The association between serum copper concentration and prevalence of diabetes among US adults with hypertension (NHANES 2011-2016).

The objective of this study was to examine the association between the serum copper concentration and the prevalence of diabetes among US adults with hypertension using the data from the National Health and Nutrition Examination Survey (NHANES). The study population was selected from adults aged over 20 years old in the three survey cycles of NHANES from 2011 to 2016. Logistic regression model analyses were applied to determine the independent risky effect of copper to the prevalence of diabetes. Also, a restricted cubic spline (RCS) model was performed to explore the potential nonlinear association between serum copper concentration and the prevalence of diabetes. A total of 1786 subjects (742 cases and 1044 controls) were included, and 924 were men (51.7%), and 742 (41.5%) were diabetic. Compared with non-diabetic individuals, the concentration of serum copper in diabetic patients with hypertension was higher. After adjusting for age, sex, race, education, marital status, body mass index (BMI), family poverty income ratio (PIR), smoking, alcohol drinking, physical activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and hyperlipidemia, the highest quartile of serum copper concentration significantly increased the risk of diabetes as compared with the lowest quartile (OR: 1.38, 95% CI: 1.01-1.92, ptrend = 0.036). The results of RCS analysis showed significant non-linear relationship between serum copper concentration and prevalence of diabetes (p-non-linear = 0.010). This study finds that serum copper concentration are significantly associated with risk of diabetes in hypertensive patients, which suggests copper as an important risk factor of diabetes development.

Preparation, Characterization, and Magnetic Resonance Imaging of Mn@SiO2 Nanowires.

The deposition time was controlled to prepare Mn nanowires of different lengths and diameters on templates of anodic aluminum oxide (AAO) with different pore sizes. The surface of as-prepared Mn nanowires was modified with SiO2 using the sol-gel method to improve their dispersion in aqueous solution. The effects of the diameter and length of the as-prepared Mn nanowires coated with SiO2 on the relaxivity were investigated. It was found that the Mn@SiO2 nanowires have smaller diameters and a higher longitudinal relaxivity (r1) with an increased length. Mn3@SiO2 nanowires had the highest r1 value of 5.8 mM-1 s-1 among the Mn@SiO2 nanowires (Mn3 nanowires have a diameter of about 30 nm and a length of about 0.5 µm length). Additionally, the biocompatibility and in vivo imaging ability of the Mn3@SiO2 nanowires were evaluated. The Mn3@SiO2 nanowires had good cytotoxicity and biocompatibility, and the kidney of SD rats showed a positive enhancement effect during small animal imaging at 1.5 T. This study showed that the Mn3@SiO2 nanowires could potentially become contrast agents (CAs) of longitudinal relaxation time (T1).

Spin-orbit splitting and piezoelectric properties of Janus Ge2XY (X ≠ Y = P, As, Sb and Bi).

The coexistence of spin-orbit coupling and piezoelectricity in a single material may have potential application in multifunctional devices, including spintronics, nanorobotics and piezotronics. Spin-orbit coupling provides a new means to manipulate electron's spin without an additional external magnetic field, while piezoelectricity refers to the interplay between mechanical stresses and electric polarization. Using first-principles calculations, the structural, electronic, optical, spin, and piezoelectric properties of the Janus Ge2XY (X ≠ Y = P, As, Sb, and Bi) monolayers were systematically investigated. All the Ge2XY are energetically and dynamically stable in the α phase. At the GW level, Ge2AsSb, Ge2AsBi, and Ge2SbBi have direct fundamental band gaps of 0.65, 0.64, and 0.91 eV. At the GW + BSE level, their optical gaps are 0.42, 0.45, and 0.63 eV, and the optical absorption coefficients can reach about 10-5 cm-1 in the infrared light region, which reveals that they have potential for application in infrared photodetectors. For Ge2PBi, Ge2AsBi, and Ge2SbBi containing the heavy Bi element, the lowermost conduction band and uppermost valence band have large spin splitting along the M-K and K-Γ lines, and the bands near the Fermi level possess Rashba spin splitting at the Γ point. Ge2PBi and Ge2SbBi have both large in-plane piezoelectric coefficients d11 (-0.75 and -3.18 pm V-1) and out-of-plane piezoelectric coefficients d31 (0.37 and 0.30 pm V-1). Our findings are helpful to understand the mechanism of the spin-orbit physics and piezoelectricity of Janus Ge2XY monolayers and guide experiments in exploring novel multifunctional materials.

