Ovarian cancer (OVCA) and cervical cancer (CECA) are lethal gynecological malignancies. Cisplatin (CDDP) and platinum derivatives are first line chemotherapeutics and their resistance impedes successful treatment. Understanding the molecular dysregulation underlying chemoresistance is important in developing rational therapeutic strategies. We have established that Protein Phosphatase Magnesium-dependent 1 D (PPM1D) confers CDDP resistance in gynecological cancer cells by deactivating p53. However, whether CDDP regulates intra-cellular PPM1D localization and whether this regulation is different between chemosensitive and chemoresistant cancer cells is unknown. Moreover, whether Akt regulates PPM1D in the context of CDDP resistance has not been studied. To illustrate the role of PPM1D in gynecological cancer cell chemoresistance and its regulation by Akt we have demonstrated that: (a) CDDP induced PPM1D downregulation through proteasomal degradation in sensitive CECA cells; (b) CDDP induced PPM1D nuclear localization in resistant CECA cells, and nuclear exclusion in sensitive CECA cells and OVCA xenografts; (c) Over-expression of active Akt in sensitive CECA cells stabilized PPM1D content through inhibition of CDDP-induced PPM1D down-regulation; (d) Inhibition of Akt activity in resistant OVCA cells leads to decreased PPM1D stability and CDDP-induced down-regulation in resistant CECA cells; and (e) PPM1D is highly expressed in human ovarian tumor subtypes and in a tissue microarray panel of human ovarian tumors. In conclusion, we have established that PPM1D plays an important role in promoting CDDP resistance and as a novel downstream target of Akt, PPM1D mediates its action in conferring CDDP resistance in gynecological cancer cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.Key words: cisplatin chemoresistance; ovarian cancer; PPM1D; Akt; apoptosis INTRODUCTIONOvarian cancer (OVCA) and cervical cancer (CECA) are the most lethal gynecological malignancies. Although OVCA ranks first in the number of deaths each year, due primarily to its late diagnosis and the development of chemoresistance [1], CECA is more frequent and less deadly due to early detection. Surgical de-bulking of the tumor mass followed by adjuvant chemotherapy is the conventional course of therapy for OVCA, whereas a combination of radiation and chemotherapy is the preferred treatment regimen for CECA. Platinum derivatives, including Cisplatin (CDDP; cis-diamminedichloroplatinum) in combination with paclitaxel, are first-line chemotherapeutic agents in the treatment of these gynecologic cancers. CDDP induces apoptosis by creating inter-and intra-strand DNA adducts through irreversible intercalation, thereby inducing both the DNA damage and the apoptotic responses [2]. The majority of patients respond to chemotherapy at first, however, recurrence of the disease is a common event and tumors are usually more aggressive, metastasize to secondary target tissues, and acquire resistance to conventional chemotherape...

Background Patients with bronchopulmonary dysplasia (BPD) may require tracheostomy for long‐term mechanical ventilation. Polysomnography (PSG) may predict successful decannulation in children, however it is unclear how this success compares with children without a PSG. To better evaluate this role, we compared decannulation outcomes between tracheostomy‐dependent children with BPD who underwent PSG before decannulation to those who did not. Methods This is a retrospective cohort study between 1 January 2007 and 1 June 2017 of tracheostomy‐dependent children with BPD who were clinically considered for decannulation. Patient demographics, PSG results, and medical comorbidities were abstracted from medical records and compared between groups. Decannulation outcomes were compared between children with BPD who underwent PSG before decannulation and those who did not. Results One hundred twenty‐five patients with BPD were considered for tracheostomy decannulation. Forty‐six (37%) had a pre‐decannulation PSG while 79 (63%) did not. Nineteen (41%) patients did not undergo decannulation within 6 months of the PSG. One (3%) patient with pre‐decannulation PSG failed decannulation. Four (5%) patients without pre‐decannulation PSG failed decannulation. Nineteen patients with PSG and no decannulation had significantly higher obstructive apnea‐hypopnea index (OAHI) (13.62 vs 2.68 events per hour, P = 0.004), higher end‐tidal CO 2 max (52.84 vs 48.03 mm Hg, P = 0.035), and were older at PSG (median age, 6.04 vs 4.04 years, P = 0.008). Conclusions While successful decannulation can be achieved without a PSG in some patients, PSG is a valuable tool to identify BPD patients undergoing clinical evaluation for decannulation who would benefit from treatment of OSA before decannulation.

