Granulocyte-Macrophage-Colony-Stimulating-Factor Combined with Prostaglandin E1 Create Dendritic Cells of Leukemic Origin from AML Patients' Whole Blood and Whole Bone Marrow That Mediate Antileukemic Processes after Mixed Lymphocyte Culture.

Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur. Strategies to stabilize remissions are greatly needed. The combination of the (clinically approved) immune-modulatory compounds Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Prostaglandine E1 (PGE-1) (Kit-M) converts myeloid blasts into dendritic cells of leukemic origin (DCleu). After stimulation with DCleu ex vivo, leukemia-specific antileukemic immune cells are activated. Therefore, Kit-M treatment may be an attractive immunotherapeutic tool to treat patients with myeloid leukemia. Kit-M-mediated antileukemic effects on whole bone marrow (WBM) were evaluated and compared to whole blood (WB) to evaluate the potential effects of Kit-M on both compartments. WB and WBM samples from 17 AML patients at first diagnosis, in persisting disease and at relapse after allogeneic stem cell transplantation (SCT) were treated in parallel with Kit-M to generate DC/DCleu. Untreated samples served as controls. After a mixed lymphocyte culture enriched with patients' T cells (MLC), the leukemia-specific antileukemic effects were assessed through the degranulation- (CD107a+ T cells), the intracellular IFNγ production- and the cytotoxicity fluorolysis assay. Quantification of cell subtypes was performed via flow cytometry. In both WB and WBM significantly higher frequencies of (mature) DCleu were generated without induction of blast proliferation in Kit-M-treated samples compared to control. After MLC with Kit-M-treated vs. not pretreated WB or WBM, frequencies of (leukemia-specific) immunoreactive cells (e.g., non-naive, effector-, memory-, CD3+ß7+ T cells, NK- cells) were (significantly) increased, whereas leukemia-specific regulatory T cells (Treg, CD152+ T cells) were (significantly) decreased. The cytotoxicity fluorolysis assay showed a significantly improved blast lysis in Kit-M-treated WB and WBM compared to control. A parallel comparison of WB and WBM samples revealed no significant differences in frequencies of DCleu, (leukemia-specific) immunoreactive cells and achieved antileukemic processes. Kit-M was shown to have comparable effects on WB and WBM samples regarding the generation of DCleu and activation of (antileukemic) immune cells after MLC. This was true for samples before or after SCT. In summary, a potential Kit-M in vivo treatment could lead to antileukemic effects in WB as well as WBM in vivo and to stabilization of the disease or remission in patients before or after SCT. A clinical trial is currently being planned.

Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/ß-catenin Signaling Pathway.

BACKGROUND: Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown. METHODS: SMC4 expression levels were initially detected by protein profiling in 20 pairs of CA tumor tissues and adjacent normal tissues. The level of SMC4 expression in CA cells was then evaluated using a western blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation tests. Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin pathway were investigated using western blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice. RESULTS: This study showed overexpression of SMC4 in CA tissues and cells. Knockdown of SMC4 can significantly inhibit the proliferation, migration and invasion, stimulate cell apoptosis, induce cell cycle arrest in the G0/G1 phase of CA cells, and inhibit tumor growth in vivo. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, ß-catenin, phosphorylated GSK-3ß, N-cadherin, and Vimentin, with an increased level of proteins, i.e., Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed. CONCLUSION: SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.

AIM2 Promotes Gastric Cancer Cell Proliferation via the MAPK Signaling Pathway.

