Search

Inhibition of the tumour suppressive function of p53 (encoded by TP53) is paramount for cancer development in humans. However, p53 remains unmutated in the majority of cases of glioblastoma (GBM)—the most common and deadly adult brain malignancy(1,2). Thus, how p53-mediated tumour suppression is countered in TP53 wild-type (TP53(WT)) GBM is unknown. Here we describe a GBM-specific epigenetic mechanism in which the chromatin regulator bromodomain-containing protein 8 (BRD8) maintains H2AZ occupancy at p53 target loci through the EP400 histone acetyltransferase complex. This mechanism causes a repressive chromatin state that prevents transactivation by p53 and sustains proliferation. Notably, targeting the bromodomain of BRD8 displaces H2AZ, enhances chromatin accessibility and engages p53 transactivation. This in turn enforces cell cycle arrest and tumour suppression in TP53(WT) GBM. In line with these findings, BRD8 is highly expressed with H2AZ in proliferating single cells of patient-derived GBM, and is inversely correlated with CDKN1A, a canonical p53 target that encodes p21 (refs. (3,4)). This work identifies BRD8 as a selective epigenetic vulnerability for a malignancy for which treatment has not improved for decades. Moreover, targeting the bromodomain of BRD8 may be a promising therapeutic strategy for patients with TP53(WT) GBM.

Salt mines are a special type of hypersaline environment. Current research mainly focuses on prokaryotes, and the understanding of viruses in salt mines remains limited. Understanding viruses in hypersaline environments is of great significance for revealing the formation and maintenance of microbial communities, energy flow and element cycling, and host ecological functions. A phage infecting Halomonas titanicae was isolated from Yipinglang Salt Mine in China, designated Halomonas titanicae phage vB_HtiS_YPHTV-1 (YPHTV-1). Transmission electron microscopy revealed that YPHTV-1 had an icosahedral head with a diameter of 49.12 ± 0.15 nm (n = 5) and a long noncontractile tail with a length of 141.7 ± 0.58 nm (n = 5), indicating that it was a siphovirus. The one-step growth curve showed that the burst size of YPHTV-1 was 69 plaque forming units (PFUs) cell−1. The genome of YPHTV-1 was 37,980 bp with a GC content of 36.2%. The phylogenetic analysis of the six conserved proteins indicated that YPHTV-1 formed a cluster with Bacillus phages and was separated from phages infecting Halomonas. The average nucleotide identity (ANI), phylogenetic, and network analyses indicated that the phage YPHTV-1 represented a new genus under Caudoviricetes. In total, 57 open reading frames (ORFs) were predicted in the YPHTV-1 genome, 30 of which could be annotated in the database. Notably, several auxiliary metabolic genes were encoded by YPHTV-1, such as ImmA/IrrE family metalloendopeptidase, mannose-binding lectin (MBL) folding metallohydrolase, M15 family of metal peptidases, MazG-like family protein, O antigen ligase, and acyltransferase. These genes potentially enabled the host bacterium to resist ionizing radiation, ultraviolet light (UV), mitomycin C, β-lactam antibiotic, high osmotic pressure, and nutritional deficiencies. These findings highlight the role of haloviruses in the life cycle of halobacteria.

To fabricate highly efficient porphyrin dyes, we designed and synthesized two dyes with different numbers of fluorine atoms, dyes ZnF1 and ZnF2, respectively. These dyes were then connected to TiO2 electrode surface to build dye sensitized solar cells, and we studied the relationship between porphyrins dyes with different numbers of fluorine atoms and the performance of dye-sensitized solar cells. Our results indicate that solar cells with fewer fluorine atoms show higher photocurrent conversion efficiency (PCE). In particular, the ZnF1 solar cell containing one fluorine atom exhibits relatively high short-circuit current density ([Formula: see text] due to its low band gap and remarkable light collection capability. ZnF1 solar cells showed relatively higher short circuit current density ([Formula: see text] due to their low energy band gap and significant light collection ability. With the purpose to further improve the efficiencies, cosensitized with chenodeoxycholic acid (CDCA) dyes approaches were employed. As a result, the efficiencies have been successfully elevated to 2.71%. Additionally, the UV-vis absorption, density functional theory (DFT) calculations, electrochemical impedance spectra (EIS) and HOMO-LUMO energy gaps are used to further verify the test results of the sensitized solar cells.

