Estimate of the degradation potentials of cellulose, xylan, and chitin across global prokaryotic communities.

Complex polysaccharides (e.g. cellulose, xylan, and chitin), the most abundant renewable biomass resources available on Earth, are mainly degraded by microorganisms in nature. However, little is known about the global distribution of the enzymes and microorganisms responsible for the degradation of cellulose, xylan, and chitin in natural environments. Through large-scale alignments between the sequences released by the Earth Microbiome Project and sequenced prokaryotic genomes, we determined that almost all prokaryotic communities have the functional potentials to degrade cellulose, xylan, and chitin. The median abundances of genes encoding putative cellulases, xylanases, and chitinases in global prokaryotic communities are 0.51 (0.17-1.01), 0.24 (0.05-0.57), and 0.33 (0.11-0.71) genes/cell, respectively, and the composition and abundance of these enzyme systems are environmentally varied. The taxonomic sources of the three enzymes are highly diverse within prokaryotic communities, and the main factor influencing the diversity is the community's alpha diversity index rather than gene abundance. Moreover, there are obvious differences in taxonomic sources among different communities, and most genera with degradation potentials are narrowly distributed. In conclusion, our analysis preliminarily depicts a panorama of cellulose-, xylan-, and chitin-degrading enzymatic systems across global prokaryotic communities.

Chemical Mechanism of Fireworm Bioluminescence - A Theoretical Proposition.

Odontosyllis undecimdonta is a marine worm, commonly known as a fireworm, that exhibits bluish-green bioluminescence (BL). The luciferin (L) and oxyluciferin (OL) during fireworm BL have been experimentally identified in vitro. The L and OL are the respective starting point and ending point of a series of complicated chemical reactions in the BL. However, the chemical mechanism of the fireworm BL remains largely unknown. Before the experiments provided strong evidence for the mechanism, based on our previously successful studies on several bioluminescent systems, we theoretically proposed the chemical mechanism of the fireworm BL in this article. By means of the spin-flip and time-dependent density functional calculations, we clearly described the complete process from L to OL: under the catalysis of luciferase, L undergoes deprotonation and reacts with 3O2 to form a dioxetanone anion via the single-electron transfer mechanism; the dioxetanone anion decomposes into the OL at the first singlet excited state (S1) by the gradually reversible charge-transfer-induced luminescence mechanism; and the S1-OL emits light and deexcites to OL in the ground state.

Integrated lactic acid production from lignocellulosic agricultural wastes under thermal conditions.

The production of lactic acid (LA) from agricultural wastes attracts great attention because of the sustainability and abundance of lignocellulosic feedstocks, as well as the increasing demand for biodegradable polylactic acid. In this study, we isolated a thermophilic strain Geobacillus stearothermophilus 2H-3 for use in robust production of L-(+)LA under the optimal conditions of 60 °C, pH 6.5, which were consistent with the whole-cell-based consolidated bio-saccharification (CBS) process. Sugar-rich CBS hydrolysates derived from various agricultural wastes, including corn stover, corncob residue, and wheat straw, were used as the carbon sources for 2H-3 fermentation by directly inoculating 2H-3 cells into the CBS system, without intermediate sterilization, nutrient supplementation, or adjustment of fermentation conditions. Thus, we successfully combined two whole-cell-based steps into a one-pot successive fermentation process to efficiently produce LA with high optical purity (99.5%), titer (51.36 g/L), and yield (0.74 g/gbiomass). This study provides a promising strategy for LA production from lignocellulose through CBS and 2H-3 fermentation integration.

Investigation of factors affecting sodium alginate fouling mechanisms in a microfiltration process under non-constant-flux and non-constant-pressure conditions.

Variations in transmembrane pressure and permeate flux are closely related to membrane fouling. In this study, a laboratory-scale submerged microfiltration system was used to investigate the influence of sodium alginate (SA) concentration and peristaltic pump rotation speed on the fouling under the conditions of (1) the same driving force and non-aerated-PAC, (2) different driving forces and non-aerated-PAC, and (3) different driving forces and aerated-PAC. The results showed that the normalized transmembrane pressure (TMP') increased linearly with decreasing normalized permeate flux (J') during the early microfiltration stage regardless of the operating conditions, indicating that the SA microfiltration process controlled by the peristaltic pump was non-constant-flux and non-constant-pressure. The latter filtration stage was considered constant-pressure filtration when 200-1,200 mg/L of SA was filtrated at the same rotation speed. During filtration of 800 mg/L of SA under the non-aerated-PAC condition, the later filtration stage was considered constant-pressure filtration when the peristaltic pump rotated at slower speeds of 15 and 30 rpm. This approached constant-flux filtration when the peristaltic pump rotated at faster speeds of 60 and 90 rpm, and PAC-aeration scouring was an effective measure for mitigating membrane fouling by SA.

