Improving ionic conductivity of von-Alpen-type NASICON ceramic electrolytes via magnesium doping

NASICON (sodium (Na) superionic conductor) compounds have attracted considerable attention as promising solid electrolyte materials for advanced Na-based batteries. In this study, we investigated the improvement in ionic conductivities of von-Alpen-type NASICON (vA-NASICON) ceramic electrolytes by introducing a magnesium ion (Mg2+) as a heterogeneous element. The optimal Mg-doped vA-NASICON exhibited a high ionic conductivity of 3.64×10−3 S·cm−1, which was almost 80% higher than that of un-doped vA-NASICON. The changes in physicochemical properties of the vA-NASICONs through the Mg introduction were systematically analyzed, and their effects on the ionic conductivities of the vA-NASICON were studied in detail. When the optimal ratio of Mg2+ was used in a synthetic process, the relative density (96.6%) and grain boundary ionic conductivity (σgb) were maximized, which improved the total ionic conductivity (σt) of the vA-NASICON. However, when Mg2+ was introduced in excess, the ionic conductivity decreased because of the formation of an undesired sodium magnesium phosphate (NaxMgyPO4) secondary phase. The results of this study are expected to be effectively applied in the development of advanced sodium-based solid electrolytes with high ionic conductivities

Decolorization of malachite green by cytochrome c in the mitochondria of the fungus Cunninghamella elegans

We studied the decolorization of malachite green (MG) by the fungus Cunninghamella elegans. The mitochondrial activity for MG reduction was increased with a simultaneous increase of a 9-kDa protein, called CeCyt. The presence of cytochrome c in CeCyt protein was determined by optical absorbance spectroscopy with an extinction coefficient (E\u2085\u2085\u2080\u2013\u2085\u2083\u2085) of 19.7 \ub1 6.3 mM-\ub9 cm-\ub9 and reduction potential of + 261 mV. When purified CeCyt was added into the mitochondria, the specific activity of CeCyt reached 440 \ub1 122 \u3bcmol min-\ub9 mg-\ub9 protein. The inhibition of MG reduction by stigmatellin, but not by antimycin A, indicated a possible linkage of CeCyt activity to the Qo site of the bc1 complex. The RT-PCR results showed tight regulation of the cecyt gene expression by reactive oxygen species. We suggest that CeCyt acts as a protein reductant for MG under oxidative stress in a stationary or secondary growth stage of this fungus.Peer reviewed: YesNRC publication: Ye

Multiscale Phase Behaviors of Nematic Solids: A Short Review

Nematic liquid crystalline solids are novel smart materials of which mesogenic molecules are incorporated within their polymeric chains via crosslinking. The material exhibits many interesting phase behaviors and is envisaged to be harnessed as a key material of soft responsive structures that are adaptive to their surroundings. These behaviors are originated by intricate interactions between diverse phenomena ranging from molecular interactions, mesoscopic phase transition, and elasticity of macroscale. The modeling and analysis of the behavior, therefore, requires the multiscale point of view in that the vast design space of such material cannot be fully exploited otherwise. In this regard, the multiscale behaviors of the nematic solids are first visited, elucidating qualitative behaviors and research of individual physics. Further, the multiscale analysis approach applied to understand and harness the behaviors of the nematic liquid crystalline solids is then reviewed

HDAC8 Deacetylates HIF-1α and Enhances Its Protein Stability to Promote Tumor Growth and Migration in Melanoma

Melanoma is the most lethal type of skin cancer, and it causes more than 55,000 deaths annually. Although regional melanoma can be surgically removed, once melanoma metastasizes to other regions of the body, the survival rate drops dramatically. The current treatment options are chemotherapy, immunotherapy, and targeted therapy. However, the low response rate and the development of resistance necessitate the search for a novel therapeutic target in melanoma. Hypoxia-inducible factor-1 α (HIF-1α) is overexpressed in melanoma and plays a crucial role in driving malignant transformation in cancer cells. Here, we identified that histone deacetylase 8 (HDAC8) enhances the protein stability of HIF-1α. HDAC8 directly binds to and deacetylates HIF-1α, thereby promoting its protein stability. This, in turn, upregulates the transcriptional activity of HIF-1α and promotes the expressions of its target genes, such as hexokinase 2 (HK2) and glucose transporter 1 (GLUT1). The inhibition of HDAC8 suppresses the proliferation and metastasis of melanoma cells. Furthermore, HDAC8 is correlated with HIF1A expression and poor prognosis in samples from patients with melanoma. These findings uncover a novel epigenetic mechanism that maintains HIF-1α stability and implicates the potential of HDAC8 inhibitors for melanoma therapy

