ZrO2/ZnO/TiO2 Nanocomposite Coatings on Stainless Steel for Improved Corrosion Resistance, Biocompatibility, and Antimicrobial Activity.

The ultrathin nanocomposite coatings made of zirconium oxide (ZrO2), zinc oxide (ZnO), and titanium oxide (TiO2) on stainless steel (SS) were prepared by the radio frequency sputtering method, and the effects of the nanocomposite coating on corrosion protection and antibacterial activities of nanocomposite coated SS were investigated. Scanning electron microscopy was conducted to observe surface morphology of nanocomposite coatings with distinct distribution of grains with the formation on SS substrate. From the electrochemical impedance spectroscopy results, ZrO2/ZnO/TiO2 nanocomposite coating showed excellent corrosion protection performance at 37 °C during immersion in simulated body fluid and saliva solution for 12 and 4 weeks, respectively. The impedance of ZrO2/ZnO/TiO2 (40/10/50) nanocomposite coated SS exhibited values about 5 orders of magnitude higher than that of uncoated SS with polarization at the low-frequency region. Cell viability of ZrO2/ZnO/TiO2 nanocomposite coated SS was examined under mouse fibroblasts culture (L929), and it was observed that the nanocomposite coating improves proliferation through effective cellular attachment compared to uncoated SS. From the antimicrobial activity results, ZrO2/ZnO/TiO2 nanocomposite-coated SS showed killing efficiency of 81.2% and 72.4% against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, respectively.

Correlation between Pitch Impregnation Pressure and Pore Sizes of Graphite Block.

This study aimed to investigate the effect of impregnation pressure on the decrease in porosity of impregnated bulk graphite. The correlation between pitch impregnation behavior and the pore sizes of the bulk graphite block was studied to determine the optimal impregnation pressure. The densities and porosities of the bulk graphite before and after pitch impregnation under various pressures between 10 and 50 bar were evaluated based on the Archimedes method and a mercury porosimeter. The density increased rates increased by 1.93-2.44%, whereas the impregnation rate calculated from the rate of open porosity decreased by 15.15-24.48%. The density increase rate and impregnation rate were significantly high when the impregnation pressures were 40 and 50 bar. Compared with impregnation pressures of 10, 20, and 30 bar, the minimum impregnatable pore sizes with impregnation pressures of 40 and 50 bar were 30-39 and 24-31 nm, respectively. The mercury intrusion porosimeter analysis results demonstrated that the pressure-sensitive pore sizes of the graphite blocks were in the range of 100-4500 nm. Furthermore, the ink-bottle-type pores in this range contributed predominantly to the effect of impregnation under pressure, given that the pitch-impregnated-into-ink-bottle-type pores were difficult to elute during carbonization.

Facile Fabric Detoxification Treatment Method Using Microwave and Polyethyleneimine Against Nerve Gas Agents.

Generally, detoxification fabrics are defined as fabrics that remove or inhibit the production of toxic compounds, especially chemical warfare agents such as nerve gas agents. They are usually prepared using a complicated and time-consuming method. This study suggests a facile treatment method for preparing detoxification fabrics against nerve gas agents using polyethyleneimine and microwave curing. The detoxification properties of polyethyleneimine and microwave-treated polypropylene nonwoven fabric were evaluated using diisopropylfluoro-phosphate, which is a nerve agent simulant. The treated polypropylene fabric decontaminated 53.6% of diisopropylfluorophosphate (DFP) in 2 h at 32 °C, and the half-life of DFP on the surface of the treated fabric was 122 min. The result indicates that the treated fabric can act as a basic organocatalyst for the DFP hydrolysis and has a shorter half-life owing to the large number of amine groups. Therefore, the facile treatment method has the potential for use in the preparation of detoxification fabrics.

Smart Coating Embedded with pH-Responsive Nanocapsules Containing a Corrosion Inhibiting Agent.

