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// Shufang Ji 1, * , Wenfang Zhang 1, * , Xiaoli Zhang 1 , Chunyan Hao 2 , Aijun Hao 1 , Qing Gao 1 , Hongying Zhang 3 , Jinhao Sun 4 , Jing Hao 1 1 Key Laboratory of The Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan 250012, PR China 2 Department of Pathology, School of Medicine, Shandong University, Jinan 250012, PR China 3 Department of Biology, Jinan Vocational College of Nursing, Jinan 250000, PR China 4 Department of Human Anatomy, School of Medicine, Shandong University, Jinan 250012, PR China * These authors contributed equally to this work Correspondence to: Jing Hao, email: haojing@sdu.edu.cn Keywords: Sohlh2, IL-8, EMT, metastasis, breast cancer Abbreviations: EMT, epithelial-to-mesenchymal transition; Sohlh2, spermatogenesis- and oogenesis- specific basic helix-loop-helix transcription factor2; IL-8, interleukin 8; FBS, fetal bovine serum; ChIP, chromatin immunoprecipitation Received: September 25, 2015 Accepted: June 16, 2016 Published: June 30, 2016 ABSTRACT Breast cancer is one of the deadliest cancers worldwide due to its strong metastasis to other organs. Metastasis of breast cancer involves a complex set of events, including epithelial-mesenchymal transition (EMT) that increases invasiveness of the tumor cells. We previously identified sohlh2 is a tumor suppressor in the pathogenesis of ovarian cancer. However, the functions of sohlh2 in breast cancer cell migration and invasion remain unknown. Here we report a novel sohlh2/IL-8 signaling pathway in the invasive breast cancer. We observed sohlh2 expression was downregulated in the metastatic breast cancer. Ectopic sohlh2 expression in breast cancer cells reduced EMT and inhibited cell migration and invasion in vitro , and metastasis in vivo . Moreover, the depletion of sohlh2 induced the opposite effects to ectopic sohlh2 expression. RNA-Seq data from a sohlh2 knockdown breast cancer cell line showed that after sohlh2 depletion, the mRNA level of interleukin 8 (IL-8) was significantly increased in these cancer cells, which consequently increased secretion of IL-8 protein. Using chromatin immunoprecipitation and reporter assays, we demonstrated that sohlh2 bound to IL-8 promoter and repressed its activities. The enhanced migration and invasion in sohlh2 -ablated MCF-7 cells were blocked by knockdown of IL-8 expression, while exogenous IL-8 neutralized the anti-migratory and invasive activities of sohlh2 in MDA-MB-231cells. Overall, these results demonstrate that sohlh2 functions as a tumor metastasis suppressor via suppressing IL-8 expression in breast cancer.

The hydrosilylation reaction is one of the largest-scale application of homogeneous catalysis and is widely used to enable the commercial manufacture of silicon products. However, considerable issues including disposable platinum consumption, undesired side reactions and unacceptable catalyst residues still remain. Here, we synthesize a heterogeneous partially charged single-atom platinum supported on anatase TiO2 (Pt1δ+/TiO2) catalyst via an electrostatic-induction ion exchange and two-dimensional confinement strategy, which can catalyze hydrosilylation reaction with almost complete conversion and produce exclusive adduct. Density functional theory calculations reveal that unexpected property of Pt1δ+/TiO2 originates from atomic dispersion of active species and unique partially positive charge Ptδ+ electronic structure that conventional nanocatalysts do not possess. The fabrication of single-atom Pt1δ+/TiO2 catalyst accomplishes a reasonable use of Pt through recycling and maximum atom-utilized efficienc...

Efficient, durable and inexpensive electrocatalysts that accelerate sluggish oxygen reduction reaction kinetics and achieve high-performance are highly desirable. Here we develop a strategy to fabricate a catalyst comprised of single iron atomic sites supported on a nitrogen, phosphorus and sulfur co-doped hollow carbon polyhedron from a metal-organic framework@polymer composite. The polymer-based coating facilitates the construction of a hollow structure via the Kirkendall effect and electronic modulation of an active metal center by long-range interaction with sulfur and phosphorus. Benefiting from structure functionalities and electronic control of a single-atom iron active center, the catalyst shows a remarkable performance with enhanced kinetics and activity for oxygen reduction in both alkaline and acid media. Moreover, the catalyst shows promise for substitution of expensive platinum to drive the cathodic oxygen reduction reaction in zinc-air batteries and hydrogen-air fuel cells., Development of fuel cells and metal-air batteries is hindered by electrocatalyst performance, which can be enhanced with uniform and atomically dispersed active sites. Here the authors report an iron-based electrocatalyst for oxygen reduction in cathodes for a zinc-air battery and a hydrogen-air fuel cell.

