Procedural Promotion of Multiple Stages in the Wound Healing Process by Graphene-Spiky Silica Heterostructured Nanoparticles.

Background: Multiple stages including hemostasis, inflammation, proliferation, and remodeling were involved in the wound healing process. The increase in nanomaterials in recent years has extended the scope of tools for wound healing; however, it is still difficult to achieve the four multistage procedures simultaneously. Materials and Methods: In this study, graphene-spiky silica heterostructured nanoparticles (GS) were synthesized for the procedural acceleration of the multistage in wound healing process. The nanobridge effect of GS was analyzed through the adhesion of two skins, the antibacterial effect was assessed in Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, cell proliferation and migration were investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the in vivo wound healing effect was examined in female BALB/c mice with a cutting wound and E. coli or S. aureus bacteria infection on the back. Results: First, GS has a strong nanobridge effect on the rapid closure of wounds because the spiky architecture on the surface of GS facilitates the adhesion of skins, promoting the hemostasis stage. Second, graphene exhibits antimicrobial activities both in chemical and physical interactions, especially under simulated sunlight irradiation. Third, graphene plays an important role in scaffolding function, together with the spiky topographical architecture of GS, accelerating the proliferation and maturation stages. Conclusion: By periodically promoting every stage of wound healing, GS combined with simulated sunlight irradiation could significantly accelerate wound healing. With a simple composition and compact structure but multiple functions, this strategy will be the guideline for the development of ideal wound-healing nanomaterials.

Connections between cohesion and properties that related to safety and effectiveness of the hyaluronic acid dermal fillers: A comparative study of the cohesive and non-cohesive gels.

BACKGROUND: Although the importance of the cohesion of a hyaluronic acid (HA) filler has been recognized, the relationship between the cohesion and the other performance that related to safety and effectiveness, as well as the underlying mechanism is barely studied. Much efforts need to be made on this subject to provide guidance for clinical practice. MATERIALS AND METHODS: Two types of the HA fillers (cohesive and particulate gels) were selected for the comparison of the cohesion and the other key physicochemical properties. RESULTS: Hyalumatrix, with significantly higher cohesion, was homogeneously smooth and showed a linearly oriented morphology, whereas Matrifill and Restylane were particulate and showed obvious boundaries between particles. The high cohesion of Hyalumatrix is beneficial to the properties that related to safety and effectiveness, including recovery under shear stress, injectability, tissue integration and in vitro resistance to enzymolysis. The underlying reason was that the strong internal interactions of the cohesive gel protect the network structure from collapse and keep the gel as an intact whole when the gel was subjected to the stress. The homogeneously smooth morphology further improved the tissue compliance and injectability. The G' of Hyalumatrix is in the middle level of the commercially available HA fillers. CONCLUSION: Hyalumatrix is a rare HA filler product to possess good cohesion and intermediate G' simultaneously. More clinical practice is needed to verify the connection between the cohesion of Hyalumatrix and the clinical performance.

Expression of CAD and SOX2 in Postoperative Intestinal Tissues of Children with Hirschsprung's Disease and Their Interrelationship.

Objective: To investigate the expression and significance of intestinal Cathepsin D (CAD) and sex-determining region Y-frame protein 2 (SOX2) in children with Hirschsprung's disease (HD) after surgery. Methods: Immunohistochemistry and Western blot techniques were employed to examine the expression of CAD and SOX2 in colonic tissues obtained from 56 children with HD (HD group) and 23 colonic tissues obtained from fistulas for intestinal obstruction or perforation (control group). Pearson linear correlation analysis was conducted to analyze the relationship between CAD and SOX2 expression, the diameter of the intermuscular plexus, and the number of ganglion cells in the diseased intestinal segment. Results: The positive expression rates of CAD protein and SOX2 protein in the intestinal tissues of children with HD were lower than those in the control group (P < .05). Furthermore, the positive expression rates of CAD protein and SOX2 protein in the narrow intestinal tissue of HD children were lower than those in the transitional colon tissue (P < .05). The diameter of the intramuscular plexus and the number of ganglion cells in the intestinal tissue of the stenosis and transitional segments in HD children were lower than those in the control group (P < .05). There was a significant positive correlation between the diameter of the intermuscular plexus and the number of ganglion cells in the intestinal tissue of HD children and the expression intensity of CAD protein and SOX2 protein (P < .05). Conclusions: The down-regulated expression intensity of CAD protein and SOX2 protein in the diseased colon of children with HD may be associated with a decrease in the diameter of the intermuscular plexus and the number of ganglion cells.

