In the last decades, the staggering progress in nanotechnology brought around a wide and heterogeneous range of nanoparticle-based platforms for the diagnosis and treatment of many diseases. Most of ...these systems are designed to be administered intravenously. This administration route allows the nanoparticles (NPs) to widely distribute in the body and reach deep organs without invasive techniques. When these nanovectors encounter the biological environment of systemic circulation, a dynamic interplay occurs between the circulating proteins and the NPs, themselves. The set of proteins that bind to the NP surface is referred to as the protein corona (PC). PC has a critical role in making the particles easily recognized by the innate immune system, causing their quick clearance by phagocytic cells located in organs such as the lungs, liver, and spleen. For the same reason, PC defines the immunogenicity of NPs by priming the immune response to them and, ultimately, their immunological toxicity. Furthermore, the protein corona can cause the physical destabilization and agglomeration of particles. These problems induced to consider the PC only as a biological barrier to overcome in order to achieve efficient NP-based targeting. This review will discuss the latest advances in the characterization of PC, development of stealthy NP formulations, as well as the manipulation and employment of PC as an alternative resource for prolonging NP half-life, as well as its use in diagnostic applications.
We report an advanced lithium-ion battery based on a graphene ink anode and a lithium iron phosphate cathode. By carefully balancing the cell composition and suppressing the initial irreversible ...capacity of the anode in the round of few cycles, we demonstrate an optimal battery performance in terms of specific capacity, that is, 165 mAhg–1, of an estimated energy density of about 190 Wh kg–1 and a stable operation for over 80 charge–discharge cycles. The components of the battery are low cost and potentially scalable. To the best of our knowledge, complete, graphene-based, lithium ion batteries having performances comparable with those offered by the present technology are rarely reported; hence, we believe that the results disclosed in this work may open up new opportunities for exploiting graphene in the lithium-ion battery science and development.
The achievement of a new generation of lithium-ion battery, suitable for a continuously growing consumer electronic and sustainable electric vehicle markets, requires the development of new, ...low-cost, and highly performing materials. Herein, we propose a new and efficient lithium-ion battery obtained by coupling exfoliated graphite/graphene nanosheets (EGNs) anode and high-voltage, spinel-structure cathode. The anode shows a capacity exceeding by 40% that ascribed to commercial graphite in lithium half-cell, at very high C-rate, due to its particular structure and morphology as demonstrated by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The Li-ion battery reveals excellent efficiency and cycle life, extending up to 150 cycles, as well as an estimated practical energy density of about 260 Wh kg–1, that is, a value well exceeding the one associated with the present-state Li-ion battery.
Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA ...analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease.
What's new?
Liquid biopsy of circulating cell‐free DNA (cfDNA) is an emerging approach in cancer screening that can potentially facilitate the early detection of tumor‐derived molecular alterations. In our study, designed to explore the utility of liquid biopsy in colorectal cancer (CRC) detection, cfDNA quantification was found to be sufficiently capable of differentiating CRC patients from healthy controls and from patients with adenomatous polyps. Moreover, among CRC patients, those with higher cfDNA levels experienced worse prognosis, suggesting that cfDNA dosage predicts survival. CRC detection through cfDNA quantification may be improved through the addition of methylation biomarkers.
Lithium-sulfur (Li-S) batteries are promising candidates for next generation electrical energy storage devices due to their high specific energy. Despite intense research, there are still a number of ...technical challenges in developing a high performance Li-S battery. To elucidate the issues, an all solid-state Li-S battery was fabricated using Li3PS4 solid electrolyte. Most of the theoretical capacity of sulfur, 1600 mAhg−1 was attained in the initial discharge-charge cycles with a high coulombic efficiency approaching 99%. To verify the benefit of the solid state electrolyte, galvanostatic stripping-deposition tests were also carried out on a symmetrical Li/Li cell and compared with those of a liquid electrolyte (1 M- lithium bis(trifluoromethane sulfonyl) imide (LiTFSI) in a mixture of 1,3-dioxolane (DOL)-diethoxyethane (DEE)). The kinetics and thermodynamics of the solid-state cell are discussed from the viewpoint of the charge transfer processes. This study demonstrates both the merits and drawbacks of using the solid sulfide electrolyte in a Li-S battery and facilitates the further improvement of this important high energy storage device.
