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Concept: In situ


Silver nanoparticle (Ag NP)-loaded chitosan composites have numerous biomedical applications; however, fabricating uniform composite microparticles remains challenging. This paper presents a novel microfluidic approach for single-step and in situ synthesis of Ag NP-loaded chitosan microparticles. This proposed approach enables obtaining uniform and monodisperse Ag NP-loaded chitosan microparticles measuring several hundred micrometers. In addition, the diameter of the composites can be tuned by adjusting the flow on the microfluidic chip. The composite particles containing Ag NPs were characterized using UV-vis spectra and scanning electron microscopy-energy dispersive X-ray spectrometry data. The characteristic peaks of Ag NPs in the UV-vis spectra and the element mapping or pattern revealed the formation of nanosized silver particles. The results of antibacterial tests indicated that both chitosan and composite particles showed antibacterial ability, and Ag NPs could enhance the inhibition rate and exhibited dose-dependent antibacterial ability. Because of the properties of Ag NPs and chitosan, the synthesized composite microparticles can be used in several future potential applications, such as bactericidal agents for water disinfection, antipathogens, and surface plasma resonance enhancers.

Concepts: Synthesis, Composite material, Silver, In situ, Microfluidics, Composite video, Aramid, Kevlar


Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

Concepts: Collagen, Stem cell, Mesenchymal stem cell, Bone marrow, Cellular differentiation, In vivo, In vitro, In situ


Objective We previously reported that a rationally designed biomimetic self-assembling peptide, P11-4, nucleated hydroxyapatite de novo and was apparently capable of in situ enamel regeneration following infiltration into caries-like lesions. Our present aim was to determine the safety and potential clinical efficacy of a single application of P11-4 on early enamel lesions.Materials and methods Fifteen healthy adults with Class V ‘white spot’ lesions received a single application of P11-4. Adverse events and lesion appearances were recorded over 180 days.Results Patients treated with P11-4 experienced a total of 11 adverse events during the study, of which two were possibly related to the protocol. Efficacy evaluation suggested that treatment with P11-4 significantly decreased lesion size (p = 0.02) after 30 days and shifted the apparent progression of the lesions from ‘arrested/progressing’ to ‘remineralising’ (p <0.001). A highly significant improvement in the global impression of change was recorded at day 30 compared with baseline (p <0.001).Conclusions The results suggest that treatment of early caries lesions with P11-4 is safe, and that a single application is associated with significant enamel regeneration, presumably by promoting mineral deposition within the subsurface tissue.

Concepts: Clinical trial, Peptide, Engineering, In situ, Ablative brain surgery, Suggestion


Arynes (aromatic systems containing, formally, a carbon-carbon triple bond) are among the most versatile of all reactive intermediates in organic chemistry. They can be ‘trapped’ to give products that are used as pharmaceuticals, agrochemicals, dyes, polymers and other fine chemicals. Here we explore a strategy that unites the de novo generation of benzynes-through a hexadehydro-Diels-Alder reaction-with their in situ elaboration into structurally complex benzenoid products. In the hexadehydro-Diels-Alder reaction, a 1,3-diyne is engaged in a [4+2] cycloisomerization with a ‘diynophile’ to produce the highly reactive benzyne intermediate. The reaction conditions for this simple, thermal transformation are notable for being free of metals and reagents. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed.

Concepts: Chemical reaction, Hydrogen, Chemistry, Carbon, Organic chemistry, In situ, Power


While lithium-sulfur batteries are poised to be the next-generation high-density energy storage devices, the intrinsic polysulfide shuttle has limited their practical applications. Many recent investigations have focused on the development of methods to wrap the sulfur material with a diffusion barrier layer. However, there is a trade-off between a perfect preassembled wrapping layer and electrolyte infiltration into the wrapped sulfur cathode. Here, we demonstrate an in situ wrapping approach to construct a compact layer on carbon/sulfur composite particles with an imperfect wrapping layer. This special configuration suppresses the shuttle effect while allowing polysulfide diffusion within the interior of the wrapped composite particles. As a result, the wrapped cathode for lithium-sulfur batteries greatly improves the Coulombic efficiency and cycle life. Importantly, the capacity decay of the cell at 1000 cycles is as small as 0.03% per cycle at 1672 mA g(-1).To suppress the polysulfide shuttling effect in Li-S batteries, here the authors report a carbon/sulfur composite cathode with a wrapping layer that overcomes the trade-off between limiting polysulfide diffusion and allowing electrolyte infiltration, and affords extraordinary cycling stability.

Concepts: Battery, Electrode, In situ, Cycle, Energy storage, British Columbia Interior, Polysulfide, Diffusion barrier


Nanoscopic uranyl coordination cages have been prepared by a facile route involving self-assembly via temperature and solvent-driven, in situ ligand synthesis. The synthesis of hydrogen arsenate and pyroarsonate ligands in situ enhances flexibility, which is an important factor in producing these compounds.

