The genetic and clinical characteristics and effects of Canakinumab on cryopyrin-associated periodic syndrome: a large pediatric cohort study from China.

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10-20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.

Upconversion Nanoparticle-Based Fluorescent Film for Distributed Temperature Monitoring of Mobile Phones' Integrated Chips.

As one of the most critical parameters to evaluate the quality and performance of mobile phones, real-time temperature monitoring of mobile phones' integrated chips is vital in the electronics industry. Although several different strategies for the measurement of chips' surface temperature have been proposed in recent years, distributed temperature monitoring with high spatial resolution is still a hot issue with an urgent need to be solved. In this work, a fluorescent film material with photothermal properties containing thermosensitive upconversion nanoparticles (UCNPs) and polydimethylsiloxane (PDMS) is fabricated for the monitoring of the chips' surface temperature. The presented fluorescent films have thicknesses ranging from 23 to 90 µm and are both flexible and elastic. Using the fluorescence intensity ratio (FIR) technique, the temperature-sensing properties of these fluorescent films are investigated. The maximum sensitivity of the fluorescent film was measured to be 1.43% K-1 at 299 K. By testing the temperature at different positions of the optical film, distributed temperature monitoring with a high spatial resolution down to 10 µm on the chip surface was successfully achieved. It is worth mentioning that the film maintained stable performance even under pull stretching up to 100%. The correctness of the method is verified by taking infrared images of the chip surface with an infrared camera. These results demonstrate that the as-prepared optical film is a promising anti-deformation material for monitoring temperature with high spatial resolution on-chip surfaces.

Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review.

BACKGROUND: Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the paternal GNAS gene. Herein, we report a case of POH caused by a novel mutation in exon 2 of the GNAS gene. CASE PRESENTATION: A 5-year-old Chinese boy was referred to our hospital for a growing mass in his right foot. Although laboratory findings were normal, radiographic imaging revealed severe ossification in his right foot and smaller areas of intramuscular ossification in his arms and legs. A de novo mutation (c.175C > T, p.Q59X) in exon 2 of the GNAS gene was identified, prompting a diagnosis of POH. We conducted a systematic literature review to better understand this rare disease. CONCLUSION: We have discovered that a de novo nonsense mutation in exon 2 of GNAS can lead to POH. Our literature review revealed that ankylosis of the extremities is the primary clinical outcome in patients with POH. Unlike other conditions such as fibrodysplasia ossificans progressiva (FOP), patients with POH do not experience respiratory failure. However, much remains to be learned about the relationship between the type of GNAS gene mutation and the resulting POH symptoms. Further research is needed to understand this complex and rare disease. This case adds to our current understanding of POH and will contribute to future studies and treatments.

Antidiabetic activity of Armillaria mellea polysaccharides: Joint ultrasonic and enzyme assisted extraction.

Armillaria mellea polysaccharides (AMPs) were obtained by ultrasonic assisted extraction (U), enzyme assisted extraction (E) and ultrasonic-enzyme assisted extraction (UE), respectively. The yield of UE-AMPs (6.32 ± 0.14%) was 1.64 times higher than that of U-AMPs (3.86 ± 0.11%) and 1.21 times higher than that of E-AMPs (5.21 ± 0.09%); meanwhile, the highest total sugar content and the lowest protein content were found in UE-AMPs. AMPs obtained from the three extraction methods had the same monosaccharide composition but in different proportions, allowing UE-AMPs to have the most potent antioxidant activity. The antidiabetic activity of UE-AMPs was investigated in streptozotocin (STZ)-induced diabetic mice. UE-AMPs, when given by gavage, greatly prevented weight loss, increased water intake, and considerably decreased blood glucose levels in diabetic mice, which were dose-dependent (P < 0.05). In addition, UE-AMPs also had a positive effect on the reduction of lipid levels in the blood, oxidative damage and liver function impairment. The pathological observation by hematoxylin-eosin staining (HE) revealed that UE-AMPs protected the organs of mice from diabetic complications (liver disease and nephropathy). Hence, our findings demonstrate that UE-AMPs are a suitable choice for improving diabetes and its complications and have great application prospects in the fields of natural medicine and functional food.

Fabrication of bilayer emulsion by ultrasonic emulsification: Effects of chitosan on the interfacial stability of emulsion.