Triethanolamine (TEA), an amine-based corrosion inhibitor, was encapsulated and then embedded into an epoxy coating to provide long-term corrosion protection of aluminum alloy 3003. TEA was encapsulated by means of free-radical polymerization, yielding an average particle size of 450 nm. An applied epoxy coating containing 10 wt % of the nanocapsules successfully protected an artificially defective area for a long period due to TEA adsorption, which resulted in the formation of an inhibiting layer. Electrochemical impedance spectroscopy showed an inhibition efficiency surpassing 85% when the metal experienced mild corrosion in its early stages, and the inhibiting layer started to form by local pH level change, which triggered the release of TEA. On the basis of the results of a scanning vibrating electrode technique, the current density of the metal surface in the presence of an encapsulated TEA coating was significantly lower than that of the control coating with no nanocapsules. Optical microscope and scanning electron microscope images revealed that the sample surface that had encapsulated TEA nearby was considerably less stained after 60 days of testing compared with that of the control sample, which indicated that the metal substrate was protected by an inhibiting layer. Elemental analysis performed by energy-dispersive X-ray spectroscopy further confirmed that the metal surface was well preserved, and a remarkably low oxygen content indicated suppressed metal oxidation. The nuclear magnetic resonance spectra also evidenced a successful release of TEA throughout the experimental period. These findings reflected a spontaneous surface repassivation with the help of encapsulated TEA coating.

Second-look arthroscopic findings and clinical outcomes of meniscal repair with concomitant anterior cruciate ligament reconstruction: comparison of suture and meniscus fixation device.

INTRODUCTION: The purpose of this study was to evaluate the healing rate of repaired meniscus and functional outcomes of patients who received all-inside meniscal repair using sutures or devices with concomitant arthroscopic anterior cruciate ligament (ACL) reconstruction. MATERIALS AND METHODS: Among the patients who have ACL tear and posterior horn tear of medial or lateral meniscus, 61 knees who received all-inside repair using sutures (suture group, n = 28) or meniscal fixation devices (device group, n = 33) with concomitant ACL reconstruction during the period from January 2012 to December 2015, followed by second-look arthroscopy, were retrospectively reviewed. Healing status of the repair site was assessed by second-look arthroscopy. Through the clinical assessment, clinical success (negative medial joint line tenderness, no history of locking or recurrent effusion, and negative McMurray test) rate of the repaired meniscus and functional outcomes (International Knee Documentation Committee subjective score and Lysholm knee score) was evaluated. RESULTS: In a comparison of healing status of repaired meniscus evaluated by second-look arthroscopy, suture group had 23 cases of complete healing (82.1%), 4 cases of incomplete healing (14.3%), and 1 case of failure (3.6%). Device group had 18 cases of complete healing (54.5%), 4 cases of incomplete healing (24.2%), and 7 cases of failure (21.2%) (p = 0.048). Clinical success rate of the meniscal repair was 89.3% (25 cases) and 81.8% (27 cases) in suture group and device group, respectively (p = 0.488). No significant difference of functional outcomes was observed between the two groups (p > 0.05, both parameters). CONCLUSIONS: Among the patients who received meniscal repair with concomitant ACL reconstruction, suture group showed better healing status of repaired meniscus based on the second-look arthroscopy than device group. However, no significant between-group difference of clinical success rate and functional outcomes was observed.

