Chemical Tailoring of Functional Graphene-Based Nanocomposites by Simple Stacking, Cutting and Folding

Got your work cut out: Stacking, cutting, and folding have been demonstrated to be a viable approach for the fabrication of robust nanocomposites from large-area graphene films and polymers. This method opens up an effective route towards strong, durable, and multifunctional nanomaterials with fascinating properties

FOXO transcription factors protect against the diet-induced fatty liver disease

Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls. However, the HFC diet led to more severe liver injury and fibrosis compared to the HFD diet. At the molecular levels, hepatic Foxo1/3/4 deficiency triggered a significant increase in the expression of inflammatory and fibrotic genes including Emr1, Ccl2, Col1a1, Tgfb, Pdgfrb, and Timp1. Thus, our data suggest that FOXO transcription factors play a salutary role in the protection against the diet-induced fatty liver disease

Prediction and Validation of Transcription Factors Modulating the Expression of Sestrin3 Gene Using an Integrated Computational and Experimental Approach

SESN3 has been implicated in multiple biological processes including protection against oxidative stress, regulation of glucose and lipid metabolism. However, little is known about the factors and mechanisms controlling its gene expression at the transcriptional level. We performed in silico phylogenetic footprinting analysis of 5 kb upstream regions of a diverse set of human SESN3 orthologs for the identification of high confidence conserved binding motifs (BMo). We further analyzed the predicted BMo by a motif comparison tool to identify the TFs likely to bind these discovered motifs. Predicted TFs were then integrated with experimentally known protein-protein interactions and experimentally validated to delineate the important transcriptional regulators of SESN3. Our study revealed high confidence set of BMos (integrated with DNase I hypersensitivity sites) in the upstream regulatory regions of SESN3 that could be bound by transcription factors from multiple families including FOXOs, SMADs, SOXs, TCFs and HNF4A. TF-TF network analysis established hubs of interaction that include SMAD3, TCF3, SMAD2, HDAC2, SOX2, TAL1 and TCF12 as well as the likely protein complexes formed between them. We show using ChIP-PCR as well as over-expression and knock out studies that FOXO3 and SOX2 transcriptionally regulate the expression of SESN3 gene. Our findings provide an important roadmap to further our understanding on the regulation of SESN3

SIRT6 protects against palmitate-induced pancreatic β-cell dysfunction and apoptosis

Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, SIRT6 has been shown to regulate insulin secretion in response to glucose stimulation. However, what roles SIRT6 play in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of high palmitate. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis

2D materials beyond graphene for high-performance energy storage applications

Energy crisis is one of the most urgent and critical issues in our modern society. Currently, there is an increasing demand for efficient, low-cost, light-weight, flexible and environmentally benign, small-, medium-, and large-scale energy storage devices, which can be used to power smart grids, portable electronic devices, and electric vehicles. Novel electrode materials, with a high energy density at high power are urgently needed for realizing high-performance energy storage devices. The recent development in the field of 2D materials, including both graphene and other layered systems, has shown promise for a wide range of applications. In particular, graphene analogues, due to their remarkable electrochemical properties, have shown great potential in energy-related applications. This review aims at providing an overview of current research and important advances on the development of 2D materials beyond graphene for supercapacitors and batteries. The major challenges to be tackled, and more generally the future directions in the field, are also highlighted

Emerging applications of nanotechnology for diagnosis and therapy of disease: a review

Nanotechnology is of increasing interest in the fields of medicine and physiology over recent years. Its application could considerably improve disease detection and therapy, and although the potential is considerable, there are still many challenges, which need to be addressed before it is accepted in routine clinical use. This review focuses on emerging applications that nanotechnology could enhance or provide new approaches in diagnoses and therapy. The main focus of recent research centres on targeted therapies and enhancing imaging; however, the introduction of nanomaterial into the human body must be controlled, as there are many issues with possible toxicity and long-term effects. Despite these issues, the potential for nanotechnology to provide new methods of combating cancer and other disease conditions is considerable. There are still key challenges for researchers in this field, including the means of delivery and targetting in the body to provide effective treatment for specific disease conditions. Nanoparticles are difficult to measure due to the size and physical properties; hence there is still a great need to improve physiological measurements method in the field to ascertain how effective their use is in the human subject. This review is a brief snapshot into the fast changing research field of measurement and physiological links to nanoparticle use and its potential in the future

O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/β, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or its O-GlcNAcylation re-sensitizes resistant cells to palbociclib. Moreover, clinical studies confirm the activation of MITF in tumors from patients who are palbociclib-resistant or undergoing palbociclib treatment. Collectively, our studies shed light on the mechanism regulating palbociclib resistance and present clinical evidence for developing therapeutic approaches to treat CDK4/6i-resistant breast cancer patients

Molecule-by-Molecule Writing Using a Focused Electron Beam

The resolution of lithography techniques needs to be extended beyond their current limits to continue the trend of miniaturization and enable new applications. But what is the ultimate spatial resolution? It is known that single atoms can be imaged with a highly focused electron beam. Can single atoms also be written with an electron beam? We verify this with focused electron-beam-induced deposition (FEBID), a direct-write technique that has the current record for the smallest feature written by (electron) optical lithography. We show that the deposition of an organometallic precursor on graphene can be followed molecule-by-molecule with FEBID. The results show that mechanisms that are inherent to the process inhibit a further increase in control over the process. Hence, our results present the resolution limit of (electron) optical lithography techniques. The writing of isolated, subnanometer features with nanometer precision can be used, for instance, for the local modification of graphene and for catalysis.</p