We previously reported that bone morphogenetic protein 4/drosophila mothers against decapentaplegic protein (BMP4/Smad) signalling pathway initiated primordial follicle growth and prevented oocyte apoptosis via up-regulation of Sohlh2 and receptor for kit ligand (c-kit). The mechanism underlying this process was not fully elucidated. In the present study, primary oocyte cultures were established from ovaries of 3-day-old female mouse pups by two-step enzyme digestion. Cultures were divided into Sohlh2 small interference RNA (SiRNA) group, negative SiRNA group, Sohlh2 overexpression plasmid group and pCAG-puro group. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay was carried out to detect the oocyte apoptosis; immunocytochemical staining and quantitative real time-polymerase chain reaction detected the expression of c-kit and Forkhead box O3a (Foxo3a); Western blot was performed to detect the expression of Sohlh2, C-kit, saerine/threonine kinases (Akt1) and Foxo3a. The results showed that Sohlh2 inhibited oocyte apoptosis and upregulated c-kit expression; Sohlh2 decreased the endonuclear Foxo3a via the upregulation of phosphorylated Akt1 (P-Akt1) and phosphorylated Foxo3a (P-Foxo3a) but not total Akt1 (T-Akt1) or total Foxo3a (T-Foxo3a); Sohlh2 increased P-Akt1 but not T-Akt1; the PI3K (phosphotidylinsitol-3-kinase) inhibitor LY294002 ameliorated the role of Sohlh2 on phosphorylation of Akt1 and Foxo3a. Sohlh2 may inhibit oocyte apoptosis via c-kit/PI3K/Akt/Foxo3a signalling pathway.

A novel polymer encapsulation strategy to synthesize metal isolated-single-atomic-site (ISAS) catalysts supported by porous nitrogen-doped carbon nanospheres is reported. First, metal precursors are encapsulated in situ by polymers through polymerization; then, metal ISASs are created within the polymer-derived p-CN nanospheres by controlled pyrolysis at high temperature (200-900 °C). Transmission electron microscopy and N2 sorption results reveal this material to exhibit a nanospheric morphology, a high surface area (≈380 m2 g-1 ), and a porous structure (with micropores and mesopores). Characterization by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure confirms the metal to be present as metal ISASs. This methodology is applicable to both noble and nonprecious metals (M-ISAS/p-CN, M = Co, Ni, Cu, Mn, Pd, etc.). In particular, the Co-ISAS/p-CN nanospheres obtained using this method show comparable (E1/2 = 0.838 V) electrochemical oxygen reduction activity to commercial Pt/C with 20 wt% Pt loading (E1/2 = 0.834 V) in alkaline media, superior methanol tolerance, and outstanding stability, even after 5000 cycles.

Here we report a novel approach to synthesize atomically dispersed uniform clusters via a cage-separated precursor preselection and pyrolysis strategy. To illustrate this strategy, well-defined Ru

The search for active, stable, and cost-efficient electrocatalysts for hydrogen production via water splitting could make a substantial impact on energy technologies that do not rely on fossil fuels. Here we report the synthesis of rhodium phosphide electrocatalyst with low metal loading in the form of nanocubes (NCs) dispersed in high-surface-area carbon (Rh

Spermatogenesis and oogenesis basic helix-loop-helix (bHLH) transcription factor 2 (Sohlh2) functions as a bhlh transcription factor to regulate mouse germ cell differentiation. Our previous data showed that Sohlh2 was highly expressed in human normal tissues, but low level of Sohlh2 was observed in many cancer cell lines, suggesting a possible role of Sohlh2 in tumorigenesis. In this study, we examined this possibility by using immunohistochemistry, MTT, 5-bromo-2-deoxyuridine, clonogenic assay and tumor xenograft techniques. Our results showed that the expression of Sohlh2 was decreased in epithelial ovarian carcinoma (EOC) tissues compared with benign ovarian tumors and ovarian tumors with low malignant potential. Forced expression of Sohlh2 led to a significant reduction in cancer cell proliferation in vitro and tumorigenesis in nude mice. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell proliferation. Furthermore, Sohlh2 had opposite effects on its two direct targets p21 and cyclin D1: overexpression of Sohlh2 upregulated p21 but downregulated cyclin D1 expression. p21 knockdown could reverse the effects of Sohlh2 overexpression on inhibiting cell proliferation, and cyclin D1 knockdown could reverse the effects of Sohlh2 ablation on promoting cell proliferation. Thus, our data indicate that Sohlh2 likely functions as a tumor suppressor in EOCs, which is achieved by inducing p21 expression but repressing cyclin D1 expression.