Intraoperative fluoroscopy reduces the variability in femoral tunnel placement during single-bundle anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the effect of using intraoperative fluoroscopy on femoral and tibial tunnel positioning variability in single-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 80 consecutive patients with single-bundle ACL reconstruction between 2014 and 2016 were retrospectively reviewed. Among them, 40 underwent ACL reconstruction without fluoroscopy (non-fluoroscopy group) and 40 underwent fluoroscopy-assisted ACL reconstruction (fluoroscopy group). Femoral and tibial tunnel locations were evaluated using a standardized grid system with three-dimensional computed tomography images. Femoral and tibial tunnel location variability was compared between the groups. RESULTS: The operation time was longer in the fluoroscopy group than in the non-fluoroscopy group (61.3 ± 5.2 min vs. 55.5 ± 4.5 min, p < 0.001). In the fluoroscopy group, a guide pin was repositioned in 16 (40%) cases on the femoral side and 2 (5%) cases on the tibial side. No significant difference in the femoral tunnel location was observed between the fluoroscopy and non-fluoroscopy groups (anterior-posterior plane, 29.0% ± 3.2% vs. 30.0% ± 6.1%; proximal-distal plane, 30.8% ± 4.8% vs. 29.4% ± 8.3%; all parameters, n.s.); variability was significantly lower in the fluoroscopy group (p < 0.001 for both anterior-posterior and proximal-distal planes). No significant difference in the tibial tunnel location and variability was observed between the fluoroscopy and non-fluoroscopy groups (medial-lateral plane, 45.8% ± 2.0% vs. 46.6% ± 2.4%; anterior-posterior plane, 31.2% ± 4.0% vs. 31.0% ± 5.4%) (all parameters, n.s.). CONCLUSIONS: Tunnel positioning with fluoroscopic assistance is feasible and effective in achieving consistency in femoral tunnel placement despite a slightly longer operation time. Intraoperative fluoroscopy can be helpful in cases wherein identifying anatomical landmarks on arthroscopy was difficult or for surgeons with less experience who performed ACL reconstruction. LEVEL OF EVIDENCE: IV.

Long-term outcomes of unicompartmental knee arthroplasty in patients requiring high flexion: an average 10-year follow-up study.

INTRODUCTION: To evaluate the long-term survival of unicompartmental knee arthroplasty (UKA) in the Asian population and assess differences in clinical outcomes between mobile- and fixed-bearing UKA. MATERIALS AND METHODS: Among 111 cases of UKA that were performed by 1 surgeon from January 2002 to December 2009, we retrospectively reviewed 96 cases (36 mobile-bearing, 62 fixed-bearing) for this study. We examined cause of revision or failure, type of reoperation/revision, and duration from the surgery date to the revision upon reviewing the medical record. Survival analysis was conducted using the Kaplan-Meier method. Functional outcomes were evaluated based on range of motion and patient-reported outcome (PRO) measures (Knee Injury and Osteoarthritis Outcome Score) for cases with at least 8 years of follow-up (average, 10.2 years). RESULTS: Overall, the 10-year survival was 88% [95% confidence interval (CI) 0.81-0.95], and the estimated mean survival time was 13.4 years (95% CI 12.5-14.2). In a comparison of survival between the mobile- and fixed-bearing groups, the former had a 10-year survival of 85% (95% CI, 0.72-0.97) and an estimated mean survival time of 13.5 years (95% CI 12.2-14.7) and the latter had a 10-year survival of 90% (95% CI 0.82-0.99) and an estimated mean survival time of 13.4 years (95% CI 12.3-14.4). Thus, there was no significant difference in survival between the two groups (log-rank test, p = 0.718). In addition, no significant difference in functional outcomes was observed between the two groups (p > 0.05 for all). CONCLUSIONS: UKA performed in the Asian population showed a relatively good functional outcome and survival rate at an average 10-year follow-up. No difference in survival and PROs was observed according to the bearing type. Although the present study demonstrated a good survival rate, similar to that in other Western studies, further studies investigating the impact of the Asian lifestyle on the long-term survival of UKA is necessary.

Multicast silicon photonic MEMS switches with gap-adjustable directional couplers.

We report on 4x20 silicon photonic MEMS switch that is capable of multicasting. The switch is built on passive optical crossbar network with gap-adjustable directional couplers. The switch has high on-off extinction ratio (59 dB), low insertion loss (< 4.0 dB), small footprint (1.2x4.5 mm2), and fast response (9.8 µs). The switching voltage is 9.6 V and 20 dB bandwidth is 31.5 nm. One-to-two and one-to-four multicast operations are demonstrated.