Stem-cell based soft tissue substitutes: Engineering of crosslinked polylysine-hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis.

BACKGROUND: The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. METHODS: The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. RESULTS: The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the green fluorescent protein-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared with the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. CONCLUSIONS: The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future.

Biocompatibility and Efficacy of a Linearly Cross-Linked Sodium Hyaluronic Acid Hydrogel as a Retinal Patch in Rhegmatogenous Retinal Detachment Repairment.

To prevent the migration of retinal pigment epithelium (RPE) cells into the vitreous cavity through retinal breaks after the pars plana vitrectomy for the repair of rhegmatogenous retinal detachment (RRD), sealing retinal breaks with an appropriate material appears to be a logical approach. According to a review of ocular experiments or clinical trials, the procedure for covering retinal breaks with adhesives is complex. A commercially available cross-linked sodium hyaluronic acid (HA) hydrogel (Healaflow®) with the injectable property was demonstrated to be a perfect retinal patch in RRD clinical trials by our team. Based on the properties of Healaflow®, a linearly cross-linked sodium HA hydrogel (HA-engineered hydrogel) (Qisheng Biological Preparation Co. Ltd. Shanghai, China) with the injectable property was designed, whose cross-linker and cross-linking method was improved. The purpose of this study is to report the characteristics of an HA-engineered hydrogel using Healaflow® as a reference, and the biocompatibility and efficacy of the HA-engineered hydrogel as a retinal patch in the rabbit RRD model. The HA-engineered hydrogel exhibited similar dynamic viscosity and cohesiveness and G' compared with Healaflow®. The G' of the HA-engineered hydrogel varied from 80 to 160 Pa at 2% strain under 25°C, and remained constantly higher than G″ over the range of frequency from 0.1 to 10 Hz. In the animal experiment, clinical examinations, electroretinograms, and histology suggested no adverse effects of the HA-engineered hydrogel on retinal function and morphology, confirming its favorable biocompatibility. Simultaneously, our results demonstrated the efficacy of the HA-engineered hydrogel as a retinal patch in the RRD model of rabbit eyes, which can aid in the complete reattachment of the retina without the need for expansile gas or silicone oil endotamponade. The HA-engineered hydrogel could play the role of an ophthalmologic sealant due to its high viscosity and cohesiveness. This pilot study of a small series of RRD models with a short-term follow-up provides preliminary evidence to support the favorable biocompatibility and efficacy of the HA-engineered hydrogel as a promising retinal patch for sealing retinal breaks in retinal detachment repair. More cases and longer follow-up studies are needed to assess its safety and long-term effects.

An Incremental Version of L-MVU for the Feature Extraction of MI-EEG.

Due to the nonlinear and high-dimensional characteristics of motor imagery electroencephalography (MI-EEG), it can be challenging to get high online accuracy. As a nonlinear dimension reduction method, landmark maximum variance unfolding (L-MVU) can completely retain the nonlinear features of MI-EEG. However, L-MVU still requires considerable computation costs for out-of-sample data. An incremental version of L-MVU (denoted as IL-MVU) is proposed in this paper. The low-dimensional representation of the training data is generated by L-MVU. For each out-of-sample data, its nearest neighbors will be found in the high-dimensional training samples and the corresponding reconstruction weight matrix be calculated to generate its low-dimensional representation as well. IL-MVU is further combined with the dual-tree complex wavelet transform (DTCWT), which develops a hybrid feature extraction method (named as IL-MD). IL-MVU is applied to extract the nonlinear features of the specific subband signals, which are reconstructed by DTCWT and have the obvious event-related synchronization/event-related desynchronization phenomenon. The average energy features of α and ß waves are calculated simultaneously. The two types of features are fused and are evaluated by a linear discriminant analysis classifier. Based on the two public datasets with 12 subjects, extensive experiments were conducted. The average recognition accuracies of 10-fold cross-validation are 92.50% on Dataset 3b and 88.13% on Dataset 2b, and they gain at least 1.43% and 3.45% improvement, respectively, compared to existing methods. The experimental results show that IL-MD can extract more accurate features with relatively lower consumption cost, and it also has better feature visualization and self-adaptive characteristics to subjects. The t-test results and Kappa values suggest the proposed feature extraction method reaches statistical significance and has high consistency in classification.

Theoretical studies on the structures, material properties, and IR spectra of polymorphs of 3,4-bis(1H-5-tetrazolyl)furoxan.

Theoretical studies on the structures, densities, and heats of formation of conformational isomers of 3,4-bis(1H-5-tetrazolyl)furoxan (H2BTF) were performed based on density functional theory (DFT) calculations. Two stable planar conformational isomers, the face-to-back and the back-to-face conformers, and one stable slightly twisted conformer, the back-to-back conformer, were predicted for H2BTF at the M06-2X/6-311 + G(d,p) level of theory. The face-to-back conformer was calculated to be the most stable conformational isomer on the potential energy surface. No stable face-to-face conformer, whether planar or tilted, was identified in the calculations. The Vienna Ab Initio Simulation Package (VASP) was used in combination with molecular dynamics simulation to explore the stable crystal forms and the densities of the stable conformational isomers. Two of them exhibited high densities: the face-to-back conformer with P21 symmetry (2.01 g/cm3) and the back-to-back conformer with Pna21 symmetry (2.05 g/cm3). Their heats of formation were also predicted to be high when calculated at the same DFT level. The detonation pressures and velocities of these polymorphs, as calculated using the EXPLO5 program, are well above those of many advanced high energy density materials, pointing to the potential use of these conformers as novel explosives with good detonation performance. Also, IR spectra are shown to be able to distinguish these denser polymorphs of H2BTF. This study suggests that it could be worth investigating whether denser polymorphs of H2BTF can be grown.

Reactivity of an amidinato silylene and germylene toward germanium(ii), tin(ii) and lead(ii) halides.

The coordination chemistry of an amidinato silylene and germylene toward group 14 element(ii) halides is described. The reaction of the amidinato silicon(ii) amide [LSiN(SiMe3)2] (1, L = PhC(NtBu)2) with SnCl2 and PbBr2 afforded the amidinato silylene-dichlorostannylene and -dibromoplumbylene adducts [L{(Me3Si)2N}SiEX2] (E = Sn, X = Cl (2); E = Pb, X = Br (3)), respectively, in which there is a lone pair of electrons on the Sn(ii) and Pb(ii) atoms. X-ray crystallography, NMR spectroscopy and theoretical studies show conclusively that the Si(ii)-E(ii) bonds are donor-acceptor interactions. Similar electronic structures were found in the amidinato germylene-dichlorogermylene and -dichlorostannylene adducts [L{(Me3Si)2N}GeECl2] (E = Ge (5), Sn (6)), which were prepared by treatment of the amidinato germanium(ii) amide [LGeN(SiMe3)2] (4) with GeCl2·dioxane and SnCl2, respectively.

Delocalized Hypervalent Silyl Radical Supported by Amidinate and Imino Substituents.

The reaction of the amidinato silylsilylene with a functionalized diaminochlorosilyl substituent, [LSiSi(Cl){(NtBu)2C(H)Ph}] (1; L = PhC(NtBu)2), with ArN═C═NAr (Ar = 2,6-iPr2C6H3) in toluene afforded the delocalized hypervalent silyl radical [LSi•(µ-CNAr)2Si{(NtBu)2C(H)Ph}] (2). It possesses a hypervalent silyl radical that delocalizes throughout the Si2C2 ring.

A smart upconversion-based light-triggered polymer for synergetic chemo-photodynamic therapy and dual-modal MR/UCL imaging.

We have developed a novel nanocomposite to achieve effective therapy and live surveillance of tumor tissue. In this study, fullerene (C60) with iron oxide (Fe3O4) nanoparticles and upconversion nanophosphors (UCNPs) was loaded into N-succinyl-N'-4-(2-nitrobenzyloxy)-succinyl-chitosan micelles (SNSC) with good biocompatibility. In addition, hydrophobic anticancer drug docetaxel (DTX) was also loaded into the nanocomposites. The experiments conducted in vitro and in vivo demonstrated that C60/Fe3O4-UCNPs@DTX@SNSC can act synergistically to kill tumor cells by releasing chemotherapy drugs at specific target site as well as generating reactive oxygen using 980nm. In addition, it can also be used for non-invasive deep magnetic resonance and upconversion fluorescence dual-mode imaging. The results indicated that this system provided an efficient method to surmount the drawback of UV or visible light-responsive polymeric systems for controlled drug release and generated reactive oxygen in deep tissues and ultimately realized the integration of dual-modal imaging and treatment.

A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data.

