantly increased the antibacterial efficiency but also was beneficial for the osteoblastic cell responses. Overall, the biocompatibility of the prepared chitosan-GS hydrogel could be tuned with both the genipin and GS concentrations, which control the available positive charged sites of chitosan. The results demonstrated that chitosan-GS hydrogel is an effective and simple approach to achieving combined antibacterial efficacy and excellent osteoblastic cell responses, which has great potential in orthopedic applications.
BackgroundMicroRNAs (miRNAs) are approximately 19¿~¿21 nucleotide noncoding RNAs produced by Dicer-catalyzed excision from stem-loop precursors. Many plant miRNAs have critical functions in development, nutrient homeostasis, abiotic stress responses, and pathogen responses via interaction with specific target mRNAs. Camellia sinensis is one of the most important commercial beverage crops in the world. However, miRNAs associated with cold stress tolerance in C. sinensis remains unexplored. The use of high-throughput sequencing can provide a much deeper understanding of miRNAs. To obtain more insight into the function of miRNAs in cold stress tolerance, Illumina sequencing of C. sinensis sRNA was conducted.ResultSolexa sequencing technology was used for high-throughput sequencing of the small RNA library from the cold treatment of tea leaves. To align the sequencing data with known plant miRNAs, we characterized 106 conserved C. sinensis miRNAs. In addition, 215 potential candidate miRNAs were found, among, which 98 candidates with star sequences were chosen as novel miRNAs. Both congruously and differentially regulated miRNAs were obtained, and cultivar-specific miRNAs were identified by microarray-based hybridization in response to cold stress. The results were also confirmed by quantitative real-time polymerase chain reaction. To confirm the targets of miRNAs, two degradome libraries from two treatments were constructed. According to degradome sequencing, 455 and 591 genes were identified as cleavage targets of miRNAs from cold treatments and control libraries, respectively, and 283 targets were present in both libraries. Functional analysis of these miRNA targets indicated their involvement in important activities, such as development, regulation of transcription, and stress response.ConclusionsWe discovered 31 up-regulated miRNAs and 43 down-regulated miRNAs in `Yingshuang¿, and 46 up-regulated miRNA and 45 down-regulated miRNAs in `Baiye 1¿ in response to cold stress, respectively. A total of 763 related target genes were detected by degradome sequencing. The RLM-5¿RACE procedure was successfully used to map the cleavage sites in six target genes of C. sinensis. These findings reveal important information about the regulatory mechanism of miRNAs in C. sinensis, and promote the understanding of miRNA functions during the cold response. The miRNA genotype-specific expression model might explain the distinct cold sensitivities between tea lines.
Radish (Raphanus sativus L., n = 9) is one of the major vegetables in Asia. Since the genomes of Brassica and related species including radish underwent genome rearrangement, it is quite difficult to perform functional analysis based on the reported genomic sequence of Brassica rapa. Therefore, we performed genome sequencing of radish. Short reads of genomic sequences of 191.1 Gb were obtained by next-generation sequencing (NGS) for a radish inbred line, and 76,592 scaffolds of ?300 bp were constructed along with the bacterial artificial chromosome-end sequences. Finally, the whole draft genomic sequence of 402 Mb spanning 75.9% of the estimated genomic size and containing 61,572 predicted genes was obtained. Subsequently, 221 single nucleotide polymorphism markers and 768 PCR-RFLP markers were used together with the 746 markers produced in our previous study for the construction of a linkage map. The map was combined further with another radish linkage map constructed mainly with expressed sequence tag-simple sequence repeat markers into a high-density integrated map of 1,166 cM with 2,553 DNA markers. A total of 1,345 scaffolds were assigned to the linkage map, spanning 116.0 Mb. Bulked PCR products amplified by 2,880 primer pairs were sequenced by NGS, and SNPs in eight inbred lines were identified.
Reduction-controlled hierarchical unpacking is proposed for the development of virus-mimicking gene carriers. Disulfide-bond-modified hyaluronic acid (HA) is deposited onto the surface of diselenide-conjugated oligoethylenimine/DNA polyplexes to form DNA/OEI-SeSex/HA-SS-COOH (DOS) polyplexes. The cleavage of the disulfide and diselenide bonds is triggered by the gradient GSH level at the tumor site and inside the cells. The transfection efficiency of DOS show significant enhancement over DNA/poly(ethylene imine) (DP) in vitro and in vivo.
