Effect of Calcination Temperature on the Microstructure, Composition and Properties of Agglomerated Nanometer CeO2-Y2O3-ZrO2 Powders for Plasma Spray-Physical Vapor Deposition (PS-PVD) and Coatings Thereof.

Self-made agglomerated nanometer CeO2-Y2O3-ZrO2 (CYSZ) powders for plasma spray-physical vapor deposition (PS-PVD) were prepared by spray-drying, followed by calcination treatment at four different temperatures (600 °C, 700 °C, 800 °C, 900 °C). The physical properties, microstructure, and phase composition of the calcined powders were investigated using a laser particle size analyzer, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results showed that compared to the agglomerated powders obtained through spray-drying, the particle size of the agglomerated powders changed with increasing calcination temperature, accompanied by an increase in the self-bonding force of the agglomerated powder particles. The proper calcination temperature improved the sprayability of the powders. Additionally, with the increase in the calcination temperature, a transformation from the m-phase to the t-phase occurred in the powder, with Ce4+ partially entering the Zr lattice to form the t-Zr0.84Ce0.16O2 phase, which facilitated the suppression of the m-phase and improved the high-temperature phase stability. It was also found that the PS-PVD coatings prepared using the aforementioned powders exhibited coarser columnar structures with increasing powder calcination temperature.

Expression Profile and Gene Regulation Network of NUSAP1 in Pan Cancers Based on Integrated Bioinformatics Analysis.

Background: Nucleolar and spindle-associated protein 1 (NUSAP1) plays key roles in microtubules and chromosomes in normal cells both structurally and functionally. In malignancies, NUSAP1 is frequently dysregulated and mutated. However, the expression profiles and biological functions of NUSAP1 in tumors remain unclear. Methods: NUSAP1 expression in BALB/c mice and human normal or tumor tissues was examined using immunohistochemistry. Kaplan-Meier survival analysis was utilized to assess the prognostic significance of NUSAP1 in tumors, and principal component analysis and co-expression analysis were performed to explore the unique roles of NUSAP1. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed with DAVID. The relevance between NUSAP1 and tumor-infiltrating immune cells was investigated using TIMER. A transcriptional regulation network was constructed using data from The Cancer Genome Atlas. Results: NUSAP1 expression levels in various mice tissues were different. Compared with normal tissues, NUSAP1 was strongly expressed in several human tumor tissues. We believe that NUSAP1 distinctly impacts the prognosis of several cancers and plays various roles in thymoma and testicular germ cell tumors. Further, NUSAP1 expression levels were significantly positively associated with diverse infiltrating levels of immune cells, including B cells, CD4+ and CD8+ T cells, dendritic cells, and macrophages, in thymoma. The expression level of NUSAP1 demonstrated strong relevance with various immune markers in thymoma. Finally, the miR-1236-5p-NUSAP1 and TCF3-NUSAP1 network revealed the tumor-promoting role of NUSAP1 and pertinent underlying mechanisms in human liver hepatocellular carcinoma. Conclusion: NUSAP1 may be regarded as a therapeutic target or potential prognostic biomarker for various cancer types.

Effect of Graphene Nanosheets on the Microstructure and Mechanical Properties of Sn-20Bi Solder.

The application of Sn-Bi series solder is limited due to the brittleness of Bi phase. Sn-20Bi solder with less Bi element content has great research prospects, but it needs modification to make it a substitute for traditional Sn-Pb solder. In this article, we mixed graphene nanosheets with nanometer Sn powder by means of ultrasonic oscillation, and Sn-20Bi-qGNS (q = 0.01, 0.02, 0.04, 0.06, and 0.1 wt.%) solder alloys were prepared by the melt-casting method. The effects of graphene nanosheets (GNSs) on the microstructure, physical properties, mechanical properties, and corrosion resistance of solder alloys were investigated. Scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy were used to determine the microstructural morphology and composition. The results showed that the melting point, density, and wettability of the solder decreased slightly with the addition of GNSs. The addition of GNSs as a second phase refined the solder structure and improved the tensile strength of the molten Sn-20Bi composite solder to 99.6 MPa, while elongation decreased with the addition of GNSs. Furthermore, GNSs prevented the MC Sn-20Bi-qGNSs/Cu intermetallic compound layers' growth by interfering with atomic diffusion and grain boundary movement. In addition, the addition of 0.02 wt.% GNSs enhanced the shear strength of MC Sn-20Bi solder joints to 46.3 MPa. The electrochemical experimental results show that the surface corrosion products of MC Sn-20Bi-qGNSs under 3.5% NaCl solution were Sn3O(OH)2Cl2, with MC Sn-20Bi-0.01GNSs exhibiting the best corrosion resistance.

LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response.

Background: Clinically, only a minority of patients benefit from immunotherapy and few efficient biomarkers have been identified to distinguish patients who would respond to immunotherapy. The tumor microenvironment (TME) is reported to contribute to immunotherapy response, but details remain unknown. We aimed to construct a prognostic model based on the TME of lung adenocarcinoma (LUAD) to predict the prognosis and immunotherapy efficacy. Methods: We integrated computational algorithms to describe the immune infiltrative landscape of LUAD patients. With the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses, we developed a LUAD tumor microenvironment prognostic signature (LATPS). Subsequently, the immune characteristics and the benefit of immunotherapy in LATPS-defined subgroups were analyzed. RNA sequencing of tumor samples from 28 lung cancer patients treated with anti-PD-1 therapy was conducted to verify the predictive value of the LATPS. Results: We constructed the LATPS grounded on four genes, including UBE2T, KRT6A, IRX2, and CD3D. The LATPS-low subgroup had a better overall survival (OS) and tended to have a hot immune phenotype, which was characterized by an elevated abundance of immune cell infiltration and increased activity of immune-related pathways. Additionally, tumor immune dysfunction and exclusion (TIDE) score was markedly decreased in the LATPS-low subgroup, indicating an enhanced opportunity to benefit from immunotherapy. Survival analysis in 28 advanced lung cancer patients treated with an anti-PD-1 regimen at Nanfang hospital revealed that the LATPS-low subgroup had better immunotherapy benefit. Conclusion: LATPS is an effective predictor to distinguish survival, immune characteristics, and immunotherapy benefit in LUAD patients.

Microstructure, Mechanical and Electrical Properties of Hybrid Copper Matrix Composites with Fe Microspheres and rGO Nanosheets.

Copper matrix composites have a wide application as magnetic conductive materials, electromagnetic materials, electrical discharge machining materials, etc. Such materials are expected to have a good combination of excellent electrical conductivity and good mechanical strength. In this work, micro/nano hybrid reinforcements with Fe microspheres and reduced graphene oxide (rGO) nanosheets were developed for copper matrix composites. The rGO/Fe/Cu powders were firstly wet-mixed and then densified by the vacuum hot-pressing sintering to obtain the bulk compacts. Microstructure, electrical conductivity and mechanical properties of such compacts were investigated. Microstructural result of as-sintered compacts shows that the Fe microspheres could distribute in the matrix uniformly, and rGO nanosheets exhibit both agglomerated and dispersed states. The grain size of Cu matrix decreased with the increase of the rGO content. Hardness, compression and tensile 0.2% yield strength of the as-sintered compacts were improved evidently by the addition of the hybrid Fe/rGO, comparing with pure Cu and single Fe-added composites. However, a lower electrical conductivity appeared in the more rGO-added composites, but still reached more than 33.0% international annealing copper standard (IACS). These performance change could be sought in the spatially geometrical distribution and characteristics of such micro/nano Fe/rGO hybrid addition, and the relevant mechanisms were discussed.

The Stability and Electronic Structure of Cu(200)/AuCu(200) Interface: An Insight from First-Principle Calculation.

AuCu phase had a significant effect on the bonding strength of Au80Sn20 alloy and Cu substrate. The formation of the AuCu(200)/Cu(200) interface significantly improves the shear strength of solder joints. Therefore, it is particularly important to analyze the strengthening mechanism of the AuCu phase in the Cu matrix. The atomic structure, interfacial stability, and interfacial bonding properties of the Cu(200)/AuCu(200) interface were investigated using first-principle calculation. The layer spacing convergence results show that seven layers of Cu(200) surface and seven layers of AuCu(200) surface are enough thick to be chosen for the interface model. The calculation shows that the surface energies are 1.463 J/m2 and 1.081 J/m2 for AuCu(200) surface and Cu(200) surface, respectively. Four interface combinations of Top sit, Long bridge, Short bridge, and Hollow were investigated by considering four stacking methods of AuCu(200). It is shown that the interfacial configuration of the Long bridge is the most stable and favorable structure, which has the largest adhesion work, the smallest interfacial energy, and the smallest interfacial spacing. The density of states and electron difference density were calculated for the four interfacial configurations, and the results showed that the main bonding mode of the Long bridge interface is composed of both Cu-Cu covalent bonds and Au-Cu covalent bonds.