Non-fluorescent nanoscopic monitoring of a single trapped nanoparticle via nonlinear point sources.

Detection of single nanoparticles or molecules has often relied on fluorescent schemes. However, fluorescence detection approaches limit the range of investigable nanoparticles or molecules. Here, we propose and demonstrate a non-fluorescent nanoscopic trapping and monitoring platform that can trap a single sub-5-nm particle and monitor it with a pair of floating nonlinear point sources. The resonant photon funnelling into an extremely small volume of ~5 × 5 × 7 nm3 through the three-dimensionally tapered 5-nm-gap plasmonic nanoantenna enables the trapping of a 4-nm CdSe/ZnS quantum dot with low intensity of a 1560-nm continuous-wave laser, and the pumping of 1560-nm femtosecond laser pulses creates strong background-free second-harmonic point illumination sources at the two vertices of the nanoantenna. Under the stable trapping conditions, intermittent but intense nonlinear optical spikes are observed on top of the second-harmonic signal plateau, which is identified as the 3.0-Hz Kramers hopping of the quantum dot trapped in the 5-nm gap.

Determination and identification of titanium dioxide nanoparticles in confectionery foods, marketed in South Korea, using inductively coupled plasma optical emission spectrometry and transmission electron microscopy.

Food-grade titanium dioxide (TiO2) is a common and widespread food additive in many processed foods, personal care products, and other industrial categories as it boosts the brightness and whiteness of colours. Although it is generally recognised as safe for humans, there is a growing interest in the health risks associated with its oral intake. This study quantified and identified TiO2 nanoparticles present in confectionery foods, which are children's favourite foods, with inductively coupled plasma optical emission spectrometry (ICP-OES) and transmission electron microscopy (TEM). A reliable digestion method using hot sulphuric acid and a digestion catalyst (K2SO4:CuSO4 = 9:1) was suggested for titanium analysis. Validations of the experimental method were quite acceptable in terms of linearity, recoveries, detection limits, and quantification limits. Of all the 88 analysed foods, TiO2 was detected in 19 products, all except three declared TiO2 in their labelling. The mean TiO2 content of candies, chewing gums, and chocolates were 0.36 mg g-1, 0.04 mg g-1, and 0.81 mg g-1, respectively. Whitish particles isolated from the confectionery foods were confirmed as TiO2 nanoparticles via TEM and energy dispersive X-ray spectroscopy (EDX), in which nanosized particles (<100 nm) were identified.

Detection of Korean Native Honey and European Honey by Using Duplex Polymerase Chain Reaction and Immunochromatographic Assay.

Korean native honey (KNH) is much more expensive than European honey (EH) in Korea, because KNH is a favored honey which is produced less than EH. Food fraud of KNH has drawn attention of the government office concerned, which is in need of a method to differentiate between KNH and EH which are produced by the Asiatic honeybee, Apis cerana and the European honeybee, Apis mellifera, respectively. A method to discriminate KNH and EH was established by using duplex polymerase chain reaction (PCR) in this study. Immunochromatographic assay (IC) was examined to analyze the duplex PCR product. The DNA sequences of primers for the duplex PCR were determined by comparing cytochrome C oxidase genes of the two honey bee species. Chelex resin method was more efficient in extracting genomic DNA from honey than the other two procedures of commercial kits. The duplex PCR amplifying DNA of 133 bp were more sensitive than that amplifying DNA of 206 bp in detecting EH in the honey mixture of KNH and EH. Agarose gel electrophoresis and IC detected the DNA of 133 bp at the ratios of down to 1% and 5% EH in the honey mixture, respectively and also revealed that several KNH products distributed by internet shopping sites were actually EH. In conclusion, the duplex PCR with subsequent IC could also discriminate between KNH and EH and save time and labor.

Structural Analysis of Recombinant Human Preproinsulins by Structure Prediction, Molecular Dynamics, and Protein-Protein Docking.

