Monoarsine-protected icosahedral cluster [Au13(AsPh3)8Cl4]+: comparative studies on ligand effect and surface reactivity with its stibine analogue.

Ligand shells of gold nanoclusters play important roles in regulating their molecular and electronic structures. However, the similar but distinct impacts of the homologous analogues of the protecting ligands remain elusive. The C2v symmetric monoarsine-protected cluster [Au13(AsPh3)8Cl4]+ (Au13As8) was facilely prepared by direct reduction of (Ph3As)AuCl with NaBH4. This cluster is isostructural with its previously reported stibine analogue [Au13(SbPh3)8Cl4]+ (Au13Sb8), enabling a comparative study between them. Au13As8 exhibits a blue-shifted electronic absorption band, and this is probably related to the stronger π-back donation interactions between the Au13 core and AsPh3 ligands, which destabilize its superatomic 1P and 1D orbitals. In comparison to the thermodynamically less stable Au13Sb8, Au13As8 achieves a better trade-off between catalytic stability and activity, as demonstrated by its excellent catalytic performance towards the aldehyde-alkyne-amine (A3) coupling reaction. Moreover, the ligand exchange reactions between Au13As8 with phosphines, as exemplified by PPh3 and Ph2P(CH2)2PPh2, suggest that Au13As8 may be a good precursor cluster for further cluster preparation through the "cluster-to-cluster" route.

Elastin-Derived VGVAPG Fragment Decorated Cell-Penetrating Peptide with Improved Gene Delivery Efficacy.

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mßCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

Ag22 Nanoclusters with Thermally Activated Delayed Fluorescence Protected by Ag/Cyanurate/Phosphine Metallamacrocyclic Monolayers through In-Situ Ligand Transesterification.

The composition of protection monolayer exerts great influence on the molecular and electronic structures of atomically precise monolayer protected metal nanoclusters. Four isostructural Ag/cyanurate/phosphine metallamacrocyclic monolayer protected Ag22 nanoclusters are synthesized by kinetically controlled in-situ ligand formation-driven strategy. These eight-electron superatomic silver nanoclusters feature an unprecedented interfacial bonding structure with diverse E-Ag (E=O/N/P/Ag) interactions between the Ag13 core and metallamacrocyclic monolayer, and displays thermally activated delayed fluorescence (TADF), benefiting from their distinct donor-acceptor type electronic structures. This work not only unmasks a new core-shell interface involving cyanurate ligand but also underlines the significance of high-electron-affinity N-heterocyclic ligand in synthesizing TADF metal nanoclusters. This is the first mixed valence Ag0/I nanocluster with TADF characteristic.

In-situ formed elastin-based hydrogels enhance wound healing via promoting innate immune cells recruitment and angiogenesis.

Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the in vivo degradation of the elastin by elastase from neutrophils, in vitro co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages in vitro. Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

MiR-296-3p inhibits cell proliferation by the SOX4-Wnt/ßcatenin pathway in triple-negative breast cancer.

MicroRNAs (miRNAs) have been demonstrated to play critical roles in the tumorigenesis of triple-negative breast cancer (TNBC). In this work, we addressed the specific role of miR-296-3p in TNBC. The levels of miR-296-3p and SOX4 were determined using RT-qPCR. The function of miR-296-3p overexpression on TNBC cell proliferation, migration, invasion, cancer stem cell (CSC)-like properties, and Wnt pathway activation was investigated by MTT, EdU, wound healing, Transwell, sphere formation assays and western blot. Mechanistic investigations, including luciferase reporter, RNA pull-down, and RIP assays, were con-ducted to explore the regulatory mechanisms of miR-296-3p. We found that miR-296-3p was downregulated in TNBC tissues and cells. Overexpression of miR-296-3p suppressed TNBC cell proliferation, migration, invasion, and CSC-like properties. Furthermore, miR-296-3p could bind to SOX4 and negatively modulate SOX4 expression. In addition, miR-296-3p was verified to inhibit Wnt/ß-catenin pathway by downregulating SOX4. Moreover, overexpression of SOX4 or activation of Wnt pathway rescued the miR-296-3p upregulation-mediated suppressive effect on cellular processes in TNBC. In conclusion, miR-296-3p inhibits Wnt/ß-catenin pathway by targeting SOX4 and exerts anti-tumor effects in TNBC.