Designing highly efficient 3D porous Ni-Fe sulfide nanosheets based catalyst for the overall water splitting through component regulation.

Constructing efficient and stable bifunctional catalysts is essential to improve the conversion efficiency of overall water splitting (OWS). In this work, 3D porous Ni-Fe sulfide nanosheets supported on nickel foam (Ni-Fe-S/NF) were synthesized by a facile hydrothermal method. The optimized Ni3S2-FeS/NF-2 electrode realized ultra-high efficiency for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Benefiting from the unique 3D porous nanosheets structure and the strong electronic interactions between Ni3S2 and FeS through component regulation, low overpotentials of 253 and 262 mV are required to drive a current density of 100 mA cm-2 for OER and HER, respectively. Importantly, Ni3S2-FeS/NF-2 bifunctional catalyst only needs 1.55 and 1.75 V at 10 and 100 mA cm-2 respectively and works continuously for at least 100 h. The work thus provides an extraordinary promising catalyst for OWS and can be envisioned of potential for large-scale applications.

Effect of Aging Treatment on the Corrosion Resistance Properties of 7N01 Extrusion Aluminum Alloy.

The influences of non-isothermal aging (the temperature range is 150-180 °C, and the heating rate is 5 and 20 °C/h alternately), single-peak aging (aging at 120 °C for 24 h, then water quenched was followed at room temperature), and two-stage aging (aging at 105 °C for 8 h first, then increasing aging temperature to 135 °C and keeping for 12 h, followed by water quenching at room temperature) on the corrosion resistance and microstructure of the 7N01 aluminum alloy under 3.5 wt.% NaCl were investigated using electric polarization curve test and exfoliation corrosion. After aging, the hardness of samples was measured by a Vickers micro-hardness tester, and the electrical conductivities were obtained using the eddy current method. The results show that the steady phase η and metastable phase η' are precipitated in the grain boundary of 7N01 aluminum alloy after non-isothermal aging, and their distribution is discontinuous. The hardness of the alloy can reach 136.9 HV1 and the electrical conductivity can reach 35.8% IACS, which is close to the hardness of single-peak aging and the conductivity of two-stage aging, respectively. Compared with single-peak aging, the corrosion current density of non-isothermal aging is reduced by 15.5%, and that of two-stage aging is reduced by 28.9%.

Effects of Yttrium Addition on the Microstructure Evolution and Electrochemical Corrosion of SN-9Zn Lead-Free Solders Alloy.

Electrochemical corrosion behavior of ternary tin-zinc-yttrium (Sn-9Zn-xY) solder alloys were investigated in aerated 3.5 wt.% NaCl solution using potentiodynamic polarization techniques, and the microstructure evolution was obtained by scanning electron microscope (SEM). Eight different compositions of Sn-9Zn-xY (x = 0, 0.02, 0.04, 0.06, 0.08, 0.10, 0.20, and 0.30 wt.%) were compared by melting. The experimental results show that when the content of Y reached 0.06 wt.%, the grain size of Zn-rich phase became the smallest and the effect of grain refinement was the best, but there was no significant effect on the melting point. With the increases of Y content, the spreading ratio first increased and then decreased. When the content of Y was 0.06 wt.%, the Sn-9Zn-0.06Y solder alloy had the best wettability on the Cu substrate, which was increased by approximately 20% compared with Sn-9Zn. Besides, the electrochemical corrosion experimental shows that the Y can improve the corrosion resistance of Sn-9Zn system in 3.5 wt.% NaCl solution, and the corrosion resistance of the alloy is better when the amount of Y added is larger within 0.02-0.30 wt.%. Overall considering all performances, the optimal performance can be obtained when the addition amount of Y is 0.06.

Effect of Graphene Nanosheet Addition on the Wettability and Mechanical Properties of Sn-20Bi-xGNS/Cu Solder Joints.