We present a case of right lateral auricle contracture malformation, auricular canal atresia, and complete facial paralysis (House-Brackmann grade VI) caused by a megatemperature hydro-aluminum injury at work. The diastrophic auricle and auricular canal atresia were reshaped. The complete facial paralysis was reanimated to House-Brackmann grade III after surgical hypoglossal-facial end-to-end anastomosis. These outcomes indicate that hypoglossal-facial end-to-end anastomosis is an effective surgical option for successful reanimation of complete facial paralysis.

C-Reactive protein (CRP) is composed of five identical noncovalently linked monomers and characterized as an important acute-phase protein. The CRP subunit obtained by denaturing treatments, which is termed modified CRP, has also been widely studied. In the current work, we found that there exists some degree of natural dissociation of CRP in stock solution. This dissociation is critically dependent on the absence of Ca2+. Low pH could enhance the dissociation of CRP, while ionic strength has little effect. Anilinonaphthalenesulfonate (ANS) fluorescence detections indicate that the exposure of hydrophobic surface increases during the dissociation. Acidic pH conditions also induce an increase in ANS fluorescence. This suggests that hydrophobic interactions between CRP subunits may contribute to the study of its pentameric structure. Surface plasmon resonance experiments indicate that monomeric CRP does not specifically bind to phosphatidylcholine-containing membrane as native CRP does. Electron microscopy shows that monomeric CRP binds to negatively charged lipid through electrostatic forces, and such lipid may induce the dissociation of CRP due to the acidic pH in the diffuse double layer near the membrane.

β-Amyloid peptide (Aβ), a normal constituent of neuronal and non-neuronal cells, has been proved to be the major component of extracellular plaque of Alzheimer's disease (AD). The interaction of Aβ with lipid membranes may be essential for its neurotoxicity. Our previous study revealed that membrane insertion may provide a possible pathway by which Aβ prevents itself from aggregation and fibril formation. In the present work we studied the membrane insertion of Aβ and the factors that affect its insertion ability using a monolayer approach. The results show that Aβ is surface active and can insert into lipid monolayers. When a high level of cholesterol is present, Aβ40 can insert into the phospholipid mixtures simulating physiological membrane composition. Acidic pH enhances Aβ insertion, while the effect of ionic strength is rather complex. Aβ insertion ability may be ultimately relative to cholesterol-rich domains in the monolayers, which indicates strong interaction between Aβ and cholesterol.

Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified Sohlh2 as an important inhibitor of ovarian cancer cell proliferation. However, the function of Sohlh2 in cell migration and invasion remains unknown. In this paper, we report a novel Sohlh2 to MMP9 signaling pathway in the invasive ovarian cancer. Using immunohistochemistry staining, we revealed Sohlh2 expression was inversely correlated with the invasive human ovarian cancers. In vitro experiments, forced expression of Sohlh2 led to a significant reduction in cancer cell migration and invasion. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell migration and invasion. Experiments using nude mice demonstrated that the ectopic Sohlh2 expression inhibited the HO8910 cell capability of the metastasis to the lungs and livers. Ectopic overexpression of Sohlh2 in the invasive HO8910 cells reduced the MMP9 expression, whereas Sohlh2 knockdown from the non-invasive, SKOV3 cells increased the MMP9 expression. Promoter activation and binding analyses indicated that Sohlh2 repressed the MMP9 expression by directly acting on the MMP9 gene promoter. Inhibition of MMP9 dramatically blocked the Sohlh2 knockdown-enhanced SKOV3 cell invasion, and ectopic expression of MMP9 compensated for the anti-invasive activity of Sohlh2 in HO8910 cells. Overall, these results demonstrate for the first time that Sohlh2 functions as a tumor metastasis suppressor. Modulation of Sohlh2 expression has the potential to be a target for cancer therapy. © 2015 Wiley Periodicals, Inc.

