Separating Charge Centers of Chain Segments in Dielectric Elastomer through Steric Hindrance Engineering.

Theoretically, separating the positive and negative charge centers of the chain segments of dielectric elastomers (DEs) is a viable alternative to the conventional decoration of chain backbone with polar handles, since it can dramatically increase the dipole vector and hence the dielectric constant (ε') of the DEs while circumvent the undesired impact of the decorated polar handles on the dielectric loss (tan δ). Herein, a novel and universal method is demonstrated to achieve effective separation of the charge centers of chain segments in homogeneous DEs by steric hindrance engineering, i.e., by incorporating a series of different included angle-containing building blocks into the networks. Both experimental and simulation results have shown that the introduction of these building blocks can create a spatially fixed included angle between two adjacent chain segments, thus separating the charge center of the associated region. Accordingly, incorporating a minimal amount of these building blocks (≈5 mol%) can lead to a considerably sharp increase (≈50%) in the ε' of the DEs while maintaining an extremely low tan δ (≈0.006@1 kHz), indicating that this methodology can substantially optimize the dielectric performance of DEs based on a completely different mechanism from the established methods.

The Enhanced Thermoelectric and Mechanical Performance of Polythiophene/Single-Walled Carbon Nanotube Composites with Polar Ethylene Glycol Branched-Chain Modifications.

In order to develop flexible thermoelectric materials with thermoelectric and mechanical properties, in this study, we designed and synthesized polythiophene derivatives with branched ethylene glycol polar side-chains named P3MBTEMT, which were used in combination with single-walled carbon nanotubes (SWCNTs) to prepare composite thin films and flexible thermoelectric devices. A comparison was made with a polymer named P3(TEG)T, which has a polar alkoxy linear chain. The UV-vis results indicated that the larger steric hindrances of the branched ethylene glycol side-chain in P3MBTEMT could inhibit its self-aggregation and had a stronger interaction with the SWCNTs compared to that of P3(TEG)T, which was also confirmed using Raman spectroscopy. When the mass ratio of SWCNTs to P3MBTEMT was 9:1 (represented as P3MBTEMT/SWCNTs-0.9), the composite film exhibited the highest thermoelectric properties with a power factor of 446.98 µW m-1 K-2, which was more than two times higher than that of P3(TEG)T/SWCNTs-0.9 (215.08 µW m-1 K-2). The output power of the thermoelectric device with P3MBTEMT/SWCNTs-0.9 was 2483.92 nW at 50 K, which was 1.66 times higher than that of P3(TEG)T/SWCNTs-0.9 (1492.65 nW). Furthermore, the P3MBTEMT/SWCNTs-0.5 showed superior mechanical properties compared to P3(TEG)T/SWCNTs-0.5. These results indicated that the mechanical and thermoelectric performances of polymer/SWCNT composites could be significantly improved by adding polar branched side-chains to conjugated polymers. This study provided a new strategy for creating high-performing novel flexible thermoelectric materials.

Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF-κB pathway in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant anti-inflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases. However, the role of wogonin in RA has not yet been demonstrated. PURPOSE: To investigate the inhibitory effect of wogonin on the invasive behavior of fibroblast-like synoviocytes and to explore the mechanism of action of wogonin in RA. METHODS: CCK-8, EdU, cell migration and invasion, immunofluorescence staining, RT-qPCR, and protein blot analysis were used to study the inhibitory effects of wogonin on migration, invasion, and pro-inflammatory cytokine overexpression in the immortalized rheumatoid synovial cell line MH7A. The therapeutic effects of wogonin were validated in vivo using arthritis scores and histopathological evaluation of collagen-induced arthritis mice. RESULTS: Wogonin inhibited the migration and invasion of MH7A cells, reduced the production of TNF-α, IL-1ß, IL-6, MMP-3 and MMP-9, and increased the expression of IL-10. Moreover, wogonin also inhibited the myofibrillar differentiation of MH7A cells, increased the expression of E-cadherin (E-Cad) and decreased the expression of α-smooth muscle actin (α-SMA). In addition, wogonin treatment effectively ameliorated joint destruction in CIA mice. Further molecular mechanism studies showed that wogonin treatment significantly inhibited the activation of PI3K/AKT/NF-κB signaling pathway in TNF-α-induced arthritic FLSs. CONCLUSION: Wogonin effectively inhibits migration, invasion and pro-inflammatory cytokine production of RA fibroblast-like synoviocytes through the PI3K/AKT/NF-κB pathway, and thus wogonin, as a natural flavonoid, has great potential for treating RA.