High-Entropy Spinel Ferrites with Broadband Wave Absorption Synthesized by Simple Solid-Phase Reaction.

In this work, high-entropy (HE) spinel ferrites of (FeCoNiCrM)xOy (M = Zn, Cu, and Mn) (named as HEO-Zn, HEO-Cu, and HEO-Mn, respectively) were synthesized by a simple solid-phase reaction. The as-prepared ferrite powders possess a uniform distribution of chemical components and homogeneous three-dimensional (3D) porous structures, which have a pore size ranging from tens to hundreds of nanometers. All three HE spinel ferrites exhibited ultrahigh structural thermostability at high temperatures even up to 800 °C. What is more, these spinel ferrites showed considerable minimum reflection loss (RLmin) and significantly enhanced effective absorption bandwidth (EAB). The RLmin and EAB values of HEO-Zn and HEO-Mn are about -27.8 dB at 15.7 GHz, 6.8 GHz, and -25.5 dB at 12.9 GHz, 6.9 GHz, with the matched thickness of 8.6 and 9.8 mm, respectively. Especially, the RLmin of HEO-Cu is -27.3 dB at 13.3 GHz with a matched thickness of 9.1 mm, and the EAB reaches about 7.5 GHz (10.5-18.0 GHz), which covers almost the whole X-band range. The superior absorbing properties are mainly attributed to the dielectric energy loss involving interface polarization and dipolar polarization, the magnetic energy loss referring to eddy current and natural resonance loss, and the specific functions of 3D porous structure, indicating a potential application prospect of the HE spinel ferrites as EM absorbing materials.

A superior allele of the wheat gene TaGL3.3-5B, selected in the breeding process, contributes to seed size and weight.

KEY MESSAGE: A superior allele of wheat gene TaGL3.3-5B was identified and could be used in marker-assisted breeding in wheat. Identifying the main genes which mainly regulate the yield-associated traits can significantly increase the wheat production. In this study, gene TaGL3.3 was cloned from common wheat according to the sequence of OsPPKL3. A SNP in the 8th exon of TaGL3.3-5B, T/C in coding sequence (CDS), which resulted in an amino acid change (Val/Ala), was identified between the low 1000-kernel weight (TKW) wheat Chinese Spring and the high TKW wheat Xinong 817 (817). Subsequently, association analysis in the mini-core collection (MCC) and the recombinant inbred lines (RIL) revealed that the allele TaGL3.3-5B-C (from 817) was significantly correlated with higher TKW. The high frequency of TaGL3.3-5B-C in the Chinese modern wheat cultivars indicated that it was selected positively in wheat breeding programs. The overexpression of TaGL3.3-5B-C in Arabidopsis resulted in shorter pods and longer grains than those of wild-type counterparts. Additionally, TaGL3.3 expressed a tissue-specific pattern in wheat as revealed by qRT-PCR. We also found that 817 showed higher expression of TaGL3.3 than that in Chinese Spring (CS) during the seed development. These results demonstrate that TaGL3.3 plays an important role in the formation of seed size and weight. Allele TaGL3.3-5B-C is associated with larger and heavier grains that are beneficial to wheat yield improvement.

A Critical Review on Nanowire-Motors: Design, Mechanism and Applications.

Nanowire-motors (NW-Ms) are promoting the rapid development of emerging biomedicine and environmental governance, and are an important branch of micro-nano motors in the development of nanotechnology. In recent years, huge research breakthroughs have been made in these fields in terms of the fascinating microstructure, conversion efficiency and practical applications of NW-Ms. This review article introduces the latest milestones in NW-Ms research, from production methods, driving mechanisms, control methods to targeted drug delivery, sewage detection, sensors and cell capture. The dynamics and physics of micro-nano devices are reviewed, and finally the current challenges and future research directions in this field are discussed. This review further aims to provide certain guidance for the driving of NW-Ms to meet the urgent needs of emerging applications.

Degradation performance and mechanism toward methyl orange via nanoporous copper powders fabricated by dealloying of ZrCuNiAl metallic glassy precursors.