The association of the fat mass and obesity-associated gene (FTO) rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of FTO rs11642015 with the risk of prediabetes, type 2 diabetes and obesity following adjustment for the corresponding confounders. A meta-analysis was also conducted to evaluate the association between FTO rs11642015 and obesity. FTO rs11642015 was significantly associated with prediabetes in the whole sample under the additive model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17-1.93; P=0.002], particularly in females. The polymorphism remained consistently significant following adjustment for age and body mass index (BMI), showing an increased prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19-2.01; P=0.001). In addition, a significant association was found for rs11642015 with prediabetes and type 2 diabetes under the dominant model. However, under the stringent Bonferroni's correction there was no evidence of positive associations for FTO rs11642015 with obesity in the whole sample, females or males. Findings of the meta-analysis showed that FTO rs11642015 was not predisposed to obesity. In conclusion, the T allele of FTO rs11642015 is positively associated with an increased risk of prediabetes, even after adjustment for age and BMI, particularly in females. Subjects carrying the CT + TT genotype are predisposed to prediabetes and type 2 diabetes. Therefore, results of the population-based study and follow-up meta-analysis suggested that FTO rs11642015 is not significantly associated with susceptibility to obesity.
Recently, the atom transfer radical polymerization (ATRP) of acrylic monomers in many reaction systems has been successfully accomplished. However, its application in aqueous solution is still a challenging task. In this work, polyacrylic acid (PAA) brushes with tunable length were directly grafted from P(St-AA)/Fe3O4 composite microspheres in aqueous solution via an improved method, activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). This reaction was carried out in environment-friendly solvent. As well, this method overcame the sensitivity of the catalyst. Due to the strong coordination interaction of carboxyl groups, PAA brushes were employed for immobilizing gold nanoparticles, which were prepared via the in situ reduction of chloroauric acid. The PAA brushes modified magnetic composite microspheres decorating with gold nanoparticles were efficient for specific immobilization and separation of bovine serum albumin (BSA) from aqueous solution under the external magnetic field.
A new strategy for synthesis of superparamagnetic molecularly imprinted polymer nanospheres (MIPNSs) for efficient protein recognition is described here. Homogeneous hydroxyl group functionalized Fe3O4/polymethyl methacrylate (PMMA) composite nanospheres were prepared using improved miniemulsion polymerization. Uniform superparamagnetic MIPNSs were obtained via self-polymerization of dopamine (DA) on the surface of Fe3O4/PMMA composite nanospheres in the presence of lysozyme (lyz) template. The as-synthesized Fe3O4/PMMA/PDA MIPNSs had average diameters of 180nm, high saturation magnetization and a good magnetic response. The lyz-imprinted Fe3O4/PMMA/PDA MIPNSs exhibited specific recognition and efficient adsorption capacity toward lyz template. The amount of lyz adsorbed onto the lyz-imprinted Fe3O4/PMMA/PDA MIPNSs was about 4 times greater than that of the Fe3O4/PMMA/PDA non-imprinted polymer nanospheres (NIPNSs) and about 14, 5, and 5 times greater than that of BSA, BHb, and cyt C, respectively.
This paper firstly demonstrated the refractive index (RI) characteristics of a singlemode-claddingless-singlemode fiber structure filter based fiber ring cavity laser sensing system. The experiment shows that the lasing wavelength shifts to red side with the ambient RI increase. Linear and parabolic fitting are both done to the measurements. The linear fitting result shows a good linearity for applications in some areas with the determination coefficient of 0.993. And a sensitivity of ~131.64nm/RIU is experimentally achieved with the aqueous solution RI ranging from 1.333 to 1.3707, which is competitively compared to other existing fiber-optic sensors. While the 2 order polynomial fitting function, which determination relationship is higher than 0.999, can be used to some more rigorous monitoring. The proposed fiber laser has a SNR of ~50dB, and 3dB bandwidth ~0.03nm.
A novel pH-sensitive polymeric micelle was reported. Methoxy poly(ethylene glycol)-b-poly(?-caprolactone) copolymer with citraconic amide as pH-sensitive bond was synthesized (mPEG-pH-PCL). The copolymers self-assembled into micelles to encapsulate anticancer drug doxorubicin (DOX). The morphology, size and size distribution, drug release profile and in vitro anticancer activity of the DOX loaded mPEG-pH-PCL micelles were studied. The results showed that the mean size of the micelles was around 120 nm, the drug loading content and encapsulation efficiency of the mPEG-pH-PCL micelles were 6.8% and 54.3%, respectively. The mean diameter and size distribution of the mPEG-pH-PCL micelles increased significantly when soaking in medium with pH 5.5. The drug release of micelles in pH 5.5 was much faster than that in pH 7.4. The confocal laser microscopy and flow cytometry measurements indicated that the weak acidity of endosomes broke the citraconic amide bonds in the copolymer backbones and triggered the fast release of DOX. The in vitro IC50 of the drug loaded mPEG-pH-PCL micelles was lower than that of drug loaded polymeric micelles without pH-sensitivity to both HepG2 and 4T1 cancer cells.
