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In this work, three iridium(III) tetrazolato complexes have been designed and successfully synthesized. Beside photophysical properties, their performances in protein staining have been comprehensively investigated in this work for the first time. Notably, these iridium(III) tetrazolato complexes with high quantum efficiency exhibited much better protein staining properties than the commercial agent Coomassie Brilliant Blue (CBB) under the same experimental conditions, which may pave the way to explore new efficient iridium-based protein staining agents both for commercial markets and academic research in the future.

Purpose: This study aimed to investigate whether long noncoding RNA (lncRNA) LINC00467 could regulate proliferative and invasive abilities of glioma cells via p53 and DNA methyltransferase 1 (DNMT1), so as to participate in the occurrence and progression of glioma. Methods: LINC00467 expression in glioma was analyzed by GEPIA database and LINC00467 expression in glioma cell lines was detected by qRT-PCR. The regulatory effects of LINC00467 and p53 on proliferative, invasive capacities and cell cycle were conducted by CCK-8 and EdU assays, transwell assay and flow cytometry, respectively. The binding conditions between LINC00467, DNMT1 and p53 were determined by RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays. Western blot was conducted to determine whether LINC00467 could regulate p53 in glioma cells. Finally, rescue experiments were carried out to evaluate whether LINC00467 regulates proliferative and invasive abilities of glioma cells through p53. Results: The expression of LINC00467 was significantly up-regulated in tumor samples than that in normal samples, which was not correlated with patient survival time. Besides, expression of LINC00467 was higher in glioma cells than that of negative control cells. Upregulation of LINC00467 promoted proliferative and invasive abilities, and accelerated cell cycle in G0/G1 phase of U87 and LN229 cells. The results of RIP and ChIP assays demonstrated that LINC00467 could bind to DNMT1 and inhibit p53 expression. Overexpression of p53 partially reversed the enhancement of LINC00467 on proliferative and invasive abilities of glioma cells. Conclusion: These results indicated that high expression of LINC00467 could promote proliferative and invasive abilities of glioma cells through targeting inhibition of p53 expression by binding to DNMT1.

Human herpesvirus 6 (HHV-6) belongs to the betaherpesvirus subfamily and is divided into two distinct species, HHV-6A and HHV-6B. HHV-6 can infect nerve cells and is associated with a variety of nervous system diseases. Recently, the association of HHV-6A infection with Alzheimer's disease (AD) has been suggested. The main pathological phenomena of AD are the accumulation of β-amyloid (Aβ), neurofibrillary tangles, and neuroinflammation; however, the specific molecular mechanism of pathogenesis of AD is not completely clear. In this study, we focused on the effect of HHV-6A U4 gene function on Aβ expression. Coexpression of HHV-6A U4 with amyloid precursor protein (APP) resulted in inhibition of ubiquitin-mediated proteasomal degradation of APP. Consequently, accumulation of β-amyloid peptide (Aβ), insoluble neurofibrillary tangles, and loss of neural cells may occur. Immunoprecipitation coupled with mass spectrometry (IP-MS) showed that HHV-6A U4 protein interacts with E3 ubiquitin ligase composed of DDB1 and cullin 4B, which is also responsible for APP degradation. We hypothesize that HHV-6A U4 protein competes with APP for binding to E3 ubiquitin ligase, resulting in the inhibition of APP ubiquitin modification and clearance. Finally, this leads to an increase in APP expression and Aβ deposition, which are the hallmarks of AD. These findings provide novel evidence for the etiological hypothesis of AD, which can contribute to the further analysis of the role of HHV-6A in AD. IMPORTANCE The association of HHV-6A infection with Alzheimer’s disease has attracted increasing attention, although its role and molecular mechanism remain to be established. Our results here indicate that HHV-6A U4 inhibits amyloid precursor protein (APP) degradation. U4 protein interacts with CRLs (cullin-RING E3 ubiquitin-protein ligases), which is also responsible for APP degradation. We propose a model in which U4 competitively binds to CRLs with APP, resulting in APP accumulation and Aβ generation. Our findings provide new insights into the etiological hypothesis of HHV-6A in AD that can help further analyses.

