Crossed Andreev reflection in normal-superconductor-normal junction based on Kekulé-Y patterned graphene.

We theoretically study the crossed Andreev reflection (CAR) of the normal metal-superconductor-normal metal (NSN) heterojunction based on Kekulé-Y patterned graphene with two doping types, i.e.nSnandnSpconfigurations. It is found that the enhanced CAR is more likely to occur in thenSpjunction rather than thenSnjunction. To be concrete, the almost perfect CAR occurs in a large range of incident angle in the single Dirac cone phase when the incident energy is inside the gap of the nonlinear band. Furthermore, the roles of the length of superconductor and pseudospin-valley coupling on conductance are also evaluated.

Assembling Silver Cluster-Based Organic Frameworks for Higher-Performance Hypergolic Properties.

Increasing research efforts have been focused on developing next-generation propellants. In this work, we demonstrated that assembling zero-dimensional (0D) silver clusters with energetic ligands into 3D metal organic frameworks (MOFs) not only inherited the short ignition delay (ID) time of the alkynyl-silver cluster but also significantly increased the output energy. Among them, the open cationic framework of ZZU-363 incorporating counter NO3 - ions achieved a considerably reduced energy barrier and eventually the shortest ID time (26 ms), together with the highest volumetric energy density (40.4 kJ cm-3) and specific impulse (263.1 s), which is far superior to traditional hydrazine-based propellants. The underlying mechanisms are clearly revealed by theoretical calculations. This work opens a venue to significantly enhancing the hypergolic activity of metal clusters and MOFs.

o-Carborane-Based and Atomically Precise Metal Clusters as Hypergolic Materials.

Atomically precise o-carboranealkynyl-protected clusters [Ag14(C4B10H11)12(CH3CN)2]·2NO3 (CBA-Ag) and [Cu6Ag8(C4B10H11)12Cl]NO3 (CBA-CuAg) have been found to exhibit hypergolic activity, such that they are capable of spontaneous ignition and combustion upon contact with the white fuming nitric acid oxidizer. In particular, CBA-CuAg has a short ignition delay time of 15 ms, whereas the o-carboranealkynyl ligand is hypergolically inert. Systematic investigation revealed that the metal cluster core catalyzed the hypergolic behavior of inert o-carboranealkynyl ligand, and Cu doping further accelerated combustion catalysis. This work provides a new prospective in the rational design of novel metal cluster-based hypergolic fuels for propellant application.

Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice.

BACKGROUND AND PURPOSE: Cancer stem cells exhibit distinctive cellular metabolism compared with the more differentiated counterparts or normal cells. We aimed to investigate the impact of a novel radionuclide anti-cancer agent (188)Re-Liposome on stemness markers' expression and cellular metabolism in an ovarian cancer model. MATERIAL AND METHODS: A 2×2 factorial experiment was designed in which factor 1 represented the drug treatment comparing (188)Re-BMEDA, a free form of (188)Re, with (188)Re-Liposome, a nanoparticle-encapsulated form of (188)Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. RESULTS: Intraperitoneal delivery of (188)Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of (188)Re-Liposome treatment was able to block epithelial-to-mesenchymal transition (EMT) and reactivate p53 function. Collectively, these molecular changes led to a striking tumour-killing effect. CONCLUSIONS: Radionuclides encapsulated in liposomes may represent a novel treatment for ovarian cancer when delivered intraperitoneally (a type of loco-regional delivery). In the future, this concept may be further extended for the treatment of several relevant cancers that have been proved to be suitable for loco-regional delivery of therapeutic agents, such as colon cancer, gastric cancer, and pancreatic cancer.

Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol(®)-resistant ovarian cancer.

Taxol(®) remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resistant cell line (TR) was established at first. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol(®) versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol(®) (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control.

The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil(®), the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future.

Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer.

Currently, epithelial ovarian cancer is viewed as a heterogeneous disease with five major histological subtypes. Clear cell carcinoma represents a specific histological subtype of epithelial ovarian cancer that demonstrates more aggressive clinical behavior and drug resistance compared with other subtypes. Nevertheless, clear cell carcinoma is treated in the same manner as the other subtypes without any particular consideration to its unique clinical characteristics. To improve the therapeutic efficacy of the current liposomal doxorubicin approach for the treatment of clear cell carcinoma, we aimed to develop a novel peptide-conjugated liposomal doxorubicin to actively target this subtype. Two phage clones (OC-6 and OC-26) that specifically bound to clear cell carcinoma were isolated from a phage peptide display library after biopanning procedures. The peptide sequences were translated and aligned (OCSP-6 for OC-6, and OCSP-26 for OC-26, respectively). Peptide-conjugated nanoparticles demonstrated better tumor endocytosis and time-dependent gradual increase of intracellular drug uptake than non-targeting liposomal nanoparticles. Furthermore, peptide-conjugated liposomal doxorubicin better controlled tumors than did non-targeting liposomal doxorubicin. The current work may pave a new way for the development of drugs that target each subtype of epithelial ovarian cancer in the future.

