Search

Soyeon Bang,1 Junhong Li,2 Meiqin Zhang,3 Renjie Cui,3 Xingwen Wu,4 Zhaochen Xin,1 Duan Ma,3,5 Jin Zhang,3 Hongwei Zhang1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Department of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Children’s Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongwei ZhangDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of ChinaTel +86-13681973106Fax +86 21-64038472Email zhang.hongwei@zs-hospital.sh.cnDuan MaKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 130 Dong an Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86-13916126452Fax +86 21-54237441Email duanma@shmu.edu.cnBackground: Krüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive.Methods: We investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan–Meier plotter dataset. The protein levels of KLF16 in breast specimens were detected by immunohistochemistry (IHC). KLF16 silencing using shRNAs was performed to explore the effects of KLF16 on breast cancer cell growth, migration, and invasion. The expression of EMT markers in cells manipulated for KLF16 expression was assessed by Western blotting.Results: Using publicly available dataset and specimens from breast cancer patients, we found that the expression levels of KLF16 were significantly higher in tumor tissues and that high levels of KLF16 were associated with poor prognosis in breast cancer patients. Moreover, KLF16 expression levels had relation to several clinicopathological parameters of breast cancer, including the molecular subtype and histological grade. Importantly, knockdown of KLF16 dramatically suppressed cell proliferation both in vitro and in vivo. Also, KLF16 deletion impaired migration, and invasion in breast cancer cells, and suppressed epithelial–mesenchymal transition (EMT).Conclusion: Our results suggest that KLF16 has important oncogenic functions in breast cancer and that the expression levels of KLF16 are associated with prognosis in breast cancer patients. Our findings also suggest that KLF16 is involved in proliferation, migration, and invasion in breast cancer cells. Thus, KLF16 might be a promising prognostic marker and a therapeutic target for breast cancer.Keywords: breast cancer, EMT, Krüppel-like factor 16, metastasis, proliferation

Hosam Serag, Shirley Bang, Y Zaki Almallah Department of Urology, Queen Elizabeth Hospital Birmingham-University Hospital Birmingham, Birmingham, UK Objectives: To report a real-time contemporary practice and outcome of artificial urinary sphincter (AUS) in patients with postradical prostatectomy urinary incontinence (PPI) in the UK. Methods: A retrospective observational study of patients who underwent AUS implantation (AMS 800) from 2007 to 2013. Data were collected on patients’ demographics, infection and erosion rate, mechanical failure, reoperation, and continence rates. The study strictly included patients with postradical PPI only. Minimum follow-up was 15 months. Results: Eighty-four AUSs were implanted over a period of 6 years. Patients’ age ranged between 51 and 78 (median 69, mean 69.25) years. Median follow-up was 37 months, mean 39 months, and range 15–92 months. Among the 83 follow-up patients, 38.5% (32/83) reported that they were completely dry with no pads; 42.2% (35/83) of patients were socially continent (using 1 pad/day) and 19.3% (16/83) using ≥2 pads /day. One patient was lost to follow-up. Reoperation rate was 13.25% (11/83), including nine mechanical failures (10.8%). Two implant infections (2.4%) required explantation, out of which one had erosion (1.2%). Bladder overactivity developed in 6% of patients. Of the 83, 15 (18%) had pelvic radiotherapy. Conclusion: The implantation of AUS in patients with post-PPI has lower complications and reoperation rates than historical impression painted in the literature. This can be beneficial in counseling as well as during the education process of patients going through the decision process for prostate cancer treatment. Furthermore, these figures can add to our quest to increase the awareness of the success of anti-incontinence surgery among patients. Keywords: Post-prostatectomy urinary incontinence, artificial urinary sphincter, male incontinence, radical prostatectomy complications, outcomes of artificial urinary sphincter, incontinence surgery counseling

Effect Ga2O3 addition on the densification and properties of Y2O3-doped AlN ceramics was investigated under the constraint of total sintering additives (Y2O3 and Ga2O3) of 4.5 wt%. Ga was detected in the AlN grain as well as the grain boundary phases. YAlO3 and Y4Al2O9 were observed as the secondary crystalline phases in all of the investigated compositions. As the substitution of Ga2O3 for Y2O3 increased, the quantity of the Y4Al2O9 phase decreased while that of YAlO3 was more or less similar. Neither additional secondary phases was identified, nor was the sinterability inhibited by the Ga2O3 addition; the linear shrinkage and apparent density were above 20 percent and 3.34-3.37 g/cm3, respectively. However, the optical reflectance and the elastic modulus generally decreased whereas the Poisson ratio increased significantly. The dielectric constant and the loss tangent of 4.0Y2O3-0.5Ga2O3-95.5Y2O3 at the resonant frequency of 8.22 GHz were 8.63 and 0.003, respectively.

SiC/Cu composite powders with the barrier coating of SiC-Al onto SiC powders were synthesized from Al-containing polycarbosilane precursor and Cu-nitrate hydrate. Curing at 200°C and high temperature pyrolysis at 1600°C was used to achieve the crystallization of precursor, forming the SiC-Al coating on the surface of SiC powders. A core-shell structure with the core of SiC and the shell of Cu was constructed by calcination and hydrogen-reduction of Cu nitrate hydrate. XRD and SEM analysis revealed that the β-SiC and 4H-SiC phases were formed on the surface of the initial α-SiC powders. Also, it was observed by EDX mapping that core powders of SiC were homogeneously surrounded with the fine Cu particles on their surface.

Abstract Background Chicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis. Methods The anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 104 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD). Results The results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation. Conclusions The combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers. Graphical Abstract

Toxoplasma gondii is an obligate intracellular parasite that can infect humans and diverse animals. Fatty acids are critical for the growth and proliferation of T. gondii, which has at least two pathways to synthesize fatty acids, including the type II de novo synthesis pathway in the apicoplast and the elongation pathway in the endoplasmic reticulum (ER). Acetyl-CoA is the key substrate for both fatty acid synthesis pathways. In the apicoplast, acetyl-CoA is mainly provided by the pyruvate dehydrogenase complex. However, how the ER acquires acetyl-CoA is not fully understood. Here, we identified a putative acetyl-CoA transporter (TgAT1) that localized to the ER of T. gondii. Deletion of TgAT1 impaired parasite growth and invasion in vitro and attenuated tachyzoite virulence in vivo. Metabolic tracing using 13C-acetate found that loss of TgAT1 reduced the incorporation of 13C into certain fatty acids, suggesting reduced activities of elongation. Truncation of AT1 was previously reported to confer resistance to the antimalarial compound GNF179 in Plasmodium falciparum. Interestingly, GNF179 had much weaker inhibitory effect on Toxoplasma than on Plasmodium. In addition, deletion of AT1 did not affect the susceptibility of Toxoplasma to GNF179, suggesting that this compound might be taken up differently or has different inhibitory mechanisms in these parasites. Together, our data show that TgAT1 has important roles for parasite growth and fatty acid synthesis, but its disruption does not confer GNF179 resistance in T. gondii.

Abstract Toxoplasma gondii (T. gondii)‐associated polymorphic effector proteins are crucial in parasite development and regulating host anti‐T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN‐I activation. Infection with Δgra4 mutant T. gondii strain induces stronger IFN‐I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27‐catalyzed K48‐ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent Δgra4 strain (ME49Δompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN‐I production. Earlier vaccination with ME49Δompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49Δompdc treatment. Notably, ME49Δompdc/gra4 vaccination induces a specific CD64+MAR‐1+CD11b+ dendritic cell subset, thereby enhancing T cell anti‐tumor responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN‐I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy.