Native Amino Group Directed Meta-Selective C-H Arylation of Primary Amines Via Pd/Norbornene Catalysis.

The selective functionalization of remote C-H bonds in free primary amines holds significant promise for the late-stage diversification of pharmaceuticals. However, to date, the direct functionalization of the meta position of amine substrates lacking additional directing groups remains underexplored. In this Letter, we present a successful meta-C-H arylation of free primary amine derivatives using aryl iodides, resulting in synthetically valuable yields. This meta-selective C-H functionalization is achieved through a sequence involving native amino-directed Pd-catalyzed seven-membered cyclometalation, followed by the utilization of a norbornene-type transient mediator.

San Pian decoction can treat nitroglycerin-induced migraine in rats by inhibiting the PI3K/AKT and MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: San Pian decoction (SPD), a traditional Chinese medicine preparation composed of eight herbs, has been reported to alleviate migraine. However, its active ingredients and the potential mechanism of action remains unclear. The purpose of this study was to comprehensively analyze SPD for the treatment of chronic migraine based on pharmacological direction and to identify the active ingredients and pharmacological mechanism of SPD in the treatment of migraine. MATERIALS AND METHODS: The active components in SPD were identified by AB SCIEX quadrupole time-of-flight mass spectrometer, and the prediction targets and pharmacological networks related to migraine were constructed. The mechanism of SPD in treating migraine was studied through network pharmacology, which was further verified using pharmacological experiments. RESULTS: A total of 489 targets of 26 compounds were identified. Based on Venn analysis, we found 117 intersection targets between SPD and migraine, that is, these targets were related to the treatment of migraine. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the treatment of migraine using SPD was related to the PI3K/AKT and MAPK signaling pathways. The effect of SPD on migraine was verified by measuring the levels of the inflammatory factors, nitric oxide (NO), interleukin (IL-6), endothelin (ET),5-hydroxytryptamine(5-HT), indoleamine 2,3-dioxygenas (IDO), tumor necrosis factor (TNF-α) and calcitonin gene-related peptide (CGRP). Lastly, real-time polymerase chain reaction and western blotting were used to verify gene and protein expression in the PI3K/AKT and MAPK signaling pathways. Expression of the genes P38, JNK, ERK, PI3K and AKT, and the protein expression of p-P38, p-JNK, p-ERK, p-AKT and p-PI3K were significantly downregulated. Our findings indicated that SPD could prevent inflammation by regulating the inflammatory cytokines and key genes and proteins in the PI3K/AKT and MAPK signaling pathways to treat migraine. CONCLUSION: Our findings reveal that SPD could treat nitroglycerin-induced migraine by regulating p-AKT, p-pI3k, p-p38, p-ERK, p-JNK, IL-6, and TNF-α inflammatory factors in the PI3K/AKT and MAPK signaling pathways.

Multi-linear antenna microwave plasma assisted large-area growth of 6 × 6 in.2 vertically oriented graphenes with high growth rate.

Vertically oriented graphenes (VGs) are promising for many emerging energy and environmental applications, while their mass production still remains a critical challenge. This note reports a multi-linear antenna microwave plasma device for fabricating VGs on a large-scale. Eight coaxial linear plasma antennas are parallelly arrayed to produce large-area plasma, depositing 6 × 6 in.2 VGs on nickel foil at a high rate of 160 nm min-1. In supercapacitor applications, the potential of VGs for AC line filtering (an RC time of 0.43 ms) and decreasing the interfacial contact resistance within commercial activated carbon supercapacitors is demonstrated.

Solar-Enhanced Plasma-Catalytic Oxidation of Toluene over a Bifunctional Graphene Fin Foam Decorated with Nanofin-like MnO2.

