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Cleft palate is a common craniofacial birth defect. The aim of the present study was to investigate the effect of excess all-trans retinoic acid (atRA) on periderm removal and the disappearance of basal medial edge epithelial (MEE) cells during palatogenesis, particularly during the stage prior to contact. atRA (200 mg/kg) was administered to C57BL/6N mice at embryonic day (E) 12.0 by gavage. Fetal palates were processed and analyzed by histology and electron microscopy. Single palate shelf peridermal cells were removed and cultured in the presence of atRA (3 µM) only or in the presence of or the caspase inhibitor, Z-VAD (100 µM) only, for 48 h. Once cultured, morphological changes were analyzed by histological staining and electron microscopy. A TUNEL assay was used to detect apoptotic neurons. Paired palatal shelves with periderm removal were cultured in the presence of atRA (3 µM) only or in the presence of Z-VAD (100 µM) only for 48 h and analyzed by hematoxylin and eosin staining. At E14.5, medial edge epithelium periderm was retained in the atRA-treated palates but had been shed prior to contact in the control groups. In addition, atRA was revealed to disrupt the cell cycle in the periderm by downregulating p21. Furthermore, atRA inhibited apoptosis in the periderm and basal MEE cells; however, atRA exhibited no effect on basement membrane degradation in single palatal organ culture. Additionally, once paired palates were cultured for 48 h, all of the groups in which the periderm had been removed exhibited confluence of the embryonic palatal mesenchyme. The present results suggest that periderm removal is inhibited in atRA-induced cleft palate in mice and that removal of the periderm contributes to EPM confluence in vitro. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine efficacy of intraoperative microvascular Doppler ultrasound in assisting subinguinal microsurgical varicocelectomy for pain relief in the treatment of painful varicoceles, compared to the microsurgery without Doppler ultrasound. METHODS: Total 153 patients underwent microsurgical varicocelectomy were randomly allocated to two groups: Groups 1 and 2 included 82 and 71 patients monitored with and without using intraoperative microvascular Doppler ultrasound, respectively. The assessments were compared between two groups, including intraoperative parameters (vessel numbers and operative time) and postoperative outcomes (pain resolution, complications and recurrence). RESULTS: The average numbers of internal spermatic veins ligated (13.87±6.43 vs 11.72±5.66) and arteries preserved (1.96±0.87 vs 1.73±0.86) were significantly greater in Group 1 with Doppler ultrasound. Precisely, the smaller size of the internal spermatic veins was ligated and the more encircled arteries were also preserved in Group 1. In two groups with and without using Doppler ultrasound, 56 (68.3%) and 36 (50.7%) patients experienced a complete resolution of pain, 21 (25.6%) and 29 (40.9%) patients experienced partial resolution, whereas 5 (6.1%) and 6 (8.5%) patients experienced no change in the chronic pain, respectively. Thus, patients in Group 1 had a better outcome in chronic pain resolution (P = 0.033). The operative time, complications and recurrence rate were not different between the two groups. CONCLUSIONS: Subinguinal microsurgical varicocelectomy is an effective method to treat painful varicoceles. With the assistance of Doppler Ultrasound monitoring, greater numbers of vessels were identified and a better outcome of pain resolution was achieved. [ABSTRACT FROM AUTHOR]

Adipogenesis is a multistep process by which 3T3-L1 preadipocytes differentiate into mature adipocytes through mitotic clonal expansion (MCE) and terminal differentiation. The CCAAT/enhancer-binding protein β (C/EBPβ) is an important transcription factor that takes part in both of these processes. C/EBPβ not only transactivates C/EBPα and the peroxisome proliferator-activated receptor γ (PPARγ), which cause 3T3-L1 preadipocytes to enter terminal adipocyte differentiation, but also is required to activate cell cycle genes necessary for MCE. The identification of potential cofactors of C/EBPβ will help to explain how C/EBPβ undertakes these specialized roles during the different stages of adipogenesis. In this study, we found that activating transcription factor 5 (ATF5) can bind to the promoter of C/EBPα via its direct interaction with C/EBPβ (which is mediated via the p300-dependent acetylation of ATF5), leading to enhanced C/EBPβ transactivation of C/EBP. We also show that p300 is important for the interaction of ATF5 with C/EBPβ as well as for the binding activity of this complex on the C/EBPα promoter. Consistent with these findings, overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas short interfering RNA-mediated ATF5 downregulation inhibited this process. Furthermore, we show that the elevated expression of ATF5 is correlated with an obese phenotype in both mice and humans. In summary, we have identified ATF5 as a new cofactor of C/EBPβ and examined how C/EBPβ and ATF5 (acetylated by a p300-dependent mechanism) regulate the transcription of C/EBPα. [ABSTRACT FROM AUTHOR]