Background: Gastric cancer (GC) is a highly prevalent tumor type. The dysregulated expression of melanoma deficiency factor 2 (AIM2) has been observed in a range of tumor types. Herein, we explore the role of AIM2 in the regulation of GC progression. Methods: Gastric cancer cells BGC-823 and MGC-803 in logarithmic growth phase were divided into blank group (control), Control group (NC) and SH-AIM2 group, respectively. Control group and SH-AIM2 group were transfected with AIM2 NC and SH-AIM2, respectively. Nude mice were divided into blank group (control) and SH-AIM2 group, and the treatment methods were the same as above. Differential AIM2 expression in GC tissues was assessed via bioinformatics analyses, after which western blotting was used for analyzing the AIM2 levels in tumor and paracancerous tissues from five stomach cancer patients. In addition, qPCR and protein imprinting were used to assess AIM2 expression levels in GC cells, and AIM2 knockdown was conducted in MGC-803 and BGC-823cells, after which colony formation and EdU incorporation assay were utilized to assess cell proliferation. The oncogenic role of AIM2 was then assessed in mice and validated through immunohistochemical analyses. Results: GC tissues and cell lines exhibited marked AIM2 overexpression. AIM2 knockdown significantly impaired GC cell proliferation and migration, as confirmed through in vitro assays. In vivo experiments showed that both the increment ability and invasion and migration ability of AIM2 knockdown group were significantly lower than that of control and NC the change of AIM2 protein level would affect the change of MAPK pathway related protein level. Conclusions: AIM2 knockdown markedly suppresses the proliferation, migration, as well as invasion of GC cells via the inhibition of MAPK signaling, thereby slowing tumor progression. Overall, these results suggest that further analyses of AIM2 may offer clinically valuable insights that can aid in the treatment of human GC.

Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis.

BACKGROUND: Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, together with all associated regulatory networks, on nasopharyngeal carcinoma (NPC) and its treatment possibilities. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed CRNDE, miR-545-5p and CCND2 expression within NPCs and representative cell lineages. CCK-8 cell counting-, EdU-, wound-healing-/transwell-assays analyzed cellular proliferation, migrative, together with invasive properties. Apoptosis/cell cycle progression were scrutinized through flow cytometry. Dual-luciferase reporter assays validated CRNDE/miR-545-5p/CCND2 interplay. Proteomic expression of apoptosis-related protein, EMT-related protein and CCND2 protein were evaluated through Western blotting. In addition, Ki67 expression was evaluated through immunohistochemical staining. The effect of CRNDE in vivo was assessed by nude murine xenograft model studies. RESULTS: This study demonstrated up-regulated expression of CRNDE and CCND2 within NPC tissues/cell lines. Meanwhile, miR-545-5p was down-regulated. CRNDE knock-down or miR-545-5p over-expression drastically reduced NPC proliferative, migrative and invasive properties, promoted apoptosis/altered cell cycle, and inhibited CCND2 expression. However, miR-545-5p down-regulation had opposing effects. All inhibiting functions generated by CRNDE down-regulation upon NPC progression could be counterbalanced or synergistically exacerbated, depending on miR-545-5p down-regulation or up-regulation, respectively. Multiple-level investigations revealed CRNDE to serve as a sponge for miR-545-5p, and can target CCND2 within NPCs. CONCLUSIONS: CRNDE increases CCND2 expression by competitive binding with miR-545-5p, thus accelerating the development of NPC. This provides potential therapeutic targets and prognostic markers against NPC.

Catalytic activity of porous carbon nitride regulated by polyoxometalates under visible light.

A series of porous carbon nitrides modified by different polyoxometalates (POMs) were prepared by the ultrasonic method. POMs were assembled on the surface of mpg-C3N4 via electrostatic attraction. The catalyst has visible light degradation activity for phenol (λ > 420 nm). mpg-C3N4 modified by H4SiW12O40 with a mass ratio of 1 : 5 showed the highest catalytic activity, which was 3.5 times higher than that of mpg-C3N4. As an electron acceptor, polyoxometalate can capture the photoelectron of C3N4, which can promote the separation of photocharge and improve the photocatalytic activity. ESR also confirmed that the superoxide radicals play a major role in degradation. The results show that the charge separation efficiency and catalytic activity can be enhanced by polyacids.

The Phytogeographic History of Common Walnut in China.