Changes of heavy metal concentrations in farmland soils affected by non-ferrous metal smelting in China: A meta-analysis.

Long-term human smelting activities have resulted in substantial heavy metals (HMs) pollution of farmland soils around smelting sites, and the safety of farmland products is critical for human health. The current study focuses on HMs in farmland soils surrounding a single smelter, therefore the impact of smelting on a national scale needs to be investigated further. This study was based on 116 papers and 1143 sets of relevant data for meta-analysis, and a hierarchical mixed-effects model was used to quantify the changes of HMs concentrations in farmland soils affected by non-ferrous metal smelting on a national scale, as well as their relationships with relevant explanatory variables in China. Results showed that: (i) non-ferrous metal smelting substantially increased farmland soils HMs concentrations (323%), with each HM concentration increasing in the following order: Cd (2753%) > Pb (562%) > Hg (455%) > Zn (228%) > Cu (158%) > As (107%) > Ni (52%); (ii) the highest increase of HMs in vegetable fields (361%), but not significant in comparison to other farmland categories, and the increase of Pb, Zn, Cu and As concentrations were significantly different in different types of smelting areas; (iii) the increase of Hg was significantly higher in the northern region than in the southern region, and the opposite increase of Cu; (iv) the soil depth from 0 to 40 cm was significantly affected by smelting, and the increase of multiple HMs were significantly positively correlated with soil pH and negatively correlated with distance; (v) the other explanatory variables (farmland category and soil organic matter) were not significantly related to the effect of smelting. The results can provide some reference for protecting and restoring farmland soils around smelting areas.

Influence of the area of the aqueduct and region of interest on quantification of stroke volume in healthy volunteers using phase-contrast cine magnetic resonance imaging.

BACKGROUND: Phase-contrast cine magnetic resonance imaging (PC-MRI) has been used to measure cerebrospinal fluid (CSF) flow dynamics, but the influence of the area of the aqueduct and region of interest (ROI) on quantification of stroke volume (SV) has not been assessed. PURPOSE: To assess the influence of the area of the ROI in quantifying the aqueductal SV measured with PC-MRI within the cerebral aqueduct. MATERIAL AND METHODS: Nine healthy volunteers (mean age = 29.6 years) were enrolled in the study, and brain MRI examinations were performed on a 3.0-T system. Quantitative analysis of the aqueductal CSF flow was performed using manual ROI placement. ROIs were separately drawn for each of the 12 phases of the cardiac cycle, and changes in aqueduct size during the cardiac cycle were determined. The SV was calculated using 12 different aqueductal ROIs and compared with the SV calculated using a fixed ROI size. RESULTS: There was variation in the size of the aqueduct during the cardiac cycle. In addition, the measured SV increased with a greater area of the ROI. A significant difference in the calculated SVs with the 12 variable ROIs was observed compared with that using a fixed ROI throughout the cardiac cycle. CONCLUSION: To establish reliable reference values for the SV in future studies, a variable ROI should be considered.

6-Shogaol inhibits the proliferation, apoptosis, and migration of rheumatoid arthritis fibroblast-like synoviocytes via the PI3K/AKT/NF-κB pathway.