Our previous studies indicate that long noncoding RNA (lncRNA) LINC00467 can act as an oncogene to participate in the malignant progression of glioma, but the underlying molecular mechanism remains to be studied further. This study aimed to explore the biological role of the LINC00467/miR-339-3p/ inositol hexakisphosphate kinase 2 (IP6K2) regulatory axis in glioma. The Cancer Genome Atlas (TCGA), Oncomine databases and reverse transcription‑quantitative PCR (RT‑qPCR) were used to analyze IP6K2 expression in glioma. RT-PCR, EdU and transwell assays were conducted to observe the effect of IP6K2 on glioma cell proliferation, migration and invasion. Using bioinformatics analysis, RT-PCR, and dual luciferase reporter gene assay, the potential role of the LINC00467/miR-339-3p/IP6K2 regulatory axis in glioma was verified. The results showed that IP6K2 was up-regulated in glioma tissues and cell lines. Moreover, the expression level of IP6K2 was correlated with the clinical features of glioma patients.

U26 is one of the roseolovirus unique genes with unknown function. Human herpesvirus 6B (HHV-6B) pU26 is predicted to be an 8-transmembrane protein containing a mitochondrion location signal. Here, we analyzed U26 function during HHV-6B infection and find that (i) HHV-6B U26 is expressed at a very early stage during HHV-6B infection, and knockdown of it results in a significant decrease of HHV-6B progeny virus production; (ii) U26 inhibits the activation of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)/mitochondrial antiviral signaling protein (MAVS) signaling pathway, an important anti-HHV-6B infection innate immune response, by targeting MAVS protein for degradation; and (iii) a portion of U26 locates to the mitochondria, which could affect the mitochondrial membrane potential and finally leads to MAVS degradation. These findings indicate that HHV-6B U26 is a novel antagonistic viral factor against host innate antiviral immunity.IMPORTANCE HHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help develop a new therapy against HHV-6B infection.

In order to improve the reliability of low-earth-orbit (LEO) satellite communications, in this paper, we propose a forwarding protocol for cooperative LEO satellites communication system, called threshold-and-forward protocol. Note that multi-satellites can receive and forward the user's signal. After one satellite receives the signal, it compares the power of the signal with a given threshold value. If the signal is higher than the threshold value, the signal is limited to a given value. Otherwise, it is linearly processed and forwarded to the receiver. Receiver combines the signal from different satellites and tries to decode it. The P.D.F. of signal with different forwarding protocols are analyzed. Simulation results show that the performance of the proposed forwarding protocol outperforms the existing forwarding protocols such as amplify-and-forward, demodulate-and-forward and estimate-and-forward in the multi-satellites cooperative scenario.

Human herpesviruses 6A and 6B (HHV-6A and HHV-6B, respectively) are two virus species in the betaherpesvirus subfamily that exhibit T cell tropism. CD46 and CD134 are the cellular receptors for HHV-6A and HHV-6B, respectively. Interestingly, the efficiency of HHV-6A/6B entry is different among different types of target cells despite similar receptor expression levels on these cells. Here, we found that the cellular factor gp96 (also known as glucose-regulated protein 94 [GRP94]) is expressed on the cell surface and interacts with viral glycoprotein Q1 (gQ1) during virus entry. gp96 cell surface expression levels are associated with the efficiency of HHV-6A and HHV-6B entry into target cells. Both loss-of-function and gain-of-function experiments indicated that gp96 plays an important role in HHV-6 infection. Our findings provide new insight into the HHV-6 entry process and might suggest novel therapeutic targets for HHV-6 infection. IMPORTANCE Although new clinical importance has been revealed for human herpesviruses 6A (HHV-6A) and 6B, much is still unknown about the life cycles of these viruses in target cells. We identified a novel cellular factor, gp96, that is critical for both HHV-6A and -6B entry into host cells. As gp96 can function as an adjuvant in vaccine development for both infectious agents and cancers, it can be a potential therapeutic target for infection by these two viruses.