The catalyst of nanoporous Cu (NP-Cu) powders, with the chemical composition of Cu79.63Ni6.85O13.53(at%), was successfully fabricated by dealloying of Zr-Cu-Ni-Al metallic glassy precursors. The as-prepared NP-Cu powders, co-existing with Cu2O phase on Cu ligament surface, had a three-dimensional network porous structure. The NP-Cu powders/H2O2system showed superior catalytic degradation efficiency toward azo dyes in both acidic (pH 2) and neutral (pH 7) environments. Moreover, the cyclic tests indicated that this powder catalyst also exhibited good durability. A novel degradation mechanism of NP-Cu powders/H2O2was proposed: the high degradation performance in acidic environment was mainly derived from heterogeneous reaction involved with a specific pathway related to Cu3+to produce HO·, while in neutral environment it was primarily resulted from homogeneous reaction with the generation of HO· from the classical Cu-based Fenton-like process. This work indicates that the NP-Cu powders have great potential applications as catalysts for wastewater treatments.

LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most significant subtype of esophageal cancer featured with high occurrence. Long noncoding RNAs (lncRNAs) have been proved to modulate the biological properties of cancer cells, including cell proliferation, invasion, migration, and apoptosis. LncRNA protein tyrosine phosphatase receptor type G-antisense RNA 1 (PTPRG-AS1) has been reported to play as an oncogene in diverse cancers. However, the detailed function PTPRG-AS1 may exert in ESCC is unclear. METHODS: PTPRG-AS1 expression in ESCC cells was investigated via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The effects of PTPRG-AS1 on ESCC cell proliferation, migration, glycolysis, and stemness were verified through functional assays. Mechanism assays including RIP assay, RNA pull down assay, and luciferase reporter assays were performed to verify the molecular mechanism of PTPRG-AS1. RESULTS: PTPRG-AS1 silencing hindered the proliferation, migration, glycolysis and stemness of ESCC cells. PTPRG-AS1 regulated pyruvate dehydrogenase kinase 1 (PDK1) expression via sponging miR-599. The PTPRG-AS1/miR-599/PDK1 axis was further verified to aggravate the progression of ESCC cells. CONCLUSION: PTPRG-AS1 sponged miR-599 to up-regulate PDK1 expression, thereby promoting the proliferation and migration as well as glycolysis and stemness properties of ESCC cells.

Janus Ga2SeTe/In2SSe heterostructures: tunable electronic, optical, and photocatalytic properties.

Vertically stacking two-dimensional materials into van der Waals (vdW) heterostructures (HS) is deemed to be an effective strategy to tailor their physical properties and enrich their applications in modern nanoelectronics. Here, we study the geometry, electronic, and optical properties of Janus Ga2SeTe/In2SSe heterostructures by using first-principles calculations. We consider four models of Ga2SeTe/In2SSe heterostructures with an alternative chalcogen atom layer sequence and five potential stacking configurations, and find that the most energy favorable stacking pattern is AB stacking for each model. The heterostructures form type II alignment with a direct band gap. Moreover, the band gap values are highly dependent on the magnitude of the electric dipole, which is related to the sublayer intrinsic dipole direction and interface charge transfer. Additionally, the optical absorption of the heterostructures is intensified in the visible and ultraviolet regime. Furthermore, we predict two heterostructures with the band edge straddling the water redox potential level. These findings can help in understanding the tailored properties of the heterostructures based on Janus two-dimensional materials, and guide experiments in designing novel optoelectronic devices.

The electromagnetic performance of transition metal-substituted monolayer black arsenic-phosphorus.

Recently, a new two-dimensional nonmagnetic semiconductor material, black arsenic-phosphorus (bAsP), has gained great research attention for experimental and theoretical works owing to its excellent physical properties. The present work attempted to investigate the electromagnetic properties of three 1 : 1 bAsP structures (bAsP-1, bAsP-2, and bAsP-3) substituted with transition metals (TM) by using first principles. Among these substituted bAsP systems, V substitutes P of bAsP-1, Ni substitutes As of bAsP-1, Mn substitutes P of bAsP-2, Fe substitutes As of bAsP-2 and Mn substitutes P of bAsP-3 and these are found to be half-metals. Among them, the system where Ni substitutes As of the bAsP-1 shows the largest binding energy and is the most stable structure. The system where one Ni atom substitutes As of bAsP-1 (As_Ni) and the system where two Ni atoms substitute As of bAsP-1 (2As_2Ni) are selected to develop magnetic tunnel junctions where it is found that the increase in the concentration of Ni in the electrodes increases the spin polarized current. More interestingly, a perfect spin filtering effect with 100% spin polarization and tunnel magnetoresistance of above 104% can be obtained in the one Ni substituted-system (As_Ni) and two Ni-substituted system (2As_2Ni). The negative differential resistance ratio is as high as 3.2 × 107% when the voltage is 0.5 V in the parallel spin configuration of As_Ni. The present research displays that the TM-substituted bAsP structure can be used in the fabrication of spintronic devices.