Development and Characterization of High Efficacy Cell-Penetrating Peptide via Modulation of the Histidine and Arginine Ratio for Gene Therapy.

Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs.

New evidence for supplementary crop production, foddering and fuel use by Bronze Age transhumant pastoralists in the Tianshan Mountains.

The nature of economies and the movement of agricultural crops across Eurasia in the Bronze Age have been the subject of significant research interest in recent years. This study presents and discusses new results of flotation, radiocarbon and carbon stable isotope analyses from the seed assemblage at the Adunqiaolu site (northwestern Xinjiang), in combination with archaeological evidence. Archaeobotanical evidence, including carbonized foxtail millet, broomcorn millet, and naked barley, documents the diversity of local cereal consumption during the mid-second millennium BC. Our results suggest that crops were not grown locally, however, but in the lower Boertala Valley, supporting the argument that Adunqiaolu was a winter camp. These new sets of data constitute an important contribution to the discussion on cereal dispersal across the Tianshan Mountains in the Bronze Age.

Iodine-catalyzed guanylation of amines with N,N'-di-Boc-thiourea.

Herein, we report that iodine-catalyzed guanylation of primary amines can be accomplished with N,N'-di-Boc-thiourea and TBHP to afford the corresponding guanidines in 40-99% yields. Oxidation of the HI byproduct by TBHP eliminates the need for an extra base to prevent the protonation of substrates and makes the reaction especially useful for both electronically and sterically deactivated primary anilines.

Farming strategies of 1st millennium CE agro-pastoralists on the southern foothills of the Tianshan Mountains: A geoarchaeological and macrobotanical investigation of the Mohuchahangoukou (MGK) site, Xinjiang, China.

Archaeological evidence emerging over the past decade clearly illustrates that agro-pastoralists living along the foothills of major mountain chains in Central Asia (the so-called "Inner Asian Mountain Corridor" or IAMC) facilitated the spread of domesticated grains through their direct involvement in farming. While the environmental conditions across the northwestern slopes of the IAMC provided adequate resources for incipient farming and herding as early as the mid-3rd mill. BCE, the development of local agricultural strategies on the extremely arid and eroded foothills on the southeastern, leeward side of the mountains remain comparatively less studied. Our study tackles this problem by combining geoarchaeological analysis with conventional macrobotanical identification in the investigation of a 1st-mill. CE agro-pastoralist farming site, Mohuchahangoukou (MGK), located on the arid foothills of the Tianshan range. Our results illustrate how ancient agro-pastoralists at MGK innovated irrigation systems both to combat water shortage and, importantly, to trap sediments carried by flood-water for crop cultivation. By synthesizing currently available data, we estimate that they managed to trap about 40 cm of fine-grained sediment within a span of 200 years or even less. These stone-built field systems helped water a diverse stand of crops and create deeper soils in an otherwise deflated landscape with thin desert soils. Since we detected high levels of salt concentration (>2 dSm-1) in the lower portions of all three test trenches we analyzed, we conclude that soil salinization might have affected the long-term sustainability of this form of irrigated field management. We also infer that, besides engineering efforts, the ancient agro-pastoralists at MGK had to resolve the scheduling conflicts between irrigated farming and animal herding through labor specialization.

Detection of nitroaromatics based on aggregation induced emission of barbituric acid derivatives.