In this study, the stable system of bilayer emulsion was fabricated by ultrasonic emulsification. The effect of chitosan (CS) addition (0.05 %-0.4 %, w/v) at pH 5.0 on the stability of rice bran protein hydrolysate-ferulic acid (RBPH-FA) monolayer emulsion was investigated. It was found that the addition of CS (0.3 %) could form a stable bilayer emulsion. The droplet size was 3.38 µm and the absolute ζ-potential value was 31.52 mV. The bilayer emulsion had better storage stability, oxidation stability and environmental stabilities than the monolayer emulsion. The results of in vitro simulations revealed the bilayer emulsion was able to deliver the ß-carotene to the small intestine digestive stage stably and the bioaccessibility was increased from 22.34 % to 61.36 % compared with the monolayer emulsion. The research confirmed that the bilayer emulsion prepared by ultrasonic emulsification can be used for the delivery of hydrophobic functional component ß-carotene.

Preparing Thick Gradient Surface Layer in Cu-Zn Alloy via Ultrasonic Severe Surface Rolling for Strength-Ductility Balance.

A gradient structure (GS) design is a prominent strategy for strength-ductility balance in metallic materials, including Cu alloys. However, producing a thick GS surface layer without surface damage is still a challenging task limited by the available processing technology. In this work, a gradient structure (GS) surface layer with a thickness at the millimeter scale is produced in the Cu-38 wt.% Zn alloy using ultrasonic severe surface rolling technology at room temperature. The GS surface layer is as thick as 1.1 mm and involves the gradient distribution of grain size and dislocation density. The grain size is refined to 153.5 nm in the topmost surface layer and gradually increases with increasing depth. Tensile tests indicate that the single-sided USSR processed alloy exhibits balanced strength (467.5 MPa in yield strength) and ductility (10.7% in uniform elongation). Tailoring the volume fraction of the GS surface layer can tune the combination of strength and ductility in a certain range. The high strength of GS surface layer mainly stems from the high density of grain boundaries, dislocations and dislocation structures, deformation twins, and GS-induced synergistic strengthening effect. Our study elucidates the effect of the thick GS surface layer on strength and ductility, and provides a novel pathway for optimizing the strength-ductility combination of Cu alloys.

High-Temperature Oxidation Behavior of a Cu-Bearing 17Cr Ferritic Stainless Steel.

The isothermal oxidation behavior of 17Cr-0.85Si-0.5Nb-1.2Cu ferritic stainless steel in air was studied from 850°C to 1050°C by analyzing its weight gain after oxidation. The kinetic curves were plotted using the oxidation weight-gain data, and the structure, surface morphology, and element distribution of the oxide films were analyzed by XRD, SEM, and EDS. The results showed that the oxidation kinetics curves at 850°C and 950°C followed a parabolic law, and a continuous and dense oxide film composed of Cr2O3 and MnCr2O4, FeCr2O4, and Cu-Cr rich spinel was formed, which reveals that the steel displayed good oxidation resistance. When the temperature was increased to 1050°C, the oxidation kinetics curves gradually changed from parabolic to linear after 40 h exposure, which indicated that the oxidation resistance significantly worsened. A lower oxidation resistance was observed at 1050°C due to the formation of a large amount of Fe2O3 on the surface and the volatilization of the inner Cr2O3 layer.

Improved Corrosion Resistance of Magnesium Alloy in Simulated Concrete Pore Solution by Hydrothermal Treatment.

Magnesium alloys are considered for building materials in this study due to their natural immunity to corrosion in alkaline concrete pore solution. But, chloride ions attack often hinders the application of most metals. Therefore, it is necessary to conduct a preliminary corrosion evaluation and attempt to find an effective way to resist the attack of chloride ions in concrete pore solution. In our study, hydrothermal treatment is carried out to modify Mg-9.3 wt. % Al alloy. After the treatment in NaOH solution for 10 h, scanning electron microscopy (SEM) reveals that a layer of dense coating with a thickness of about 5 µm is formed on Mg alloy. Energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and X-ray Diffraction (XRD) are combined to analyze the coating, and it is thereby confirmed that the coating is mainly composed of Mg(OH)2. As expected, both immersion test and electrochemical corrosion test show that the coated magnesium alloy has a better corrosion resistance than the uncoated one in simulated concrete pore solution with and without chloride ions. In summary, it indicates that hydrothermal treatment is a feasible method to improve the corrosion resistance of Mg alloys used for building engineering from the perspective of corrosion science.

Wear Behavior of the Multiheterostructured AZ91 Mg Alloy Prepared by ECAP and Aging.