Confined metal clusters as sub-nanometer reactors for electrocatalytic N2 reduction reaction (eNRR) have received increasing attention due to the unique metal-metal interaction and higher activity than single-atom catalysts. Herein, the inspiration of the superior capacitance and unique microenvironment with regular surface cavities of the porous boron nitride (p-BN) nanosheets, we systematically studied the catalytic activity for NRR of transition-metal single-clusters in the triplet form (V3, Fe3, Mo3 and W3) confined in the surface cavities of the p-BN sheets by spin-polarized density functional theory (DFT) calculations. After a two-step screening strategy, Mo3@p-BN was found to have high catalytic activity and selectivity with a rather low limiting potential (–0.34 V) for the NRR. The anchored Mo3 single-cluster can be stably embedded on the surface cavities of the substrate preventing the diffusion of the active Mo atoms. More importantly, the Mo atoms in the Mo3 single-cluster would act as “cache” to accelerate electron transfer between active metal centers and nitrogen-containing intermediates via the intimate Mo-Mo interactions. The cooperation of Mo atoms can also provide a large number of occupied and unoccupied d orbitals to make the "donation–backdonation" mechanism more effective. This work not only provides a quite promising electrocatalyst for NRR, but also brings new insights into the rational design of triple-atom NRR catalysts.

Co3O4-HCNFs were fabricated and proved to be effective for the full composition/decomposition of generated Li2O2 thin films during the oxygen reduction reaction and oxygen evolution reaction processes.

The lotus seedpod-based activated carbon (LSAC) is derived from pyrolysis of lotus seedpod as biomass carbon precursor, and Co3O4 is then deposited to LSAC by oxidation-precipitation and crystallization process of Co ions from Co(NO3)2 solution. The Co3O4 particles uniformly decorate on the surface and/or the inner channels of LSAC. The optimal reflection loss (RL) value of LSAC/Co3O4-paraffin wax (PW) composite reaches −39.8 dB, and the bandwidth for RL below −10 dB and −20 dB are 10.3 and 3.0 GHz, respectively, much better than that of LSAC-PW composite for the higher magnetic loss. The addition of Co3O4 particles in LSAC-PW composite significantly enhance the RL values in various thicknesses. The channels of the LSAC and decorated Co3O4 can improve the abilities of multiple scattering, dipole polarization, interface polarization and magnetic loss. This composite provides a promising method to construct high performance absorbers by using biomass carbon to tune the dielectric properties of the ferromagnetic materials.

The investigation of inexpensive, effective, environmentally friendly next-generation energy storage devices is an urgent task due to the discontinuities of new generation energy that hinder their further widely application. Among the multitudinous explored energy storage devices, supercapacitors have been regarded as the most potential energy storage systems thanks to their distinctive features of ultralong cycling lifespan, ultrafast charge/discharge process, and high power density compared with batteries and conventional capacitors. Nevertheless, the existing defect of low energy density has always been a bottleneck problem to their long-term development and widespread applications. Meanwhile, the electrodes are the core component in supercapacitors, determining the electrochemical performance directly. Consequently, transition metal oxides were chosen as the promoting materials to design and fabricate appropriately and rationally act as supercapacitor electrodes to harvest the outstanding electrochemical performance of both high energy and power density simultaneously. Here, we summarized the recent advances in transition metal oxides with different dimensions as electrodes for high-performance supercapacitors, including zero-dimensional nanostructures (nanospheres, nanocrystals, nanoparticles), one-dimensional nanostructures (nanorods, nanowires and nanotubes), two-dimensional nanostructures (nanoflakes, nanoplatelets), three-dimensional nanostructures (spherical structure, hollow structure, flower-like structure, honeycomb structure, mesoporous structure), and the corresponding supercapacitors electrochemical performance, expecting to make a thorough inquiry of the relationship between structure and property for highlighting the route to design and synthesis high-performance transition metal oxide-based supercapacitor electrodes.