Comparative Studies on the Proton Conductivities of Hafnium-Based Metal-Organic Frameworks and Related Chitosan or Nafion Composite Membranes.

Hafnium (Hf)-based UiO-66 series metal-organic frameworks (MOFs) have been widely studied on gas storage, gas separation, reduction reaction, and other aspects since they were first prepared in 2012, but there are few studies on proton conductivity. In this work, one Hf-based MOF, Hf-UiO-66-fum showing UiO-66 structure, also known as MOF-801-Hf, was synthesized at room temperature using cheap fumaric acid as the bridging ligand, and then imidazole units were successfully introduced into MOF-801-Hf to obatin a doped product, Im@MOF-801-Hf. Note that both MOF-801-Hf and Im@MOF-801-Hf demonstrate excellent thermal, water, and acid-base stabilities. Expectedly, the maximum proton conductivity (σ) of Im@MOF-801-Hf (1.46 × 10-2 S·cm-1) is nearly 4 times greater than that of MOF-801-Hf (3.98 × 10-3 S·cm-1) under 100 °C and 98% relative humidity (RH). To explore their possible practical application value, we doped them into chitosan (CS) or Nafion membranes as fillers, namely, CS/MOF-801-Hf-X, CS/Im@MOF-801-Hf-Y, and Nafion/MOF-801-Hf-Z (X, Y, and Z are the doping percentages of MOF in the membrane, respectively). Intriguingly, it was found that CS/MOF-801-Hf-6 and CS/Im@MOF-801-Hf-4 indicated the highest σ values of 1.73 × 10-2 and 2.14 × 10-2 S·cm-1, respectively, under 100 °C and 98% RH and Nafion/MOF-801-Hf-9 also revealed a high σ value of 4.87 × 10-2 S·cm-1 under 80 °C and 98% RH, which showed varying degrees of enhancement compared to the original MOFs or pure CS and Nafion membranes. Our study illustrates that these Hf-based MOFs and related composite membranes offer great potential in electrochemical fields.

Biological cellulose saccharification using a coculture of Clostridium thermocellum and Thermobrachium celere strain A9.

An anaerobic thermophilic bacterial strain, A9 (NITE P-03545), that secretes ß-glucosidase was newly isolated from wastewater sediments by screening using esculin. The 16S rRNA gene sequence of strain A9 had 100% identity with that of Thermobrachium celere type strain JW/YL-NZ35. The complete genome sequence of strain A9 showed 98.4% average nucleotide identity with strain JW/YL-NZ35. However, strain A9 had different physiological properties from strain JW/YL-NZ35, which cannot secrete ß-glucosidases or grow on cellobiose as the sole carbon source. The key ß-glucosidase gene (TcBG1) of strain A9, which belongs to glycoside hydrolase family 1, was characterized. Recombinant ß-glucosidase (rTcBG1) hydrolyzed cellooligosaccharides to glucose effectively. Furthermore, rTcBG1 showed high thermostability (at 60°C for 2 days) and high glucose tolerance (IC50 = 0.75 M glucose), suggesting that rTcBG1 could be used for biological cellulose saccharification in cocultures with Clostridium thermocellum. High cellulose degradation was observed when strain A9 was cocultured with C. thermocellum in a medium containing 50 g/l crystalline cellulose, and glucose accumulation in the culture supernatant reached 35.2 g/l. In contrast, neither a monoculture of C. thermocellum nor coculture of C. thermocellum with strain JW/YL-NZ35 realized efficient cellulose degradation or high glucose accumulation. These results show that the ß-glucosidase secreted by strain A9 degrades cellulose effectively in combination with C. thermocellum cellulosomes and has the potential to be used in a new biological cellulose saccharification process that does not require supplementation with ß-glucosidases. KEY POINTS: • Strain A9 can secrete a thermostable ß-glucosidase that has high glucose tolerance • A coculture of strain A9 and C. thermocellum showed high cellulose degradation • Strain A9 achieves biological saccharification without addition of ß-glucosidase.