It is well recognized that PIAS1, a SUMO (small ubiquitin-like modifier) E3 ligase, modulates such cellular processes as cell proliferation, DNA damage responses, and inflammation responses. Recent studies have shown that PIAS1 also plays a part in cell differentiation. However, the role of PIAS1 in adipocyte differentiation remains unknown. CCAAT/enhancer-binding protein (C/EBPβ), a major regulator of adipogenesis, is a target of SUMOylation, but the E3 ligase responsible for the SUMOylation of C/EBPβ has not been identified. The present study showed that PIAS1 functions as a SUMO E3 ligase of C/EBPβ to regulate adipogenesis. PIAS1 expression was significantly and transiently induced on day 4 of 3T3-L1 adipocyte differentiation, when C/EBPβ began to decline. PIAS1 was found to interact with C/EBPβ through the SAP (scaffold attachment factor A/B/acinus/ PIAS) domain and SUMOylate it, leading to increased ubiquitination and degradation of C/EBPβ. C/EBPβ became more stable when PIAS1 was silenced by RNA interference (RNAi). Moreover, adipogenesis was inhibited by overexpression of wild-type PIAS1 and promoted by knockdown of PIAS1. The mutational study indicated that the catalytic activity of SUMO E3 ligase was required for PIAS1 to restrain adipogenesis. Importantly, the inhibitory effect of PIAS1 overexpression on adipogenesis was rescued by overexpressed C/EBPβ. Thus, PIAS1 could play a dynamic role in adipogenesis by promoting the SUMOylation of C/EBPβ. [ABSTRACT FROM AUTHOR]

It is well recognized that PIAS1, a SUMO (small ubiquitin-likemodifier) E3 ligase, modulates such cellular processes as cell proliferation, DNA damage responses, and inflammation responses. Recent studies have shown that PIAS1 also plays a part in cell differentiation. However, the role of PIAS1 in adipocyte differentiation remains unknown. CCAAT/enhancer-binding protein β (C/EBPβ), a major regulator of adipogenesis, is a target of SUMOylation, but the E3 ligase responsible for the SUMOylation of C/EBPβ has not been identified. The present study showed that PIAS1 functions as a SUMO E3 ligase of C/EBPβ to regulate adipogenesis. PIAS1 expression was significantly and transiently induced on day 4 of 3T3-L1 adipocyte differentiation, when C/EBPβ began to decline. PIAS1 was found to interact with C/EBPβ through the SAP (scaffold attachment factor A/B/acinus/ PIAS) domain and SUMOylate it, leading to increased ubiquitination and degradation of C/EBPβ. C/EBPβ became more stable when PIAS1 was silenced by RNA interference (RNAi). Moreover, adipogenesis was inhibited by overexpression of wild-type PIAS1 and promoted by knockdown of PIAS1. The mutational study indicated that the catalytic activity of SUMO E3 ligase was required for PIAS1 to restrain adipogenesis. Importantly, the inhibitory effect of PIAS1 overexpression on adipogenesis was rescued by overexpressed C/EBPβ. Thus, PIAS1 could play a dynamic role in adipogenesis by promoting the SUMOylation of C/EBPβ. [ABSTRACT FROM AUTHOR]