Endometriosis is a common gynecological disease that seriously affects women's health and quality of life. However, the pathogenesis of endometriosis remains uncertain. This study aims to find the key microRNAs (miRNAs) and mRNAs and further to elucidate the pathogenesis of endometriosis.Differentially expressed mRNAs (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) were obtained by Gene Expression Omnibus (GEO) datasets integration analysis. Functional enrichment analysis of DEmRNAs and DEmRNAs targeted by DEmiRNAs was enforced using GeneCodis3. The DEmiRNA-DEmRNA interaction network was built using Cytoscape. The expression of candidate DEmRNA and DEmiRNA was verified using quantitative real time-polymerase chain reaction (QRT-PCR) and online datasets followed by diagnostic and immune cell infiltration analysis.A total of 835 (327 down-regulated and 508 up-regulated) DEmRNAs and 39 (24 down-regulated and 15 up-regulated) DEmiRNAs were identified between ectopic endometria (EC) group and eutopic endometria (EU) group. DEmRNAs targeted by DEmiRNAs were markedly enriched in cell adhesion molecules, pathways in cancer, leukocyte transendothelial migration, cytokine-cytokine receptor interaction and MAPK signaling pathway. The DEmiRNA-DEmRNA interaction network of up-regulated miRNAs was consisted of 15 miRNAs and 188 corresponding mRNAs. For down-regulated miRNAs, the DEmiRNA-DEmRNA interaction network was consisted of 24 miRNAs and 305 corresponding mRNAs. QRT-PCR validation results of IRF6, PTGER3, NTRK2, hsa-miR-449a and hsa-miR-873-5p were in line with the GEO analysis result. RF6, PTGER3 and NTRK2 had a potential diagnostic value for endometriosis. In addition, the infiltration of macrophages M2 and NK cells activated was the most significantly increased and reduced in ectopic endometrial, respectively.These identified DEmRNAs and DEmiRNAs may be may be associated with the pathogenesis of endometriosis. The integrated analysis of miRNA and mRNA expression profiles may provide a new perspective for understanding the mechanisms of endometriosis and developing new treatments.

Enhancer of zeste homolog 2 (EZH2) and SET domain bifurcated 1 (SETDB1, also known as ESET) are oncogenic methyltransferases implicated in a number of human cancers. These enzymes typically function as epigenetic repressors of target genes by methylating histone H3 K27 and H3-K9 residues, respectively. Here, we show that EZH2 and SETDB1 are essential to proliferation in 3 SCC cell lines, HSC-5, FaDu, and Cal33. Additionally, we find both of these proteins highly expressed in an aggressive stem-like SCC sub-population. Depletion of either EZH2 or SETDB1 disrupts these stem-like cells and their associated phenotypes of spheroid formation, invasion, and tumor growth. We show that SETDB1 regulates this SCC stem cell phenotype through cooperation with ΔNp63α, an oncogenic isoform of the p53-related transcription factor p63. Furthermore, EZH2 is upstream of both SETDB1 and ΔNp63α, activating these targets via repression of the tumor suppressor RUNX3. We show that targeting this pathway with inhibitors of EZH2 results in activation of RUNX3 and repression of both SETDB1 and ΔNp63α, antagonizing the SCC cancer stem cell phenotype. This work highlights a novel pathway that drives an aggressive cancer stem cell phenotype and demonstrates a means of pharmacological intervention.

Considerable efforts have been made to enhance the hydrogen evolution reaction (HER) catalytic performance of Janus MoSSe monolayer, which have been considered to be a promising candidate due to the unique asymmetry structure. However, the activation effect remains non-optimal for the inert Janus MoSSe basal plane at present. Herein, a train of transition metal (TM) atoms were anchored on the S-/Se-/Mo-defective MoSSe basal plane to screen effective TM single-atom catalysts for HER through density functional theory (DFT) computations. Interestingly, the single Co atom anchored on Mo-defective MoSSe and the single Zn or Cd atom anchored on S-defective MoSSe were judged to possess excellent HER performance yielding a near-zero ΔGH (ΔGH = −0.050, −0.095, −0.098 eV, respectively), which is comparable to the optimized Pt-SACs. The enhanced HER activity is attributed to the doping of TM atoms (Co, Zn and Cd) which improves the conductivity of the original MoSSe and offers unoccupied states near the Fermi level decreasing the energy barrier of electrons transfer between H and TMs@MoSSe surface. In addition, the change of unoccupied antibonding states of active atoms leads to appropriate interaction between the active sites and H. The hybridization between H-s orbital and the TMs@MoSSe systems around the Fermi level also suggests the formation of stable bonding-antibonding hydrogen adsorption states. This work reveals an effective way of activating MoSSe basal plane for HER.