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.

Recombinant Glargine Insulin Production Process Using Escherichia coli.

Glargine insulin is a long-acting insulin analog that helps blood glucose maintenance in patients with diabetes. We constructed the pPT-GI vector to express prepeptide glargine insulin when transformed into Escherichia coli JM109. The transformed E. coli cells were cultured by fed-batch fermentation. The final dry cell mass was 18 g/l. The prepeptide glargine insulin was 38.52% of the total protein. It was expressed as an inclusion body and then refolded to recover the biological activity. To convert the prepeptide into glargine insulin, citraconylation and trypsin cleavage were performed. Using citraconylation, the yield of enzymatic conversion for glargine insulin increased by 3.2-fold compared with that without citraconylation. After the enzyme reaction, active glargine insulin was purified by two types of chromatography (ion-exchange chromatography and reverse-phase chromatography). We obtained recombinant human glargine insulin at 98.11% purity and verified that it is equal to the standard of human glargine insulin, based on High-performance liquid chromatography analysis and Matrix-assisted laser desorption/ionization Time-of-Flight Mass Spectrometry. We thus established a production process for high-purity recombinant human glargine insulin and a method to block Arg (B31)-insulin formation. This established process for recombinant human glargine insulin may be a model process for the production of other human insulin analogs.

Large-Scale Refolding and Enzyme Reaction of Human Preproinsulin for Production of Human Insulin.

Human insulin is composed of 21 amino acids of an A-chain and 30 amino acids of a B-chain. This is the protein hormone that has the role of blood sugar control. When the recombinant human proinsulin is expressed in Escherichia coli, a serious problem is the formation of an inclusion body. Therefore, the inclusion body must be denatured and refolded under chaotropic agents and suitable reductants. In this study, H27R-proinsulin was refolded from the denatured form with ß-mercaptoethanol and urea. The refolding reaction was completed after 15 h at 15°C, whereas the reaction at 25°C was faster than that at 15°C. The refolding yield at 15°C was 17% higher than that at 25°C. The refolding reaction could be carried out at a high protein concentration (2 g/l) using direct refolding without sulfonation. The most economical and optimal refolding condition for human preproinsulin was 1.5 g/l protein, 10 mM glycine buffer containing 0.6 M urea, pH 10.6, and 0.3 mM ß-mercaptoethanol at 15°C for 16 h. The maximum refolding yield was 74.8% at 15°C with 1.5 g/l protein. Moreover, the refolded preproinsulin could be converted into normal mature insulin with two enzymes. The average amount of human insulin was 138.2 g from 200 L of fermentation broth after enzyme reaction with H27R-proinsulin. The direct refolding process for H27R-proinsulin was successfully set up without sulfonation. The step yields for refolding and enzyme reaction were comparatively high. Therefore, our refolding process for production of recombinant insulin may be beneficial to the large-scale production of other biologically active proteins.

Identification of Porcine Endogenous Retrovirus (PERV) packaging sequence and development of PERV packaging viral vector system.

Studies of the retroviruses have focused on the specific interaction of the nucleocapsid protein with a packaging signal in the viral RNA as important for this selectivity, but the packaging signal in porcine endogenous retrovirus (PERV) has not been defined. Herein, we identified and analyzed this packaging signal in PERV and found hairpin structures with conserved tetranucleotides in their loops and nucleocapsid recognition sequences; both of which are key elements in the viral packaging signal of MLV. We evaluated packaging efficiency of sequence variants isolated from viral and proviral integrated genomes. All viral packaging sequences (Ψ) were identical, while five distinct packaging sequences were identified from proviral sources. One proviral sequence (Ψ1) was identical to that of the viral Ψ and had the highest packaging efficiency. Three variants (Ψ2, Ψ3, Ψ4) maintained key elements of the viral packaging signal, but had nucleotide replacements and consequently demonstrated reduced packaging efficiency. Despite of the same overall hairpin structure, the proviral variant (Ψ5) had only one GACG sequence in the hairpin loop and showed the lowest packaging efficiency other than ∆Ψ, in which the essential packaging sequence was removed. This result, thus, defined the packaging sequences in PERV and emphasized the importance of nucleotide sequence and RNA structure in the determination of packaging efficiency. In addition, we demonstrate efficient infection and gene expression from the PERV based viral vector, which may serve as a novel alternative to current retroviral expression systems.