Barbituric acid derivatives with typical aggregation induced emission (AIE) are reported. Their emission wavelengths varied with water fraction of their solution. UV-visible absorption spectroscopy and theoretical calculations revealed the intramolecular charge transfer (ICT) possibility from donor to acceptor and the mechanism was confirmed as a restriction of intramolecular motion (RIM). The AIE properties were affected by the different substituents on barbituric acid. When the molecular volume increased, the AIE effect decreased. Fluorescent quenching mechanism was applied to detect nitroaromatic explosives. For 2,4,6-trinitrophenol (PA), one of the derivatives 5-(4-diphenylamino styrene)-1,3-diphenyl-barbituric acid in THF/H2O mixture (1:9, v/v), showed amplified fluorescence quenching with a maximum Stern-Volmer quenching constant of 4.1 × 104 M-1. The solid phase paper test based on 5-(4-diphenylamino styrene)-1,3-diphenyl-barbituric acid also showed a superior sensitivity toward PA both in vapor and solution.

Correction: Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

[This corrects the article DOI: 10.1371/journal.pone.0187405.].

Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

Today, farmers in many regions of eastern Asia sow their barley grains in the spring and harvest them in the autumn of the same year (spring barley). However, when it was first domesticated in southwest Asia, barley was grown between the autumn and subsequent spring (winter barley), to complete their life cycles before the summer drought. The question of when the eastern barley shifted from the original winter habit to flexible growing schedules is of significance in terms of understanding its spread. This article investigates when barley cultivation dispersed from southwest Asia to regions of eastern Asia and how the eastern spring barley evolved in this context. We report 70 new radiocarbon measurements obtained directly from barley grains recovered from archaeological sites in eastern Eurasia. Our results indicate that the eastern dispersals of wheat and barley were distinct in both space and time. We infer that barley had been cultivated in a range of markedly contrasting environments by the second millennium BC. In this context, we consider the distribution of known haplotypes of a flowering-time gene in barley, Ppd-H1, and infer that the distributions of those haplotypes may reflect the early dispersal of barley. These patterns of dispersal resonate with the second and first millennia BC textual records documenting sowing and harvesting times for barley in central/eastern China.

New views on the reaction of primary amine and aldehyde from DFT study.

A general theoretical investigation on the reaction of primary amine with aldehyde was carried out by density functional theory. The calculation systems involve three kinds of primary amines (methylamine, vinylamine, and phenylamine) and three kinds of aldehydes (formaldehyde, acetaldehyde, and acrylaldehyde). The steric and electronic inductive effects on the reaction mechanism were studied. Results reveal that the nucleophilic attack of primary amine on aldehyde under neutral conditions leads to carbinolamines, rather than Schiff bases. The nucleophilic attack on the protonated aldehyde produces the protonated Schiff base. The steric hindrance of the aldehyde slows down the nucleophilic attack but allows enough time to abstract a H; consequently, the formation of the protonated Schiff base is preferred. During the carbinolamine protonation, the H(+) preferably locates on the amine nitrogen and then is abstracted by the hydroxyl oxygen over an energy barrier, leaving protonated Schiff base after timely water liberation. The formation of a prereaction potential energy well obviously softens the steric and electronic inductive effects on the active barrier for different reactants.

FOXA1 positively regulates gene expression by changing gene methylation status in human breast cancer MCF-7 cells.

OBJECTIVE: DNA methylation is an important epigenetic modification with tumor suppressor gene silencing in cancer. The mechanisms underlying DNA methylation patterns are still poorly understood. This study aims to evaluate the potential value of FOXA1 for controlling gene CpG island methylation in breast cancer. METHODS: FOXA1 was down-regulated by transfection with siRNA and up-regulated by transfection with plasmid in MCF-7 cell lines. The DNA methylation and mRNA levels were examined by qMSP and qRT-PCR. The cell proliferation and apoptosis was detected by MTT and Flow cytometry. RESULTS: Suppression of FOXA1 enhanced the methylation status of DAPK, MGMT, RASSF1A, p53, and depressed mRNA levels of these tumor suppressor genes, whereas over-expression of FOXA1 showed the opposite effects. DNMT1, DNMT3A and DNMT3B mRNA were up-regulated by siRNA knock-down of FOXA1. At the same time, FOXA1 suppression promoted cell growth and inhibited apoptosis. CONCLUSIONS: FOXA1 may be associated with methylation of the tumor suppressor genes promoter through changing DNMTs expression. FOXA1 could be a potential demethylation target for prevention and treatment of breast cancer.