Nanoparticle-based drug delivery systems promise the safety and efficacy of anticancer drugs. Herein, we presented a facile approach to fabricate novel nanoparticles generated by PEG-Chrysin conjugates for the delivery of anticancer drug doxorubicin. Chrysin was immobilized on the terminal group of methoxy poly(ethylene glycol) (mPEG) to form mPEG-Chrysin conjugate. The conjugates were self-assembled into nanoparticles. Doxorubicin (DOX) was loaded in the nanoparticles. The self-assembly, drug release profiles, interactions between nanoparticle and drug, cellular uptake and in vitro anticancer activity of the DOX loaded nanoparticles were investigated. The results showed that the mean diameters of drug loaded nanoparticles were below 200 nm. Strong ?-? stacking interaction was tested within the drug loaded nanoparticles. The drug release rate was closely related to the chain length of PEG, shorter PEG chain resulted faster release. The mPEG-Chrysin conjugate was non-toxic to both 3T3 fibroblasts and HepG2 cancer cells. The cellular uptake measurements demonstrated that the mPEG1000-Chrysin nanoparticles exhibited higher capability in endocytosis. The IC50 of drug loaded mPEG1000-Chrysin nanoparticles was 4.4 ?g/mL, which was much lower than that of drug loaded mPEG2000-Chrysin nanoparticles (6.8 ?g/mL). These nanoparticles provided a new strategy for fabricating antitumor drug delivery systems.
Filamentous bulking is a complicated problem in wastewater treatment plants treating various wastewaters, leading to the deterioration of the settling properties and the effluent quality. This study systematically investigated long-term effects of various carbon sources and feeding patterns on the growth of filamentous bacteria, in order to reveal the mechanism of filamentous bulking. Sludge volume index (SVI), microscopic observations, staining (Gram and Neisser staining), scan electron microscopic, and fluorescent in situ hybridization (FISH) were used to monitor the bulking and track the changes of microbial morphology and community structure of activated sludge in six lab-scale sequencing batch reactors (SBRs) fed with different carbon sources. Filamentous bulking was not observed in all SBRs under anoxic feeding pattern with a short fill time, in which SVI remained below 150 mL/g. In contrast, serious bulking (SVI?>?500 mL/g) occurred under aerobic feeding pattern when fed with ethanol, propionate, acetate, and glucose, in which Thiothrix and Sphaerotilus natans proliferated as dominant filaments. Compared to glucose-fed reactor, relatively light bulking was caused in starch-fed reactor with the growth of Nostocoida limicola II. In addition, flocs in starch-fed reactor were more open and fluffy than flocs formed on readily biodegradable substrates. Finally, a framework integrating kinetic selection, diffusion selection, storage selection, and protozoa capture mechanism was proposed to explain filamentous bulking.
Similar histology and clinical behavior of both intraventricular central neurocytomas (CNs) and extraventricular neurocytomas (EVNs) may argue against the idea that EVNs were the distinct entity to distinguish from CNs in the 2007 World Health Organization classification. To explore respective characteristics and compare similarities and differences in CNs and EVNs, relevant clinical, radiological, operative and pathological data of 49 patients (35 CNs and 14 EVNs) in the Department of Neurosurgery at our hospital from 2005 to 2012 was reviewed and some comparisons between CNs and EVNs were conducted. The factors affecting posttreatment recurrence of CNs and EVNs were assessed by Cox regression analysis. In comparison, CNs showed a more typical clinical manifestation, and radiological and histopathological features, while EVNs demonstrated more malignant biological behavior, with higher MIB-1 index (p = 0.006), higher rate of atypia (p = 0.042), higher recurrence rate (p = 0.028), and shorter time to recurrence (p = 0.049). Subtotal resection was associated with higher rates of recurrence in both CNs (hazard ratio [HR] 6.16, p = 0.046) and EVNs (HR 5.26, p = 0.045), and atypia was also associated with a higher recurrence rate in CNs (HR 5.03, p = 0.042). CNs were thus easier to diagnose than EVNs, with typical clinical, radiological, and histopathological features, while the latter were more likely to show malignant biological behavior associated with atypia and recurrence. Total surgical resection is the optimal treatment choice for both CNs and EVNs, and patients with either CN or EVN with typical and/or totally resected lesions showed favorable clinical outcomes.
Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe(3)O(4) composite microspheres composed of an inner cavity, PLGA inner shell and Fe(3)O(4) outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe(3)O(4) nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 ?m showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g(-1)) and high efficiency in lysozyme adsorption.
Peptide dendrimers have shown promise as an attractive platform for drug delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive drug delivery vehicle. The drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale drug delivery vehicle for the breast cancer therapy.
Four arm star-shaped poly(?-caprolactone)-b-poly((N,N-diethylaminoethyl methacrylate)-r-(N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine)) (4sPCLDEAS) micelles were loaded with anticancer drug doxorubicin to track their endocytosis in Hela cancer cell line. The effects of mean diameters and surface charges of the drug loaded micelles on the cellular uptake were studied in details. The results demonstrated that the internalization of micelles was both time and energy dependent process. Endocytic pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis were all involved in the internalization; caveolae-mediated endocytosis was the main pathway for the internalization of 4sPCLDEAS micelles. The assays for cell apoptosis and growth inhibition of tumor spheroids identified that these doxorubicin loaded micelles could induce cell apoptosis and inhibit tumor spheroids growth efficiently, which was even equal to free DOX·HCl. This study provided a rational design strategy for fabricating diverse micellar drug delivery systems with high anticancer efficiency.
