Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

有晶状体眼后房型人工晶状体植入矫正近视及散光的长期临床研究

目的:评价有晶状体眼后房型人工晶状体植入术的长期安全性及稳定性。方法:回顾性非随机临床试验研究。选取2013-01/2014-12于成都爱尔眼科医院行有晶状体眼后房型人工晶状体(V4,ICL)植入手术患者64例107眼,分别于术前,术后1wk,1、3、6、12mo及术后每年随访裸眼视力(UCVA)、最佳矫正视力(BCVA)、屈光度数、眼压、拱高、角膜内皮计数、眼轴以及手术安全性、有效性等,所有患者随访至2019-12均完成术后5a或以上的末次随访。结果:术前BCVA(LogMAR)为-0.08(0,-0.08),术后1a裸眼视力为0(-0.076,0),末次随访裸眼视力0.096(0,0.221),较术后1a,末次随访裸眼视力有所下降,这种视力改变主要与眼轴较术前有明显增长有关。BCVA在术后1a及末次随访结束较术前相比均无明显改变。末次随访的手术安全指数平均为1.19±0.24,有效指数为1.00±0.29。散光晶状体在眼内长期稳定性良好,没有出现明显的旋转等。拱高的变化主要发生在术后1a内,其后变化缓慢。眼压、角膜内皮计数无明显变化。本研究中2眼分别于术后3、5a出现晶状体前囊下混浊,无青光眼、色素播散等并发症出现。结论:ICL植入术矫正近视具有良好的安全性、稳定性及可预测性。

In-situ synchrotron X-ray diffraction investigation on deformation behavior of Nb/NiTi composite during pre-straining process

The mechanisms responsible for deformation behavior in Nb/NiTi composite during pre-straining were investigated systematically using in-situ synchrotron X-ray diffraction, transmission electron microscopy and tensile test. It is shown that upon loading, the composite experiences elastic elongation and slight plastic deformation of B19′,B2 and β-Nb phases, together with the forward stress-induced martensitic(SIM) transformation from B2 to B19′. Upon unloading, the deformation mechanisms of the composite mainly involve elastic recovery of B19′, B2 and β-Nb phases,compression deformation of β-Nb phase and incomplete B19′→B2 reverse SIM transformation. In the tensile loading-unloading procedure, besides the inherent elastic deformation and SIM transformation, the(001) compound twins in B19′ martensite can also be conducive to the elastic deformation occurring in B19′-phase of the composite.Therefore, this composite can exhibit a large recoverable strain after unloading owing to the elastic deformation, and the partially reversible and consecutive SIM transformation together with the(001) compound twins.

A Time-Dependent-Density-Functional-Theory Study of Charge Transfer Processes of Li^(2+) Colliding with Ar in the MeV Region

We study charge transfer of a multi-electron collision system Li^(2+)+ Ar using the time-dependent density functional theory non-adiabatically coupled to the molecular dynamics.By implementing the particle number projection method,the single-and double-charge transfer cross sections are extracted at MeV energies,which are in good agreement with the experimental data available.The analysis of charge transfer probabilities shows that for energies higher than 1.0 MeV,the single-charge transfer occurs for a broader range of impact parameters,while the double-charge transfer is dominated by close collisions.To gain the population of captured electrons on the projectile,we compute the orbital projection probabilities.It is found that the electrons of the Ar atom will most possibly transfer to the 2p orbitals of the Li^(2+),and only a small portion of captured electrons distribute on the s orbitals.This work verifies the capability of the present methodology in dealing with charge transfer in dressed ion collisions at Me V energies.

Midline Prostatic Cysts Presenting with Chronic Prostatitis or Secondary Infertility and Minimally Invasive Treatment: Endoscopic or Laparoscopic Approach?

Backgrounds: Surgical interventions especially minimally invasive treatments are recommended for symptomatic midline prostatic cysts. The endoscopic unroofing of cysts close to urethra is easy and simple, but it has little effect on the large cysts and cysts lying deeply, in contrast with the laparoscopic approach. Therefore, the selection of minimally invasive therapeutic approaches is important. The aim of this study is to describe our experience in the diagnosis and selection of minimally invasive treatment for midline prostatic cyst. Methods: 15 cases of midline prostatic cyst were studied.10 cases presented with prostatitis-like symptoms, 1 with dysuria and acute urinary retention, 3 with secondary infertility and the rest 1 with hemospermia. 6 patients presented with small cysts (≤2 cm × 2 cm) close to urethra and underwent transurethral unroofing. The other 9 patients with large cysts (>2 cm × 2 cm) or cysts lying closely behind the prostate received the laparoscopic excision. Results: The average duration of transurethral unroofing and laparoscopic excision was 39 mins and 118 mins respectively, whereas the average time of hospitalization was 2.7 days and 4.5 days respectively. After a follow-up of 21 months, all cases were treated successfully without complications and recurrence. Their prostatitis-like symptoms disappeared, and the three patients presented with secondary infertility achieved conception within one year after the operation. Conclusions: A midline prostatic cyst can present with chronic prostatitis-like symptoms and secondary infertility. It can be cured by minimally invasive treatments, but these procedures should be carefully selected according to the size and location of the cyst.