Solid-state structure of gelatin-mono epoxy terminated polydimethylsiloxane polymer: effect of electrostatic and hydrophobic interactions.

In this study, a hybrid synthetic gelatin-mono epoxy terminated polydimethylsiloxane polymer (PDMS-E grafted gelatin (PGG)) was successfully synthesized on a large scale. Supramolecular structure of gelatin, which was decided by the sophisticated inter- and intra-molecular interactions, significantly affected the self-assembly and phase behavior of PGG. Interestingly, the supramolecular organization of PGG could be tuned finely by negatively charged surfactants, such as sodium dodecyl sulfate (SDS) and sodium tetradecyl sulfonate (STSo), as revealed by high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), light microscopy (LM), and atomic force microscopy (AFM). SEM images exhibited the presence of spherical aggregates in PGG/SDS films while hexagonal array was observed in PGG/STSo films. The results of LM revealed that when PGG/STSo solution was dried, a successive structural transformation from spheres to hexagons, via sticks and butterfly-shaped aggregates as intermediates, was observed. However, the morphologies of the aggregates formed in PGG/SDS system did not exhibit any obvious change upon drying. Attenuated total reflection-Fourier transform infrared spectra combined with AFM observations indicated that the secondary structure and aggregation behavior of gelatin was modified with the change in the electrostatic and hydrophobic interactions, leading to the formation of diversified solid-state structures of PGG.

Effect of anionic surfactants on grafting density of gelatin modified with PDMS-E.

The effect of anionic surfactants on the interfacial compatibility in mono epoxy terminated polydimethylsiloxane (PDMS-E) macromonomer and gelatin mixed system was studied by Gibbs free energy (ΔGM), which played a crucial role in deciding the grafting density of immiscible polymer in heterogeneous system. Aggregation behavior of gelatin chains at boundary between gelatin phase and solvent phase was investigated using viscosity, surface tension and conductivity measurements. Viscosity analysis showed a regular increase in viscosity with the increasing alkyl chain length from C7 to C16 of the homologous alkyl sulfate surfactants. Changes of surface tension exhibited the regular curves of polyelectrolyte-anionic surfactant for alkyl sulfate surfactant systems. The results demonstrated that aggregate structure of gelatin-sulfate surfactants was dominated by electrostatic and hydrophobic interactions, which resulted in a self-assembly process of the hydrophobic segments and hydrophilic segments among gelatin chains and surfactant molecules. However, the interactions between gelatin and alkyl sulfonate surfactants were mainly governed by hydrophobic interactions, which induced conformation change of gelatin molecules. Well-ordered arrangement of gelatin chains at a fluid interface has observed by high-resolution transmission electron microscopy (HR-TEM). It is a key factor to contribute to the reduction of interfacial free energy, which mainly depends on the hydrophobic interaction between gelatin and alkyl sulfate/sulfonate surfactants. MD simulations conclusions are great agreement with our experimental results.

Microstructure transformation of PDMS-E grafted gelatin polymers induced by SDS and SDBS.