In this study, we propose a novel micro-/nanofluidic device that can generate a chemical concentration gradient using a parallel nanochannel as gradient generator. This device is easy to fabricate, showing high reproducibility. Its main feature is the multiple-nanochannel-based gradient generator, which permits the diffusion of small molecules and tunably generates concentration gradients. The nanopattern for the nanochannels can be rapidly and easily fabricated by wrinkling a diamond-like carbon thin film which is deposited on a polydimethylsiloxane substrate; the generation of the concentration gradient can be adjusted by controlling the dimensions of the nanochannels. The developed gradient generator is embedded into a microfluidic device to study chemotaxis in the nematode Caenorhabditis elegans, which has a highly developed chemosensory system and can detect a wide variety of chemical molecules. This device shows good performance for rapid analysis of C. elegans chemotaxis under sodium chloride stimuli.
Considerable evidence suggests that the gut microbiota is complex in many mammals and gut bacteria communities are essential for maintaining gut homeostasis. To date the research on the gut microbiota of donkey is surprisingly scarce. Therefore, we performed high-throughput sequencing of the 16S rRNA genes V5-V6 hypervariable regions from gut fecal material to characterize the gut microbiota of healthy donkeys and compare the difference of gut microbiota between male and female donkeys. Sixty healthy donkeys (30 males and 30 females) were enrolled in the study, a total of 915,691 validated reads were obtained, and the bacteria found belonged to 21 phyla and 183 genera. At the phylum level, the bacterial community composition was similar for the male and female donkeys and predominated by Firmicutes (64 % males and 64 % females) and Bacteroidetes (23 % males and 21 % females), followed by Verrucomicrobia, Euryarchaeota, Spirochaetes, and Proteobacteria. At the genus level, Akkermansia was the most abundant genus (23 % males and 17 % females), followed by Sporobacter, Methanobrevibacter, and Treponema, detected in higher distribution proportion in males than in females. On the contrary, Acinetobacter and Lysinibacillus were lower in males than in females. In addition, six phyla and 15 genera were significantly different between the male and female donkeys for species abundance. These findings provide previously unknown information about the gut microbiota of donkeys and also provide a foundation for future investigations of gut bacterial factors that may influence the development and progression of gastrointestinal disease in donkey and other animals.
Musashi1(MSI1) belongs to the RNA-binding protein (RBP) family, with functions as translational activator or suppressor of specifically bound mRNA. However, its function in hepatocellular carcinoma (HCC) has been deeply unexplored.
Simulation for the smooth muscle layer of blood vessel plays a key role in tubular tissue engineering. However, fabrication of biocompatible tube with defined inner nano/micro-structure remains a challenge. Here, we show that a biocompatible polymer tube from poly(l-lactide) (PLLA) and polydimethylsiloxane (PDMS) can be prepared by using electrospinning technique, with assistance of rotating collector and parallel auxiliary electrode. The tube has circumferentially aligned PLLA fibers in the inner surface for cell growth regulation and has a PDMS coating for better compressive property. MTT assay showed the composite PLLA/PDMS tube was suitable for various cells growth. In vitro smooth muscle cells (SMCs) cultured in the tube showed that the aligned PLLA fibers could induce SMCs' orientation, and different expression of ?-SMA and OPN genes were observed on the aligned and random PLLA fibers, respectively. The successful fabrication of composite PLLA/PDMS tubular scaffold for regulating smooth muscle cells outgrowth has important implications for tissue-engineered blood vessels.
Collagen fibrous network not only provides structural support for cells but also serves as critical environment modulating various cell functions. Various factors would influence the collagen self-assembly but the effect of substrate surface on such process has been rarely studied. Here we examined the effects of materials (Ti and hydroxyapatite) and their surface characteristics (with and without the enrichment of hydroxyl group) on collagen self-reconstitution and fibrous network formation, and on subsequent cell adhesion and cytoskeleton organization of mesenchymal stem cells (MSCs). For both Ti and hydroxyapatite (HA) substrates, the enrichment of hydroxyl group (OH) on substrate surfaces promoted the collagen self-reconstitution and facilitated the formation of the fibrous network after 4h immersion in phosphate buffer solution (PBS), while all samples showed clear fibrous network formation after 2 day soaking in PBS. Compared with the Ti surfaces, the HA surfaces facilitated the self-reconstitution of collagen, leading to a more mature fibrous network with a twisted structure and enhanced lateral aggregation of fibrils. The fibrous network difference resulted in different behaviors of the subsequent MSC adhesion and spreading. The MSCs had the best adhesion and cytoskeleton organization on the OH enriched HA surface with collagen modification. Our results suggested that both the material selection and the hydroxyl group significantly influenced the collagen self-assembly and fibrous network formation and, as a result, the subsequent cell adhesion behaviors.