p38αMAP kinase promotes asthmatic inflammation through modulation of alternatively activated macrophages

Asthma is characterized by reversible airflow obstruction, bronchial hyper-reactivity, and chronic airway remodeling (Al-Muhsen et al., 2011). Pulmonary macrophages have been implicated in asthmatic inflammation (Lee et al., 2015;Qian et al., 2015). The p38 mitogen-activated protein kinase (MAPK) plays an essential role in inflammation, but its role in asthma has not been determined (Kim et al., 2008). Here, our data show that macrophage-specific p38α MAPK-deficient mice displayed attenuated asthmatic inflammation in response to three allergens (dust mite, ragweed, and Aspergillus;DRA). Furthermore, we found that the protective effect was strongly associated with a reduction in the alternatively activated macrophage (AAM) polarization in vivo and in vitro. Taken together, our data indicate that p38α MAPK in macrophages contributes to AAM polarization and could be a therapeutic target for asthma.

Physical and chemical characteristics of PM_(2.5) and its toxicity to human bronchial cells BEAS-2B in the winter and summer

With the increasing occurrence of haze during the summer, the physicochemical characteristics and toxicity differences in PM2.5 in different seasons are of great concern. Hangzhou is located in an area that has a subtropical monsoon climate where the humidity is very high during both the summer and winter. However, there are limited studies on the seasonal differences in PM2.5 in these weather conditions. In this test, PM2.5 samples were collected in the winter and summer, the morphology and chemical composition of PM2.5 were analyzed, the toxicity of PM2.5 to human bronchial cells BEAS-2B was compared, and the correlation between PM2.5 toxicity and the chemical compo- sition was discussed. The results showed that during both the winter and summer, the main compounds in the PM2.5 samples were water-soluble ions, particularly SO4^2-, NO3^-, and NH4^＋, followed by organic components, while heavy metals were present at lower levels. The higher the mass concentration of PM2.5, the greater its impact on cell viability and ROS levels. However, when the mass concentration of PM2.5 was similar, the water extraction from the summer samples showed a greater impact on BEAS-2B than that from the winter samples. The cytotoxicity of PM2.5 was closely associated with heavy metals and organic pollutants but less related to water-soluble ions.

Microstructure and mechanical properties of TC4 joints brazed with Ti-Zr-Cu-Sn amorphous filler alloy

The Ti_(51.44)Zr_(16.26)Cu_(30)Sn_(2.3)(at%)amorphous filler alloy in a ribbon form was prepared by melt spinning.The Ti-6 Al-4 V alloy was brazed in vacuum furnace by using the Ti_(51.44)Zr_(16.26)Cu_(30)Sn_(2.3)amorphous filler alloy.The effects of brazing temperature and holding time on the interfacial microstructure and mechanical properties of the Ti-6 Al-4 V brazed joints were investigated.The brazed joints are composed ofα-Ti,β-Ti,and(Ti,Zr)_(2)Cu phases.The shear strength of the joints increases with brazing temperature increasing from 1153 to 1193 K and holding time from 10 to 15 min,while decreases with brazing temperature and time further increasing.Low temperature brazing results in the formation of microcracks and voids in the seams,which are harmful for the shear strength of the joints.In the joint brazed at 1193 K for 15 min,a fineα+βWidmansta¨tten structure beneficial to the mechanical property is formed,and the joint exhibits relatively high joint strength of 180 MPa.

Characterization of neutral lipases revealed the tissue-specific triacylglyceroi hydrolytic activity in Nilaparvata lugens

The lipid metabolism plays an essential role in the development andreproduction of insects, and lipases are important enzymes in lipid metabolism. In Nilaparvatalugens, an important insect pest on rice, triacylglycerol hydrolytic activities weredifferent among tissues, with high activity in integument, ovary, and fat body, but low activityin intestine. To figure out the tissue-specific triacylglycerol hydrolytic activity, weidentified 43 lipases in N. lugens. Of these 43 lipases, 23 belonged to neutral lipases, sothis group was selected to perform further experiments on triacylglycerol hydrolysis. Thecomplete motifs of catalytic triads, β9 loop, and lid motif, are required for the triacylglycerolhydrolytic activity in neutral lipases, which were found in some neutral lipases withhigh gene expression levels in integument and ovary, but not in intestine. The recombinantproteins of 3 neutral lipases with or without 3 complete motifs were obtained, and the activitydetermination confirmed the importance of 3 motifs. Silencing XM_022331066.1,which is highly expressed in ovary and with 3 complete motifs, significantly decreasedthe egg production and hatchability of N. lugens, partially through decline of the lipidmetabolism. In summary, at least one-third of important motifs were incomplete in allneutral lipases with high gene expression in intestine, which could partially explain whythe lipase activity in intestine was much lower than that in other tissues. The low activityto hydrolyze triacylglycerol in N. lugens intestine might be associated with its food resourceand nutrient components, and the ovary-specific neutral lipases were important forN. lugens reproduction.