Inorganic-organic hybrid materials with tunable chemical and physical properties were prepared from mono epoxy terminated polydimethylsiloxane (PDMS) macromonomer and gelatin for improving their flexibility and hydrophobicity. Sodium dodecyl sulfate (SDS) and sodium dodecyl benzene sulfonate (SDBS) were used to enhance the compatibility of two polymers phases. Measurement of grafting density indicated that anionic surfactants played a crucial role in deciding the detailed microstructure of PDMS-E grafted gelatin (PGG) polymers in alkaline solution. The interaction between gelatin and SDS/SDBS was investigated by viscosity and SEM. Viscosity analysis showed a regular increase in SDS system and a steeper change in the case of SDBS. SEM micrographs displayed a series of structural transitions (spherical, spindle, irregular granular and spherical aggregates) with the increase of SDS concentration, but spindle and granular aggregates appeared alternately as varying SDBS concentrations. The results demonstrated that both the electrostatic and hydrophobic interactions between anionic surfactant and gelatin controlled the aggregate structure of gelatin-SDS/SDBS, which affected the compatibility between gelatin and PDMS. Thermal properties of PGG polymers had changed with the modification of polymer microstructure. The results above revealed that microstructure transformation of PGG polymers was determined by the compatibility of two polymers in anionic surfactant aqueous solution and the chemical nature of their monomers.

Effect of aggregation behavior of gelatin in aqueous solution on the grafting density of gelatin modified with glycidol.

The effect of aggregation behavior of gelatin in aqueous solution on the grafting density of glycidol grafted gelatin polymers (GGG polymers) was investigated. The grafting density was measured using the Van Slyke method by calculating the conversion rate of free - NH(2) groups of gelatin. The conversion rate reached peak values at 6% and 14% of the gelatin aqueous solution. SEM micrographs displayed a series of structural transitions (i.e., spherical, spindle, butterfly, irregular and dendritic aggregates) at varying concentrations from 2% to 16% (w/w) at an interval of 2% (w/w). The spindle aggregates reappeared at the concentrations of 6% and 14%. Viscosity measurements indicated that the physicochemical properties of the gelatin solution had changed with increasing concentration. UV and CD analysis indicated that hydrophobic interactions competed with hydrogen bonding, and the random coils partly transformed to ß-sheet structure by changing the concentration. Zeta potential and pH data confirmed the increasing electrostatic repulsion associated with increasing the hydrophobic region. XPS analysis revealed that the elemental composition of the gelatin particle surface changed with variation in the aggregate structure, determining the monotonic variation of the grafting density with increasing concentration. Results demonstrate that aggregation behavior of gelatin in aqueous solution plays a crucial role in deciding the grafting density of gelatin modified products.

N,N,N',N'-Tetra-kis(2-hy-droxy-5-methyl-benz-yl)ethane-1,2-diamine dimethyl-formamide disolvate.

The title compound, C(34)H(40)N(2)O(4)·2C(3)H(7)NO, was synthesized by the Mannich condensation of ethane-diamine, formaldehyde and p-cresol. In the crystal, the tetra-phenol mol-ecule is arranged around an inversion center. The mol-ecule and the dimethyl-formamide solvate are linked through an O-H⋯O hydrogen bond. An intra-molecular O-H⋯N hydrogen bond occurs in the tetra-phenol mol-ecule, which may influence the mol-ecular confomation. Futhermore, C-H⋯O and π-π stacking inter-actions [centroid-centroid distance = 3.7081 (14) Å] stabilize the crystal packing, building a three-dimensional network.

9-{4-[(E)-2-(4,6-Dimethyl-1,3,5-triazin-2-yl)ethen-yl]phen-yl}-9H-carbazole.

In the crystal structure of the title compound, C(25)H(20)N(4), the triazinyl ring is nearly coplanar with the planar (r.m.s. deviation = 0.028 Å) phenyl-ethenyl unit, the twist being only 5.8 (2)°; however, the planar carbazolyl unit (r.m.s. deviation = 0.008 Å) is twisted by 47.8 (1)° with respect to the phenyl-ethenyl unit. The nonplanar nature of the mol-ecule explains the phenomenon of light emission at short wavelengths in the solid state but at long wavelengths in solution.