A low-cost high-performance solid-state flexible asymmetric supercapacitor (ASC) with ?-MnO2 nanowires and amorphous Fe2O3 nanotubes grown on flexible carbon fabric is first designed and fabricated. The assembled novel flexible ASC device with an extended operating voltage window of 1.6 V exhibits excellent performance such as a high energy density of 0.55 mWh/cm(3) and good rate capability. The ASC devices can find numerous applications as effective power sources, such as powering color-switchable sun glasses and smart windows.
Gene therapy has provided great potential to revolutionize the treatment of many diseases. This therapy is strongly relied on whether a delivery vector efficiently and safely directs the therapeutic genes into the target tissue/cells. Nonviral gene delivery vectors have been emerging as a realistic alternative to the use of viral analogs with the potential of a clinically relevant output. Dendritic polymers were employed as nonviral vectors due to their branched and layered architectures, globular shape and multivalent groups on their surface, showing promise in gene delivery. In the present review, we try to bring out the recent trend of studies on functional and biodegradable dendritic polymers as nontoxic and efficient gene delivery vectors. By regulating dendritic polymer design and preparation, together with recent progress in the design of biodegradable polymers, it is possible to precisely manipulate their architectures, molecular weight and chemical composition, resulting in predictable tuning of their biocompatibility as well as gene transfection activities. The multifunctional and biodegradable dendritic polymers possessing the desirable characteristics are expected to overcome extra- and intracellular obstacles, and as efficient and nontoxic gene delivery vectors to move into the clinical arena.
We aimed to report the feasibility and safety of the technique after laparoscopy-assisted total gastrectomy (LATG) or laparoscopy-assisted proximal gastrectomy (LAPG): intracorporeal circular stapling esophagogastrostomy/esophagojejunostomy using the reverse puncture device (RPD).
It has been reported that host genetic factors may play a crucial role in pneumoconiosis susceptibility. The present study aimed to study the association between IL-1RA +2018 polymorphism and pneumoconiosis by Meta-analysis.
Intramuscular injection of plasmid DNA (pDNA) to express a therapeutic protein is a promising method for the treatment of many diseases. However, the therapeutic applications are usually hindered by gene delivery efficiency and expression level. In this study, critical factors in a pDNA-based gene therapy system, such as gene delivery materials, a therapeutic gene, and its regulatory elements, were optimized to establish an integrated system for the treatment of mouse hindlimb ischemia. The results showed that Pluronic L64 (L64) was an efficient and safe material for gene delivery into mouse skeletal muscle. It also showed intrinsic ability to promote in vivo angiogenesis in a concentration-dependent manner, which might be through the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-?B)-regulated angiogenic factors. The combination of 0.1% L64 with a hybrid gene promoter (pSC) increased the gene expression level, elongated the gene expression duration, and enhanced the number of transfected muscle fibers. In mice ischemic limbs, a gene medicine (pSC-HIF1?(tri)/L64) composed of L64 and pSC-based expression plasmid encoding hypoxia-inducible factor 1-alpha triple mutant (HIF-1?(tri)), improved the expression of stable HIF-1?, and in turn, the expression of multiple angiogenic factors. As a result, the ischemic limbs showed accelerated function recovery, reduced foot necrosis, faster blood reperfusion, and higher capillary density. These results indicated that the pSC-HIF1?(tri)/L64 combination presented a potential and convenient venue for the treatment of peripheral vascular diseases, especially critical limb ischemia.
Well-ordered, one-dimensional H2Ti2O5, H2Ti8O17, TiO2-B, and anatase TiO2/TiO2-B nanowire arrays were innovatively designed and directly grown on current collectors as high performance three dimensional (3D) anodes for binder and carbon free lithium ion batteries (LIBs). The prepared thin nanowires exhibited a single crystalline phase with highly uniform morphologies, diameters ranging from 70-80 nm, and lengths of around 15 ?m. Specifically, reversible Li insertion and extraction reactions around 1.6-1.8 V with initial intercalation capacities of 326 and 271 mA h g(-1) at a cycling rate of 0.1 C (where 1 C = 335 mA g(-1)) were observed for H2Ti8O17 and TiO2-B nanowire arrays, respectively. Among the four compounds investigated, the H2Ti8O17 nanowire electrode demonstrated optimal cycling stability, delivering a high specific discharge capacity of 157.8 mA h g(-1) with a coulombic efficiency of 100%, even after the 500th cycle at a current rate of 1 C. Furthermore, the H2Ti8O17 nanowire electrode displayed superior rate performance with rechargeable discharge capacities of 127.2, 111.4, 87.2, and 73.5 mA h g(-1) at 5 C, 10 C, 20 C, and 30 C, respectively. These results present the potential opportunity for the development of high-performance LIBs based on nanostructured Ti-based anode materials in terms of high stability and high rate capability.
