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The poor prognosis of pancreatic cancer is primarily due to the development of resistance to therapies, including gemcitabine. The long noncoding RNA PVT1 (lncRNA PVT1) has been shown to interact with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), promoting gemcitabine resistance in pancreatic cancer. In this study, we found histone acetyltransferase 1 (HAT1) enhanced the tolerance of pancreatic cancer cells to gemcitabine and HAT1-mediated resistance mechanisms were regulated by PVT1 and EZH2. Our results showed that the aberrant HAT1 expression promoted gemcitabine resistance, while silencing HAT1 restored gemcitabine sensitivity. Moreover, HAT1 depletion caused a notable increase of gemcitabine sensitivity in gemcitabine-resistant pancreatic cancer cell lines. Further research found that HAT1 increased PVT1 expression to induce gemcitabine resistance, which enhanced the binding of bromodomain containing 4 (BRD4) to the PVT1 promoter, thereby promoting PVT1 transcription. Besides, HAT1 prevented EZH2 degradation by interfering with ubiquitin protein ligase E3 component n-recognin 4 (UBR4) binding to the N-terminal domain of EZH2, thus maintaining EZH2 protein stability to elevate the level of EZH2 protein, which also promoted HAT1-mediated gemcitabine resistance. These results suggested that HAT1 induced gemcitabine resistance of pancreatic cancer cells through regulating PVT1/EZH2 complex. Given this, Chitosan (CS)-tripolyphosphate (TPP)-siHAT1 nanoparticles were developed to block HAT1 expression and improve the antitumor effect of gemcitabine. The results showed that CS-TPP-siHAT1 nanoparticles augmented the antitumor effects of gemcitabine in vitro and in vivo. In conclusion, HAT1-targeted therapy can improve observably gemcitabine sensitivity of pancreatic cancer cells. HAT1 is a promising therapeutic target for pancreatic cancer.

The LiNi0.6Co0.2Mn0.2O2 (NCM) cathode material is highly potential for the wide application in lithium-ion batteries due to its moderate cost and high specific capacity. However, the problems of its poor cycling stability and rate performance need to be further solved. Designing a single-crystal nanostructure of the NCM materials is an effective strategy to increase the rate characteristics, however, the performance decay and safety issues are still there due to the irreversible side reactions and structure degradation. In this study, the single crystalline hexagonal nanosheets of NCM material have been prepared using a hydrothermal process, and various amounts of Al2O3 are further controllably coated on the surface of NCM. The results show that a suitable amount of Al2O3 coating is conducive to the formation of a better layered structure NCM with smaller cation disorder and leads to higher discharge capacity, rate performance and longer cyclic life than the pristine material, due to the stabilized layered structure of cathode materials, the alleviated electrode/electrolyte side reactions and the favored diffusion of lithium ions.

Silicon is getting much attention as the promising next-generation negative electrode materials for lithium-ion batteries with the advantages of abundance, high theoretical specific capacity and environmentally friendliness. In this work, a series of phosphorus (P)-doped silicon negative electrode materials (P-Si-34, P-Si-60 and P-Si-120) were obtained by a simple heat treatment method, which can maintain the original nanoparticle morphology. The P-Si-60 material shows excellent discharge specific capacity, rate performance and cycling performance. The discharge specific capacity after 50 cycles remains > 2000 mAh g−1 with a capacity retention rate of 74.3%. The excellent electrochemical properties of P-Si-60 material can be attributed to the phosphorus doping without destroying the original particle morphology and nanostructure and the higher intrinsic electric conductivity. It will bring new thoughts for the further application of silicon negative electrode materials.

Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy. Geminin-Cdt1 plays essential roles in the regulation of DNA replication. Here the authors reveal that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP prevents DNA replication over-firing and genome instability by affecting Geminin ubiquitination.

The solid electrolyte interphase (SEI) film plays a significant role in the capacity and storage performance of lithium primary batteries. The electrolyte additives are essential in controlling the morphology, composition and structure of the SEI film. Herein, fluoroethylene carbonate (FEC) is chosen as the additive, its effects on the lithium primary battery performance are investigated, and the relevant formation mechanism of SEI film is analyzed. By comparing the electrochemical performance of the Li/AlF3 primary batteries and the microstructure of the Li anode surface under different conditions, the evolution model of the SEI film is established. The FEC additive can decrease the electrolyte decomposition and protect the lithium metal anode effectively. When an optimal 5% FEC is added, the discharge specific capacity of the Li/AlF3 primary battery is 212.8 mAh g−1, and the discharge specific capacities are respectively 205.7 and 122.3 mAh g−1 after storage for 7 days at room temperature and 55 °C. Compared to primary electrolytes, the charge transfer resistance of the Li/AlF3 batteries with FEC additive decreases, indicating that FEC is a promising electrolyte additive to effectively improve the SEI film, increase discharge-specific capacities and promote charge transfer of the lithium primary batteries.

Polymetallic transition metal phosphides (TMPs) exhibit quasi-metallic properties and a high electrical conductivity, making them attractive for high-performance hybrid supercapacitors (HSCs). Herein, a nanohoneycomb (NHC)-like FeNi layered double hydroxide (LDH) array was grown in situ on 3D current collector nickel foam (NF), which is also the nickel source during the hydrothermal process. By adjusting the amount of NaH2PO2, an incomplete phosphated FeNi(OH/P) nanosheet array was obtained. The optimized FeNi(OH/P) nanosheet array exhibited a high capacity up to 3.6 C cm−2 (408.3 mAh g−1) and an excellent long-term cycle performance (72.0% after 10,000 cycles), which was much better than FeNi LDH’s precursor. In addition, the hybrid supercapacitor (HSC) assembled with FeNi(OH/P) (cathode) and polypyrrole (PPy/C, anode) achieved an ultra-high energy density of 45 W h kg−1 at a power density of 581 W kg−1 and an excellent cycle stability (118.5%, 2000 cycles), indicating its great potential as an HSC with a high electrochemical performance.