In this work, we propose a hybrid and unique process combining solar irradiation and post-plasma catalysis (PPC) for the effective oxidation of toluene over a highly active and stable MnO2/GFF (bifunctional graphene fin foam) catalyst. The bifunctional GFF, serving as both the catalyst support and light absorber, is decorated with MnO2 nanofins, forming a hierarchical fin-on-fin structure. The results show that the MnO2/GFF catalyst can effectively capture and convert renewable solar energy into heat (absorption of >95%), leading to a temperature rise (55.6 °C) of the catalyst bed under solar irradiation (1 sun, light intensity 1000 W m-2). The catalyst weight (9.8 mg) used in this work was significantly lower (10-100 times lower) than that used in previous studies (usually 100-1000 mg). Introducing solar energy into the typical PPC process via solar thermal conversion significantly enhances the conversion of toluene and CO2 selectivity by 36-63%, reaching ∼93% for toluene conversion and ∼83% for CO2 selectivity at a specific input energy of ∼350 J L-1, thus remarkably reducing the energy consumption of the plasma-catalytic gas cleaning process. The energy efficiency for toluene conversion in the solar-enhanced post-plasma catalytic (SEPPC) process reaches up to 12.7 g kWh-1, ∼57% higher than that using the PPC process without solar irradiation (8.1 g kWh-1), whereas the energy consumption of the SEPPC process is reduced by 35-52%. Moreover, the MnO2/GFF catalyst exhibits an excellent self-cleaning capability induced by solar irradiation, demonstrating a superior long-term catalytic stability of 72 h at 1 sun, significantly better than that reported in previous works. The prominent synergistic effect of solar irradiation and PPC with a synergistic capacity of ∼42% can be mainly attributed to the solar-induced thermal effect on the catalyst bed, boosting ozone decomposition (an almost triple enhancement from ∼0.18 gO3 g-1 h-1 for PPC to ∼0.52 gO3 g-1 h-1 for SEPPC) to generate more oxidative species (e.g., O radicals) and enhancing the catalytic oxidation on the catalyst surfaces, as well as the self-cleaning capacity of the catalyst at elevated temperatures driven by solar irradiation. This work opens a rational route to use abundant, renewable solar power to achieve high-performance and energy-efficient removal of volatile organic compounds.

Highly Thermo-Conductive Three-Dimensional Graphene Aqueous Medium.

Highly thermo-conductive aqueous medium is a crucial premise to demonstrate high-performance thermal-related applications. Graphene has the diamond comparable thermal conductivity, while the intrinsic two-dimensional reality will result in strong anisotropic thermal conductivity and wrinkles or even crumples that significantly sacrifices its inherent properties in practical applications. One strategy to overcome this is to use three-dimensional (3D) architecture of graphene. Herein, 3D graphene structure with covalent-bonding nanofins (3D-GS-CBF) is proposed, which is then used as the filler to demonstrate effective aqueous medium. The thermal conductivity and thermal conductivity enhancement efficiency of 3D-GS-CBF (0.26 vol%) aqueous medium can be as high as 2.61 W m-1 K-1 and 1300%, respectively, around six times larger than highest value of the existed aqueous mediums. Meanwhile, 3D-GS-CBF can be stable in the solution even after 6 months, addressing the instability issues of conventional graphene networks. A multiscale modeling including non-equilibrium molecular dynamics simulations and heat conduction model is applied to interpret experimental results. 3D-GS-CBF aqueous medium can largely improve the solar vapor evaporation rate (by 1.5 times) that are even comparable to the interfacial heating system; meanwhile, its cooling performance is also superior to commercial coolant in thermal management applications.

Tree-inspired radially aligned, bimodal graphene frameworks for highly efficient and isotropic thermal transport.

