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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.
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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.
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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.
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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.
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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.
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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.
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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-Hâ¯O hydrogen bond. An intra-molecular O-Hâ¯N hydrogen bond occurs in the tetra-phenol mol-ecule, which may influence the mol-ecular confomation. Futhermore, C-Hâ¯O and π-π stacking inter-actions [centroid-centroid distance = 3.7081â (14)â Å] stabilize the crystal packing, building a three-dimensional network.
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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.
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MicroRNAs/genética , Fatores de Transcrição SOXC/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Fatores de Transcrição SOXC/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismoRESUMO
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.
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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.
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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 = 0.028â Å) phenyl-ethenyl unit, the twist being only 5.8â (2)°; however, the planar carbazolyl unit (r.m.s. deviation = 0.008â Å) is twisted by 47.8â (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.
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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.
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Agricultura/métodos , Arqueologia , Botânica , ChinaRESUMO
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 4.1â¯×â¯104â¯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.
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[This corrects the article DOI: 10.1371/journal.pone.0187405.].
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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.
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Flores/fisiologia , Hordeum/fisiologia , Triticum/fisiologia , China , HaplótiposRESUMO
OBJECTIVE: To study the characteristics of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H-ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in predicting the outcome of syndrome. METHODS: Five hundred and forty cases fulfilling the criteria of MODS were divided into four groups according to the altitude of their inhabitation area: control group (on plain, CG, n=113, altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517 m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the diagnostic criteria of Lushan conference and Marshall (1995) commonly used on plain, and Lanzhou criteria drafted by the authors, three data analyzing models were set up to draw the receiver operating characteristic (ROC) curves, the Yordon Index and the optimum cutoff points of the parameters were calculated and the accuracy of the three respective diagnostic criteria was evaluated in predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of MODS were analyzed using the method of stepwise forward regress model. RESULTS: Following the increase in altitude, Lanzhou criteria was clearly superior to the other two criteria in the area of ROC, the sensitivity, the specificity, and also for the optimum cutoff points of MODS. Multi-variable regression analysis showed that the impacting factor of Lanzhou criteria was the highest (P<0.05). CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS are not suitable in moderately high or high altitude areas. It is necessary to set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics might change in areas 1,500 m altitude or higher. The pathophysiological mechanism might be attributable to peculiar biologic reactions due to hypoxia stress reaction, and it is worth further study.
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Altitude , Insuficiência de Múltiplos Órgãos/diagnóstico , Síndrome do Desconforto Respiratório/diagnóstico , Humanos , Prognóstico , Curva ROC , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To compare the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plain, and to establish a more practical diagnostic criterion of H-ARDS/MODS. METHODS: Five hundred and five cases fulfilled the criteria for the diagnosis of ARDS/MODS were divided into three groups according to the altitude of their habitation: control group including inhabitants (<430 m) on plain (CG, n=113), moderate high altitude group 1 inhabitants at the altitude of 1,517 m (H1G, n=314), moderate high altitude group 2 inhabitants at the altitude of 2,261 m to 2,400 m (H2G, n=78). The ARDS/MODS scores of the three groups were made according to the diagnostic criteria of Lushan conference, Marshall(1995) and Lanzhou criteria drafted by the authors respectively to set up three data analyzing models, followed by plotting of receiver operating characteristic curves (ROC curve) and calculation of the Yordon Index and the optimum cutoff points of the parameters,in order to study the accuracy of the three diagnostic criteria in predicting the outcome of the patients suffering from ARDS/MODS. RESULTS: In CG group, the differences were not significant in area of ROC, the maximal Yordon Index, the optimum cutoff points and the sensitivity and the specificity for three criteria; but the differences were significant for the three criteria in H1G group. Further investigation in comparing the ROC values of lung, brain, heart and kidney, the Lanzhou criteria were more advantageous in the high altitude than the other criteria. CONCLUSION: (1)The current diagnostic criteria of ARDS/MODS are not suitable for the diagnosis of these syndromes in moderately high or high altitude areas. It is necessary to revise the diagnostic criteria of H-ARDS/MODS. (2)One thousand five hundred and seventeen meters in altitude might be considered to be an important borderline, above with the diagnostic criteria of ARDS/MODS for patients inhabiting on plain could not be suitably applied to those living above this level.
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Altitude , Insuficiência de Múltiplos Órgãos/diagnóstico , Síndrome do Desconforto Respiratório/diagnóstico , Humanos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
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.
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Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Citometria de Fluxo , Humanos , Células MCF-7 , Reação em Cadeia da Polimerase em Tempo Real , TransfecçãoRESUMO
OBJECTIVE: To investigate the effect of Shengmai Injection (SMI) on blood coagulation in patients with chronic heart failure (CHF). METHODS: Sixty patients with CHF were randomly divided into two groups, the 30 patients in the treated group were treated with SMI plus conventional treatment of western medicine, and the 30 in the control group treated with conventional treatment alone. The changes of cardiac function were observed and levels of plasma P-selectin, von Willebrand's factor (vWF) and D-dimer were determined. RESULTS: The total effective rate and the markedly effective rate in the treated group were higher than those in the control group respectively. The levels of P-selectin, vWF and D-dimer lowered in both groups significantly after treatment, but the effect of lowering was better in the treated group than that in the control group. CONCLUSION: Hypercoagulative state exist in patients with chronic heart failure. SMI could improve the state in patients, which may reduce the occurrence and developing of emboic events to certain extent.
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Coagulação Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Fitoterapia , Fator de von Willebrand/metabolismo , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Insuficiência Cardíaca/sangue , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Panax/químicaRESUMO
OBJECTIVE: To study the characteristics of systemic inflammatory response syndrome (SIRS) of inpatients with nosocomial G- bacteria infection in order to find on effective treatment. METHODS: Eighty-two inpatients of SIRS with lower respiratory tract infection with G- bacteria were studied prospectively until discharge or death. They were divided into two groups: observation group (42 cases) and control group (40 cases). Bacteria culture of sputum and drug sensitivity was performed. Routine treatment was carried out in the control group, and rhubarb and antibiotics with lower endotoxin releasing property were given to the observation group. The course of SIRS, the incidence of MODS, and the mortality were compared. RESULTS: The duration with SIRS in observation group and control group was respectively (6.2+/-1.3) days and (7.4+/-1.2) days, u=3.91, P<0.05; the incidence of MODS was 11.4 percent and 32.3 percent, respectively, chi(2)=4.27, P<0.05. The mortality rates of the patients with SIRS in two groups were 8.6 percent and 29.0 percent, respectively. CONCLUSION: The results indicated that the treatment with rhubarb could obviously reduce the duration of SIRS compared with routine method. The same is true in the incidence of MODS and mortality rate.