The microstructure design based on the development of heterostructure provides a new way for high strength and ductility Mg alloys. However, the wear property, as an important service performance, of Mg alloys with heterostructure is scarcely investigated. In this work, a high strength and ductility AZ91 Mg alloy with multiheterostructure was prepared via a processing route combined industrial-scale equal channel angular pressing (ECAP) and aging. The multiheterostructure consists of the heterogeneous grain structure and heterogeneous precipitates. The dry sliding wear behavior of this multiheterostructured (MH) alloy is investigated compared to the as-cast alloy. The impacts of the applied load and duration time on the wear volume and coefficient of friction (COF) are analyzed, and the wear mechanism is further discussed. The result indicates that although the MH alloy exhibits high-desirable strength-ductility synergy, it shows a poorer wear resistance but a relatively lower COF compared to the as-cast alloy at the present condition. The wear mechanism of both alloys mainly involves abrasive wear, as well as mild adhesion, delamination, and oxidation. In comparison, the MH alloy shows relatively severe adhesion, delamination, and oxidation. The poor wear resistance of the MH alloy at the present dry sliding wear condition is linked to the abundant grain boundaries and fine precipitates. Therefore, one should reasonably use the MH Mg alloy considering the service conditions to seek advantages and avoid disadvantages.

Reveal the Deformation Mechanism of (110) Silicon from Cryogenic Temperature to Elevated Temperature by Molecular Dynamics Simulation.

Silicon undergoes a brittle-to-ductile transition as its characteristic dimension reduces from macroscale to nanoscale. The thorough understanding of the plastic deformation mechanism of silicon at the nanoscale is still challenging, although it is essential for developing Si-based micro/nanoelectromechanical systems (MEMS/NEMS). Given the wide application of silicon in extreme conditions, it is, therefore, highly desirable to reveal the nanomechanical behavior of silicon from cryogenic temperature to elevated temperature. In this paper, large-scale molecular dynamics (MD) simulations were performed to reveal the spherical nanoindentation response and plastic deformation mechanism of (110)Si at the temperature range of 0.5 K to 573 K. Special attention was paid to the effect of temperature. Multiple pop-ins detected in load/pressure-indentation strain curves are impacted by temperature. Four featured structures induced by nanoindentation, including high-pressure phases, extrusion of α-Si, dislocations, and crack, are observed at all temperatures, consistent with experiment results. The detailed structure evolution of silicon was revealed at the atomic scale and its dependence on temperature was analyzed. Furthermore, structure changes were correlated with pop-ins in load/pressure-indentation strain curves. These results may advance our understanding of the mechanical properties of silicon.

Promoted Anodizing Reaction and Enhanced Coating Performance of Al-11Si Alloy: The Role of an Equal-Channel-Angular-Pressed Substrate.

In this paper, the effect of the equal-channel-angular-pressed (ECAPed) substrate on the coating formation and anticorrosion performance of the anodized Al-11Si alloy was systematically investigated. The ECAP process dramatically refines both Al and Si phases of the alloy. The parallel anodizing circuit is designed to enable a comparative study of anodizing process between the cast and the ECAPed alloys by tracking their respective anodizing current quota. The optimum coatings of both alloys were obtained after anodization for 30 min. The ECAPed alloy attained a thicker, more compact, and more uniform coating. Energetic crystal defects in the fine Al grains of the ECAPed substrate promote the anodizing reaction and lead to the thicker coating. Fragmented and uniformly distributed fine Si particles in the ECAPed alloy effectively suppress the coating cracks, enhancing the compactness of the coating. Overall, the ECAP-coated sample exhibits the best anticorrosion performance, which is evidenced by the concurrently enhanced prevention of coating and improved corrosion resistance of the substrate.

Coupling Effect of Porosity and Cell Size on the Deformation Behavior of Al Alloy Foam under Quasi-Static Compression.

Closed-cell AlCu5Mn alloy foam with porosity range of ~45⁻90% were fabricated by the melt-foaming route. The pore structure of the fabricated Al alloy foam was analyzed and the coupling effect of porosity and cell size on the quasi-static compression behavior of the foam was investigated. The results show that the cell size of the foam decreases with the porosity decline from the view of the contribution rate to the porosity and the hierarchical pore structure characteristics becomes obvious when the foam porosity is low; the compression stress⁻strain curves of the foams with high porosity (>74%) are serrated due to the large cell size being easy to deform and more strain needed to let the stress recover. Meanwhile, the compression curve of the foams with low porosity (<74%) are smooth without serration, which is attributed to the hierarchical pore structure and less strain needed to let the stress recovery.