Concepts: Ammonia, Chemical reaction, Coordination complex, Ligand, Carbon monoxide, Inorganic chemistry, In situ, Coordination number


Lindane is a notorious organochlorine pesticide due to its high toxicity, persistence in the environment and its tendency to bioaccumulate. A yeast strain isolated from sorghum cultivation field was able to use lindane as carbon and energy source under aerobic conditions. With molecular techniques, it was identified and named as Rhodotorula strain VITJzN03. The effects of nutritional and environmental factors on yeast growth and the biodegradation of lindane was investigated. The maximum production of yeast biomass along with 100 % lindane mineralization was noted at an initial lindane concentration of 600 mg l(-1) within a period of 10 days. Lindane concentration above 600 mg l(-1) inhibited the growth of yeast in liquid medium. A positive relationship was noted between the release of chloride ions and the increase of yeast biomass as well as degradation of lindane. The calculated degradation rate and half life of lindane were found to be 0.416 day(-1) and 1.66 days, respectively. The analysis of the metabolites using GC-MS identified the formation of seven intermediates including γ-pentachlorocyclohexane(γ-PCCH), 1,3,4,6-tetrachloro-1,4-cyclohexadiene(1,4-TCCHdiene), 1,2,4-trichlorobenzene (1,2,4 TCB), 1,4-dichlorobenzene (1,4 DCB), chloro-cis-1,2-dihydroxycyclohexadiene (CDCHdiene), 3-chlorocatechol (3-CC) and maleylacetate (MA) derivatives indicating that lindane degradation follows successive dechlorination and oxido-reduction. Based on the results of the present study, the possible pathway for lindane degradation by Rhodotorula sp. VITJzN03 has been proposed. To the best of our knowledge, this is the first report on lindane degradation by yeast which can serve as a potential agent for in situ bioremediation of medium to high level lindane-contaminated sites.

Concepts: Metabolism, Environment, Yeast, Ion, In situ, Chloride, Bioremediation, Rhodotorula


A novel calcium phosphate silicate bone cement (CPSC) was synthesized in a process, in which nanocomposite forms in situ between calcium silicate hydrate (C-S-H) gel and hydroxyapatite (HAP). The cement powder consists of tricalcium silicate (C(3)S) and calcium phosphate monobasic (CPM). During cement setting, C(3)S hydrates to produce C-S-H and calcium hydroxide (CH); CPM reacts with the CH to precipitate HAP in situ within C-S-H. This process, largely removing CH from the set cement, enhances its biocompatibility and bioactivity. The testing results of cell culture confirmed that the biocompatibility of CPSC was improved as compared to pure C(3)S. The results of XRD and SEM characterizations showed that CPSC paste induced formation of HAP layer after immersion in simulated body fluid for 7 days, suggesting that CPSC was bioactive in vitro. CPSC cement, which has good biocompatibility and low/no cytotoxicity, could be a promising candidate as biomedical cement.

Concepts: Bone, Calcium, In vitro, Toxicity, In situ, Portland cement, Cement, Calcium compounds


The objective of this study was to develop a controlled delivery system for PEGylated octreotide using a Poloxamer based in situ gel forming polymer. PEGylated octreotide kept its full biological activity and higher serum half-life compared to the original octreotide. The designed drug delivery system contained low concentration of Poloxamer 407 (P407) (<0.16%) with polyvinyl alcohol (PVA) as a polymeric additive. Rheological measurements of gel vehicle formulations indicated that the in situ gel forming system with optimum sol-gel transition temperature of 28.7°C could be formed using a combination of P407 and PVA at ratio of 15-10% (w/v). The effect of formulation additives such as buffering agents on rheological behavior demonstrated that sodium bicarbonate and lactic acid have opposite effect on sol-gel transition temperature of the system. Using buffering agents, it was possible to shift the sol-gel transition to lower or higher temperatures. The in vitro release profiles of octreotide and PEGylated octreotide from the selected P407/PVA formulations were measured using a membrane-less device. PEGylated octreotide showed slower release rate from the gel system with different release kinetic compared to octreotide. In animal studies, a sustained release rate was achieved with both PEGylated and non-PEGylated octreotide, but longer delivery was observed for PEGylated octreotide. Tissue histopathological studies confirmed the biocompatibility of the delivery system for PEGylated octreotide, supporting the suitability of P407/PVA mixture as an injectable drug delivery system. The total effects of increasing PEGylated peptide half-life and prolonged release from thermoresponsive gel system offer the potential for sustained delivery of PEGylated octreotide.

Concepts: Pharmacology, In vivo, In vitro, In Silico, In situ, Polyvinyl alcohol, Injection, Polyvinyl acetate


The neutral red retention assay has been proposed to determine the lysosomal membrane stability in immune cells. Nevertheless, this assay implies many examinations under a microscope at short time intervals and therefore the analysis of few samples. The present study proposes two more rapid, efficient, and sensitive sample analyses using flow cytometry method. Lysosomal presence and lysosomal membrane integrity (LMI) were evaluated on the three-spined stickleback, Gasterosteus aculeatus (L.), a well-described model fish species for aquatic ecotoxicology studies. After development of the two biomarkers, they were validated by ex vivo contamination with endosulfan and copper and by in situ sampling. These immunomarkers were clearly modulated by pollutants and their variations seemed to be correlated with leucocyte mortality. Thus, from a practical point of view, lysosomal presence and LMI may provide novel and efficient means of evaluating immune capacities and indicating the toxic effects of environmental pollution.

Concepts: In vivo, Toxicology, Flow cytometry, Cytotoxicity, Pollution, In situ, Three-spined stickleback, Gasterosteiformes