Magnetic nanowires in biomedical applications.

Magnetic nanostructures and nanomaterials play essential roles in modern bio medicine and technology. Proper surface functionalization of nanoparticles (NPs) allows the selective bonding thus application of magnetic forces to a vast range of cellular structures and biomolecules. However, the spherical geometry of NPs poises a series of limitations in various potential applications. Mostly, typical spherical core shell structure consists of magnetic and non-magnetic layers have little tunability in terms of magnetic responses, and their single surface functionality also limits chemical activity and selectivity. In comparison to spherical NPs, nanowires (NWs) possess more degrees of freedom in achieving magnetic and surface chemical tenability. In addition to adjustment of magnetic anisotropy and inter-layer interactions, another important feature of NWs is their ability to combine different components along their length, which can result in diverse bio-magnetic applications. Magnetic NWs have become the candidate material for biomedical applications owing to their high magnetization, cheapness and cost effective synthesis. With large magnetic moment, anisotropy, biocompatibility and low toxicity, magnetic NWs have been recently used in living cell manipulation, magnetic cell separation and magnetic hyperthermia. In this review, the basic concepts of magnetic characteristics of nanoscale objects and the influences of aspect ratio, composition and diameter on magnetic properties of NWs are addressed. Some underpinning physical principles of magnetic hyperthermia (MH), magnetic resonance imaging (MRI) and magnetic separation (MS) have been discussed. Finally, recent studies on magnetic NWs for the applications in MH, MRI and MS were discussed in detail.

Enhanced electro-catalytic performance of Pd-based hierarchical nanoporous structures fabricated by micropatterning and dealloying of Pd-Ni-P metallic glass.

Pd-based catalysts are of significance for their application in direct alcohol fuel cells, due to the superior electro-catalytic performance and CO poisoning resistance. In this work, using Pd32Ni48P20 metallic glassy ribbon as precursor, micro/nano hierarchical nanoporous structure was constructed by the hybrid approach of thermal plastic micropatterning and subsequently electrochemical dealloying at 0.88 V for 120 min in 0.5 M H2SO4 and 0.5 M H3PO4. This hierarchical structure was composed of the periodical micro-rods and nanoporous structure, where the chemical constituent was 80.33 at% Pd, 4.87 at% Ni, 4.96 at% P, and 9.84 at% O. The nanoporous structures showed an enhanced methanol electro-oxidation performance in alkaline medium, owing to their enlarged specific surface area. Compared to single nanoporous structure, the hierarchical nanoporous structure exhibited much better electro-catalysis, mainly attributed to the large surface area and high mass transfer efficiency, indicating a promising perspective for the application in alkaline direct alcohol fuel cells.

Performance of Surveillance MR Enterography (MRE) in Asymptomatic Children and Adolescents With Crohn's Disease.

BACKGROUND: MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. PURPOSE: To determine whether MRE imaging features are associated with clinical recurrence. STUDY TYPE: Retrospective. POPULATIONS: Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. FIELD STRENGTH/SEQUENCE: 1.5T including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T1 -weighted gradient recalled echo sequences. ASSESSMENT: MREs were reviewed by three radiologists independently for mural thickening, T2 -weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. STATISTICAL TESTS: Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. RESULTS: Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T2 -weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). DATA CONCLUSION: MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;50:1955-1963.

Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells.