Silicon has been considered as an ideal anode material for next generation of lithium ion batteries, due to its 10 times higher capacity than graphite. (3600 mA h g-1 for Li15Si4 vs. 372 mA h g-1 for LiC6). The poor electrode integrity, leading to the electrical isolation of Si particles, is a critical issue for applying Si as the anode in lithium ion batteries, besides the Si fracture and unstable solid electrolyte interphase. In this work, we address those critical issues through a simplified post-electrode-fabrication flash treatment strategy. The one-step process not only mitigates the mechanical degradation to Si particles, but also significantly improves the electrode integrity. Meanwhile, it also generates a unique C/SiO2/Si core shell structure to stabilize the solid electrolyte interphase. The synergetic combination of the enhanced microscopic interfacial bonding and the improved macroscopic electrode integrity allows for the controlled expansion of Si, achieve first cycle efficiency of ~84% and a maximum charge capacity of 3525 mA h g-1 (voltage range 1.5 - 0.005V), 84% of silicons theoretical maximum. Further, a stable reversible charge capacity of 1150 mA h g-1 at 1.2 A g-1 (voltage range 1 - 0.05V) can be maintained over 500 cycles.
This study reports a facile method for the synthesis of multi-enzyme co-embedded organic-inorganic hybrid nanoflowers, using glucose oxidase (GOx) and horseradish peroxidase (HRP) as the organic components, and Cu3(PO4)2·3H2O as the inorganic component. The synthesized nanoflowers enable the combination of a two-enzyme cascade reaction in one step, in which the GOx component of the nanoflowers oxidizes glucose to generate H2O2, which then reacts with the adjacent HRP component on the nanoflowers to oxidize the chromogenic substrates, resulting in an apparent color change. Given the close proximity of the two enzyme components in a single nanoflower, this novel sensor greatly reduces the diffusion and decomposition of H2O2, and greatly enhances the sensitivity of glucose detection. Thus, the obtained multi-enzyme co-embedded organic-inorganic hybrid nanoflowers can be unquestionably used as highly sensitive colorimetric sensors for the detection of glucose. Notably, this work presents a very facile route for the synthesis of multi-enzyme co-embedded nanomaterials for the simultaneous catalysis of multi-step cascade enzymatic reactions. Furthermore, it has great potential for application in biotechnology, and biomedical and environmental chemistry.
Viral nanoparticles (VNPs) have shown great potential as platforms for biomedical applications. Before using VNPs for further biomedical applications, it is important to clarify their biological behavior in vivo, which is rare for rod-like VNPs. In this paper, a study of tobacco mosaic virus (TMV), a typical rod-like VNP, is performed on blood clearance kinetics, biodistributions in both normal and tumor-bearing mice, histopathology and cytotoxicity. TMV was radiolabeled with (125)I using Iodogen method for in vivo quantitative analysis and imaging purpose. In the normal mice, the accumulation of TMV in the immune system led to a rapid blood clearance. The uptake of TMVs in the liver was less than that in the spleen, which is opposite to the results observed in the case of spherical VNPs. No signs of overt toxicity were observed in examined tissues according to the results of histological analysis. In addition, similar biodistribution patterns were observed in U87MG tumor-bearing mice.
Self-powered systems usually consist of energy-acquisition components, energy-storage components and functional components. The development of nanoscience and nanotechnology has greatly improved the performance of all the components of self-powered systems. However, huge differences in the materials and configurations in the components cause large difficulties for integration and miniaturization of self-powered systems. Design and fabrication of different components in a self-powered system with the same or similar materials/configurations should be able to make the above goal easier. In this work, a proof-of-concept experiment involving an integrated self-powered color-changing system consisting of TiO2 nanowire based sandwich dye-sensitized solar cells (DSSCs) and electrochromic devices (ECDs) is designed and demonstrated. When sunlight illuminates the entire system, the DSSCs generate electrical power and turn the ECD to a darker color, dimming the light; by switching the connection polarity of the DSSCs, the lighter color can be regained, implying the potential application of this self-powered color-changing system for next generation sun glasses and smart windows.
An interferometric fiber-optic vibration sensing system using the phase-generated carrier (PGC) method is proposed and experimentally demonstrated. The sensing section consists of a Sagnac interferometer combined with a Mach-Zehnder interferometer, a length of sensing fiber is shared between the two interferometers. The PGC demodulation scheme is used to demodulate the time-varying phase shifts induced by vibrations. Spatial information can be extracted from the demodulated results. A prototype sensing system with a 628 m long sensing fiber has been tested and a spatial resolution better than 12 m is successfully achieved.