Carbon super‐heterostructures with high nitrogen contents from the covalent hybrid precursors of covalent triazine frameworks (CTFs) and zeolitic imidazolic frameworks (ZIFs) are scarcely explored because of CTF's ordered structure and toxic superacid that dissolves or destabilizes the metal nodes. To solve this problem, herein, we report a straightforward two‐step pathway for the covalent hybridization of disordered CTF (d–CTF)–ZIF composites via preincorporation of an imidazole (IM) linker into ordered CTFs, followed by the imidazole‐site‐specific covalent growth of ZIFs. Direct carbonization of these synthesized d–CTF−IM−ZIF hybrids results in unique hollow carbon super‐heterostructures with ultrahigh nitrogen content (>18.6%), high specific surface area (1663 m2 g−1), and beneficial trace metal (Co/Zn NPs) contents for promoting the redox pseudocapacitance. As proof of concept, the obtained carbon super‐heterostructure (Co–Zn–NCSNH–800) is used as a positive electrode in an asymmetric supercapacitor, demonstrating a remarkable energy density of 61 Wh kg−1 and extraordinary cyclic stability of 97% retention after 30,000 cycles at the cell level. Our presynthetic modifications of CTF and their covalent hybridization with ZIF crystals pave the way toward new design strategies for synthesizing functional porous carbon materials for promising energy applications.

ZnMn 2 O 4 has been intensively researched over the past two decades as a potential alternative to graphite anode material in the lithium-ion battery (LIB). The positive impact of the ZnMn 2 O 4 anodes on high capacity and rate capability has been consistently proven in lithium half-batteries. However, there are currently insufficient studies to support these effects in Li-ion full cell configuration by pairing with a state-of-the-art cathode. Herein, we report ball-in-ball hollow structured ZnMn 2 O 4 , which was synthesized by a facile solvothermal method. The synthesized ZnMn 2 O 4 showed high capacity, good cycling stability, and excellent rate capability as an anode material for LIBs in a half cell. The reaction mechanism was followed through a combination of in situ X-ray diffraction (XRD) and ex situ synchrotron X-ray absorption spectroscopy (sXAS) techniques. In situ XRD analysis reveals the ZnO and MnO phase formation with no evidence of Mn 3 O 4 upon delithiation. The sXAS study shows that the reduction of ZnO to metallic Zn proceeds efficiently, whereas the reduction of MnO to metallic Mn is nominal during lithiation. The expected formation of the LiZn alloy is the first to be reported under the tested conditions. Overall, the results indicate that the Li-driven conversion reaction of the ZnMn 2 O 4 anode is only partially reversible. However, the ZnMn 2 O 4 anode displayed its sustainability in a full cell by pairing with a commercial LiNi 0.5 Mn 1.5 O 4 cathode. The battery energy density reached 561.5 Wh Kg À1 , which was calculated based on the cathode mass, and exhibited a total specific capacity of 113 mAhg À1 . Thus, this study presents a comparison between the half and full cell data demonstrating that the half-cell predicts the overrated capacity value of a conversion-type anode in LIBs. Furthermore, it highlights the reporting practices in a Li-ion full cell for properly resolving its advantages. K E Y W O R D Sanode materials, in situ X-ray diffraction, lithium-ion batteries, synchrotron X-ray absorption, ZnMn 2 O 4