Taiwan Y-chromosomal DNA variation and its relationship with Island Southeast Asia.

BACKGROUND: Much of the data resolution of the haploid non-recombining Y chromosome (NRY) haplogroup O in East Asia are still rudimentary and could be an explanatory factor for current debates on the settlement history of Island Southeast Asia (ISEA). Here, 81 slowly evolving markers (mostly SNPs) and 17 Y-chromosomal short tandem repeats were used to achieve higher level molecular resolution. Our aim is to investigate if the distribution of NRY DNA variation in Taiwan and ISEA is consistent with a single pre-Neolithic expansion scenario from Southeast China to all ISEA, or if it better fits an expansion model from Taiwan (the OOT model), or whether a more complex history of settlement and dispersals throughout ISEA should be envisioned. RESULTS: We examined DNA samples from 1658 individuals from Vietnam, Thailand, Fujian, Taiwan (Han, plain tribes and 14 indigenous groups), the Philippines and Indonesia. While haplogroups O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 follow a decreasing cline from Taiwan towards Western Indonesia, O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 decline northward from Western Indonesia towards Taiwan. Compared to the Taiwan plain tribe minority groups the Taiwanese Austronesian speaking groups show little genetic paternal contribution from Han. They are also characterized by low Y-chromosome diversity, thus testifying for fast drift in these populations. However, in contrast to data provided from other regions of the genome, Y-chromosome gene diversity in Taiwan mountain tribes significantly increases from North to South. CONCLUSION: The geographic distribution and the diversity accumulated in the O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 haplogroups on one hand, and in the O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 haplogroups on the other, support a pincer model of dispersals and gene flow from the mainland to the islands which likely started during the late upper Paleolithic, 18,000 to 15,000 years ago. The branches of the pincer contributed separately to the paternal gene pool of the Philippines and conjointly to the gene pools of Madagascar and the Solomon Islands. The North to South increase in diversity found for Taiwanese Austronesian speaking groups contrasts with observations based on mitochondrial DNA, thus hinting to a differentiated demographic history of men and women in these populations.

Calorimetry study of microwave absorption of some solid materials.

In practice, the dielectric constant of a material varies the applied frequency the material composition, particle size, purity, temperature, physical state (solid or liquid), and moisture content. All of these parameters might change during processing, therefore, it is difficult to predict how well a material will absorb microwave energy in a given process. When the temperature is measured by a digital thermometer, it could not accurately reflect the true temperature of the bulk materials, especially for mixed materials. Thus, in this paper we measured the microwave absorption characteristics of different materials by calorimetry. The microwave power levels, irradiation times, and masses of the materials were varied. It was difficult to predict the microwave energy absorption characteristics of reagent-grade inorganic compounds based on their color, metallic cation, or water stoichiometry. CuO, MnO2, Fe3O4, and MnSO4 x H2O (Taishan) strongly absorbed microwave energy. Most of the remaining inorganic compounds were poor absorbers, with silica hardly absorbing any microwave energy. Carbon-based materials had significantly different microwave absorption characteristics. Activated carbon and coke were especially sensitive to microwaves, but different types of coal were poor absorbers. The jamesonite concentrate absorbed microwave energy strongly, while the zinc concentrate was a poor absorber.

Screening for membrane proteins differentially expressed between the lung adenocarcinoma cell lines with high- and low-metastatic potential using iTRAQ technology / 肿瘤