The unique TiO2-C/MnO2 core-double-shell nanowires are synthesized for the first time using as anode materials for lithium ion batteries (LIBs). They combine both advantages from TiO2 such as excellent cycle stability and MnO2 with high capacity (1230 mA h g(-1)). The additional C interlayer intends to improve the electrical conductivity. The self-supported nanowire arrays grown directly on current-collecting substrates greatly simplify the fabrication processing of electrodes without applying binder and conductive additives. Each nanowire is anchored to the current collector, leading to fast charge transfer. The unique one-dimensional core-double-shell nanowires exhibit enhanced electrochemical performance with a higher discharge/charge capacity, superior rate capability, and longer cycling lifetime.
pH-sensitive micelles are considered promising carriers for tumor targeted drug delivery. In this study, novel pH-sensitive star-shape copolymers of amphiphilic poly(epsilon-caprolactone)-b-poly(N, N-diethylaminoethyl methacrylate)-r-poly(N-(3-sulfopropyl)-N-methacryloxyethy-N, N-diethylammoniumbetaine) (4sPCLDEAS) are designed and synthesized with the combination of ring opening polymerization (ROP) and atom radical transferpolymerization (ATRP). The structure of the copolymers is characterized by proton nuclear magnetic resonance spectra (1HNMR). The poly(N-(3-sulfopropyl)-N-methacryloxyethy-N, N-diethylammoniumbetaine) segment is used instead of poly(ethylene glycol) (PEG) as hydrophilic block in the copolymers to form polymeric micelles. The micelles present spherical shape, narrow size distribution, and are reponsive to the acidity. The CMC of the micelles is as low as 1 x 10(-3) mg mL(-1). Doxorubin (DOX) is efficiently encapsulated in the micelles and the drug release is pH dependant. The cytotoxicity as well as the intracellular drug delivery of the micelles are investigated. The micelles are nontoxic to human cervical carcinoma (Hela) cells. The DOX-loaded micelles are internalized in Hela cells efficiently, which are better than that of hydrophilic doxorubicin hydrochloride (DOX x HCl). These pH-sensitive micelles are potential promising carriers for anti-cancer drug delivery.
Superparamagnetic magnetite nanoparticles (MNPs) of different surface properties are incubated in complicated living fluid, including fetal bovine serum solution, cell complete culture medium and cell culture system with/without serum, to investigate the alteration of protein corona and its impact on cell internalization. The MNPs prepared by co-precipitation method are functionalized with L-Lysine (Lys), Glucosamic acid (GA) to obtain amine, carboxyl and hydroxyl groups, separately. All the particles adsorb serum proteins to form MNPs-protein complexes with the surface charge changing into negative. 1D SDS/PAGE gel images analysis indicates that the composition and content of hard protein corona on the surface of NPs are related to their functional groups and agglomeration, and the total amount of protein in the medium. In cell culture system, particles not only adsorb serum proteins, but also associate with cytosolic proteins arising from HepG2 and L02 cells. GA modified MNPs (MNPs-GA) exhibit bovine serum albumin anti-adsorption capability because of the terminal hydroxyl and carboxyl groups. MNPs-GA also shows the highest cellular uptake and label efficiency compared with uncoated MNPs and Lys modified MNPs, due to larger aggregates formation and specific protein corona composition, rather than commonly approved electrostatic interaction between particles and cells. For the first time, our results provide visualized reports on previously neglected, but indispensable protein corona of the MNPs after interaction with both healthy and cancer cells, suggesting that cytosolic protein corona from cells and aggregation of particles are important factors needed to be account for on studying the nano-bio interface.
Reduction-sensitive hyaluronic acid derivatives (HA-SS-COOH) were shielded on the DNA/polyethylenimine (PEI) to construct ternary complexes (DNA/PEI/HA-SS-COOH, DPS ternary complexes) with efficient gene transfection. Details studied were conducted to investigation of factors influencing transfection efficiency, including the gene compression by fluorescence resonance energy transfer (FRET) spectrum and the intracellular fate of fluorescent labeled complexes by the confocal laser scanning microscope (CLSM). In the FRET study, DPS complexes were found to enhance condensation of DNA in preparation, while timely loosen gene under exposure to reductive reagent. Similar cellular uptake levels were observed for the designed reduction sensitive complexes and the stable one (DNA/PEI/HA, DPH ternary complexes), but the intracellular process was strikingly different for the two types of complexes. Only DPS showed obvious desired intracellular deshielding and endosomal escape, which contributed to highly efficient gene delivery. After loading with p53 plasmid, DPS complexes achieved significantly up-regulated p53 tumor suppressor gene expression at both mRNA and protein levels, as revealed by quantitative polymerase chain reaction (qPCR) and western blot investigations. Transgene induced apoptosis was evaluated by propidium iodide staining and flow cytometry analysis of cell cycle. Tumor cells transfected by DPS complexes containing p53 gene displayed almost 50% higher suppression in proliferation compared to those untreated cells, accompanied with a 46% elevation in the number of cells at sub-G1 phase and remarkable p53 dependent cell cycle perturbations prior to apoptosis. These results demonstrated that targeted delivery of p53 gene via reduction-sensitive DPS ternary complexes enabled up-regulated cellular p53 mRNA level through the exogenous p53 gene, inducing a significant p53-dependent anti-proliferative effect on tumor cells, which could be effective means of cancer treatment.