Morphological changes of the root apex in anterior teeth with periapical periodontitis: an in-vivo study.

INTRODUCTION: The aim was to analyze the morphological changes of root apex in anterior teeth with periapical periodontitis. METHODS: 32 untreated anterior teeth with periapical periodontitis were enrolled, compared with the healthy contralateral teeth. Two-dimensional measurement of Cone-beam computed tomography was used to determine the location and measure diameter of the apical constriction according to Schell's methods. An open-source software (3D Slicer) was used to reconstruct the teeth. The apical constriction form was analysis according to Schell's topography. The distances of apical constriction to apical foramen and anatomical apex were measured respectively. RESULTS: The difference value between buccolingual and mesiodistal diameter was (0.06 ± 0.09) mm and (0.04 ± 0.04) mm in periapical periodontitis and controls (p < 0.05). The mean distance between apical constriction and anatomical apex was significantly shorter in periapical periodontitis than controls, so was the mean distance of apical constriction to apical foramen. The most common form of apical constriction was flaring (65.6%) in periapical periodontitis. CONCLUSIONS: The anterior teeth with periapical periodontitis had shorter distances of apical constriction to anatomical apex and apical foramen, bigger disparities between the diameters of buccolingual and mesiodistal, and higher proportion of flaring apical constriction.

A review and meta-analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand-foot-mouth disease in China and global implications.

Coxsackievirus A6 (CV-A6) has been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events in many countries. In order to understand epidemiological characteristics of CV-A6, we collected the information describing HFMD caused by CV-A6 to describe the detection rate, severe rate and onychomadesis rate, which is defined as one or more nails defluvium, caused by CV-A6 from 2007 to 2017. The results showed that there was an outbreak of CV-A6 every other year, and overall trend of the epidemic of CA6-associated HFMD was increasing in China. The detection rate of CV-A6 in other countries was 32.0% (95% CI: 25.0%~40.0%) before 2013 and 28.0% (95% CI: 20.0%~36.0%) after 2013, respectively. Although the severe rate of HFMD caused by CV-A6 was low (0.10%, 95% CI: 0.01%~0.20%), CV-A6 can cause a high incidence of onychomadesis (28.0%, 95%CI: 21.9%-34.3%). Thus, it would be worthwhile to research and develop an effective multivalent vaccine for CV-A6 to achieve a more powerful prevention of HMFD.

A leucine-rich repeat-receptor-like kinase gene SbER2-1 from sorghum (Sorghum bicolor L.) confers drought tolerance in maize.

BACKGROUND: ERECTA (ER) is a leucine-rich repeat-receptor-like kinase gene (LRR-RLK) encoding a protein isolated from Arabidopsis. Although the regulatory functions of ER genes have been widely explored in plant development and disease resistance, their roles in drought stress responses remain to be clarified. RESULTS: In this study, we cloned and characterized two ER genes, SbER1-1 and SbER2-1, from the drought-tolerant model plant sorghum (Sorghum bicolor L.). Under drought stress, the two genes were expressed in the leaves and stems but not in the roots, and SbER2-1 transcript accumulation in the stem was increased. SbER2-1 was localized both on the plasma membrane and in the chloroplast. Moreover, SbER2-1 expression in Arabidopsis and maize conferred increased drought tolerance, especially in regard to water-use efficiency, increasing the net photosynthetic rate in maize under drought stress. Based on RNA-Seq analysis together with the physiological data, we conclude that the transgenic maize plants have upregulated phenylpropanoid metabolism and increased lignin accumulation under drought stress. CONCLUSIONS: Our results demonstrate that SbER2-1 plays an important role in response to drought stress. Furthermore, photosynthetic systems and phenylpropanoid metabolism are implicated in SbER2-1-mediated drought stress tolerance mechanisms. The use of genetic engineering to regulate SbER2-1 expression in plants and to breed new varieties tolerant to drought is a research field full of potential.

Tumor Microenvironmental pH and Enzyme Dual Responsive Polymer-Liposomes for Synergistic Treatment of Cancer Immuno-Chemotherapy.

Despite recent advances in tumor treatment through cancer immunotherapy, the efficacy of this approach remains to be improved. Looking forward to high rates of objective clinical response, cancer immunotherapy combined with chemotherapy has gained increasing attention recently. Here, we constructed liposomes with matrix metalloproteinases (MMPs) responsive moiety and PD-L1 inhibitor conjugate combine with low dose chemotherapy to achieve enhanced antitumor efficacy. Upon introduction of the pH-responsive polymer to LPDp, the coassembly could be almost stable in physiological conditions and tumor microenvironments and release the loaded cargos at the lysosome. MMP-2 enzyme extracellularly secreted by the B16F10 cells could cleave the cross-linker and liberate the PD-L1 inhibitor effectively disrupting the PD-1/PD-L1 interaction in vitro. Low dose DOX encapsulated in the LPDp was capable of sensitizing B16F10 cells to CTLs by inducing overexpression of M6PR on tumor cell membranes. In comparison with free PD-L1 inhibitor, LPDp improved the biodistribution and on-demand release of the peptide inhibitor in tumor regions following administration. LPDp achieved the optimal tumor suppression efficiency (∼78.7%), which demonstrated the significantly enhanced antitumor effect ( P < 0.01) than that of LPp (∼57.5%) as well as that of LD (<40%), attributing to synergistic contribution from the substantial increase in M6PR expression on tumor cells and the blockade of immune checkpoints. This strategy provides a strong rationale for combining standard-of-care chemotherapy with relative nontoxic and high specific immunotherapy.

Preparation of chitosan-based molecularly imprinted material for enantioseparation of racemic mandelic acid in aqueous medium by solid phase extraction.

An S-mandelic acid imprinted chitosan resin was synthesized by cross-linking chitosan with glutaraldehyde in 2% acetic acid solution. S-Mandelic acid imprinted chitosan resin was used to enantioselectively separate racemic mandelic acid in aqueous medium. When keeping the pH of sample solution (100 mM Tris-H3 PO4 ) at 3.5 and adsorption time at 40 min, the enantiomer excess of mandelic acid in supernatant was 78.8%. The adsorption capacities of S-mandelic acid imprinted chitosan resin for S- and R-mandelic acid were determined to be 29.5 and 2.03 mg/g, respectively. While the adsorption capacities of non-imprinted cross-linked chitosan for S- and R-mandelic acid were 2.10 and 2.08 mg/g, respectively. The result suggests that the imprinted caves in S-mandelic acid imprinted chitosan resin are highly matched with S-mandelic acid molecule in space structure and spatial arrangement of action sites. Interestingly, the enantiomer excess value of mandelic acid in supernatant after adsorption of racemic mandelic acid by R-mandelic acid imprinted cross-linked chitosan was 25.4%. The higher enantiomer excess value by S-mandelic acid imprinted chitosan resin suggests that the chiral carbons in chitosan and the imprinted caves in S-mandelic acid imprinted chitosan resin combine to play roles for the enantioselectivity of S-mandelic acid imprinted chitosan resin toward S-mandelic acid. Furthermore, the excellent enantioselectivity of S-mandelic acid imprinted chitosan resin toward S-mandelic acid demonstrates that using chiral chitosan as functional monomer to prepare molecularly imprinted polymers has great potential in enantioseparation of chiral pharmaceuticals.

Modeling Biofilm Formation on Dynamically Reconfigurable Composite Surfaces.

We augment the dissipative particle dynamics (DPD) simulation method to model the salient features of biofilm formation. We simulate a cell as a particle containing hundreds of DPD beads and specify p, the probability of breaking the bond between the particle and surface or between the particles. At the early stages of film growth, we set p = 1, allowing all bonding interactions to be reversible. Once the bound clusters reach a critical size, we investigate scenarios where p = 0, so that incoming species form irreversible bonds, as well as cases where p lies in the range of 0.1-0.5. Using this approach, we examine the nascent biofilm development on a coating composed of a thermoresponsive gel and the embedded rigid posts. We impose a shear flow and characterize the growth rate and the morphology of the clusters on the surface at temperatures above and below Tc, the volume phase transition temperature of a gel that displays lower critical solubility temperature (LCST). At temperatures above Tc, the posts effectively inhibit the development of the nascent biofilm. For temperatures below Tc, the swelling of the gel plays the dominant role and prevents the formation of large clusters of cells. Both these antifouling mechanisms rely on physical phenomena and, hence, are advantageous over chemical methods, which can lead to unwanted, deleterious effects on the environment.