Expeditious low-temperature sintering of copper nanoparticles with thin defective carbon shells.

The realization of air-stable nanoparticles, well-formulated nanoinks, and conductive patterns based on copper is a great challenge in low-cost and large-area flexible printed electronics. This work reports the synthesis of a conductively interconnected copper structure via thermal sintering of copper inks at a low temperature for a short period of time, with the help of thin defective carbon shells coated onto the copper nanoparticles. Air-stable copper/carbon core/shell nanoparticles (typical size ∼23 nm, shell thickness ∼1.0 nm) are prepared by means of an electric explosion of wires. Gaseous oxidation of the carbon shells with a defective structure occurs at 180 °C, impacting the choice of organic solvents as well as the sintering conditions to create a crucial neck formation. Isothermal oxidation and reduction treatment at 200 °C for only about 10 min yields an oxide-free copper network structure with an electrical resistivity of 25.1 µΩ cm (14.0 µΩ cm at 250 °C). Finally, conductive copper line patterns are achieved down to a 50 µm width with an excellent printing resolution (standard deviation ∼4.0%) onto a polyimide substrate using screen printing of the optimized inks.

Isolation of Legionella pneumophila from cooling towers, public baths, hospitals, and fountains in Seoul, Korea, from 2010 to 2012.

Legionnaire's disease is associated with a high mortality rate. The authors collected 3,495 water samples in Seoul, Korea, between 2010 and 2012 from public facilities (cooling towers, public baths, hospitals, and decorative fountains), which are considered the major habitats of Legionella pneumophila. In all, 527 (15.1%) isolates of L. pneumophila were obtained by microbial culture and polymerase chain reaction. Serological diagnosis and pulsed-field gel electrophoresis (PFGE) analysis were performed for the samples. The authors categorized the samples into four groups (A-D) on the basis of PFGE results. The analysis revealed that cooling towers containing the most samples with L. pneumophila serogroup 1 constituted the highest proportion of isolate. Samples from public facilities and serogroups could be distinctively classified by PFGE patterns. Thus, it is expected that source-specific features revealed through PFGE and serological analyses could serve as the basis for effectively coping with future outbreaks of L. pneumophila.

Formaldehyde and heavy metal migration from rubber and metallic packaging/utensils in Korea.

The aim of this study was to determine the non-intentionally added substances--formaldehyde and trace metals--at 4% acetic acid conditions in rubber and metallic packaging/utensils. The temperature effect on migration in rubber and metallic packaging/utensils was monitored at 60 °C and 100 °C under acidic (pH < 3) circumstances. The concentrations were: formaldehyde--23.1 µg kg⁻¹, lead--13.41 µg kg⁻¹, cadmium--0.15 µg kg⁻¹, total arsenic--2.02 µg kg⁻¹ and nickel--2.92 µg kg⁻¹ at 60 °C and formaldehyde--148.9 µg kg⁻¹, lead--17.04 µg kg⁻¹, cadmium--0.14 µg kg⁻¹, total arsenic--7.25 µg kg⁻¹ and nickel--8.7 µg kg⁻¹ at 100 °C. A significant difference was noticed in formaldehyde and total arsenic between both temperatures (p < 0.01), which was not present in other trace metals. In conclusion, formaldehyde and total arsenic were more sensitive with cooking temperature than the other metals.

Enhanced Anti-inflammatory Effects of γ-irradiated Pig Placenta Extracts.

Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1ß, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1ß, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.