BACKGROUND/AIMS: Colon cancer, also known as colorectal cancer (CRC), is one of the most common malignant tumors globally. Although significant advances have been made for developing novel therapeutics, the mechanisms of progression of colorectal cancer are still poorly understood. METHODS: In this study, we identified down-regulation of microRNA-214 (miR-214) as the contributing factor for CRC. Mitochondrial transcription factor A (TFAM) and miR-214 expression in tumor samples from colorectal cancer patients and cancer cell lines were examined by reverse transcription and real-Time PCR (qPCR) or Western Blotting. RESULTS: Our data demonstrated that miR-214 was significantly down-regulated in the tissue samples from CRC patients as well as CRC derived cell lines. TFAM overexpression was also observed in CRC patients and identified as a target for miR-214. Knockdown of TFAM by miR-214 mimics significantly inhibited the proliferation of CRC cell lines. Also, down-regulation of TFAM inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes. CONCLUSION: In conclusion, our data suggested that down-regulation of MiR-214 contributed to the enhanced TFAM expression and decreased proliferation of CRC cells.

Long noncoding RNA FAL1 promotes proliferation and inhibits apoptosis of human colon cancer cells.

Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with a variety of malignancies including colon cancer. In this study, we aimed to characterize the biological mechanisms of focally amplified lncRNA on chromosome 1 (FAL1) in colon cancers. Here, our results indicate that FAL1 expression was remarkably up-regulated in colon tumor tissues as compared to corresponding tumor-adjacent normal tissues. Importantly, the cumulative survival rate of patients with high levels of FAL1 in tumor tissues was considerably lower than those with low FAL1 levels in tumor tissues. Cox regression analysis showed that lncRNA FAL1 could act as an independent prognostic factor in CRC. Knockdown of FAL1 in HT29 cells attenuated cell proliferation and stimulated cell apoptosis. In contrast, overmetastasis-related molecules Bcl-2, TGF-ß1, p65, and PCNA at the mRNA and protein levels. Mechanistically, FAL1 was found to interact with STAT3 at 200 to 400 bp and promote phosphorylation of STAT3. In addition, we found that knockdown of STAT3 in HT29 cells abolished the effects of FAL1 on cell proliferation as well as the expression of TGF-ß1 and Bcl-2. Based on these findings, we concluded that FAL1 might be a potential oncogene for the progression of colon cancer. © 2018 IUBMB Life, 70(11):1093-1100, 2018.

Negative differential resistance, perfect spin-filtering effect and tunnel magnetoresistance in vanadium-doped zigzag blue phosphorus nanoribbons.

We investigate the electronic and transport properties of vanadium-doped zigzag blue phosphorus nanoribbons by first-principles quantum transport calculations. We study the spin-dependent transport properties and obtain current-voltage curves showing obvious spin polarization and negative differential behaviors. These interesting transport behaviors can be explained by the band structure of the vanadium-doped zigzag blue phosphorus nanoribbons. The tunnel magnetoresistance and spin-filtering effects under different magnetic configurations originate predominately from the symmetry matching between the band structures of the electrodes. According to our results, vanadium-doped zigzag blue phosphorus nanoribbons can be used as a perfect spin filter with a large tunnel magnetoresistance. This also indicates that blue phosphorus nanoribbons are a promising candidate for their future application in spintronics.

Half-metallic and magnetic semiconducting behaviors of metal-doped blue phosphorus nanoribbons from first-principles calculations.

We investigate the electronic and magnetic properties of substitutional metal atom impurities in two-dimensional (2D) blue phosphorene nanoribbons using first-principles calculations. In impure zigzag blue phosphorene nanoribbons (zBPNRs), a metal atom substitutes for a P atom at position "A/B". The V-"B"structure shows half-metallic properties, while the Mn-"A/B", V-"A", Fe-"B", and Cr-"A/B" structures show magnetic semiconductor properties. In addition, the Fe-"A" system shows magnetic metallic properties. On the other hand, for metal-doped armchair blue phosphorene nanoribbons (aBPNRs), the Mn-"A/B", V-"A", Fe-"A/B", and Cr-"A/B" structures show magnetic semiconductor properties, while the V-"B" structure shows nonmagnetic properties. We find that the magnetic properties of such substitutional impurities can be understood by regarding the exchange splitting of the metal 3d orbitals. And from analyzing the electron orbitals, we conclude that the main contribution of the DOS for every system comes from the d and p orbitals. These results suggest excellent candidates for new magnetic semiconductors and half-metals for spintronic devices based on blue phosphorenes.