Liposomes are extensively used as drug carriers because of their biocompatibility, low toxicity, and controlled release properties, however challenges exist in the control of their particle size, surface properties and targeting functionality. In this work, we report a peptide–lipid nanoparticle platform that can achieve nanoparticle formation, surface functionalization and hydrophobic drug loading in an integrated assembly process. A designer peptide that harbors bivalent amphipathic α-helices linked by a central loop (ALA peptide) was used to encapsulate lipid nanoparticles (LNPs). The bivalency design affords higher peptide helicity and lipid-packaging efficiency, and allows encapsulated hydrophobic molecules for more stability under long-term storage. The central loop structure displays sufficient surface exposure as demonstrated by the interaction between penta-histidine installed LNPs and Ni-NTA agarose. RGD-inserted and cytotoxic iridium complex-encapsulated LNPs showed preferential entry and selective cytotoxicity to integrin high expression cancer cells, while showing reduced toxicity to non-cancer cells. Further study indicates that a constrained cyclic conformation of RGD is required to fully exert targeting capability, suggesting an intact structural exposure on the LNP surface. In summary, we demonstrate a simple yet effective method of peptide-based LNP surface modification with potential for various targeted deliveries of hydrophobic drugs.

Three new luminescent platinum(ii) complexes with bidentate C^N and O^O ligands have been designed and synthesized in this work. Along with the changing of C^N ligands, the emission peaks of these complexes range from 489 to 629 nm and the photoluminescence quantum efficiencies are up to 55% at room temperature. DFT and TD-DFT calculations have also been employed to investigate the ground and excited states of these platinum(ii) complexes. Most importantly, these platinum(ii) complexes with bidentate ligands have almost no cytotoxicity towards HeLa cells and their applications in living cell imaging and protein staining are focused on in this work.

Additional file 5 Nonsynonymous and synonymous mutations in the cox1 gene of isopod mitogenomes. The numbers of nonsynonymous (dN) and synonymous (dS) mutations are shown in grey above the branches (dN/dS), and their ratios (ω) in red, below the branch. The numbers were inferred using free-ratio branch evolutionary model implemented in the ete-evol tool. The phylogram shown in Fig. 3 was used for the analysis. Corresponding GenBank numbers are shown next to species names.

Additional file 2 18S-based phylogenetic analysis of the entire isopod dataset. The analysis was conducted using Maximum Likelihood algorithm and nucleotide sequences. Lengths are shown on the branches, GenBank numbers next to species names, and taxonomic identity (family and suborder) to the right. The studied specimen is named “Argeia pugettensis 18S new”.

Additional file 8 Alignment of the 3′ end of selected isopod nad6 orthologues with the A. pugettensis ORF identified in the NCR between pseudo-cytb-2 and trnS2.

Additional file 3 Branch lengths inferred using mitochondrial phylogenomics of Isopoda (nucleotides dataset). Phylogenetic reconstruction was conducted using nucleotides of concatenated 13 protein-coding genes and ML algorithm. The figure shows (from left to right): a phylogram with branch lengths shown, names of taxa with GenBank numbers for mitogenomes, GC skew on the entire mitochondrial majority strand, and suborder. Limulus polyphemus is the outgroup.

Additional file 6 Primers, organization, size confirmation, cox1 sequencing chromatogram and palindromic repeat analysis.

A new species of the genus Xenylla Tullberg, 1869 is described. The new species, Xenylla weinerae sp. nov., from China, resembles X. acauda Gisin, 1947, X. brevicauda Tullberg, 1869, X. caudata Jordana, 1993, X. lesnei Denis, 1935, X. nirae Gama & Oliveira, 1994, X. wandae Queiroz & Mendonça, 2016 and X. vanharteni Weiner et al., 2012 due to unique feature––six thickened cylindrical sensilla on antennal segment IV. X. weinerae sp. nov. having moderately modified chaetotaxy (b h1 h2 q t, head with dorsal setae l1 and l3 subequal, dorsal setae a3 on Abd. IV present) and well-developed furca (mucro separated from the dens, bearing 2 setae) is also similar to some populations of X. obscura Imms, 1912 sensu Thibaud et al. (2004). An identification key to Asian Xenylla species is provided.