Objective: To screen for the membrane proteins differentially expressed between the lung adenocarcinoma cell lines with high- and low- metastatic potential, and to explore the potential targets for biomarkers and biological therapy. Methods: The membrane proteins were extracted from lung adenocarcinoma SPC-A-1 and SPC-A-1 sci cells which were generated from the same parental cell type and had low- and high- metastatic potential, respectively. The membrane proteins were labeled and the peptides were separated and analyzed by iTRAQ (isobaric tags for relative and absolute quantitation) technology combined with Nano-LC-MS/MS (nano liquid chromatography-tandem mass spectrometry). The identification and quantitation of the proteins were analyzed by Proteinpilot 4.0 solfware. The membrane proteins differentially expressed were analyzed and verified by GO (Gene Ontology) terms and real-time fluorescence quantitative-PCR in combination with Western blotting, respectively. Results: The identified numbers of proteins with FDRs (false discovery rates) < 1% were 1 413, 1 374, 1 297, and 1 351 in the experiment which were repeated four times by Nano LC-MS/MS, and the rate of labelling was above 95%. Among the 27 proteins up-regulated in total four experiments, 20 proteins were identified as membrane protein. Among the 32 proteins down-regulated in total four experiments, 25 proteins were identified as membrane protein. The GO analysis demonstrated the major molecular functions of the proteins differentially expressed including cytoskeletal protein binding, identical protein binding and enzyme binding as well as the catabolic process and cellular localization in biological processes. The expression levels of ITGA3 (integrin alpha-3), MYH9 (myosin, heavy chain 9), PLEC1 (plectin 1), HADHA (3-hydroxyacyl- CoA dehydrogenase), HK1 (hexokinase-1), KTN1 (kinectin 1), ESYT1 (extended synaptotagmin-like protein 1), ALDH18A1 (aldehyde dehydrogenase 18 family, member A1), ATP5A1 (ATP synthase alpha-subunit), LMNB2 (lamin-B2), CAV1 (caveolin-1) and CK-19 (keratin, type I cytoskeletal 19) mRNAs in SPC-A-1 sci cells were higher than those in the SPC-A-1 cells. The expression levels of CLTC (clathrin, heavy chain), HK1, LMNB2 and CK-19 in SPC-A-1 sci cells were also higher than those in SPC-A-1 cells. These results were consistent with those from quantitative mass spectrometry. Conclusion: A high-throughput screen for metastasis-related membrane proteins can be performed by a combined use of iTRAQ and Nano LCMS/ MS and may provide the potential metastasis-related biomarkers and therapeutic targets in diagnosis, prognostic prediction and treatment for patients with lung adenocarcinoma. Copyright © 2013 by TUMOR.

1,5-Diamino-tetra-zolium chloride.

The title compound, CH(5)N(6) (+)·Cl(-), crystallized with two indepedent 1,5-diamino-tetra-zolium cations and two independent chloride anions in the asymmetric unit. In the crystal, there are a number of N-H⋯Cl hydrogen-bonding inter-actions, which generate a three-dimensional network.

(5Z,7Z)-6,8-Dimethyl-9H-tetra-zolo[1,5-b][1,2,4]triazepine.

The mol-ecule of the title compound, C(6)H(8)N(6), is approximately planar, with a maximum deviation from planarity of 0.099 (1) Å. In the crystal, mol-ecules are linked to each other via pairs of N-H⋯N hydrogen bonding, forming inversion dimers. The crystal structure is further stabilized by π-π stacking inter-actions, with a centroid-centroid distance of 3.419 (1) Å.

N-(5-Amino-1H-tetra-zol-1-yl)formamide.

In the title compound, C(2)H(4)N(6)O, the planar [maximum deviation = 0.006 (2) Å] amino-tetra-zole group makes a dihedral angle of 83.65 (8)° with the formamide unit. In the crystal structure, inter-molecular N-H⋯N, N-H⋯O and C-H⋯N hydrogen bonds are responsible for the formation of a three-dimensional network.

1-Isopropyl-ideneamino-1H-tetra-zol-5-amine.

The mol-ecule of the title compound, C(4)H(8)N(6), assumes an approximately planar structure, the methyl C atoms and the C atom to which they are bonded being out of the mean tetrazole ring plane by 0.108 and 0.139, and 0.144 Å, respectively. π-π stacking between parallel tetra-zole rings [centroid-centroid distance = 3.4663 (11) Å] is observed in the crystal structure. Inter-molecular N-H⋯N hydrogen bonding further helps to stabilize the crystal structure.

N-(1-Diacetyl-amino-1H-tetra-zol-5-yl)acetamide.

In the crystal structure of the title compound, C(7)H(10)N(6)O(3), there are N-H⋯O, N-H⋯N and C-H⋯O inter-actions, generating a three-dimensional supra-molecular network structure. A short intermolecular O⋯C contact of 2.8994 (18) Šis alsopresent in the crystal structure, but no π-π contacts are observed.

Traces of archaic mitochondrial lineages persist in Austronesian-speaking Formosan populations.

