Three-dimensional bioprinting has emerged as a promising technique in tissue engineering applications through the precise deposition of cells and biomaterials in a layer-by-layer fashion. However, ...the limited availability of hydrogel bioinks is frequently cited as a major issue for the advancement of cell-based extrusion bioprinting technologies. It is well known that highly viscous materials maintain their structure better, but also have decreased cell viability due to the higher forces which are required for extrusion. However, little is known about the effect of the two distinct components of dynamic modulus of viscoelastic materials, storage modulus (G') and loss modulus (G″), on the printability of hydrogel-based bioinks. Additionally, 'printability' has been poorly defined in the literature, mostly consisting of gross qualitative measures which do not allow for direct comparison of bioinks. This study developed a framework for evaluating printability and investigated the effect of dynamic modulus, including storage modulus (G'), loss modulus (G″), and loss tangent (G″/G') on the printing outcome. Gelatin and alginate as model hydrogels were mixed at various concentrations to obtain hydrogel formulations with a wide range of storage and loss moduli. These formulations were then evaluated for the quantitatively defined values of extrudability, extrusion uniformity, and structural integrity. For extrudability, increasing either the loss or storage modulus increased the pressure required to extrude the bioink. A mathematical model relating the G' and G″ to the required extrusion pressure was derived based on the data. A lower loss tangent was correlated with increased structural integrity while a higher loss tangent correlated with increased extrusion uniformity. Gelatin-alginate composite hydrogels with a loss tangent in the range of 0.25-0.45 exhibited an excellent compromise between structural integrity and extrusion uniformity. In addition to the characterization of a common bioink, the methodology introduced in this paper could also be used to evaluate the printability of other bioinks in the future.
Abstract Objective To investigate the renoprotective effects of exogenous endothelial progenitor cells (EPCs) on acute renal ischemia-reperfusion (I/R) injury in rats. Methods EPCs were collected by ...in vitro culture of mononuclear cells derived from rat bone marrow. The EPC labeling was performed using chloromethyl-benzamidodialkylcarbocyanine (CM-Dil). Sprague-Dawley rats were equally randomized into an I/R, an EPC, and a control group. We evaluated blood urea nitrogen (BUN) and serum creatinine (Scr), kidney morphology, apoptosis and microvessel density. EPC homing into I/R injured kidneys was observed using a fluorescence microscope. Results After EPC transplantation, CM-Dil-labeled EPCs were noted at the corticomedullary junction of injured kidneys. The levels of BUN and Scr were markedly lower among the EPC than the I/R group ( P < .05). The histopathologic score was higher in the I/R than the EPC group ( P < .05). Apoptosis of tubular epithelial cells was substantially reduced among EPC-treated rats ( P < .01). In addition, more CD34+ microvessels were documented among the EPC than the other two groups ( P < .01). The expression levels of vascular endothelial growth factor (VEGF) were also increased greatly in the EPC group ( P < .05). Conclusion Transplanted exogenous EPCs exert protective effects on renal function by maintaining the integrity of peritubular capillaries after I/R injury.
The staphylococcal chromosome cassette (SCC)mec types of 382 hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) isolates in Taiwan were analysed over a 7-year period (1999–2005). ...There was an abrupt increase in SCCmec type IV in HA-MRSA during 2005. The molecular epidemiology of a subset (n = 69) of HA-MRSA isolates with SCCmec types III, IV or V was characterised and compared with that of community-acquired MRSA (CA-MRSA) (n = 26, collected during 2005). Pulsed-field gel electrophoresis revealed three major pulsotypes (A, B and C) and 15 minor clones. Pulsotypes B and C, which contained isolates carrying SCCmec types IV and V, respectively, included both CA-MRSA and HA-MRSA isolates. Among 24 toxin genes analysed, five genes had significant differential distribution between CA-MRSA and SCCmec type III HA-MRSA. Furthermore, among SCCmec type IV isolates, the seb gene was detected more commonly in HA-MRSA. Analysis of representative members of the three major pulsotypes by multilocus sequence typing revealed two sequence types (STs), namely ST239 (SCCmec III) and ST59 (SCCmec IV or SCCmec V). This suggests that ST59:SCCmec IV, which is usually community-acquired, has become an important nosocomial pathogen in the hospital studied.