AluYb8 insertion polymorphism in the MUTYH gene impairs mitochondrial DNA maintenance and affects the age of onset of IPF.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with an unknown etiology. Increased oxidative stress and mitochondrial dysfunction are thought to be involved in its pathogenesis. However, the effect of the AluYb8MUTYH polymorphism on IPF is not known. RESULTS: The mean age of onset for IPF in patients homozygous for the AluYb8MUTYH variant (P/P) was 66.5 years old, which was significantly earlier than that in patients with the wild-type (A/A, 70.45 years old). For the 97 male IPF patients with lung function data, the FVC% of the P/P patients was lower than that of the wild-type (A/A) or heterozygous (A/P) patients. The laboratory analysis indicated that an increased mtDNA content and impaired mitochondrial quality control were associated with the P/P genotype. We also confirmed that AluYb8 insertion into MUTYH caused decreased MUTYH1 expression in lung tissues. METHODS: We compared the lung function of IPF patients and observed the mtDNA content, mtDNA integrity and molecular expression of mitochondrial quality control among subjects with different AluYb8MUTYH genotypes. Additionally, immunoblotting and a reporter gene system were used to test whether altered mitochondrial MUTYH1 expression was linked to AluYb8MUTYH. CONCLUSIONS: The AluYb8 insertion polymorphism in MUTYH impairs mtDNA stability and affects the age of onset of IPF.

Microarray expression profile of circular RNAs and mRNAs in children with systemic lupus erythematosus.

BACKGROUND: Recently, it was reported that circular RNAs (circRNAs) play the crucial role in many physiological and biological processes and can be used as biomarkers. However, the information about circRNAs in children with systemic lupus erythematosus (SLE) is limited. The aim of this study is to determine the expression of circRNAs in children with SLE and investigate the significance of circRNA for diagnosing SLE. METHODS: Microarray profile of circRNAs and mRNAs was performed for identifying the changes in expression of circRNAs and mRNAs between children with SLE and healthy children. Quantitative polymerase chain reaction (qPCR) was used to confirm the results. Spearman correlation test was performed to assess the correlation between circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value. RESULTS: A comparison between the children with SLE and healthy children revealed that 348 circRNAs and 1162 mRNAs were expressed differentially. The authors constructed a complex circRNA target network consisting of 307 matched circRNA-mRNA pairs for 124 differentially expressed circRNAs (74 circRNAs were upregulated, and 50 circRNAs were downregulated) and 142 differentially expressed mRNAs (83 mRNAs were upregulated, and 59 mRNAs were downregulated) by using gene co-expression network analysis. The competing for endogenous RNA (ceRNA) network includes 42 differentially expressed circRNAs, 41 differentially expressed mRNAs, and 71 predicted miRNAs. Among these SLE patients, we detected that the hsa_circ_0021372 and hsa_circ_0075699 levels are associated with C3 and C4 levels in children with SLE. The hsa_circ_0057762 level is positively associated with the SLEDAI-2K score. The ROC curves of circRNAs showed that the levels of hsa_circ_0057762 (AUC 0.804, 95% CI 0.607-1.0, P = 0.02) and hsa_circ_0003090 (AUC 0.848, 95% CI 0.688-1.0, P = 0.008) could differentiate the patients with SLE from the healthy controls. CONCLUSIONS: We firstly characterized the expression profiles of circRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insight into the mechanisms of SLE pathogenesis, and circRNAs may serve as useful biomarkers for SLE.

Expression profile of long noncoding RNAs in children with systemic lupus erythematosus: a microarray analysis.

OBJECTIVES: Long noncoding RNAs (lncRNAs) are reported to play crucial roles in several physiological and biological processes. However, knowledge of lncRNAs in children with systemic lupus erythematosus (cSLE) remains limited. We investigate lncRNA expression profiling of cSLE and explore the potential function of lncRNAs. METHODS: LncRNA and mRNA microarrays were performed to identify changes in lncRNA and mRNA expression between children with SLE and paired healthy children. Quantitative polymerase chain reaction (qPCR) validated these results. A Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the potential lncRNA function. RESULTS: A comparison between children with SLE and paired healthy children revealed that 1042 lncRNAs and 1162 mRNAs were differentially expressed. By using gene co-expression network analysis, we constructed a complex lncRNA target network consisting of 817 matched lncRNA-mRNA pairs for 309 differentially expressed lncRNAs and 210 differentially expressed mRNAs. The results of further GO and KEGG pathway analyses indicated that lncRNAs were involved mainly in pathways with crucial pathobiological relevance in SLE. CONCLUSIONS: We firstly characterised the expression profiles of lncRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insights into the mechanisms of SLE pathogenesis and may serve as diagnostic biomarkers for SLE therapy.