External ventricular drainage (EVD) combined with intraventricular fibrinolysis (IVF) is rarely used in severe spontaneous cerebellar hemorrhage (SCH) with intraventricular hemorrhage (IVH). Recently, the treatment strategy was repeatedly performed in our hospital to elderly patients with severe SCH + IVH. To analyze its clinical value, we compared it to two treatment strategies which now commonly are used for these patients: conservative management (CM) and clot evacuation (CE). In this study, a total of 118 cases were observed, of which 28 cases received CM, 43 cases received EVD + IVF and 47 cases received CE. The Glasgow Coma Scale score, frequency of complication, mortality in one month, modified Rankin Scale (mRS) at six months, and causes of death were analyzed. The outcomes of patients in the CM group were extremely poor compared to patients undergoing surgery (P = 0.034) and the mortality was up to 61.3 % (18/28), which was much higher than those of the two surgical groups (P = 0.026). No significant difference was found in mortality and mRS between the two surgical groups (P > 0.05). Patients in the CE group mostly died of deterioration of comorbidities and postoperative complications, whereas more deaths occurred in the CM group and the EVD + IVF group due to rebleeding, brainstem compression, perilesional edema and tight posterior fossa (? (2), P = 0.006). It is suggested that EVD + IVF is a treatment option for elderly patients with severe SCH + IVH.
In recent years, the self-assembly polymeric nanoparticles are widely used for anti-tumor drug delivery. Multiple interactions such as hydrogen bonding, host-guest interaction, hydrophobic interaction and electrostatic interaction have been utilized to generate the nanoparticles. Herein, a new polymeric amphiphile with methoxy poly(ethylene glycol) (mPEG) as hydrophilic block and pi-pi conjugated small molecule N-(9-Fluorenylmethoxycarbonyl)-L-phenylalanines (Fmoc-Phe-OH) instead of hydrophobic polymer chain as lipophilic segment was synthesized. Anti-tumor drug doxorubicin (DOX) was trapped in the self-assembly nanoparticles via the dual hydrophobic and pi-pi stacking interactions. The synthesis and morphology of the self-assembly nanoparticles were studied. The interactions between drug and carrier, release profile, cellular uptake and in vitro anti-tumor efficiency of the drug loaded nanoparticles were investigated in details. The results showed that the amphiphiles self-assembled into spindle nanoparticles with the size around 200 nanometers. The pi-pi stacking interaction between DOX and Fmoc-Phe-OH achieved great performance for the efficient drug encapsulation. The DOX could be sustaingly released for 50 hours. The drug loaded nanoparticles were internalized in HepG2 cancer cells efficiently and exhibited good anti-tumor activity in vitro. The nanoparticles generated by mPEG-Phe-Fmoc amphiphiles provided a new strategy to fabricate polymeric nanoparticles for anti-tumor drug delivery.
We reported a novel hydrogelator with L-lysine as a linker to connect 7-carboxyl methoxycoumarin and hydrazine as lipophilic and water-soluble moieties. Ultrasound accelerated the gelation and induced homogenous self-assembly of fibrils into entangled 3D networks. The hydrogel exhibits great potential for future biomedical applications.
A novel type of nanovehicle (NV) based on stimuli-responsive supramolecular peptide-amphiphiles (SPAs, dendritic poly (L-lysine) non-covalently linked poly (L-leucine)) is developed for intracellular drug delivery. To determine the pH-dependent mechanism, the supramolecular peptide-amphiphile system (SPAS) is investigated at different pH conditions using a variety of physical and chemical approaches. The pH-triggered disassembly of SPAS can be attributed to the disappearance of non-covalent interactions within SPAs around the isoelectric point of poly (L-leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX-loaded NVs are approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH-dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX-loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence-activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei.
Polymeric nanoparticles have shown great promise as attractive vehicles for drug delivery. In this study, we designed, prepared and characterized biodegradable amphiphilic triblock HPMA copolymer-doxorubicin (copolymer-DOX) conjugate based nanoparticle as enzyme-sensitive drug delivery vehicle. The enzyme-sensitive peptide GFLGKGLFG was introduced to the main chain of the copolymer with hydrophilic and hydrophobic blocks. The triblock HPMA polymer-DOX conjugate with high molecules (Mw 90 kDa) can be degraded to product with low molecule weight (Mw 44 kDa) below the renal threshold. The copolymer-DOX conjugate can self-assemble into compact nanoparticle, which was characterized by scanning electron microscope (SEM) and atomic force microscope (AFM) studies. This polymeric nanoparticle substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis on the 4T1 murine breast cancer model confirmed by the evidences from mice weight shifts, tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The in vivo toxicity evaluation demonstrated that the polymeric nanoparticle reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shift, blood routine test and histological analysis. Therefore, the triblock HPMA copolymer-DOX conjugate based nanoparticle is promising as a potential drug delivery vehicle for breast cancer therapy.
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