In this work we characterize a solid-state lithium–sulfur battery using a Li2S–P2S5 glass-type electrolyte. The electrolyte is prepared by powder pellet-pressing and the effect of the applied ...pressure on the ionic conductivity as well as its temperature dependence is studied by electrochemical impedance spectroscopy. The lithium–sulfur battery electrochemical process is studied by potentiodynamic cycling with galvanostatic acceleration (PCGA) at an operating temperature of 80°C. The cycling behavior of the battery is studied by repeated charge/discharge in galvanostatic conditions. The results demonstrate that the electrolyte has a conductivity ranging from 1*10−4 to 5*10−3 S cm−1 by increasing the temperature from 0°C to 80°C, respectively. Furthermore, the PCGA measurement shows a maximum capacity referred versus sulfur mass of the order of 1200 mAh g−1, while the cycling test, performed at C/20, indicates a steady-state capacity of the order of 400 mAh g−1, a working voltage of 2.1V and a resulting theoretical energy density of 840Whkg−1. Considering the results we believe that the solid-state, lithium sulfur cell with the Li2S–P2S5 electrolyte may be proposed as high-energy density battery for safe, low-cost energy storage applications.
•A solid-state lithium–sulfur battery with a Li2S–P2S5 electrolyte is here reported•The electrolyte has high ionic conductivity and excellent stability against lithium•The lithium sulfur solid cell has a maximum capacity of 1200 mAh g−1.•The cell has a stable capacity of 400 mAh g−1 vs. sulfur and a working voltage of 2.1V•The solid battery is proposed as advanced, safe and low-cost energy storage system.
The mechanisms by which mitochondrial metabolism supports cancer anabolism remain unclear. Here, we found that genetic and pharmacological inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit ...of the pyruvate dehydrogenase complex (PDC), inhibits prostate cancer development in mouse and human xenograft tumor models by affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer, PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC controls the expression of sterol regulatory element-binding transcription factor (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors. Together, these findings demonstrate that both mitochondrial and nuclear PDC sustain prostate tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as a potential target for cancer therapy.
In this paper, we report a lithium-ion battery employing a lithium sulfide cathode and a silicon-based anode. The high capacity of the silicon anode and the high efficiency and cycling rate of the ...lithium sulfide cathode allowed optimal full cell balance. We show in fact that the battery operates with a very stable capacity of about 280 mAh g–1 at an average voltage of 1.4 V. To the best of our knowledge, this battery is one of the rare examples of lithium-metal-free sulfur battery. Considering the high theoretical capacity of the employed electrodes, we believe that the battery here reported may be of potential interest as high-energy, safe, and low-cost power source for electric vehicles.
Mass spectrometry-based proteomics is a key player in research efforts to characterize aberrant epigenetic alterations, including histone post-translational modifications and DNA methylation. Data ...generated by this approach complements and enrich datasets generated by genomic, epigenetic and transcriptomics approaches. These combined datasets can provide much-needed information on various mechanisms responsible for drug resistance, the discovery and validation of potential biomarkers for different diseases, the identification of signaling pathways, and genes and enzymes to be targeted by future therapies. The increasing use of high-resolution, high-accuracy mass spectrometers combined with more refined protein labeling and enrichment procedures enhanced the role of this approach in the investigation of these epigenetic modifications. In this review, we discuss recent MS-based studies, which are contributing to current research efforts to understand certain mechanisms behind drug resistance to therapy. We also discuss how these MS-based analyses are contributing to biomarkers discovery and validation.
Drug resistance remains one of the main causes of poor outcome in cancer therapy. It is also becoming evident that drug resistance to both chemotherapy and to antibiotics is driven by more than one ...mechanism. So far, there are at least eight recognized mechanisms behind such resistance. In this review, we choose to discuss one of these mechanisms, which is known to be partially driven by a class of transmembrane proteins known as ATP-binding cassette (ABC) transporters. In normal tissues, ABC transporters protect the cells from the toxic effects of xenobiotics, whereas in tumor cells, they reduce the intracellular concentrations of anticancer drugs, which ultimately leads to the emergence of multidrug resistance (MDR). A deeper understanding of the structures and the biology of these proteins is central to current efforts to circumvent resistance to both chemotherapy, targeted therapy, and antibiotics. Understanding the biology and the function of these proteins requires detailed structural and conformational information for this class of membrane proteins. For many years, such structural information has been mainly provided by X-ray crystallography and cryo-electron microscopy. More recently, mass spectrometry-based methods assumed an important role in the area of structural and conformational characterization of this class of proteins. The contribution of this technique to structural biology has been enhanced by its combination with liquid chromatography and ion mobility, as well as more refined labelling protocols and the use of more efficient fragmentation methods, which allow the detection and localization of labile post-translational modifications. In this review, we discuss the contribution of mass spectrometry to efforts to characterize some members of the ATP-binding cassette (ABC) proteins and why such a contribution is relevant to efforts to clarify the link between the overexpression of these proteins and the most widespread mechanism of chemoresistance.
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