Common walnut (Juglans regia L.) is an economically important hardwood tree species cultivated worldwide for its high quality wood and edible nuts. It is generally accepted that after the last glaciation J. regia survived and grew in almost completely isolated stands in Asia, and that ancient humans dispersed walnuts across Asia and into new habitats via trade and cultural expansion. The history of common walnut in China is a matter of debate, however. We estimated the genetic diversity and spatial genetic structure of 31 walnut populations sampled across its Chinese range using 22 microsatellite markers (13 neutral and 9 non-neutral). Using historical data and population genetic analysis, including approximate Bayesian analysis (ABC), we reconstructed the demographic history of J. regia in China. The genetic data indicated the likely presence of J. regia in glacial refugia in the Xinjiang province (Northwest China), Northeastern China (Beijing, Shandong, and Changbai Mountains), Central China (Qinling and Baishan Mountains and Xi'an), and Southwestern China (Tibet, Yunnan, Guizhou, and Sichuan provinces). Based on DIY-ABC analysis, we identified three ancient lineages of J. regia in China. Two lineages (subpopulation A and subpopulation B+C) diverged about 2.79 Mya, while Southwestern China, and Qinling and Baishan Mountains lineages diverged during the Quaternary glaciations (about 1.13 Mya). Remnants of these once-distinct genetic clusters of J. regia may warrant ecological management if they are to be retained as in situ resources. A population size expansion in Northeastern China was detected in the last five centuries. The present distribution of walnut in China resulted from the combined effects of expansion/contraction from multiple refugia after the Last Glacial Maximum and later human exploitation.

Population genetics, phylogenomics and hybrid speciation of Juglans in China determined from whole chloroplast genomes, transcriptomes, and genotyping-by-sequencing (GBS).

Genomic data are a powerful tool for elucidating the processes involved in the evolution and divergence of species. The speciation and phylogenetic relationships among Chinese Juglans remain unclear. Here, we used results from phylogenomic and population genetic analyses, transcriptomics, Genotyping-By-Sequencing (GBS), and whole chloroplast genomes (Cp genome) data to infer processes of lineage formation among the five native Chinese species of the walnut genus (Juglans, Juglandaceae), a widespread, economically important group. We found that the processes of isolation generated diversity during glaciations, but that the recent range expansion of J. regia, probably from multiple refugia, led to hybrid formation both within and between sections of the genus. In southern China, human dispersal of J. regia brought it into contact with J. sigillata, which we determined to be an ecotype of J. regia that is now maintained as a landrace. In northern China, walnut hybridized with a distinct lineage of J. mandshurica to form J. hopeiensis, a controversial taxon (considered threatened) that our data indicate is a horticultural variety. Comparisons among whole chloroplast genomes and nuclear transcriptome analyses provided conflicting evidence for the timing of the divergence of Chinese Juglans taxa. J. cathayensis and J. mandshurica are poorly differentiated based our genomic data. Reconstruction of Juglans evolutionary history indicate that episodes of climatic variation over the past 4.5 to 33.80 million years, associated with glacial advances and retreats and population isolation, have shaped Chinese walnut demography and evolution, even in the presence of gene flow and introgression.

Polyoxometalate-Based Metal-Organic Frameworks for Selective Oxidation of Aryl Alkenes to Aldehydes.