This research focuses on the psychologic status of children patients with congenital malformation of external and middle ear by Achenbach's Child Behavior Checklist (CBCL) in order to explore the degree of the influence.The 66 patients of 4-16 years old were assessed psychologic status with CBCL filled in by their parents according to their performance in half a year. Then calculated the detection rate of behav ioral disorders of these patients. Collected all patients' general information and Marx's grade of malformed ears. Then analyzed the relationship between the detection rate and these factors.The detection rate of behavioral disorders of 4-16 years old patients, 21.21%, which is higher than that of Chinese norm. The Marx's grade and parents' mental stress relate with the behavioral disorders. In Logistic regression analysis, the value of CoxSnell coefficient of the regression model is 0. 153. The detection rate of behavioral disorders in grade III patients (36.4%) is greater than that of grade II (4.3%), P = 0.004.Congenital malformation of external and middle ear has an absolute influence on the patients' psychologic status, but its effect is only about 15% parts of the multitudinous influential factors. And grade III patients carry a high-risk for behavioral disorders.

To investigate the clinical presentation, diagnosis and therapy of syphilis with sensorineural deafness.Three patients of syphilis with sensorineural deafness were analyzed including the clinical manifestation, serum and therapy response.Three patients of syphilis with sensorineural deafness: 2 cases with rapid plasma reagin (RPR) and treponema pallidum particle agglutination (TPPA) positive, 1 case with RPR negative and TPPA positive; 2 cases had been diagnosed with syphilis and treated once; 2 cases with sudden sensorineural deafness and tinnitus, 1 case with tinnitus and high-frequency hearing loss. All cases hadn't another identified cause of the hearing loss or tinnitus. Their hearing loss level weren't improved after therapy.Sudden hearing loss or nervous tinnitus may be the clinical manifestations of syphilis with sensorineural deafness. It is easy to miss diagnosis in clinical work. Some lab examinations were necessary to diagnose the cases with the etiology unknown of hearing loss, tinnitus or nystagmic.

Objective: To explore treatments for postirradiation otitis media with effusion (OME) in patients with nasopharyngeal carcinoma. Study Design: This study is a prospective quasi-randomized clinical trial. Methods: Ninety-six patients (135 ears) with OME after the first course of radiotherapy for nasopharyngeal carcinoma were divided into three groups: simple auripuncture plus aspiration, tympanic membrane fenestration with cauterization, and myringotomy plus grommet insertion. Cure rates and incidences of complications were compared. Results: Two deaths occurred. The other 94 patients (132 ears) finished a 2-year follow-up. In group 1, four ears (8.9%) were cured after the first treatment and 17 ears overall (37.8%) were cured by the end of the follow-up. Twenty ears (44.4%) had persistent fluid, two ears (4.4%) developed chronic suppurative otitis media, and five ears (11.1%) developed dry eardrum perforation. In group 2, seven ears (15.6%) were cured after the first treatment and 21 ears overall (46.7%) were cured by the end of the follow-up. Fourteen ears (31.1%) had persistent fluid, three ears (6.7%) developed chronic suppurative otitis media, and seven ears (15.6%) developed dry eardrum perforation. In group 3, eight ears (17.8%) were cured after the first treatment and 23 ears overall (51.1%) were cured by the end of the follow-up. Seven ears (15.6%) had persistent fluid, five ears (11.1%) developed chronic suppurative otitis media, three ears (6.7%) developed eardrum perforation with effusion, and five ears (11.1%) developed dry eardrum perforation. Conclusion: The methods each have advantages and disadvantages. We believe that a step by step approach should be used when choosing the treatment method for postirradiation OME. That is, first apply auripuncture plus aspiration, and then the other methods if this approach is inadequate. Enhanced local care after grommet insertion can effectively reduce the incidence of complications.

To explore the influence of hypoxemia on the hearing of children with childhood obstructive sleep apnea-hypopnea syndrome (OSAHS).Auditory brainstem response (ABR) and distortion-product otoacoustic emission (DPOAE) was recorded in 68 ears and 60 ears respectively of children suffering from OSAHS with "A" tympanogram. Meanwhile, ABR and DPOAE was also recorded in 30 controls of children with "A" tympanogram.There was no statistical difference between the mild OSAHS group and the control group in the latency of wave I, III and V, the interval between wave I and III, III and V, I and V. There was significant difference between the moderate and severe OSAHS group and the control group in the delayed latency of wave I. There was significant difference between the mild OSAHS group and the control group in the amplitudes of DPOAE at 8 kHz. There was significant difference between the moderate and severe OSAHS group and the control group in the amplitudes of DPOAE at 6 kHz and 8 kHz.Cochlear function was affected when AHIor = 10/h. ABR and DPOAE could be used to detect the early damagement of auditory function in childhood OSAHS.