Objective.Sparse-view computed tomography (SVCT), which can reduce the radiation doses administered to patients and hasten data acquisition, has become an area of particular interest to researchers. Most existing deep learning-based image reconstruction methods are based on convolutional neural networks (CNNs). Due to the locality of convolution and continuous sampling operations, existing approaches cannot fully model global context feature dependencies, which makes the CNN-based approaches less efficient in modeling the computed tomography (CT) images with various structural information. Approach. To overcome the above challenges, this paper develops a novel multi-domain optimization network based on convolution and swin transformer (MDST). MDST uses swin transformer block as the main building block in both projection (residual) domain and image (residual) domain sub-networks, which models global and local features of the projections and reconstructed images. MDST consists of two modules for initial reconstruction and residual-assisted reconstruction, respectively. The sparse sinogram is first expanded in the initial reconstruction module with a projection domain sub-network. Then, the sparse-view artifacts are effectively suppressed by an image domain sub-network. Finally, the residual assisted reconstruction module to correct the inconsistency of the initial reconstruction, further preserving image details. Main results. Extensive experiments on CT lymph node datasets and real walnut datasets show that MDST can effectively alleviate the loss of fine details caused by information attenuation and improve the reconstruction quality of medical images. Significance. MDST network is robust and can effectively reconstruct images with different noise level projections. Different from the current prevalent CNN-based networks, MDST uses transformer as the main backbone, which proves the potential of transformer in SVCT reconstruction.

Glioblastoma (GBM) is the most notorious primary brain tumor. The median survival of GBM patients is only about one year and about 95% patients succumb after five years. This gloomy picture has not been improved for decades, even with extensive treatments including surgery, radiotherapy, and chemotherapy. Hence, a better understanding of the mechanisms underlying GBM development may provide new therapeutic opportunities. Primary GBM generally harbors a low mutational load when compared to other human cancers. Even P53—the guardian of the genome that is essentially disabled in nearly all human cancers, remains unmutated in about 71% of GBM cases. Moreover, these P53 wildtype GBM cases are as aggressive as those with P53 mutations. To explore the mechanism by which P53 wildtype GBM thrive in the presence of intact P53, we performed CRISPR screens in a panel of human cancer cell lines using an sgRNA library specifically targeting the functional domains of ~200 chromatin regulators. We discovered that BRD8’s bromodomain—a druggable domain as shown by the tremendous success in preclinical and clinical trial in diverse cancers—is a vulnerability specifically in P53 wildtype GBM cases. Our mechanistic studies demonstrate that BRD8 functions through the EP400 chromatin remodeling complex and hijacks the histone variant H2AZ at P53 target loci, enforcing a compact chromatin state that blocks P53’s accessibility to its targets. We show that targeting the BRD8 bromodomain releases H2AZ, opens up chromatin, engages P53-mediated transactivation, and triggers growth arrest. Consistent with these findings, BRD8 is highly expressed with H2AZ in patient-derived proliferating GBM cells, and is inversely correlated with the expression of P53 targets. Our work solves a long-standing mystery in P53 wildtype GBM, and presents a promising therapeutic target for the majority of GBM patients. Citation Format: Sherine Xueqin Sun, Olaf Klingbeil, Christopher Vakoc, Alea Mills. BRD8-driven EP400 complex hijacks H2AZ to maintain proliferation in glioblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4734.

Three kinds of Ti3C2Tx modified metal sulfide composites have been prepared via a universal one-step strategy. First, three Ti3C2Tx MXene supported MoS3 composites with different surface F/O ratios and layer distances are synthesized. The abundant –OH groups on the surface of LiOH-treated Ti3C2Tx facilitate the effective bonding with MoS3, forming a robust sandwich-like structure (LF/O-Ti3C2Tx/MoS3). As anode material for sodium-ion batteries (SIBs), it shows outstanding long-term cycling performance in comparison with the other two Ti3C2Tx supported MoS3 composites. Its reversible capacity can be maintained at 611 mA h g−1 after 1000 long cycles at 2 A g−1, obviously superior to those of single LF/O-Ti3C2Tx and MoS3. Besides SIBs, LF/O-Ti3C2Tx/MoS3 also exhibits satisfying lithium storage performance. Kinetics analysis and theoretical calculation further explain the outstanding performance of LF/O-Ti3C2Tx/MoS3. Moreover, LF/O-Ti3C2Tx modified CuS/SnS2 composites also show similar and excellent electrochemical results for SIBs and LIBs. This facile synthesis strategy opens a door to prepare high-performance Ti3C2Tx supported conversion-type anode materials for large-scale energy storage.