The limited rate performance of Li||CFx batteries hinders their wide application, owing to the low conductivity of CFx cathode material and the undesirable solid electrolyte interface (SEI) layer formed on the Li anode surface. Herein, a strategy for constructing a three-dimensional lithium anode (3D-Li anode) with high specific surface area and an in situ formed favorable SEI layer is proposed to enhance the interfacial stability and uniformity of ion transport and realize a Li||CFx battery with remarkable comprehensive performance. A 3D-Li anode (Li@CuO-Cu foam) is successfully constructed by molten Li infusion of a thermal oxidation processed copper foam. The lithiophilicity of the Cu foam framework is optimized by the formed CuO. The Li@CuO-Cu foam||CFx battery exhibits a high discharge specific capacity (1149.6 mAh g−1 at 0.1 C) along with a high discharge plateau voltage (2.65 V). At a high rate of 10 C, the 3D-Li anode-based batteries still demonstrate a discharge specific capacity of 463 mAh g−1, which is about 2.5 times that of the conventional Li||CFx, and exhibit excellent storage performance (620.3 mAh g−1 after storage at 55 °C for 90 days) and a low monthly self-discharge rate (1.28%). This work demonstrates a promising strategy to construct a three-dimensional lithium metal anode and significantly improve the rate and storage performance of Li||CFx batteries.

53BP1 promotes nonhomologous end joining (NHEJ) over homologous recombination (HR) repair by mediating inactivation of DNA end resection. Ubiquitination plays an important role in regulating dissociation of 53BP1 from DNA double-strand breaks (DSBs). However, how this process is regulated remains poorly understood. Here, we demonstrate that TRABID deubiquitinase binds to 53BP1 at endogenous level and regulates 53BP1 retention at DSB sites. TRABID deubiquitinates K29-linked polyubiquitination of 53BP1 mediated by E3 ubiquitin ligase SPOP and prevents 53BP1 dissociation from DSBs, consequently inducing HR defects and chromosomal instability. Prostate cancer cells with TRABID overexpression exhibit a high sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. Our work shows that TRABID facilitates NHEJ repair over HR during DNA repair by inducing prolonged 53BP1 retention at DSB sites, suggesting that TRABID overexpression may predict HR deficiency and the potential therapeutic use of PARP inhibitors in prostate cancer. The retention of 53BP1 at DNA double strand breaks (DSBs) is inhibitory to homologous recombination repair. Following ionising radiation, the authors demonstrate that TRABID-mediated deubiquitination of 53BP1 promotes its retention, sensitising prostate cancer to PARP inhibition.

As a potential negative electrode material for lithium-ion batteries (LIBs), silicon has a relatively high specific lithium storage capacity. However, the large volume change during the cycle may result in the isolation with the current collector and therefore the rapid capacity decay during cycling. The poor electric conductivity of the silicon limits the high-power density application in LIBs. To meet the above challenges, a stable Si/Ti3C2Tx composite material was designed. Si nanoparticles are bonded with -NH2 group so that the silicon surface has a positive charge, which can then be electrostatic self-assembly with negatively charged MXene nanosheets in a facile freeze-drying method. Silicon nanoparticles were anchored on the surface or inside the interspace of the MXene nanosheets, which could improve the conductivity of the composites. The composite material (NH2-Si/MXene) presented a stable and porous structure with extra room for silicon expansion and plentiful channels for carrier transportation. Benefiting from the improved structural stability and enhanced charge storage dynamics, the discharge capacity of NH2-Si/MXene is 1203.3 mAh g−1 after 100 cycles at 200 mA g−1. These results provide new insights for the application of silicon-based negative electrode materials in high-energy-density LIBs.

NR5A2 is a transcription factor regulating the expression of various oncogenes. However, the role of NR5A2 and the specific regulatory mechanism of NR5A2 in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly studied. In our study, Western blotting, real-time PCR, and immunohistochemistry were conducted to assess the expression levels of different molecules. Wound-healing, MTS, colony formation, and transwell assays were employed to evaluate the malignant potential of pancreatic cancer cells. We demonstrated that NR5A2 acted as a negative prognostic biomarker in PDAC. NR5A2 silencing inhibited the proliferation and migration abilities of pancreatic cancer cells in vitro and in vivo. While NR5A2 overexpression markedly promoted both events in vitro. We further identified that NR5A2 was transcriptionally upregulated by BRD4 in pancreatic cancer cells and this was confirmed by Chromatin immunoprecipitation (ChIP) and ChIP-qPCR. Besides, transcriptome RNA sequencing (RNA-Seq) was performed to explore the cancer-promoting effects of NR5A2, we found that GDF15 is a component of multiple down-regulated tumor-promoting gene sets after NR5A2 was silenced. Next, we showed that NR5A2 enhanced the malignancy of pancreatic cancer cells by inducing the transcription of GDF15. Collectively, our findings suggest that NR5A2 expression is induced by BRD4. In turn, NR5A2 activates the transcription of GDF15, promoting pancreatic cancer progression. Therefore, NR5A2 and GDF15 could be promising therapeutic targets in pancreatic cancer.