Polyoxometalates (POMs) show considerable catalytic performance toward the selective oxidation of alkenes to aldehydes, which is commercially valuable for the production of pharmaceuticals, dyes, perfumes, and fine chemicals. However, the low specific surface area of POMs as heterogeneous catalysts and poor recyclability as homogeneous catalysts have hindered their wide application. Dispersing POMs into metal-organic frameworks (MOFs) for the construction of POM-based MOFs (POMOFs) suggests a promising strategy to realize the homogeneity of heterogeneous catalysis. Herein, we report two new POMOFs with chemical formulas of [Co(BBTZ)2][H3BW12O40]·10H2O (1) and [Co3(H2O)6(BBTZ)4][BW12O40]·NO3·4H2O (2) (BBTZ = 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene) for the selective oxidation of alkenes to aldehydes. Compound 1 possesses a non-interpenetrated three-dimensional (3D) cds-type open framework with a 3D channel system. Compound 2 displays a 3D polyrotaxane framework with one-dimensional channels along the [100] direction. In the selective oxidation of styrene into benzaldehyde, compound 1 can achieve a 100% conversion in 4 h with 96% selectivity toward benzaldehyde, which is superior to that of compound 2. A series of control experiments reveal that the co-role of [BW12O40]5- and Co2+ active center as well as a more open framework feature co-promote the catalytic property of the POMOFs in this case. This work may suggest a new option for the development of POMOF catalysts in the selective oxidation of alkenes.

Polyoxometalate and Resin-Derived P-Doped Mo2 C@N-Doped Carbon as a Highly Efficient Hydrogen-Evolution Reaction Catalyst at All pH Values.

A new type of P-doped Mo2 C coated by N-doped carbon (P-Mo2 C@NC) has been successfully prepared by calcining a mixture of H3 [PMo12 O40 ] polyoxometalates (POMs) and urea-formaldehyde resin under an N2 atmosphere. Urea-formaldehyde resin not only serves as the carbon source to ensure carbonization but also facilitates the uniform distribution of POM precursors, which efficiently avoid the aggregation of Mo2 C particles at high temperatures. TEM analysis revealed that the average diameter of the Mo2 C particles was about 10 nm, which is coated by a few-layer N-doped carbon sheet. The as-prepared P-Mo2 C@NC displayed excellent hydrogen-evolution reaction (HER) performance and long-term stability in all pH environments. To reach a current density of 10 mA cm-2 , only 109, 159, and 83 mV were needed for P-Mo2 C@NC in 0.5 m H2 SO4 (pH 0), 0.1 m phosphate buffer (pH 7), and 1 m KOH (pH 14), respectively. This could provide a high-yield and low-cost method to prepare uniform nanosized molybdenum carbides with highly efficient and stable HER performance.

Tuning of the photocatalytic performance of g-C3N4 by polyoxometalates under visible light.

Carbon nitride (g-C3N4), as a rising star of metal-free photocatalysts, has received considerable attention. However, for practical application, the photocatalytic efficiency of g-C3N4 remains to be further improved. Herein, a series of Keggin-type polyoxoanion (polyoxoanions = SiW12O404-, PW12O403-, PMo12O403-) modified g-C3N4 (POM/C3N4) composites have been successfully prepared. The results of XRD, TEM, XPS and EDAX reveal that a small amount of polyoxoanions was modified on the surface of g-C3N4 with electrostatic and hydrogen bonding interactions. Photocatalytic experiments indicate that these composites exhibit enhanced methyl orange (MO) degradation photocatalytic activity and water splitting H2 production under visible light irradiation. The loading amount and the type of polyoxoanion can tune the photocatalytic performance of the composites. Among these catalysts, 5% SiW12O404- (SiW12)-modified g-C3N4 has the best photocatalytic performance, which is 4.4 times higher than that of pure g-C3N4 for the degradation of MO. The photocatalytic mechanism reveals that polyoxoanions can act as electron traps, which can efficiently promote the separation of photogenerated electrons and holes of C3N4, thus resulting in the enhanced photocatalytic performance of the composites.

A Surfactant-Encapsulating Polyoxometalate Nanowire Assembly as a New Carrier for Nanoscale Noble-Metal Catalysts.