Highly-oriented, interconnected graphene frameworks have been considered as promising candidates to realize high-performance thermal management in microelectronics. However, the obvious thermal boundary resistance and anisotropic heat conduction still remain major bottlenecks for efficient heat dissipation. Herein, a biomimetic design enabled by radially aligned, bimodal graphene frameworks (RG-Fin) is proposed to achieve highly efficient and isotropic thermal transport. An interconnected RG skeleton is prepared via a radial ice-template method, serving as the primary expressway for isotropic heat conduction. Tree-leaf-like graphene nanofins are vertically grown on the RG surface to provide additional thermal pathways for bimodal phonon transportation, which can reduce the thermal boundary resistance without degrading the thermal properties of the skeleton. An RG-Fin composite exhibits a superior thermal conductivity of 4.01 W m-1 K-1 (almost 20 times that of a polymer) at an ultralow loading of 1.53 vol%, demonstrating an exceptionally large thermal conductivity enhancement efficiency of 1247%, which far exceeds those of graphene-based polymer composites. Further theoretical analysis and finite element simulations reveal the critical role of the nanofins in significantly decreasing the thermal boundary resistance (by almost 27-fold). Finally, the practical thermal management of running a CPU module is demonstrated, in which the heating-up rate of the RG-Fin composite is ∼2.0 times that of a pure polymer. This strategy provides an innovative avenue for designing radially aligned networks to realize isotropic and efficient thermoconductive composites for thermal management.

[Inhibitory effect of endophytic fungi from Dysosma versipellis on HIV-1 IN-LEDGF/p75 interaction].

To determine the inhibitory effect of endophytic fungi from Dysosma versipellis on HIV-1 IN-LEDGF/p75 interaction,the protein-protein interaction between human immunodeficiency virus type 1( HIV-1) integrase and lens epithelial growth factor p75 protein( LEDGF/p75) was used as a target. The homogeneous time-resolved fluorescence( HTRF) technique was used in the inhibitory activity assay. The results showed that eight endophytic fungi with anti-IN-LEDGF/p75 interaction activity were screened out from fifty-three strains with different morphological characteristic. Among them,106 strain showed strong inhibitory activity against HIV-1 IN-LEDGF/p75 interaction with IC50 value of 5. 23 mg·L-1,and was identified as a potential novel species of Magnaporthaceae family by the analyses of ITS-rDNA,LSU and RPB2 sequences data. This study demonstrated that potential natural active ingredients against the HIV-1 IN-LEDGF/p75 interaction exist in the endophytic fungi of D. versipellis. These results may provide available candidate strain resources for the research and development of new anti-acquired immunodeficiency syndrome drugs.

Mannan Oligosaccharide Protects against the Aflatoxin-B1-Promoted Influenza Replication and Tissue Damages in a Toll-Like-Receptor-4-Dependent Manner.

Our previous study reported that aflatoxin B1 (AFB1) promoted influenza replication. Mannan oligosaccharide (MOS), derived from the cell walls of yeast, is a potent immunomodulator. Here, we investigated the role of MOS in AFB1-promoted influenza replication and further explored the underlying mechanisms. In vitro and in vivo, the exposure to AFB1 alone resulted in significantly decreased weight gain and increased viral replication as well as lung and spleen damages. Increased influenza replication coupled with increases in toll-like receptor 4 (TLR4), phosphorylated nuclear factor κB, and tumor necrosis factor α (TNF-α) levels. However, MOS given in conjunction with exposure to AFB1 significantly reversed these above changes. A further study indicated that MOS activity was abolished by TLR4 knockout or TLR4 overexpression. Surprisingly, TNF-α played no role in the MOS-mediated protective effects. Collectively, our data suggest that MOS alleviates the AFB1-promoted influenza replication, inflammation, and tissue damages in a TLR4-dependent manner.

Enhanced plasma-catalytic decomposition of toluene over Co-Ce binary metal oxide catalysts with high energy efficiency.

In-plasma catalysis has been considered as a promising technology to degrade volatile organic compounds. Heterogeneous catalysts, especially binary metal oxide catalysts, play an important role in further advancing the catalytic performance of in-plasma catalysis. This work investigates the toluene decomposition performance over Co-Ce binary metal oxide catalysts within the in-plasma catalysis. Co-Ce catalysts with different Co/Ce molar ratios are synthesized by a citric acid method. Results show that the catalytic activity of Co-Ce catalysts is obviously superior to those of monometallic counterparts. Especially, Co0.75Ce0.25O x catalyst simultaneously realizes highly efficient toluene conversion (with a decomposition efficiency of 98.5% and a carbon balance of 97.8%) and a large energy efficiency of 7.12 g kW h-1, among the best performance in the state-of-art literature (0.42 to 6.11 g kW h-1). The superior catalytic performance is further interpreted by the synergistic effect between Co and Ce species and the significant plasma-catalyst interaction. Specifically, the synergistic effect can decrease the catalyst crystallite size, enlarge the specific surface area and improve the amount of oxygen vacancies/mobility, providing more active sites for the adsorption of surface active oxygen species. Meanwhile, the plasma-catalyst interaction is able to generate the surface discharge and reinforce the electric field strength, thereby accelerating the plasma-catalytic reactions. In the end, the plasma-catalytic reaction mechanism and pathways of toluene conversion are demonstrated.