In the field of peptide drug discovery, structural constraining and fluorescent labeling are two sought-after techniques important for both basic research and pharmaceutical development. In this work, we describe an easy-to-use approach for simultaneous peptide cyclization and luminescent labeling based on iridium(III)-histidine coordination (Ir-HH cyclization). Using a series of model peptides with histidine flanking each terminus, the binding activity and reaction kinetics of Ir-HH cyclization of different ring sizes were characterized. In the series, Ir-HAnH (n = 2, 3) with moderate ring sizes provides appropriate flexibility and proper distance between histidines for cyclic formation, which leads to the best binding affinity and structural stability in physiological conditions, as compared to other Ir-HH-cyclized peptides with smaller (n = 0, 1) or larger (n = 4, 5) ring sizes. Ir-HRGDH, an Ir-HH-cyclized peptide containing integrin targeting motif Arg-Gly-Asp (RGD), showed better targeting affinity than its linear form and enhanced membrane permeability in comparison with fluorescein-labeled cyclic RGDyK peptide. Cell death inducing peptide KLA-linked Ir-HRGDH (Ir-HRGDH-KLA) showed dramatically enhanced cytotoxicity and high selectivity for cancer cells versus noncancer cells. These data demonstrate that the method conveniently combines structural constraining of peptides with luminescent imaging capabilities, which facilitates functional and intracellular characterization of potential peptide-based drug leads, thus introducing a new tool to meet emerging needs in medicinal research.

The cellular behavior and toxicity effect of organometallic complexes depend largely on their peripheral ligands. In this study, we have synthesized a series of novel luminescent cationic iridium(III) complexes by tuning the ancillary N(∧)N ligand based on a structure [Ir(ppy)2(N(∧)N)](+) (ppy = 1-phenyl-pyridine; N(∧)N = 2,2'-bipyridine (bpy, 1) or phenanthroline (phen, 2) or 4,7-diphenyl-1,10- phenanthroline (DIP, 3)). As the size of coordinated N(∧)N ligand increases, absorbance/emission efficiency, quantum yields, lipophilicity, and cell uptake rates of the complexes also increase, in a general order: 321. All three complexes display anticancer activity, with 3 exhibiting the highest cellular uptake efficiency and the greatest cytotoxic activities in several cancer cell lines with IC50s lower than that of cisplatin. Because of its strong hydrophobic nature, the death inducer 3 was found to accumulate favorably to endoplasmic reticulum (ER) and to cause ER stress in cells. The fast cytosolic release of calcium from stressed ER disturbed the morphology and function of mitochondria, initiating an intrinsic apoptotic pathway. Understanding of the cell death mechanism would help further structure-activity optimization on these novel Ir(III) complexes as emerging cancer therapeutics.

Increasing evidence has accrued which indicates that mesenchymal stem cells (MSCs) have a potential clinical value in the treatment of certain diseases. Globally, nonalcoholic steatohepatitis (NASH) is a widespread disorder. In the present study, MSCs were isolated successfully from compact bone and a mouse model of NASH was established as achieved with use of a methionine-choline deficient (MCD) diet. Compact bone-derived MSCs transplantation reduced MCD diet-induced weight loss, hepatic lipid peroxidation, steatosis, ballooning, lobular inflammation and fibrogenesis. It was shown that MSCs treatment hampered MCD diet-induced proliferation of CD4+ IFN-γ+ and CD4+IL-6+ T spleen cells. In addition, CD4+IL-17+ lymphocytes that associated with anti-inflammation show little change in MCD as well as in MCD+MSCs splenocytes. We conclude that MSCs may have a potential clinical value upon NASH, through their capacity to suppress activation of CD4+ IFN-γ+ and CD4+IL-6+ lymphocytes.

Cationic amphipathic peptides (CAPs) are known to be able to cause membrane destabilization and induce cell death, yet how the hydrophobicity, amphipathicity, and lysine (K)/arginine (R) composition synergistically affect the peptide activity remains incompletely understood. Here, we designed a panel of peptides based on the well-known anticancer peptide KLA. Increasing hydrophobicity enhanced the cytotoxicities of both the K- and R-rich peptides. Peptides with an intact amphipathic helical interface can cause instant cell death through a membrane lysis mechanism. Interestingly, rearranging the residue positions to minimize amphipathicity caused a great decrease of cytotoxicity to the K-rich peptides but not to the R-rich peptides. The amphipathicity-minimized R-rich peptide 6 (RL2) (RLLRLLRLRRLLRL-NH2) penetrated the cell membrane and induced caspase-3-dependent apoptotic cell death. We found that the modulation of hydrophobicity, amphipathicity, and K/R residues leads to distinct mechanisms of action of cationic hydrophobic peptides. Amphipathicity-reduced, arginine-rich cationic hydrophobic peptides (CHPs) may represent a new class of peptide therapeutics.