Graphene nanosheets (GNSs) have an extensive application in materials modification. In this study, the effects of graphene nanosheets on the wettability of Sn-20Bi lead-free solder on copper (Cu) substrate and the growth behavior of intermetallic compound (IMC) layers at Sn-20Bi-xGNS/Cu solder joints were investigated. The experimental results indicate that the wettability of Sn-20Bi solder firstly diminished and then increased by the addition of GNSs. Meanwhile, a prism-shaped and scallop-shaped Cu6Sn5 IMC layer was clearly observed at the interface of the solder/substrate system. Moreover, it was found that a small amount of GNS addition can significantly inhibit the growth of the IMC layer at the interface as well as refine the microstructure. Additionally, by nano-indentation apparatus, it can be concluded that the hardness and elastic module of IMCs show the same variation trend, which firstly decreased and then increased. Besides, to intuitively demonstrate the reliability of IMCs, the relationship between the hardness and elastic module was established, and the ratio of hardness/elastic module (H/E) was adopted to characterize the reliability of IMCs. The results show that when the addition of GNSs was 0.02 wt%, the value of H/E is the minimum and the solder joint has the highest reliability.

New Zr-25Ti-xMo alloys for dental implant application: Properties characterization and surface analysis.

A series of Zr-25Ti-xMo (x = 0, 2.5, 5, 7.5, 10 and 12.5 wt %) as-cast alloys were designed to advance a new-brand Zr-based alloy with low Young's elastic, moderate compression strength, superior corrosion resistance and good wear behavior for the application of dental implant materials. In the present study, the microstructures of the alloys were evaluated by X-ray diffraction, scanning electron microscopy and X-ray photoelectron spectroscopy. The microhardness and uniaxial compression measurement were performed to evaluate the mechanical properties of the alloys. The electrochemical behaviors of the alloys was investigated in artificial saliva solution. The friction and wear performances of the Zr-25Ti-xMo alloys were examined by pin-on-disk under the load of 15 N. The results shows that the crystalline structure transforms from hexagonal close-pack (α phase, x = 0 wt %) to body-centered cubic structure (ß phase, 5 ≤ x ≤ 12.5 wt %) through a α + ß dual-phase region (x = 2.5 wt %). They exhibits excellent mechanical properties with low elastic modulus (from 17.7 to 24.4 GPa) and moderate compression strength (from 1154.4 to 1310.8 MPa). The Zr-25Ti-xMo alloys possess good corrosion resistance due to the formation of a protective passive film consisting mainly of ZrO2, TiO2 and minor MoO3. Especially, the polarization curves demonstrates that the Zr-25Ti-7.5Mo alloy has a wider passive region than the other five alloys and it possesses the lower corrosion current density and corrosion rate. Furthermore, this alloy exhibits good abrasion resistance with the lowest coefficients of friction and volume wear loss. Thus, the Zr-25Ti-7.5Mo alloy has a combination of excellent mechanical properties such as low elastic modulus, moderate yield strength and the compression strength, good electrochemical stability and well wear resistance, it is considered a promising candidate for orthopedic materials as dental implant.

Characterization of CT scans of patients with Birt-Hogg-Dubé syndrome compared with those of Chinese patients with non-BHD diffuse cyst lung diseases.

BACKGROUND AND OBJECTIVE: The purpose of this study was to create a practical CT-based algorithm to differentiate Birt-Hogg-Dubé (BHD) syndrome from other diffuse cystic lung diseases (DCLD). METHODS: The study was a retrospective review of the CT images of 33 patients with BHD syndrome, 33 patients with LAM, and 23 patients with NBNL (non-BHD and non-LAM) among DCLD patients. On the basis of the data collected, the CT images were reviewed again to evaluate the characteristics (size, number, distribution, and morphology) of pulmonary cysts. RESULTS: Lower lung-predominant cysts were more likely to be found in patients with BHD syndrome than in patients with LAM or in the NBNL DCLD group. In the axial distribution, 18 of 33 patients in BHD group had cysts that were predominantly near the mediastinum, and all the patients in the LAM and NBNL DCLD groups had diffuse cysts. The appearance of fusiform cysts was more easily observed in patients in the BHD group. In total, 58% patients in the BHD group had less than 50 lung cysts, while all patients in the non-BHD group had more than 50 lung cysts. The biggest cyst was located in the lower lobe in 28 of 33 patients in the BHD group, while 11 of 33 patients in LAM group and 10 patients in the NBNL DCLD group had the biggest cyst in the lower lobe. CONCLUSION: The pulmonary cysts in patients with BHD tended to be fusiform, less numerous and located predominantly in the lower lobe and near the mediastinum. These radiologic pulmonary features could assist physicians in differentiating BHD from other DCLDs.