Depletion of abundant human serum proteins by per se imprinted cryogels based on sample heterogeneity.

Macroporous cryogels were prepared and used to deplete abundant proteins. It was accomplished based on the sample heterogeneity rather than any exogenous assistance. Human serum was added in monomer solutions to synthesize molecularly imprinted polymers; therein some abundant proteins were imprinted in the polyacrylamide cryogels. Meanwhile the rare components remained aqueous. Chromatography and electrophoresis showed that albumin, serotransferrin, and most globulins were depleted by columns packed with the molecularly imprinted polymers. After the depletion, lower abundance proteins were revealed by SDS-PAGE, peptide fingerprint analysis, and identified by MALDI-TOF-MS. This is an example that a "per se imprint" protocol enables to gradually dimidiate proteomes, simplify sample complexities, and facilitate further proteome profiling or biomarker discovery.

Dynamin-2 mutations associated with centronuclear myopathy are hypermorphic and lead to T-tubule fragmentation.

Skeletal muscle requires adequate membrane trafficking and remodeling to maintain its normal structure and functions. Consequently, many human myopathies are caused by mutations in membrane trafficking machinery. The large GTPase dynamin-2 (Dyn2) is best known for catalyzing membrane fission during clathrin-mediated endocytosis (CME), which is critical for cell signaling and survival. Despite its ubiquitous expression, mutations of Dyn2 are associated with two tissue-specific congenital disorders: centronuclear myopathy (CNM) and Charcot-Marie-Tooth (CMT) neuropathy. Several disease models for CNM-Dyn2 have been established to study its pathogenic mechanism; yet the cellular and biochemical effects of these mutations are still not fully understood. Here we comprehensively compared the biochemical activities of disease-associated Dyn2 mutations and found that CNM-Dyn2 mutants are hypermorphic with enhanced membrane fission activity, whereas CMT-Dyn2 is hypomorphic. More importantly, we found that the expression of CNM-Dyn2 mutants does not impair CME in myoblast, but leads to T-tubule fragmentation in both C2C12-derived myotubes and Drosophila body wall muscle. Our results demonstrate that CNM-Dyn2 mutants are gain-of-function mutations, and their primary effect in muscle is T-tubule disorganization, which explains the susceptibility of muscle to Dyn2 hyperactivity.

Characterization of a hybrid polyacrylamide and its flocculation properties in cyanide tailing suspensions.

An inorganic-organic hybrid flocculant Al(OH)3-polyacrylamide (Al-PAM) with narrow molecular weight distribution was synthesized using inverse microemulsion polymerization. The hybrid polymer Al-PAM was characterized by Infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and scanning electron microscopy, and it was found that it had a 'star-like' structure in which Al(OH)3 colloidal particles acted as cores linking PAM chains. The properties of Al-PAM were investigated in flocculating 10 wt% cyanide tailing suspensions. It was found that as the amount of Al-PAMM1 with high molecular weight and aluminum content increased, the initial settling rate of particles accelerated, achieving the maximum 6.6 m/h, 17.3 times the rate of the control without flocculants. The turbidity of the supernatant decreased to 35 ± 2 NTU accordingly, compared to 353 ± 2 NTU of that in the control, which meant that 90.0% of turbidity was removed from the cyanide tailing suspensions. The flocculation mechanism was further explored by floccule size and ζ potential measurements. The superior performance of cationic Al-PAM in flocculating negatively charged particles compared to commercial non-ionic GG indicated that electrostatic repulsion between tailing particles was a crucial factor in deciding the flocculation performance of the polymer. The study demonstrated that both charge neutralization and bridge adsorption were conductive to the particle flocculation.

Transcriptome changes during TNF-α promoted osteogenic differentiation of dental pulp stem cells (DPSCs).