Development of High-Performance Enamel Coating on Grey Iron by Low-Temperature Sintering.

In this study, we report on a low-temperature sintered enamel coating with a high-strength bonding and wear-resistance that protected a grey cast iron substrate. The SiO2⁻Al2O3⁻B2O3 composited prescription for the enamel coating was modified by the partial substitutions of SiO2 for B2O3 and alkali metals for Li2O. The optimized enamel coating was prepared by sintering at a relatively low temperature (730 °C) for seven minutes. Due to the composition of both the amorphous and crystalline phases, the enamel coating presented sufficient hardness and excellent wear resistance. The wear volume loss and the specific wear rate of the enamel coating were obviously lower than that of the metal substrate. The enamel coating can effectively improve the service life of the grey cast iron substrate in a complex frictional environment.

Rebuilding the Strain Hardening at a Large Strain in Twinned Au Nanowires.

Metallic nanowires usually exhibit ultrahigh strength but low tensile ductility, owing to their limited strain hardening capability. Here, our larger scale molecular dynamics simulations demonstrated that we could rebuild the highly desirable strain hardening behavior at a large strain (0.21 to 0.31) in twinned Au nanowires by changing twin orientation, which strongly contrasts with the strain hardening at the incipient plastic deformation in low stacking-fault energy metals nanowires. Because of this strain hardening, an improved ductility is achieved. With the change of twin orientation, a competing effect between partial dislocation propagation and twin migration is observed in nanowires with slant twin boundaries. When twin migration gains the upper hand, the strain hardening occurs. Otherwise, the strain softening occurs. As the twin orientation increases from 0° to 90°, the dominating deformation mechanism shifts from slip-twin boundary interaction to dislocation slip, twin migration, and slip transmission in sequence. Our work could not only deepen our understanding of the mechanical behavior and deformation mechanism of twinned Au nanowires, but also provide new insights into enhancing the strength and ductility of nanowires by engineering the nanoscale twins.

The differential effects of microcystin-LR on mitochondrial DNA in the hippocampus and cerebral cortex.

Microcystin-LR (MC-LR) is the most abundant toxicant among microcystin variants produced by cyanobacteria. MC-induced toxicity is broadly reported to pose a threat to aquatic animals and humans and has been associated with the dysfunction of some organs such as liver and kidney. However, MC-induced neurotoxicity has not been well characterized after long-term exposure. This study was designed to investigate the neurotoxic effects after chronic oral administration of MC-LR. In our trial, C57/BL6 mice received MC-LR at 0, 1, 5, 10, 20 and 40 µg/L in drinking water for twelve months. Our data demonstrated that mitochondrial DNA (mtDNA) damage was evident in the damaged neurons as a result of chronic exposure. Histopathological abnormalities and mtDNA damage were observed in the hippocampus and cerebral cortex. Furthermore, MC-LR exerted distinct effects on these two brain regions. The hippocampus was more susceptible to the treatment of MC-LR compared with the cerebral cortex. However, no strong relationships were observed between the genotoxic effects and exposure doses. In conclusion, this study has provided a mtDNA-related mechanism for underlying chronic neurotoxicity of MC-LR and suggested the presence of differential toxicant effects on the hippocampus and cerebral cortex.

Nanoindentation and deformation behaviors of silicon covered with amorphous SiO2: a molecular dynamic study.

A fundamental understanding of the mechanical properties and deformation behaviors of surface modified silicon during chemical mechanical polishing (CMP) processes is difficult to obtain at the nanometer scale. In this research, MD simulations of monocrystalline silicon covered with an amorphous SiO2 film with different thickness are implemented by nanoindentation, and it is found that both the indentation modulus and hardness increase with the growing indentation depth owning to the strongly silicon substrate effect. At the same indentation depth, the indentation modulus decreases shapely with the increase of film thickness because of less substrate influence, while the hardness agrees well with the trend of modulus at shallow depth but mismatches at larger indentation depth. The observed SiO2 film deformation consists of densification and thinning along indentation direction and extension in the deformed area due to the rotation and deformation of massive SiO4 tetrahedra. The SiO2 film plays an important role in the onset and development of silicon phase transformation. The thinner the SiO2 film is, the earlier the silicon phase transformation takes place. So the numbers of phase transformation atoms increase with the decrease of SiO2 film thickness at the same indentation depth. It is suggested that the thicker film should be better during CMP process for higher material removal rate and less defects within silicon substrate.