Glargine is widely used as a long-acting insulin analogue in the treatment of diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk of ...cancer. The aim of this study was to investigate the influence of glargine on proliferation of breast adenocarcinoma cell line (MCF-7) and its possible mechanism. Effects of glargine and regular human insulin on the cell proliferation were tested in ER-positive MCF-7 cells by MTT assay. Apoptosis in MCF-7 cells was measured by flow cytometry. The protein levels of p-AKT, Bcl-2, and Bax were also determined by Western blotting and immunohistochemistry, respectively. The result showed that glargine (100, 200 nmol/l) stimulated proliferation of ER-positive MCF-7 cells compared with regular human insulin. At the same time, glargine decreased the percentage of early apoptosis in MCF-7 cells. Otherwise, glargine (100 nmol/l) stimulated the p-AKT in a time-dependent manner in MCF-7 cells. Furthermore, we found that glargine downregulated the level of Bax protein and upregulated that of Bcl-2 (p <0.05). These data show that glargine promote the proliferation of breast adenocarcinoma cells in vitro, probably by preventing apoptosis.
Background and Aims
Regulations in some wine‐producing countries allow water addition to grape must. The research presented compared the impact of water addition to must on wine phenolics and colour ...relative to that of wines at the same alcohol concentration, prepared from fruit harvested earlier.
Methods and Results
Shiraz grapes were harvested at three stages; earlier harvest at 13.4 and 14.4°Bé (H‐1, H‐2) and a later harvest at 15.6°Bé (H‐3). Water was then added to H‐3 must to match the sugar concentration of H‐1 and H‐2, respectively. Two modes of water addition were followed: (i) water was directly added to the must; or (ii) juice was substituted for water. Both water addition treatments significantly decreased the concentration of phenolics throughout the winemaking process. At the end of malolactic fermentation, the concentration of phenolics, tannin and non‐bleachable pigments, tannin molecular mass and wine colour density were lower in the water addition treatments compared with that of H‐3, but in all other compositional aspects were higher than that of H‐1 and H‐2. Interestingly, where the extent of alcohol reduction by water addition was equivalent, no difference in any of the measured wine attributes was found between the two modes of water addition.
Conclusions
Water addition to the H‐3 treatment led to higher wine tannin, colour and non‐bleachable pigment than were found in wines made from grapes harvested at a lower sugar concentration.
Significance of the Study
The study presents a meaningful comparison of potential outcomes in Shiraz wine phenolics and colour for producers who aim to lower alcohol using the approaches of either water addition or early harvest.
The virus-encoded microRNAs (miRNAs) have been demonstrated to have important regulatory roles in herpesvirus biology, including virus replication, latency, pathogenesis and/or tumorigenesis. As an ...emerging efficient tool for gene editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system has been successfully applied in manipulating the genomes of large DNA viruses. Herein, utilizing the CRISPR/Cas9 system with a double-guide RNAs transfection/virus infection strategy, we have established a new platform for mutagenesis of viral miRNAs encoded by the Marek's disease virus serotype 1 (MDV-1), an oncogenic alphaherpesvirus that can induce rapid-onset T-cell lymphomas in chickens. A series of miRNA-knocked out (miR-KO) mutants with deletions of the Meq- or the mid-clustered miRNAs, namely RB-1B∆Meq-miRs, RB-1B∆M9-M2, RB-1B∆M4, RB-1B∆M9 and RB-1B∆M11, were generated from vvMDV strain RB-1B virus. Interestingly, mutagenesis of the targeted miRNAs showed changes in the in vitro virus growth kinetics, which is consistent with that of the in vivo proliferation curves of our previously reported GX0101 mutants produced by the bacterial artificial chromosome (BAC) clone and Rec E/T homologous recombination techniques. Our data demonstrate that the CRISPR/Cas9-based gene editing is a simple, efficient and relatively nondisruptive approach for manipulating the small non-coding genes from the genome of herpesvirus and will undoubtedly contribute significantly to the future progress in herpesvirus biology.
We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
A bstract Using e + e − collision data collected with the BESIII detector at the BEPCII collider at center-of-mass energies between 3.510 and 4.914 GeV, corresponding to an integrated luminosity of ...25 fb − 1 , we measure the Born cross sections for the process $$ {e}^{+}{e}^{-}\to {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ e + e − → K − Ξ ¯ + Λ / Σ 0 at thirty-five energy points with a partial-reconstruction strategy. By fitting the dressed cross sections of $$ {e}^{+}{e}^{-}\to {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ e + e − → K − Ξ ¯ + Λ / Σ 0 , evidence for $$ \psi (4160)\to {K}^{-}{\overline{\Xi}}^{+}\Lambda $$ ψ 4160 → K − Ξ ¯ + Λ is found for the first time with a significance of 4.4 σ , including systematic uncertainties. No evidence for other possible resonances is found. In addition, the products of electronic partial width and branching fraction for all assumed resonances decaying into $$ {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ K − Ξ ¯ + Λ / Σ 0 are determined.
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