Special AT-rich sequence binding protein 1 promotes tumor growth and metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is one of the most aggressive malignancies worldwide. Special AT-rich sequence binding protein 1 is a nuclear matrix attachment region binding protein which participates in higher order chromatin organization and tissue-specific gene expression. However, the role of special AT-rich sequence binding protein 1 in esophageal squamous cell carcinoma remains unknown. In this study, western blot and quantitative real-time polymerase chain reaction analysis were performed to identify differentially expressed special AT-rich sequence binding protein 1 in a series of esophageal squamous cell carcinoma tissue samples. The effects of special AT-rich sequence binding protein 1 silencing by two short-hairpin RNAs on cell proliferation, migration, and invasion were assessed by the CCK-8 assay and transwell assays in esophageal squamous cell carcinoma in vitro. Special AT-rich sequence binding protein 1 was significantly upregulated in esophageal squamous cell carcinoma tissue samples and cell lines. Silencing of special AT-rich sequence binding protein 1 inhibited the proliferation of KYSE450 and EC9706 cells which have a relatively high level of special AT-rich sequence binding protein 1, and the ability of migration and invasion of KYSE450 and EC9706 cells was distinctly suppressed. Special AT-rich sequence binding protein 1 could be a potential target for the treatment of esophageal squamous cell carcinoma and inhibition of special AT-rich sequence binding protein 1 may provide a new strategy for the prevention of esophageal squamous cell carcinoma invasion and metastasis.

Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT.

MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of the present study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently in vitro and in vivo Histological and immunohistological examinations were performed to evaluate the inhibitory effects and mechanism of Ad-TuD-21 delivery into carbon tetrachloride (CCl4) induced hepatic fibrosis rats by targeting extracellular signal-regulated kinase 1 (ERK1) signalling in hepatic stellate cells (HSC) and hepatocyte epithelial-mesenchymal transition (EMT). Our results revealed that enhanced miR-21 levels in cirrhotic patients were related to the severity and activity of liver cirrhosis. Ad-TuD-21 administered to liver fibrosis rats could remarkably suppress profibrotic gene expression, cause histological improvements in liver and attenuate hepatic fibrosis significantly. More importantly, after Ad-TuD-21 treatment, inhibition of both the ERK1 signalling pathway in HSC and hepatocyte EMT was confirmed, which paralleled the enhancement of miR-21 target genes-sprouty2 (SPRY2) and hepatocyte nuclear factor 4α (HNF4α)-expression in vivo These data demonstrated that miR-21 is a key regulator to promote hepatic fibrogenesis, and sponging miR-21 expression may present a novel potentially therapeutic option for hepatic fibrosis.

Motility characteristics in the transition zone in Gastroesophageal Reflux Disease (GORD) patients.

BACKGROUND: Defects in distal oesophageal peristalsis was thought to be an indication of incomplete bolus transit (BT). However, the role of transition zone (TZ) defects in the BT in gastroesophageal reflux disease (GORD) patients needs clarification. The aim of this study was to assess the TZ defects in GORD patients and to explore the relationship between TZ defects and BT. METHODS: One hundred and two patients with reflux symptoms and 20 healthy adults were included in the study. All subjects underwent upper gastrointestinal endoscopy, high resolution impedance manometry (HRiM) and 24-h ambulatory multichannel impedance-pH (MII-pH) monitoring. Patients were subgrouped into reflux oesophagitis (RE), non-erosive reflux disease (NERD), hypersensitive oesophagus (HO) and functional heartburn (FH) classified following MII-pH monitoring. Oesophageal pressure topography was analysed to define TZ defects by spatial or temporal TZ measurements exceeding 2 cm or 1 s, weak and fragmented swallows were excluded, and the association between TZ and BT was investigated. RESULTS: Following liquid swallows, there were no significant differences in TZ delay time and TZ length between groups (RE: 1.75 s (1.32-2.17) and 2.50 cm (2.40-3.20); NERD: 1.60 s (1.10-2.00) and 2.20 cm (2.10-2.65); HO: 1.60 s (1.30-1.80) and 2.70 cm (2.30-3.00); FH: 1.55 s (1.20-2.17) and 3.10 cm (2.25-5.00); Healthy volunteers: 1.50 s (1.20-1.90) and 2.30 cm (2.10-3.00). However, individuals with TZ defects had lower complete BT rates compared with those without TZ defects (p < 0.001). There were also significantly more incomplete BT in patients with RE, HO and FH than in healthy controls (p < 0.05). CONCLUSIONS: In GORD patients, TZ defects correlated with proximal bolus retention in the corresponding area independent of distal weak peristalsis.