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are essential for joint destruction in rheumatoid arthritis (RA). 6-Shogaol, a phenolic extract isolated from ginger, has been found to have potential benefits in the treatment of diverse inflammatory and immune disorders. However, the role of 6-shogaol in RA has yet to be explored. PURPOSE: To reveal the effect of 6-shogaol on RA FLSs and MH7A cells and to investigate the molecular mechanism of 6-shogao in RA. METHODS: We performed MTT, EdU, cell apoptosis, cell migration and invasion, RT-qPCR, western blot analysis, and immunofluorescence to elucidate the effect of 6-shogaol on the proliferation, apoptosis, and migration of RA FLSs and MH7A cells and revealed its modulation of the PI3K/AKT/NF-κB pathway. The in vivo therapeutic effect of 6-shogaol was verified in mice with collagen-induced arthritis (CIA). RESULTS: 6-Shogaol suppressed proliferation, migration, and invasion, and induced apoptosis in RA FLSs and MH7A cells. 6-Shogaol also reduced the production of TNF-α, IL-1ß, IL-6, IL-8, MMP-2, and MMP-9. Molecular analysis revealed that 6-shogaol inhibited the PI3K/AKT/NF-κB pathway by activating PPAR-γ. Treatment with 6-shogaol ameliorated joint destruction of mice with CIA. CONCLUSION: This study revealed that 6-shogaol inhibited proliferation, migration, invasion, cytokine, and MMPs production, and induced apoptosis in RA FLSs via the PI3K/AKT/NF-κB pathway, providing a new natural potential drug for future RA treatments.

Redox-sensitive transcriptional regulator SoxR directly controls antibiotic production, development and thiol-oxidative stress response in Streptomyces avermitilis.

The redox-sensitive transcriptional regulator SoxR is conserved in bacteria. Its role in mediating protective response to various oxidative stresses in Escherichia coli and related enteric bacteria has been well established. However, functions and regulatory mechanisms of SoxR in filamentous Streptomyces, which produce half of known antibiotics, are unclear. We report here that SoxR pleiotropically regulates antibiotic production, morphological development, primary metabolism and thiol-oxidative stress response in industrially important species Streptomyces avermitilis. SoxR stimulated avermectin production by directly activating ave structural genes. Four genes (sav_3956, sav_4018, sav_5665 and sav_7218) that are homologous to targets of S. coelicolor SoxR are targeted by S. avermitilis SoxR. A consensus 18-nt SoxR-binding site, 5'-VSYCNVVMHNKVKDGMGB-3', was identified in promoter regions of sav_3956, sav_4018, sav_5665, sav_7218 and target ave genes, leading to prediction of the SoxR regulon and confirmation of 11 new targets involved in development (ftsH), oligomycin A biosynthesis (olmRI), primary metabolism (metB, sav_1623, plcA, nirB, thiG, ndh2), transport (smoE) and regulatory function (sig57, sav_7278). SoxR also directly activated three key developmental genes (amfC, whiB and ftsZ) and promoted resistance of S. avermitilis to thiol-oxidative stress through activation of target trx and msh genes. Overexpression of soxR notably enhanced antibiotic production in S. avermitilis and S. coelicolor. Our findings expand our limited knowledge of SoxR and will facilitate improvement of methods for antibiotic overproduction in Streptomyces species.

Ventriculoperitoneal shunt malfunction diagnosis based on substance dilution.

OBJECTIVE: Current methods for the diagnosis of ventriculoperitoneal (VP) shunt malfunction lack specific standards; therefore, it may be missed or misdiagnosed. Hence, providing a reliable diagnostic method will help improve the accuracy of preoperative decision-making. Therefore, the aim of the study was to provide a new method for the diagnosis of VP shunt malfunction. METHODS: After in vitro testing, we enrolled a total of 12 patients with VP shunt malfunction. Before revision surgery, 0.1 mL of a 5% sodium valproate (SV) solution was injected into the reservoir; 0.1 mL of the cerebrospinal fluid (CSF) was withdrawn 20 minutes later from the reservoir to measure the SV concentration. The process was repeated on the seventh day after surgery and compared with the preoperative results. RESULTS: The mean ±â€Šstandard deviation preoperative SV concentration in the cerebrospinal fluid was greater than the postoperative concentration (5967.8 ±â€Š1281.3 vs 391.1 ±â€Š184.6 µg/mL, P = .001). CONCLUSION: The proposed method is a reliable, safe, and relatively simple alternative for the diagnosis of VP shunt malfunction and further provides a reference for treatment.