One-dimensional Na2(TiO)SiO4 (SNTO) nanotubes have been successfully synthesized by a straightforward hydrothermal method with the assistance of cetyltetramethyl ammonium bromide (CTAB). Herein, the influence of the Si/Ti ratio on the morphology or composition of SNTO hollow nanotubes has been investigated, and the result shows that the optimum molar ratio of the optimal morphology is 1 : 1. The prepared samples were first applied as anodes in lithium ion batteries (LIBs) for the time being and superior rate capability, ultralong and stable cycling lifespan performance were obtained. The facile and uniquely designed one-dimensional SNTO nanotube electrodes delivered a high reversible capacity of 121.9 mA h g−1 after 5000 cycles at a high current of 1.0 A g−1 without significant attenuation. The superior electrochemical properties are attributed to their special nanotube structure with a high specific surface area, which could shorten the ion/electron transport pathway, and increase the number of active sites and the contact area between the electrolyte and active electrodes. Meanwhile, the kinetic analysis of the electrochemical behaviors of SNTO hollow nanotube electrodes was carried out by performing calculations using cyclic voltammograms recorded at different scan rates, and the results showed that the obtained reversible capacity is mainly due to the capacitive contribution. This work expands the types of anode materials for LIBs, which will further promote the development of LIBs.

Achieving ultrathin two-dimensional (2D) metal–organic framework (MOF) nanosheets is an extremely meaningful topic and still remains a great challenge. Herein, for the first time, a single-layer 2D Zn-MOF nanosheet was obtained by a facile top-down strategy based on 3D layered Zn-MOF crystals. It involves two steps: firstly, weakening the van de Waals interactions between layers by the protonation of the Zn-MOF under acidic conditions; secondly, further destroying the weakened van der Waals interactions through electrostatic interactions using negatively charged tape molecules, congo red (CR) or methyl orange (MO). Transmission electron microscopy and atomic force microscopy studies demonstrated that ultrathin single-layer (3.4 nm) 2D Zn-MOF nanosheets were obtained, with an ultra-large lateral size (ca. 6 μm), and showed unprecedented adsorption performance toward CR. For CR, the 2D Zn-MOF nanosheets could not only achieve record high uptake capacity (6639.55 mg g−1), but also present efficient and rapid removal. It is worth noting that the adsorption of CR could prevent restacking of the exfoliated 2D Zn-MOF nanosheets and facilitate further exfoliation, which in turn provided more 2D Zn-MOF nanosheets for CR adsorption. Moreover, CR can be selectively and efficiently removed even from the mixed dye solution with different charges. It is anticipated that this methodology could provide a concept to integrate exfoliation and pollutant removal into one process, fulfilling the facile synthesis of ultrathin functionalized 2D nanosheets, with high performance for pollutant removal.

To make use of two waste natural corncob and rosewood, activated carbons are obtained through KOH activation at 1073 K. The two samples show sheet like morphology with some swells on the surface of the corncob activated carbon and pores in the rosewood activated carbon. The higher ID/IG value of rosewood activated carbon for the Raman spectrum measurement indicates its lower graphitization degree than corncob activated carbon, which is proved by X-ray diffraction patterns. The higher real and imaginary parts of the complex permittivity for the rosewood activated carbon are benefited from the differences of morphology and graphitization degree of the two samples. Apart from the dipole polarization, the charge polarization and interfacial polarization also contribute to the dielectric loss for the porous rosewood activated carbon.

Designing a battery-type electrode material with high electrochemical performance based on eco-friendly and sustainable strategy has great significance for the development of supercapacitors. Herein, NiS nanoparticles are deposited on the surface of the porous hollow carbon spheres (PHCSs) derived from inexpensive and pollution-free yeast cells wall by an in situ hydrothermal process, forming a litchi shell-like three-dimensional (3D) double-shell structure. The PHCSs as a carbon substrate can effectively suppress the aggregation of NiS nanoparticles and ensure more ground storage sites to enhance the performance of the electrode material. More notably, the reaction concentration of nickel ion has a remarkable effect on the electrochemical performance of composites. The optimized sample shows a high specific capacity of 531.5 C g−1 at 1 A g−1, excellent rate capability of 412.1 C g−1 at 10 A g−1 and outstanding cycling life span of 83.3% after 5000 cycles. Furthermore, the assembled hybrid device delivers a high energy density of 24.4 Wh kg−1 at a power density of 767 W kg−1 and an excellent cycle stability by delivering 89.3% capacitance retention after 5000 ultralong cycles. This work offers a feasible strategy to synthesize economical and efficient electrode materials and demonstrates its enormous potential in energy storage. A novel NiS/porous hollow carbon sphere composite with double-shell structure was synthesized by a green and available self-template method, which exhibits superior supercapacitor performance.