Genetic affinities between aboriginal Taiwanese and populations from Oceania and Southeast Asia have previously been explored through analyses of mitochondrial DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic studies have supported the "slow boat" and "entangled bank" models according to which the Polynesian migration can be seen as an expansion from Melanesia without any major direct genetic thread leading back to its initiation from Taiwan. We assessed mtDNA variation in 640 individuals from nine tribes of the central mountain ranges and east coast regions of Taiwan. In contrast to the Han populations, the tribes showed a low frequency of haplogroups D4 and G, and an absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although indicating a common origin of the populations of insular Southeast Asia and Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped separately from those found in China and the Taiwan general (Han) population, suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late Pleistocene settlers. Interestingly, from complete mtDNA sequencing information, most B4a lineages were associated with three coding region substitutions, defining a new subclade, B4a1a, that endorses the origin of Polynesian migration from Taiwan. Coalescence times of B4a1a were 13.2 +/- 3.8 thousand years (or 9.3 +/- 2.5 thousand years in Papuans and Polynesians). Considering the lack of a common specific Y chromosomal element shared by the Taiwanese aboriginals and Polynesians, the mtDNA evidence provided here is also consistent with the suggestion that the proto-Oceanic societies would have been mainly matrilocal.

Differential messenger RNA transcription of androgen receptor and estrogen receptor in gonad in relation to the sex change in protandrous black porgy, Acanthopagrus schlegeli.

Black porgy, Acanthopagrus schlegeli Bleeker, is a marine protandrous hermaphrodite fish. All are functional males at 1-2 yr of age and then become either males or females at 3 yr of age. To study the process of sex change in this species, mRNA transcripts of two estrogen receptors (ERalpha and ERbeta) and an androgen receptor (AR) were monitored. An AR cDNA was cloned and characterized. ERalpha, ERbeta, and AR were differentially transcribed in bisexual testicular and ovarian tissue according to reverse transcription polymerase chain reaction (RT-PCR) and Southern analysis. A real-time quantification PCR analysis was further developed for the measurement of AR, ERalpha, and ERbeta transcripts. ERalpha and AR transcripts were significantly more plentiful in bisexual testis than in bisexual ovary in 1(+)- and 2(+)-yr-old fish. ERalpha, ERbeta, and AR transcripts decreased in the functional testis of 3-yr-old fish. Similar levels of ERbeta and AR were detected in the ovary of sex-changed females and in functional testis of 3-yr-old males. Significantly decreased AR transcripts were found in testicular tissue of bisexual and functional male and female gonads in 3-yr-old fish as compared with 1- and 2-yr-old fish. In contrast, increased ERalpha transcripts were detected in the bisexual ovary and sex-changed ovary of 3-yr-old fish as compared with the bisexual ovary of 1- and 2-yr-old fish. The data suggest a differential sensitivity in the bisexual testicular and ovarian tissue of black porgy.

Estradiol-17beta triggers luteinizing hormone release in the protandrous black porgy (Acanthopagrus schlegeli Bleeker) through multiple interactions with gonadotropin-releasing hormone control.

We investigated the mechanism of estradiol-17beta (E2) action on stimulation of LH (=gonadotropin II) release in the black porgy fish (Acanthopagrus schlegeli Bleeker) using an in vivo approach and primary cultures of dispersed pituitary cells in vitro. In vivo, E2 but not androgens (testosterone [T] and 11-ketotestosterone [11-KT]) significantly stimulated plasma LH in a dose-dependent manner. Estradiol-17beta also increased brain content of seabream GnRH. GnRH antagonist prevented E2 stimulation of LH release in vivo, indicating that the effect of E2 on LH was mediated by GnRH. In vitro, sex steroids (E2, T, 11-KT) alone had no effect on basal LH release in the cultured pituitary cells, but GnRH significantly stimulated LH release. Estradiol-17beta potentiated GnRH stimulation of LH release, an effect that was inhibited by GnRH antagonist, and 11-KT, but not T, also potentiated GnRH stimulation of LH release. The potentiating effect of 11-KT on GnRH-induced LH release in vitro was stronger than that of E2. These data suggest that E2 triggers LH release in vivo by acting both on GnRH production at the hypothalamus and on GnRH action at the pituitary. In contrast, 11-KT may only stimulate GnRH action at the pituitary. The E2) induction of LH release, through multiple interactions with GnRH control, supports a possible central role of E2in the sex change observed in the protandrous black porgy.