High‐Performance and Stable Perovskite Solar Cells Based on Dopant‐Free Arylamine‐Substituted Copper(II) Phthalocyanine Hole‐Transporting Materials

A power conversion efficiency (PCE) as high as 19.7% is achieved using a novel, low‐cost, dopant‐free hole transport material (HTM) in mixed‐ion solution‐processed perovskite solar cells (PSCs). Following a rational molecular design strategy, arylamine‐substituted copper(II) phthalocyanine (CuPc) derivatives are selected as HTMs, reaching the highest PCE ever reported for PSCs employing dopant‐free HTMs. The intrinsic thermal and chemical properties of dopant‐free CuPcs result in PSCs with a long‐term stability outperforming that of the benchmark doped 2,2′,7,7′‐Tetrakis‐(N,N‐di‐p‐methoxyphenylamine)‐9,9′‐Spirobifluorene (Spiro‐OMeTAD)‐based devices. The combination of molecular modeling, synthesis, and full experimental characterization sheds light on the nanostructure and molecular aggregation of arylamine‐substituted CuPc compounds, providing a link between molecular structure and device properties. These results reveal the potential of engineering CuPc derivatives as dopant‐free HTMs to fabricate cost‐effective and highly efficient PSCs with long‐term stability, and pave the way to their commercial‐scale manufacturing. More generally, this case demonstrates how an integrated approach based on rational design and computational modeling can guide and anticipate the synthesis of new classes of materials to achieve specific functions in complex device structures.     

Development of Beet necrotic yellow vein virus‐based vectors for multiple‐gene expression and guide RNA delivery in plant genome editing

Many plant viruses with monopartite or bipartite genomes have been developed as efficient expression vectors of foreign recombinant proteins. Nonetheless, due to lack of multiple insertion sites in these plant viruses, it is still a big challenge to simultaneously express multiple foreign proteins in single cells. The genome of Beet necrotic yellow vein virus (BNYVV) offers an attractive system for expression of multiple foreign proteins owning to a multipartite genome composed of five positive‐stranded RNAs. Here, we have established a BNYVV full‐length infectious cDNA clone under the control of the Cauliflower mosaic virus 35S promoter. We further developed a set of BNYVV‐based vectors that permit efficient expression of four recombinant proteins, including some large proteins with lengths up to 880 amino acids in the model plant Nicotiana benthamiana and native host sugar beet plants. These vectors can be used to investigate the subcellular co‐localization of multiple proteins in leaf, root and stem tissues of systemically infected plants. Moreover, the BNYVV‐based vectors were used to deliver NbPDS guide RNAs for genome editing in transgenic plants expressing Cas9, which induced a photobleached phenotype in systemically infected leaves. Collectively, the BNYVV‐based vectors will facilitate genomic research and expression of multiple proteins, in sugar beet and related crop plants.     

BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation

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DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane

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Exploring proteasome complexes by proteomic approaches

The ubiquitin proteasome system (UPS) represents a major pathway for intracellular protein degradation. Proteasome dependent protein quality control participates in cell cycle, immune response and apoptosis. Therefore, the UPS is in focus of therapeutic investigations and the development of pharmaceutical agents. Detailed analyses on proteasome structure and function are the foundation for drug development and clinical studies. Proteomic approaches contributed significantly to our current knowledge in proteasome research. In particular, 2-DE has been essential in facilitating the development of current models on molecular composition and assembly of proteasome complexes. Furthermore, developments in MS enabled identification of UPS proteins and their PTMs at high accuracy and high-throughput. First results on global characterization of the UPS are also available. Although the UPS has been intensively investigated within the last two decades, its functional significance and contribution to the regulation of cell and tissue phenotypes remain to be explored. This review recapitulates a variety of applied proteomic approaches in proteasome exploration, and presents an overview of current technologies and their potential in driving further investigations.     

Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis

Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-alpha(2) activity by 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with beta-guanidinopropionic acid (beta-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.     

ncRNAs associated with drug resistance and the therapy of digestive system neoplasms

Digestive system cancer remains a common cancer and the main cause of cancer-related death worldwide. Drug resistance is a major challenge in the therapy of digestive system cancer, and represents a primary obstacle in the treatment of cancer by restricting the efficiency of both traditional chemotherapy and biological therapies. Existing studies indicate that noncoding RNAs play an important role in the evolution and progression of drug resistance in digestive system cancer, mainly by modulating drug transporter-related proteins, DNA damage repair, cell-cycle-related proteins, cell apoptosis-related proteins, drug target-related proteins, and the tumor microenvironment. In this review, we address the potential mechanisms of ncRNAs underlying drug resistance in digestive system tumors and discuss the possible application of ncRNAs against drug resistance in digestive system tumors.