Armature plays an important role in the electromagnetic launch process. Due to the skin effect, the current density distribution is neither uniform on the rail, nor on the armature. High current density centralization in one part could lead to a partial high temperature and make the armature material melt down and be ablated, especially at low velocity. In this paper we try to change the geometry of a Cshaped armature to improve the current density distribution and reduce the ablation. Four variants of C-shaped armatures are designed to study the specific features, including a conventional C-shaped armature (CCA), a rounded leading edge C-shaped armature (LCA), a rounded trailing edge C-shaped armature (TCA), and a rounded incorporate edge C-shaped armature (ICA). A novel low-speed experiment is constructed and tested. The armatures are ablated and recovered to compare the improved effects. Then finite element simulations according to the experimental results are performed to further analyze the experimental results. It is proved that the current density and hence the temperature distribution can be immensely improved by simply changing the armature geometry. LCA and ICA show that the erosion is more uniform on the contact surface due to the rounded leading edge. The curved trailing edge could improve the uniformity of the current on the interface. ICA which combines the effects of LCA and TCA is the best option in the four armatures. How much the leading edge and the trailing edge should be curved involves the geometry of CCA and the posture of the interface on the rail. A saddle shape is a good option to improve the current density and temperature distribution in the throat. Erosion mechanism is analyzed finally. The experiments and simulations support the erosion and transition mechanism. A detailed description of the experiments and simulations is also presented in this paper. [ABSTRACT FROM AUTHOR]

Background We compare the differences in the efficacy of percutaneous transforaminal endoscopic diskectomy (PTED) between the younger (age <60 years) and older (age ≥60 years) patients with lumbar disk herniation (LDH). Methods From December 2016 to December 2017, 128 patients with symptomatic LDH underwent PTED and were followed up. Forty-four 60 years old and above, including 19 males and 25 females with an average age of 68.7 (61–82) years, were classified as the elderly age group. Eighty-four patients younger than 60 years were classified as the young age group, which included 48 males and 36 females with an average age of 44.7 (16–58) years. The visual analog scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, and satisfaction rates of the two groups before and after surgery were compared. Results The operation was completed successfully in both groups. The average follow-up times of the elderly and young age groups were 18.47 ± 2.62 (12–23) and 17.90 ± 3.27 (12–23) months, respectively. One patient in the young age group had recurrence 7 months after surgery, and the symptoms were relieved after PTED was performed again. Two patients with nerve root injury after surgery in the young age group completely recovered after 2 months of conservative treatment. There were no significant surgical complications in the elderly age group. There was no significant difference in postoperative VAS, JOA, and MacNab scores between the two groups. The MacNab scores in the elderly age group were excellent for 28 patients, good for 10 patients, and fair for 6 patients; the satisfaction rate was 86.3%. In the young age group, scores were excellent for 63 patients, good for 14 patients, fair for 5 patients, and poor for 2 patients; the satisfaction rate was 91.7%. Conclusion The clinical effectiveness of PTED for treatment of LDH in both elderly and young patients is satisfactory. Age is not a predictor of poor outcomes of PTED. [ABSTRACT FROM AUTHOR]

The energy conversion efficiency of a multistage synchronous induction coilgun (MSSICG) has become one of the key factors that restricts its industrialization. To improve the launch efficiency of medium- and high-velocity MSSICG, we propose an optimization design scheme combining orthogonal experimental design (OED) and self-consistent design method in this paper. The OED is introduced to reduce the number of iterations and improve the identification accuracy and efficiency. A self-consistent design model is established to overcome a defect that the parameters that need to be optimized will multiply as the number of coil stages increases. The influence of six factors (radial thickness of armature, axial length of armature, axial length of coil, capacitance, wire diameter, and slip speed) on the launch efficiency are then evaluated by range analysis. This work presents a valuable reference for optimizing medium- and high-velocity MSSICG. [ABSTRACT FROM AUTHOR]

Employing a spin trapping agent combined with electron spin resonance spectroscopy, we were able to capture reactive oxygen species (ROS) in living hepatoma cells and first found that the trapped ROS was superoxide anion (O2⋅−). O2⋅− suppressed by treatment with diphenylene iodonium, a flavoprotein inhibitor, was generated by the flavoprotein-containing NADPH-oxidase complex. Applying endogenous/exogenous pro-oxidant or antioxidant causes different redox states in hepatoma cells. Akt activity and cell growth were significantly stimulated by treating hepatoma cells with low concentration of ROS, which could be abolished by adding antioxidants. The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (0.15 μM) inhibited Akt phosphorylation induced by ROS. Our results indicate that hepatoma cell growth is ROS-dependent, and fluctuation of the intracellular redox state may regulate hepatoma cell growth through Akt phosphorylation and the PI3K/Akt pathway, resulting in a broad array of responses from cellular proliferation to apoptosis. [Copyright &y& Elsevier]