A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with high-throughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability and improve our understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the creation of tissue-specific models, which reduces the available reactions in an organism model, and does not provide an objective function for the estimation of fluxes. We develop a method, flux assignment with LAD (least absolute deviation) convex objectives and normalization (FALCON), that employs metabolic network reconstructions along with expression data to estimate fluxes. In order to use such a method, accurate measures of enzyme complex abundance are needed, so we first present an algorithm that addresses quantification of complex abundance. Our extensions to prior techniques include the capability to work with large models and significantly improved run-time performance even for smaller models, an improved analysis of enzyme complex formation, the ability to handle large enzyme complex rules that may incorporate multiple isoforms, and either maintained or significantly improved correlation with experimentally measured fluxes. FALCON has been implemented in MATLAB and ATS, and can be downloaded from: https://github.com/bbarker/FALCON. ATS is not required to compile the software, as intermediate C source code is available. FALCON requires use of the COBRA Toolbox, also implemented in MATLAB.

Transumbilical Single-Site Laparoscopic Inguinal Hernia Inversion and Ligation in Girls.

OBJECTIVES: The combination of transumbilical single-site laparoscopic inguinal hernia inversion and ligation is a new approach for girls. We have done 13 cases in our hospital since May 2013. MATERIALS AND METHODS: Thirteen girls with inguinal hernia, from 6 months to 10 years of age, were treated with transumbilical single-site laparoscopy. RESULTS: None of the patients underwent conversion from single-site laparoscopy to the open approach or conventional laparoscopic surgery. The average operation time was 35.15±6.68 minutes. Four cases were found to have a contralateral inguinal hernia. The patients were discharged the day after operation. Follow-up of 7 months to a year with all cases showed no recurrence and no incision complication. CONCLUSIONS: The combination of transumbilical single-site laparoscopic inguinal hernia inversion and ligation is a reliable, safe, and cosmetic herniorrhaphy for girls with inguinal hernia.

Laparoscopic cyst excision and Roux-Y hepaticojejunostomy for children with choledochal cysts in China: a multicenter study.

AIMS: Laparoscopic hepaticojejunostomy (LH) for children with choledochal cyst (CDC) has become feasible and popular recently. The purpose of this study is to evaluate the safety and efficacy of LH for CDC in a large multicenter series. PATIENTS AND METHODS: Medical records of 956 consecutive patients who underwent LH for CDC at seven academic institutions from June 2001 to May 2012 were retrospectively analyzed. Ultrasonography, upper gastrointestinal contrast studies, and laboratory tests were performed during the follow-up period. RESULTS: A total of 956 patients of CDC treated with LH were identified and included in this study. Of these patients, there were no significant differences in age, gender ratio, and the subtypes of CDC among the seven centers. The operative time of all patients decreased significantly as time went by. Interestingly, the centers that began to perform LH earlier, like cohort A, B, and C, took much more time in the initial cases than the later centers. The postoperative complications included 12 (1.3 %) intra-abdominal fluid collection, 6 (0.6 %) anastomotic stenosis, 14 (1.5 %) bile leak, 8 (0.8 %) Roux loop obstruction and 4 (0.4 %) gastrointestinal bleeding, and one case developed intrahepatic stone formation; two mortalities occurred; one died of hyperkalemia, and the other one died of postoperative bleeding. No other complication occurred during the mean follow-up of 5.7 years (ranged from 4 month to 11 years). CONCLUSIONS: We reported a multi-institutional series of LH in children with CDC. Our findings suggested that LH represents a feasible treatment option for CDC by offering reliable middle and long-term outcome, low surgical morbidity.

Group II metal complexes of the germylidendiide dianion radical and germylidenide anion.

The two-electron reduction of a Group 14-element(I) complex [RË⋅] (E=Ge, R=supporting ligand) to form a novel low-valent dianion radical with the composition [RË:]˙(2-) is reported. The reaction of [LGeCl] (1, L=2,6-(CH=NAr)2C6H3, Ar=2,6-iPr2C6H3) with excess calcium in THF at room temperature afforded the germylidenediide dianion radical complex [LGe]˙(2-)⋅Ca(THF)3(2+) (2). The reaction proceeds through the formation of the germanium(I) radical [LGe⋅], which then undergoes a two-electron reduction with calcium to form 2. EPR spectroscopy, X-ray crystallography, and theoretical studies show that the germanium center in 2 has two lone pairs of electrons and the radical is delocalized over the germanium-containing heterocycle. In contrast, the magnesium derivative of the germylidendiide dianion radical is unstable and undergoes dimerization with concurrent dearomatization to form the germylidenide anion complex [C6H3-2-{C(H)=NAr}Ge-Mg-6-{C(H)-NAr}]2 (3).

An extensive n, π, σ-electron delocalized Si(4) ring.

The tetrasilacyclobutadiene [LSi(µ-SiL')2 SiL] (L=PhC(NtBu)2 , L'=2,6-iPr2 C6 H3 NSiMe3 ) consists of an aromatic silicon-containing four-membered ring in which two π, two σ, and two lone-pair electrons are cyclically delocalized. The electron delocalization was illustrated by theoretical studies and reactivity with elemental sulfur to form the allylic zwitterionic cyclic compound [(LSi)2 (µ-SiL')(µ-Si(S)L')] with 2π-electron delocalization along the Si3 skeleton.

Zwitterionic base-stabilized digermadistannacyclobutadiene and tetragermacyclobutadiene.

The syntheses of a zwitterionic base-stabilized digermadistannacyclobutadiene and tetragermacyclobutadiene supported by amidinates and low-valent germanium amidinate substituents are described. The reaction of the amidinate Ge(I) dimer, [LGe:]2 (1, L=PhC(NtBu)2 ), with two equivalents of the amidinate tin(II) chloride, [LSnCl] (2), and KC8 in tetrahydrofuran (THF) at room temperature afforded a mixture of the zwitterionic base-stabilized digermadistannacyclobutadiene, [L2 Ge2 Sn2 L'2 ] (3; L'=LGe:), and the bis(amidinate) tin(II) compound, [L2 Sn:] (4). Compound 3 can also be prepared by the reaction of 1 with [L(Ar) SnCl] (5, L(Ar) =tBuC(NAr)2 , Ar=2,6-iPr2 C6 H3 ) in THF at room temperature. Moreover, the reaction of 1 with the "onio-substituent transfer" reagent [4-NMe2 -C5 H4 NSiMe3 ]OTf (8) in THF and 4-(N,N-dimethylamino)pyridine (DMAP) at room temperature afforded a mixture of the zwitterionic base-stabilized tetragermacyclobutadiene, [L4 Ge6 ] (9), the amidinium triflate, [PhC(NHtBu)2 ]OTf (10), and Me3 SiSiMe3 (11). X-ray structural data and theoretical studies show conclusively that compounds 3 and 9 have a planar and rhombic charge-separated structure. They are also nonaromatic.

A silyliumylidene cation stabilized by an amidinate ligand and 4-dimethylaminopyridine.

The synthesis and reactivity of a silyliumylidene cation stabilized by an amidinate ligand and 4-dimethylaminopyridine (DMAP) are described. The reaction of the amidinate silicon(I) dimer [LSi:]2 (1; L = PhC(NtBu)2) with one equivalent of N-trimethylsilyl-4-dimethylaminopyridinium triflate [4-NMe2C5H4NSiMe3]OTf and two equivalents of DMAP in THF afforded [LSi(DMAP)]OTf (2). The ambiphilic character of 2 is demonstrated from its reactivity. Treatment of 2 with 1 in THF afforded the disilylenylsilylium triflate [L'2(L)Si]OTf (3; L' = LSi:) with the displacement of DMAP. The reaction of 2 with [K{HB(iBu)3}] and elemental sulfur in THF afforded the silylsilylene [LSiSi(H){(NtBu)2C(H)Ph}] (4) and the base-stabilized silanethionium triflate [LSi(S)DMAP]OTf (5), respectively. Compounds 2, 3, and 5 have been characterized by X-ray crystallography.

Reactivity of a tin(II) (iminophosphinoyl)(thiophosphinoyl)methanediide complex toward sulfur: synthesis and 119Sn Mössbauer spectroscopic studies of [{(µ-S)SnC(PPh2═NSiMe3)(PPh2═S)}3Sn(µ3-S)].

Reaction of [(PPh(2)═NSiMe(3))(PPh(2)═S)CSn:](2) (1) with elemental sulfur in toluene afforded [{(µ-S)Sn(IV)C(PPh(2)═NSiMe(3))(PPh(2)═S)}(3)Sn(II)(µ(3)-S)] (2) and [CH(2)(PPh(2)═NSiMe(3))(PPh(2)═S)] (3). Compound 2 comprises a Sn(II)S moiety coordinated with the Sn(IV) and S atoms of a trimeric 2-stannathiomethendiide {(PPh(2)═NSiMe(3))(PPh(2)═S)CSn(µ-S)}(3). Compound 2 has been characterized by NMR spectroscopy, (119)Sn Mössbauer studies, X-ray crystallography, and theoretical studies. (119)Sn NMR spectroscopy and Mössbauer studies show the presence of Sn(IV) and Sn(II) atoms in 2. X-ray crystallography suggests that the Sn(II)S moiety does not have multiple bond character. Theoretical studies illustrate that the C(methanediide)-Sn bonds comprise a lone pair orbital on each C(methanediide) atom and an C-Sn occupied σ orbital.