CircRNA_103762 promotes multidrug resistance in NSCLC by targeting DNA damage inducible transcript 3 (CHOP).

BACKGROUND: CircRNAs have been found to play crucial roles in multiple tumor including non-small cell lung cancer (NSCLC). Here, we researched the correlation between circRNA_103762 and chemotherapy resistance. METHODS: RT-PCR assay was performed to detect circRNA_103762 and DNA damage inducible transcript 3 (CHOP) expression. CCK8 assay was performed to examine cell proliferation and IC50 of different drug. Migration and invasion assay was used to detect cell migration and invasion. RESULTS: In our study, circRNA_103762 expression was upregulated in NSCLC tissues and cell. Knockdown of circRNA_103762 can inhibited cell proliferation, migration and invasion in NSCLC. In addition, downregulation of circRNA_103762 promoted CHOP expression and inhibited multidrug resistance (MDR) in NSCLC. CONCLUSION: Together, we demonstrated that circRNA_103762 is upregulated in NSCLC and functions as an oncogene in NSCLC, and circRNA_103762 enhanced MDR by inhibited CHOP expression in NSCLC cells. These results will help us understand the MDR of NSCLC, providing better effective therapy strategies for patients.

The Effect of Rare Earths Additions on the Microstructure and the Corrosion Behavior of Sn-0.7Cu-0.075Al Solder Alloy.

Sn-0.7Cu-0.075Al solder alloy adding with Ce and La had been successfully prepared by applying ball-milling and vacuum arc remelting. The influence of Ce and La on microstructure and corrosion behavior of Sn-0.7Cu-0.075Al solder alloy was investigated. The results showed that Ce (La)-containing solders had refined grains and obvious directional tendency due to the dispersive refiner (CeO2 and La2O3). Electrochemical potentiodynamic curves revealed three different stages of the reaction, including anodic and cathodic processes, prepassivation section, and stable passivation stages. The self-corrosion potential (Ecorr) of alloys with Ce and La addition were a little bit more negative, hardly making a difference on corrosion occurrence. However, the corrosion current density (Icorr) and passivation current density (Ip) decreased by two-thirds and one-half respectively, which indicated a better corrosion resistant after adding rare earths. The recorded micrographs of corroded surface at different polarized points witnessed the formation of corrosion product film both on prepassivation and passivation stage. Moreover, the cross section of corrosion product film showed the coarse, loose film in Sn-0.7Cu-0.075Al solder and adherent, compact film in Ce (La)-containing solders, which further indicated an excellent anti-corrosion property.

Effect of Aluminum Addition on the Microstructure and Properties of Non-Eutectic Sn-20Bi Solder Alloys.

This study investigates the effect of aluminum (Al) on the microstructure, micro-hardness, and wettability of environmentally friendly Sn-20Bi-xAl (x = 0, 0.1, 0.3, 0.5 (wt.%)) solder alloys. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) analysis, and X-ray diffraction (XRD), were used to identify the microstructure morphology and composition. The spreading area and contact angle of the Sn-20Bi-xAl alloys on Cu substrates were used to measure the wettability of solder alloys. The results indicate that Al increased the hardness to a maximum value of ~27.1 HV for x = 0.5. When the content of Al was more than 0.3 wt.%, the hardness change value gradually flattened. From the spreading test results, Al reduced the wettability of solder alloys. When the content of Al was 0.1 wt.%, the change was slight. When more than 0.3 wt.%, the wettability of Sn-20Bi-xAl solder alloys sharply dropped. The corrosion resistance of Sn-20Bi-0.1Al alloy was the best, and the corrosion rate was at the lowest value at 0.092 mm/a due to the dense corrosion products.

Solid State Phase Equilibria of an Al⁻Sn⁻Y Ternary System.