The loading of noble-metal nanoparticles (NMNPs) onto various carriers to obtain stable and highly efficient catalysts is currently an important strategy in the development of noble metal (NM)-based catalytic reactions and their applications. We herein report a nanowire supramolecular assembly constructed from the surfactant-encapsulating polyoxometalates (SEPs) CTAB-PW12 , which can act as new carriers for NMNPs. In this case, the Ag NPs are loaded onto the SEP nanowire assembly with a narrow size distribution from 5 to 20 nm in diameter; the average size is approximately 10 nm. The Ag NPs on the nanowire assemblies are well stabilized and the over agglomeration of Ag NPs is avoided owing to the existence of well-arranged polyoxometalate (POM) units in the SEP assembly and the hydrophobic surfactant on the surface of the nanowire assembly. Furthermore, the loading amount of the Ag NPs can be adjusted by controlling the concentration of the AgNO3 aqueous solution. The resultant Ag/CTAB-PW12 composite materials exhibit high activity and good stability for the catalytic reduction of 4-nitrophenol (4-NP) with NaBH4 in isopropanol/H2 O solution. The NMNPs-loaded SEP nanoassembly may represent a new composite catalyst system for application in NM-based catalysis.

Hybrid Coordination Networks Constructed from ɛ-Keggin-Type Polyoxometalates and Rigid Imidazole-Based Bridging Ligands as New Carriers for Noble-Metal Catalysts.

Three hybrid coordination networks that were constructed from ɛ-Keggin polyoxometalate building units and imidazole-based bridging ligands were prepared under hydrothermal conditions, that is, H[(Hbimb)2 (bimb){Zn4 PMo(V8) Mo(VI) 4O40}]⋅6 H2O(1), [Zn(Hbimbp)(bimbp)3 {Zn4 PMo(V8) Mo(VI) 4O40}]⋅DMF⋅3.5 H2O(2), and H[Zn2 (timb)2 (bimba)2 Cl2 {Zn4 PMo(V8) Mo(VI) 4O40}]⋅7 H2O(3) (bimb=1,4-bis(1-imidazolyl)benzene, bimbp=4,4'-bis(imidazolyl)biphenyl, timb=1,3,5-tris(1-imidazolyl)benzene, bimba=3,5-bis(1-imidazolyl)benzenamine). All three compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction. The mixed valence of the Mo centers was analyzed by XPS spectroscopy and bond-valence sum calculations. In all three compounds, the ɛ-Keggin polyoxometalate (POM) units acted as nodes that were connected by rigid imidazole-based bridging ligands to form hybrid coordination networks. In compound 1, 1D zigzag chains extended to form a 3D supramolecular architecture through intermolecular hydrogen-bonding interactions. Compound 2 consisted of 2D curved sheets, whilst compound 3 contained chiral 2D networks. Because of the intrinsic reducing properties of ɛ-Keggin POM species, noble-metal nanoparticles were loaded onto these POM-based coordination networks. Thus, compounds 1-3 were successfully loaded with Ag nanoparticles, and the corresponding composite materials exhibited high catalytic activities for the reduction of 4-nitrophenol.

The complete chloroplast genome of common walnut (Juglans regia).

Common walnut (Juglans regia L.) is cultivated in temperate regions worldwide for its wood and nuts. The complete chloroplast genome of J. regia was sequenced using the Illumina MiSeq platform. This is the first complete chloroplast sequence for the Juglandaceae, a family that includes numerous species of economic importance. The chloroplast genome of J. regia was 160 367 bp in length, with 36.11% GC content. It contains a pair of inverted repeats (26 035 bp) which were separated by a large single copy (89 872 bp) and a small single copy region (18 425 bp). A total of 137 genes were annotated, which included 86 protein-coding genes, three pseudogenes (two ycf15 and one infA), 40 tRNA genes and eight rRNA genes. The neighbour-joining phylogenetic analysis with the reported chloroplast genomes showed that common walnut chloroplasts are most closely related to those of the Fagaceae family.

Polyoxometalate-supported 3d-4f heterometallic single-molecule magnets.

The reactions of [CuTbL(Schiff)(H(2)O)(3)Cl(2)]Cl complexes with A- or B-type Anderson polyoxoanions lead to new polyoxometalate-supported 3d-4f heterometallic systems with single-molecule-magnet behavior.