Searching the co-occurrence of pathogenic mutations for Leber's hereditary optic neuropathy and hearing loss in more than 26,000 whole mitochondrial genomes.

The co-occurrence of pathogenic or candidate mutations for Leber's hereditary optic neuropathy (LHON) and hearing loss has long been suggested to be a rare incident. The "rare" is probably caused by inadequate database searches. In this study, we created and released a comprehensive database with detailed information of haplogroup, variants, coding sites, and potential pathogenic mutations for more than 26,000 whole mitochondrial genomes. We found the co-occurrence in more than 200 individuals including not only LHON or hearing loss patients but also individuals sampled from general populations with various haplogroup backgrounds. The results highlighted the significant importance of adequate database searching in the genetic analysis of mitochondrial disorders.

Preliminary results of cord blood mononuclear cell therapy for multiple system atrophy: a report of three cases.

OBJECTIVES: This study was designed to evaluate the effects of cord blood mononuclear cell transplantation in multiple system atrophy (MSA). CLINICAL PRESENTATION AND INTERVENTION: Cord blood mononuclear cells (1-2 × 10(8) cells/6 ml) were injected into the subarachnoid space using lumbar puncture in patients 1 and 2 and cisterna magna puncture in patient 3 in the 3 patients with MSA. The cord blood mononuclear cell transplantation was repeated 30 days after the first treatment in patients 1 and 2; it was repeated twice in patient 3. The clinical outcomes of treatment were used to assess the Unified Multiple System Atrophy Rating Scale (UMSARS) before, 90 and 180 days after the cell transplantation. There were no clinically noticeable side effects from the cord blood mononuclear cells. The UMSARS scores improved after 90 days of the cord blood mononuclear cell therapy in all 3 patients, the most significant improvement being that in urinary incontinence and ability to walk. CONCLUSIONS: Cord blood mononuclear cell transplantation was safe and potentially effective in the treatment of MSA in the 3 patients.

[Effect of Eupolyphaga Sinensis Walker on mandibular distraction osteogenesis in rabbits].

OBJECTIVE: To study the effect of Eupolyphaga Sinensis Walker on mandibular distraction osteogenesis (DO) in rabbits. METHODS: 30 Japanese white rabbits (weight 2.0-2.5 kg, about 3 months old) were divided randomly into control group (n = 15) and experimental group (n = 15). Unilateral mandibular DO models were established at the right mandible of the rabbits. Distraction was started 7 days after the surgery at the speed of 0.4 mm per time twice a day and continued for 10 days. From the first day of distraction to the day of execution, the experimental group rabbits were fed with 2 g of ESW power once a day at 9 o' clock. Three animals in each group were executed respectively at 24 hours, 72 hours, 1 week, 4 weeks and 7 weeks after completion of distraction, and the specimens of DO were harvested. The general observation, X-ray examination, histological study and immunohistochemical staining of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) were performed. The images of immunohistochemical staining of BMPs and VEGF were analyzed by the image analysis software, and the results were analyzed by statistical software SPSS 17.0. RESULTS: The rate of the new bone formation in the experimental group was faster than that in the control group, and the immunohistochemical staining of BMPs and VEGF in the experimental group was higher than that in the control group. CONCLUSIONS: ESW can promote the formation of the new bone in the distracted gap during mandibular DO in rabbits, which may be due to its enhancement effect on the expression of BMPs and VEGF.