A complete understanding of the solid-state phase equilibria of the ternary Al⁻Sn⁻Y system is essential for the development of both Al-based structural materials and Sn-based lead-free solders. In this work, the phase relationships in the Al⁻Sn⁻Y ternary system at 473 K were investigated mainly by means of X-ray powder diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) with energy disperse spectroscopy (EDS) analysis. The existence of 12 binary compounds, namely Sn3Y, Sn5Y2, Sn2Y, Sn10Y11, Sn4Y5, Sn3Y5, AlY2, Al3Y5, Al2Y3, AlY, Al2Y and α⁻Al3Y, was confirmed. Controversial phases (Sn5Y2 and Al3Y5) were found in this work. This isothermal section consisted of 15 single-phase regions, 27 two-phase regions and 13 three-phase regions. No ternary compounds were found and none of the other phases in this system revealed a remarkable solid solution at 473 K.

Functional improvements in patients with lymphangioleiomyomatosis after sirolimus: an observational study.

BACKGROUND: Sirolimus has been shown to be effective in patients with lymphangioleiomyomatosis (LAM). We wish to summarize our experience using sirolimus and its effectiveness in LAM patients. METHODS: We analyzed data from 98 patients who were diagnosed with definite or probable sporadic LAM based on the European Respiratory Society diagnosis criteria for LAM in 2010 at Peking Union Medical College Hospital and who had received sirolimus during January 2007 to June 2015. The data before and after the initiation of sirolimus therapy included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), size of chylous effusion and renal angiomyolipomas (AML), St. George's Respiratory Questionnaires (SGRQ) and vascular endothelial growth factor-D (VEGF-D) levels. Serum levels of sirolimus and adverse events were collected. RESULTS: Median follow-up was 2.5 years. Most patients had forced expiratory volume in 1 s (FEV1) values less than 70% predicted or symptomatic chylothorax. The mean changes before and after the initiation of sirolimus were - 31.12 ± 30.78 mL/month and 16.11 ± 36.00 mL/month (n = 18,p = 0.002) for FEV1 change, and - 0.55 ± 0.60 mmHg/month and 0.30 ± 1.19 mmHg/month (n = 17, p = 0.018) for PaO2 change. 6MWD improved from 358.8 ± 114.4 m to 415.6 ± 118.6 m (n = 46, p = 0.004) and SGRQ total score from 57.2 ± 21.0 to 47.5 ± 22.8 (n = 50, p < 0.001). The median VEGF-D concentration decreased to 1609.4 pg/mL from 3075.6 pg/mL after sirolimus therapy (n = 41, p < 0.001). Patients with sirolimus trough levels of 5-9.9 ng/mL had an increase in FEV1 (p < 0.05). Sixty-five percent of patients (13/20) had almost complete resolution of chylous effusions. The most frequent adverse events were mouth ulcers, menstrual disorder, hyperlipidemia and acneiform rash, all were mild. CONCLUSION: Long-term use of sirolimus is safe in patients with LAM. LAM patients with FEV1 less than 70% predicted and symptomatic chylothorax are suitable for receiving sirolimus therapy. The maintaining serum trough levels of sirolimus are recommended between 5 to 9.99 ng/mL.

Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder, the main manifestations of which are fibrofolliculomas, renal tumors, pulmonary cysts and recurrent pneumothorax. The known causative gene for BHD syndrome is the folliculin (FLCN) gene on chromosome 17p11.2. Studies of the FLCN mutation for BHD syndrome are less prevalent in Chinese populations than in Caucasian populations. Our study aims to investigate the genotype spectrum in a group of Chinese patients with BHD. METHODS: We enrolled 51 patients with symptoms highly suggestive of BHD from January 2014 to February 2017. The FLCN gene was examined using PCR and Sanger sequencing in every patient, for those whose Sanger sequencing showed negative mutation results, multiplex ligation-dependent probe amplification (MLPA) testing was conducted to detect any losses of large segments. MAIN RESULTS: Among the 51 patients, 27 had FLCN germline mutations. In total, 20 mutations were identified: 14 were novel mutations, including 3 splice acceptor site mutations, 2 different deletions, 6 nonsense mutations, 1 missense mutation, 1 small insertion, and 1 deletion of the whole exon 8. CONCLUSIONS: We found a similar genotype spectrum but different mutant loci in Chinese patients with BHD compared with European and American patients, thus providing stronger evidence for the clinical molecular diagnosis of BHD in China. It suggests that mutation analysis of the FLCN gene should be systematically conducted in patients with cystic lung diseases.

Enhancement of wear and corrosion resistance of low modulus ß-type Zr-20Nb-xTi (x=0, 3) dental alloys through thermal oxidation treatment.

