Cullin 4B (CUL4B) is a component of the Cullin4B-Ring E3 ligase complex (CRL4B) that functions in proteolysis and is implicated in tumorigenesis. Here, we report that CRL4B is associated with histone methyltransferase SUV39H1, heterochromatin protein 1 (HP1) and DNA methyltransferases 3A (DNMT3A). We showed that CRL4B, through catalyzing H2AK119 monoubiquitination, facilitates H3K9 tri-methylation and DNA methylation, two key epigenetic modifications involved in DNA methylation-based gene silencing. Depletion of CUL4B resulted in loss of not only H2AK119 monoubiquitination but also H3K9 trimethylation and DNA methylation, leading to derepression of a collection of genes, including the tumor suppressor IGFBP3. We demonstrated that CUL4B promotes cell proliferation and invasion, which are consistent with a tumorigenic phenotype, at least partially by repressing IGFBP3. We found that the expression of CUL4B is markedly upregulated in samples of human cervical carcinoma and is negatively correlated with the expression of IGFBP3. Our experiments unveiled a coordinated action between histone ubiquitination/methylation and DNA methylation in transcription repression, providing a mechanism for CUL4B in tumorigenesis.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

The two-dimensional (2D)/three-dimensional (3D) heterojunction perovskite solar cell (PSC) has recently been recognized as a promising photovoltaic structure for achieving high efficiency and long-term stability. Rational design of the 2D spacer cation is important to achieve a win–win situation for defects’ passivation and photogenerated carrier extraction. Herein, we carry out first-principles calculation to analyze the dipole moment of phenethylamine-type molecules and their resulting 2D/3D perovskites. Based on the results of theoretical calculation, the dipole moment of 2D cations can be well tuned by varying the number of fluorine atoms on the para-position of the benzene ring, which further determines the interfacial dipole across the 2D/3D heterojunction interface. A high dipole 2D perovskite layer at the interface between the 3D perovskite and hole-transporting material is found to promote charge transport and suppress charge trapping efficiently. As a result, our 2D/3D PSCs exhibit a champion power conversion efficiency over 22% and a fill factor over 83%. Moreover, our solar cells also show a remarkable stability, maintaining 80% of its initial efficiency for more than 1400 h without encapsulation under a 30 ± 5% relative humidity.

BackgroundThere is increasing evidence implicating atrial mitochondrial dysfunction in the pathogenesis of atrial fibrillation. In this study, we explored whether alogliptin, a dipeptidyl peptidase‐4 inhibitor, can prevent mitochondrial dysfunction and atrial remodeling in a diabetic rabbit model.Methods and ResultsA total of 90 rabbits were randomized into 3 groups as follows: control group (n=30), alloxan‐induced diabetes mellitus group (n=30), and alogliptin‐treated (12.5 mg/kg per day for 8 weeks) diabetes mellitus group (n=30). Echocardiographic and hemodynamic assessments were performed in vivo. The serum concentrations of glucagon‐like peptide‐1, insulin, and inflammatory and oxidative stress markers were measured. Electrophysiological properties of Langendorff‐perfused rabbit hearts were assessed. Mitochondrial morphology, respiratory function, membrane potential, and reactive oxygen species generation rate were assessed. The protein expression of transforming growth factor β1, nuclear factor κB p65, and mitochondrial biogenesis–related proteins were measured by Western blot analysis. Diabetic rabbits exhibited left ventricular hypertrophy and left atrial dilation without obvious hemodynamic abnormalities, and all of these changes were attenuated by alogliptin. Compared with the control group, higher atrial fibrillation inducibility in the diabetes mellitus group was observed, and markedly reduced by alogliptin. Alogliptin decreased mitochondrial reactive oxygen species production rate, prevented mitochondrial membrane depolarization, and alleviated mitochondrial swelling in diabetic rabbits. It also improved mitochondrial biogenesis by peroxisome proliferator–activated receptor‐γ coactivator 1α/nuclear respiratory factor‐1/mitochondrial transcription factor A signaling regulated by adiponectin/AMP‐activated protein kinase.ConclusionsDipeptidyl peptidase‐4 inhibitors can prevent atrial fibrillation by reversing electrophysiological abnormalities, improving mitochondrial function, and promoting mitochondrial biogenesis.

In the journey to obtain well-crystallized mixed tin (Sn) -lead (Pb) iodide perovskite films for solar cell application, great difficulties have been presented due to very different crystallization rates between...