Most synthetic building blocks self-assemble into one- or three-dimensional architectures. However, fewer examples have been reported on the aggregation of amphiphiles to form optically-active two-dimensional (2D) structures. Herein, we report the self-assembly of tetraphenylethylene (TPE)-containing hydrophilic dendrons into 2D sheet structures in aqueous methanol solution. TEM and AFM investigations showed that the self-assembly of disubstituted TPE generates helical nanofibers as an intermediate structure which, in turn, laterally associate into a chiral sheet structure with a thickness of 4.6 nm, whereas tetrasubstituted TPE self-assembles into a nonchiral sheet structure with a thickness of 3.8 nm. In great contrast to the nonchiral sheets, the chiral sheets are able to preferentially absorb the d-enantiomer in a racemic phenylalanine derivative solution accompanied by fluorescence enhancement, thus indicating that the single-layered chiral sheets act as an enantioselective membrane that can be used for fluorescence sensing. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Invited for this month's cover are the groups of George John at the City College of New York-CUNY, Leela R. Arava at Wayne State University, and Pulickel Ajayan at Rice University. The image portraits future prospects of bioderived molecular electrodes for next-generation energy-storage materials. The Minireview itself is available at 10.1002/cssc.201903589. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.A number of hormones and growth factors stimulate target cells via the second messenger pathways, which in turn regulate cellular phenotypes. Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that facilitates numerous signal transduction pathways; its production in cells is tightly balanced by ligand-stimulated receptors that activate adenylate cyclases (ACs), that is, "source" and by phosphodiesterases (PDEs) that hydrolyze it, that is, "sinks." Because it regulates various cellular functions, including cell growth and differentiation, gene transcription and protein expression, the cAMP signaling pathway has been exploited for the treatment of numerous human diseases. Reduction in cAMP is achieved by blocking "sources"; however, elevation in cAMP is achieved by either stimulating "source" or blocking "sinks." Here we discuss an alternative paradigm for the regulation of cellular cAMP via GIV/Girdin, the prototypical member of a family of modulators of trimeric GTPases, Guanine nucleotide Exchange Modulators (GEMs). Cells upregulate or downregulate cellular levels of GIV-GEM, which modulates cellular cAMP via spatiotemporal mechanisms distinct from the two most often targeted classes of cAMP modulators, "sources" and "sinks." A network-based compartmental model for the paradigm of GEM-facilitated cAMP signaling has recently revealed that GEMs such as GIV serve much like a "tunable valve" that cells may employ to finetune cellular levels of cAMP. Because dysregulated signaling via GIV and other GEMs has been implicated in multiple disease states, GEMs constitute a hitherto untapped class of targets that could be exploited for modulating aberrant cAMP signaling in disease states. This article is categorized under Models of Systems Properties and Processes > Mechanistic Models Biological Mechanisms > Cell Signaling. © 2020 Wiley Periodicals LLC.Chemotherapy still constitutes the standard of care for the treatment of most neoplastic diseases. Certain chemotherapeutics from the oncological armamentarium are able to trigger pre-mortem stress signals that lead to immunogenic cell death (ICD), thus inducing an antitumor immune response and mediating long-term tumor growth reduction. Here, we used an established model, built on artificial intelligence to identify, among a library of 50,000 compounds, anticancer agents that, based on their molecular descriptors, were predicted to induce ICD. This algorithm led us to the identification of dactinomycin (DACT, best known as actinomycin D), a highly potent cytotoxicant and ICD inducer that mediates immune-dependent anticancer effects in vivo. Since DACT is commonly used as an inhibitor of DNA to RNA transcription, we investigated whether other experimentally established or algorithm-selected, clinically employed ICD inducers would share this characteristic. As a common leitmotif, a panel of pharmacological ICD stimulators inhibited transcription and secondarily translation. These results establish the inhibition of RNA synthesis as an initial event for ICD induction. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co-expression network of transcriptomics data in addition to laser-microdissected proteomics from human and murine prostate FFPE samples. We show up-regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up-regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis. https://www.selleckchem.com/products/zanubrutini-bgb-3111.html © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Aging involves coordinated yet distinct changes in organs and systems throughout life, including changes in essential trace elements. However, how aging affects tissue element composition (ionome) and how these changes lead to dysfunction and disease remain unclear. Here, we quantified changes in the ionome across eight organs and 16 age groups of mice. This global profiling revealed novel interactions between elements at the level of tissue, age, and diet, and allowed us to achieve a broader, organismal view of the aging process. We found that while the entire ionome steadily transitions along the young-to-old trajectory, individual organs are characterized by distinct element changes. The ionome of mice on calorie restriction (CR) moved along a similar but shifted trajectory, pointing that at the organismal level this dietary regimen changes metabolism in order to slow down aging. However, in some tissues CR mimicked a younger state of control mice. Even though some elements changed with age differently in different tissues, in general aging was characterized by the reduced levels of elements as well as their increased variance.