In order to obtain material with low elastic modulus, good abrasion resistance and high corrosion stability as screw for dental implant, the biomedical Zr-20Nb and Zr-20Nb-3Ti alloy with low elastic modulus were thermal oxidized respectively at 700°C for 1h and 600°C for 1.25h to obtain the compact oxidized layer to improve its wear resistance and corrosion resistance. The results show that smooth compact oxidized layer (composed of monoclinic ZrO2, tetragonal ZrO2 and 6ZrO2-Nb2O5) with 22.6µm-43.5µm thickness and 1252-1306HV hardness can be in-situ formed on the surface of the Zr-20Nb-xTi (x=0, 3). The adhesion of oxidized layers to the substrates is determined to be 58.35-66.25N. The oxidized Zr-20Nb-xTi alloys reveal great improvement of the pitting corrosion resistance in comparison with the un-oxidized alloys. In addition, the oxidized Zr-20Nb-3Ti exhibits sharply reduction of the corrosion rates and the oxidized Zr-20Nb shows higher corrosion rates than un-oxidized alloys, which is relevant with the content of the t-ZrO2. Wear test in artificial saliva demonstrates that the wear losses of the oxidized Zr-20Nb-xTi (x=0, 3) are superior to pure Ti. All of the un-oxidized Zr-20Nb-xTi (x=0, 3) alloys suffer from serious adhesive wear due to its high plasticity. Because of the protection from compact oxide layer with high adhesion and high hardness, the coefficients of friction and wear losses of the oxidized Zr-20Nb-xTi (x=0, 3) alloys decrease 50% and 95%, respectively. The defects on the oxidized Zr-20Nb have a negative effect on the friction and wear properties. In addition, after the thermal oxidation, compression test show that elastic modulus and strength of Zr-20Nb-xTi (x=0, 3) increase slightly with plastic deformation after 40% of transformation. Furthermore, stripping of the oxidized layer from the alloy matrix did not occur during the whole experiments. As the surface oxidized Zr-20Nb-3Ti alloy has a combination of excellent performance such as high chemical stability, good wear resistance performance and low elastic modulus, moderate strength, it is considered an alternative material as dental implant.

Rapamycin-insensitive up-regulation of adipocyte phospholipase A2 in tuberous sclerosis and lymphangioleiomyomatosis.

Tuberous sclerosis syndrome (TSC) is an autosomal dominant tumor suppressor gene syndrome affecting multiple organs, including renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM). LAM is a female-predominant interstitial lung disease characterized by the progressive cyst formation and respiratory failure, which is also seen in sporadic patients without TSC. Mutations in TSC1 or TSC2 cause TSC, result in hyperactivation of mammalian target of rapamycin (mTOR), and are also seen in LAM cells in sporadic LAM. We recently reported that prostaglandin biosynthesis and cyclooxygenase-2 were deregulated in TSC and LAM. Phospholipase A2 (PLA2) is the rate-limiting enzyme that catalyzes the conversion of plasma membrane phospholipids into prostaglandins. In this study, we identified upregulation of adipocyte AdPLA2 (PLA2G16) in LAM nodule cells using publicly available expression data. We showed that the levels of AdPLA2 transcript and protein were higher in LAM lungs compared with control lungs. We then showed that TSC2 negatively regulates the expression of AdPLA2, and loss of TSC2 is associated with elevated production of prostaglandin E2 (PGE2) and prostacyclin (PGI2) in cell culture models. Mouse model studies also showed increased expression of AdPLA2 in xenograft tumors, estrogen-induced lung metastatic lesions of Tsc2 null leiomyoma-derived cells, and spontaneous renal cystadenomas from Tsc2+/- mice. Importantly, rapamycin treatment did not affect the expression of AdPLA2 and the production of PGE2 by TSC2-deficient mouse embryonic fibroblast (Tsc2-/-MEFs), rat uterine leiomyoma-derived ELT3 cells, and LAM patient-associated renal angiomyolipoma-derived "mesenchymal" cells. Furthermore, methyl arachidonyl fluorophosphate (MAFP), a potent irreversible PLA2 inhibitor, selectively suppressed the growth and induced apoptosis of TSC2-deficient LAM patient-derived cells relative to TSC2-addback cells. Our findings suggest that AdPLA2 plays an important role in promoting tumorigenesis and disease progression by modulating the production of prostaglandins and may serve as a potential therapeutic target in TSC and LAM.