Dental pulp stem cells (DPSCs), due to the ease of isolation and their capacities of multi-lineage differentiation, are considered as attractive resources for regenerative medicine. In a previous study, we showed that TNF-α promoted the osteogenic differentiation of DPSCs via the NF-κB signaling pathway. However, the mechanisms of such differentiation were largely unknown. Here, we examined the gene expression profiles between undifferentiated, partially differentiated and fully differentiated DPSCs induced by TNF-α by performing the next-generation sequencing technique (RNA-Seq). Our results revealed a continuous transition of the transcriptome changes during TNF-α promoted osteogenic differentiation of DPSC. Bioinformatics analysis revealed a relatively general to specific transformation of the involved signaling pathways from the early to late stages of differentiation. Gene regulatory network analysis highlighted novel, key genes that are essential for osteogenic differentiation at different time points. These results were further validated by quantitative RT-PCR, confirming the high reliability of the RNA-Seq. Our data therefore will not only provide novel insights into the molecular mechanisms that drive the osteogenic differentiation of DPSCs, but also promote the studies of bone tissue engineering that utilizes DPSCs as a crucial resource.

Picometer-resolution dual-comb spectroscopy with a free-running fiber laser.

Dual-comb spectroscopy holds the promise as real-time, high-resolution spectroscopy tools. However, in its conventional schemes, the stringent requirement on the coherence between two lasers requires sophisticated control systems. By replacing control electronics with an all-optical dual-comb lasing scheme, a simplified dual-comb spectroscopy scheme is demonstrated using one dual-wavelength, passively mode-locked fiber laser. Pulses with a intracavity-dispersion-determined repetition-frequency difference are shown to have good mutual coherence and stability. Capability to resolve the comb teeth and a picometer-wide optical spectral resolution are demonstrated using a simple data acquisition system. Energy-efficient, free-running fiber lasers with a small comb-tooth-spacing could enable low-cost dual-comb systems.

Integration of bacterial expansin-like proteins into cellulosome promotes the cellulose degradation.

Cellulosomes are multi-enzyme complexes assembled by cellulases and hemicellulases through dockerin-cohesin interactions, which are the most efficient system for the degradation of lignocellulosic resources in nature. Recent genomic analysis of a cellulosome-producing anaerobe Clostridium clariflavum DSM 19732 revealed that two expansin-like proteins, Clocl_1298 and Clocl_1862, contain a dockerin module, which suggests that they are components of the cellulosome. Bacterial expansin-like proteins do not have hydrolytic activities, but can facilitate the degradation of cellulosic biomass via synergistic effects with cellulases. In this study, the synergistic effect of the expansin-like proteins with both native and designer cellulosomes was investigated. The free expansin-like proteins, including expansin-like domains of Clocl_1298 and Clocl_1862, as well as a well-studied bacterial expansin-like protein BsEXLX1 from Bacillus subtilis, promoted the cellulose degradation by native cellulosomes, indicating the cellulosomal expansin-like proteins have the synergistic function. When they were integrated into a trivalent designer cellulosome, the synergistic effect was further amplified. The sequence and structure analyses indicated that these cellulosomal expansin-like proteins share the conserved functional mechanism with other bacterial expansin-like proteins. These results indicated that non-catalytic expansin-like proteins in the cellulosome can enhance the activity of the cellulosome in lignocellulose degradation. The involvement of functional expansin-like proteins in the cellulosome also implies new physiological functions of bacterial expansin-like proteins and cellulosomes.

In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants.

Cochlear implants have been widely used for patients with profound hearing loss and partial deafness. Residual low-frequency hearing, however, may deteriorate due to insertion trauma and tissue response around the electrode array. The present study investigated in vitro and in vivo release of dexamethasone from silicone used for cochlear implant electrode carriers. The in vitro experiment involved an apparatus simulating the inner ear fluid environment in humans. Release from two sizes of silicone films (200 µm × 1 mm × 10 mm and 500 µm × 1 mm × 10 mm), each loaded with 2 % dexamethasone, and was measured for 24 weeks. In the in vivo experiment, silicone rods loaded with 2 or 10 % dexamethasone, respectively, were implanted into the scala tympani of guinea pigs. Perilymph concentrations were measured during the first week after implantation. The results showed that dexamethasone was released from the silicone in a sustained manner. After a burst release, perilymph concentration was similar for silicone incorporated with 2 and 10 % dexamethasone, respectively. The similar pharmacokinetic profile was found in the in vitro experiment. The period of sustained drug delivery was maintained for 20 weeks in vitro and for 1 week in vivo. The results of the present study suggest that drugs like dexamethasone are released in a controlled manner from silicon electrode carriers of cochlear implants. Further studies will identify optimal release profiles for the use with cochlear implants to improve their safety and long-term performance.