This article reports a new class of luminescent metal complexes, biscyclometalated iridium(III) complexes with an ancillary bathophenanthroline disulfonate ligand, for staining protein bands that are separated by electrophoresis. The performances of these novel staining agents have been studied in comparison with tris(bathophenanthroline disulfonate) ruthenium(II) tetrasodium salt (i.e. RuBPS) using a commercially available imaging system. The staining agents showed different limits of detection, linear dynamic ranges, and protein-to-protein variations. The overall performances of all three stains were found to be better than or equivalent to RuBPS under the experimental conditions.

This article reports a new class of luminescent metal complexes, biscyclometalated iridium(III) complexes with an ancillary bathophenanthroline disulfonate ligand, for staining protein bands that are separated by electrophoresis. The performances of these novel staining agents have been studied in comparison with tris(bathophenanthroline disulfonate) ruthenium(II) tetrasodium salt (i.e. RuBPS) using a commercially available imaging system. The staining agents showed different limits of detection, linear dynamic ranges, and protein-to-protein variations. The overall performances of all three stains were found to be better than or equivalent to RuBPS under the experimental conditions.

There are two levels of higher education in China: one is higher education institutes, consists of junior colleges, four-year colleges and comprehensive universities. The other one is higher vocational education institutes, consists of higher vocational colleges only, that is to say, the student studying in that ones cannot get the bachelor certification. But with the development of Chinese economy and living standard, the companies need higher skilled talents cultivated. Except for employment, the students long for continuing education. However, they found there was no way to choose when they graduated from the higher vocational colleges. They must enroll four-year colleges to get bachelor degree, not certification, which were not suitable to their learned knowledge. In China, there are two different kinds of higher education, either professional or academic. However there is no higher diploma for students in higher vocational education. It is necessary to build the higher vocational education system including junior colleges, four-year level colleges and graduate level colleges. Here we discuss the route choice including education objective, teaching mode, curriculum, practical exercise and setting standard.

Five iridium(III) complexes with two N-heterocyclic carbene (NHC) ligands and an ancillary ligand have been designed and successfully synthesized. With multicolor photoluminescence and low toxicity, these carbene complexes were tested, for the first time, as living cell imaging reagents and showed promise for application beyond the OLED (organic light emitting diode) area.

A new species of the Hypogastrura trybomi group is described from Shanxi province, China. Because of the presence of prolonged maxillary lamellae and 6 setae on the dens, H. manghe sp. nov. resembles H. hexasetata Jiang & Yin, 2010. H. yosii Stach, 1964, equal to H. sheyangensis Jiang, Tang & Chen, 2010, is redescribed based on syntypes. The latter species was recognized as a junior synonym of the former. A key to the Chinese Hypogastrura Bourlet, 1839 species is also given.

A new species of the Ceratophysella denticulata group is described from Shanxi province, China. Because of the presence of prolonged empodial appendages and reduced number of setae on dens C. taiguensis sp. nov. resembles: C. kapoviensis Babenko, 1994, C. kutyrevae Babenko, 1994, C. robustiseta Skarzynski & Smolis, 2006, C. sedecimocellata (Yosii, 1962) and C. vargovychi Skarzynski et al., 2001. A checklist of the Ceratophysella Borner, 1932 species hitherto recorded from China is also given. The present list contains 14 species, including C. anshanensis (Wu & Xie, 2007) comb. nov., C. quinidentis (Jia et al., 2005) comb. nov., C. xiaoi (Tamura, 1998) comb. nov., C. yinae (Yue & Fu, 2000) comb. nov. and C. zhangi (Zhao, 1998) comb. nov.