Pathological Role of HDAC8: Cancer and Beyond

Histone deacetylase 8 (HDAC8) is a class I HDAC that catalyzes the deacetylation of histone and non-histone proteins. As one of the best-characterized isoforms, numerous studies have identified interacting partners of HDAC8 pertaining to diverse molecular mechanisms. Consequently, deregulation and overexpression of HDAC8 give rise to diseases. HDAC8 is especially involved in various aspects of cancer progression, such as cancer cell proliferation, metastasis, immune evasion, and drug resistance. HDAC8 is also associated with the development of non-cancer diseases such as Cornelia de Lange Syndrome (CdLS), infectious diseases, cardiovascular diseases, pulmonary diseases, and myopathy. Therefore, HDAC8 is an attractive therapeutic target and various HDAC8 selective inhibitors (HDAC8is) have been developed. Here, we address the pathological function of HDAC8 in cancer and other diseases, as well as illustrate several HDAC8is that have shown anti-cancer effects

Modulation of RNase E Activity by Alternative RNA Binding Sites

<div><p>Endoribonuclease E (RNase E) affects the composition and balance of the RNA population in <i>Escherichia coli</i> via degradation and processing of RNAs. In this study, we investigated the regulatory effects of an RNA binding site between amino acid residues 25 and 36 (²⁴LYDLDIESPGHEQK³⁷) of RNase E. Tandem mass spectrometry analysis of the N-terminal catalytic domain of RNase E (N-Rne) that was UV crosslinked with a 5′-³²P-end-labeled, 13-nt oligoribonucleotide (p-BR13) containing the RNase E cleavage site of RNA I revealed that two amino acid residues, Y25 and Q36, were bound to the cytosine and adenine of BR13, respectively. Based on these results, the Y25A N-Rne mutant was constructed, and was found to be hypoactive in comparison to wild-type and hyperactive Q36R mutant proteins. Mass spectrometry analysis showed that Y25A and Q36R mutations abolished the RNA binding to the uncompetitive inhibition site of RNase E. The Y25A mutation increased the RNA binding to the multimer formation interface between amino acid residues 427 and 433 (⁴²⁷LIEEEALK⁴³³), whereas the Q36R mutation enhanced the RNA binding to the catalytic site of the enzyme (⁶⁵HGFLPL*K⁷¹). Electrophoretic mobility shift assays showed that the stable RNA-protein complex formation was positively correlated with the extent of RNA binding to the catalytic site and ribonucleolytic activity of the N-Rne proteins. These mutations exerted similar effects on the ribonucleolytic activity of the full-length RNase E <i>in vivo</i>. Our findings indicate that RNase E has two alternative RNA binding sites for modulating RNA binding to the catalytic site and the formation of a functional catalytic unit.</p></div

Mass spectrometry analysis of wild-type and mutant N-Rne proteins obtained from UV-crosslinking.

<p>(A) Partial peptide sequence of the wild-type N-Rne showing the regions of an internal standard (IS) sequence and nucleoside-bound peptides, denoted as R, P, and M sites, corresponding to an uncompetitive site (a.a. 26–37), a catalytic site (a.a. 65–71) and an allosteric site (a.a. 427–433), respectively. (B) Extracted ion chromatograms (XICs: panels a, c and e) and corrected PSM levels (panels b, d and f) of nucleoside-bound peptides and their parent peptides of wild-type N-Rne (a and b) and Q36R (c and d) and Y25A (e and f) mutants. Nucleoside-bound peptide peaks in the XICs are denoted with asterisks to the right of the symbols, R, P, and M, corresponding to the trypsin/chymotrypsin-digested peptides, ²⁶DLDIESPGHEQK³⁷, ⁶⁵HGFLPLK⁷¹, and ⁴²⁷LIEEEALK⁴³³, respectively, in the sequence of the wild-type N-Rne. The Y25A and Q36R mutants replace the R sequence with ²⁴LADLDIESPGHEQK³⁷ and ²⁶DLDIESPGHER³⁶, respectively. In the right panels, the numbers of peptide spectrum matches (PSMs) of the parental and nucleoside-bound peptides are shown in parentheses above the black and gray bars of the corrected PSM levels. The relative levels of internal standard (IS), ¹⁶VALVDGQR²³, are expressed as 100 and one unit for the calculation of relative intensity of XIC and correction of PSM levels, respectively. Tandem mass spectrometry data are given in Table S1 and Figure S2 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090610#pone.0090610.s001" target="_blank">File S1</a>.</p