Two diphosphonate-functionalized asymmetric polyoxomolybdates with catalytic activity for oxidation of benzyl alcohol to benzaldehyde.

Two asymmetric polyoxomolybdates Na(6){Mo(2)O(5)[(Mo(2)O(6))NH(3)CH(2)CH(2)CH(2)C(O)(PO(3))(2)](2)}·16H(2)O (1) and (NH(4))(7)Na{MoO(2)[(Mo(2)O(6))NH(3)CH(2)CH(2)CH(2)C(O)(PO(3))(2)]}(4)·H(2)O (2) have been synthesized by the reactions of alendronic acid with molybdate. Structure analysis revealed that the polyoxoanions 1 and 2 can be described as dimeric and tetrameric aggregates of the {MoO(3)[(Mo(2)O(6))NH(3)CH(2)CH(2)CH(2)C(O)(PO(3))(2)]} units respectively. Their tetrabutylammonium salts show efficient selective oxidation of benzyl alcohol to benzaldehyde with 72.5% and 81.5% benzyl alcohol conversion, and 87.1% and 82.4% benzaldehyde selectivity, respectively.

A new Ni12 cluster based on polyoxometalate ligands.

A new Ni(12) cluster based on polyoxometalate ligands [Ni(12)(OH)(9)WO(4)(W(7)O(26)(OH))(PW(9)O(34))(3)](25-) (1) has been assembled in aqueous solution containing [PW(9)O(34)](9-), WO(4)(2-), and NiCl(2) x 6 H(2)O. The Ni(12) core in 1 shows a unique three-petal flower-shaped structure composed of three Ni(4) cubane units. Magnetic investigation indicates the presence of dominantly ferromagnetic interactions within the Ni(12) core.

Language proficiency and executive control in proactive interference: evidence from monolingual and bilingual children and adults.

Two studies are reported in which monolingual and bilingual children (Study 1) and adults (Study 2) completed a memory task involving proactive interference. In both cases, the bilinguals attained lower scores on a vocabulary test than monolinguals but performed the same on the proactive interference task. For the children, bilinguals made fewer intrusions from previous lists even though they recalled the same number of words. For the adults, bilinguals recalled more words than monolinguals when the scores were corrected for differences in vocabulary. In addition, there was a strong effect of vocabulary in which higher vocabulary participants recalled more words irrespective of language group. These results point to the important role of vocabulary in verbal performance and memory. They also suggest that bilinguals may compensate for weaker language proficiency with their greater executive control to achieve the same or better levels of performance as monolinguals.

A new supramolecular assembly based on triple-Dawson-type polyoxometalate and 3d-4f heterometallic cluster.

The introduction of hexavacant Dawson-type precursor K(12)[H(2)P(2)W(12)O(48)] x 24 H(2)O into a HOAc/NaOAc (OAc(-) = acetate) buffer system containing (NH(4))(2)[Ce(IV)(NO(3))(6)] and Mn(II)(OAc)(2) x 4 H(2)O led to the isolation of a new compound, Na(20)[Ce(IV)(3)Mn(IV)(2)O(6)(OAc)(6)(H(2)O)(9)](2)[Mn(III)(2)P(2)W(16)O(60)](3) x 21 H(2)O (1). Compound 1 contains unusual triple-Dawson-type polyoxoanions [Mn(III)(2)P(2)W(16)O(60)](3)(24-) and bipyramid-like 3d-4f heterometallic clusters [Ce(IV)(3)Mn(IV)(2)O(6)(OAc)(6)(H(2)O)(9)](2+), which are arranged in a 3-D supramolecular assembly with 1-D channels. The Na(+) cations and solvent water molecules reside in the channels. Crystal data for 1 are as follows: hexagonal, P6(3)/mcm (No. 193), a = 24.959(4) A, c = 26.923(5) A, gamma = 120 degrees, V = 14525(4) A(3), and Z = 2. The electrochemical and electrocatalytic properties of compound 1 have been investigated.