An Early Cretaceous eutherian and the placental-marsupial dichotomy.

Molecular estimates of the divergence of placental and marsupial mammals and their broader clades (Eutheria and Metatheria, respectively) fall primarily in the Jurassic period. Supporting these estimates, Juramaia-the oldest purported eutherian-is from the early Late Jurassic (160 million years ago) of northeastern China. Sinodelphys-the oldest purported metatherian-is from the same geographic area but is 35 million years younger, from the Jehol biota. Here we report a new Jehol eutherian, Ambolestes zhoui, with a nearly complete skeleton that preserves anatomical details that are unknown from contemporaneous mammals, including the ectotympanic and hyoid apparatus. This new fossil demonstrates that Sinodelphys is a eutherian, and that postcranial differences between Sinodelphys and the Jehol eutherian Eomaia-previously thought to indicate separate invasions of a scansorial niche by eutherians and metatherians-are instead variations among the early members of the placental lineage. The oldest known metatherians are now not from eastern Asia but are 110 million years old from western North America, which produces a 50-million-year ghost lineage for Metatheria.

Warming-induced northwestward migration of the East Asian monsoon rain belt from the Last Glacial Maximum to the mid-Holocene.

Glacial-interglacial changes in the distribution of C3/C4 vegetation on the Chinese Loess Plateau have been related to East Asian summer monsoon intensity and position, and could provide insights into future changes caused by global warming. Here, we present δ(13)C records of bulk organic matter since the Last Glacial Maximum (LGM) from 21 loess sections across the Loess Plateau. The δ(13)C values (range: -25‰ to -16‰) increased gradually both from the LGM to the mid-Holocene in each section and from northwest to southeast in each time interval. During the LGM, C4 biomass increased from <5% in the northwest to 10-20% in the southeast, while during the mid-Holocene C4 vegetation increased throughout the Plateau, with estimated biomass increasing from 10% to 20% in the northwest to >40% in the southeast. The spatial pattern of C4 biomass in both the LGM and the mid-Holocene closely resembles that of modern warm-season precipitation, and thus can serve as a robust analog for the contemporary East Asian summer monsoon rain belt. Using the 10-20% isolines for C4 biomass in the cold LGM as a reference, we derived a minimum 300-km northwestward migration of the monsoon rain belt for the warm Holocene. Our results strongly support the prediction that Earth's thermal equator will move northward in a warmer world. The southward displacement of the monsoon rain belt and the drying trend observed during the last few decades in northern China will soon reverse as global warming continues.

Development of a SCAR (sequence-characterised amplified region) marker for acid resistance-related gene in Lactobacillus plantarum.

A sequence characterised amplified region marker was developed to determine an acid resistance-related gene in Lactobacillus plantarum. A random amplified polymorphic DNA marker named S116-680 was reported to be closely related to the acid resistance of the strains. The DNA band corresponding to this marker was cloned and sequenced with the induction of specific designed PCR primers. The results of PCR test helped to amplify a clear specific band of 680 bp in the tested acid-resistant strains. S116-680 marker would be useful to explore the acid-resistant mechanism of L. plantarum and to screen desirable malolactic fermentation strains.

[Influence of silver/silicon dioxide on infrared absorption spectroscopy of sodium nitrate].

Quickly detecting of ocean nutrient was one important task in marine pollution monitoring. We discovered the application of surface-enhanced infrared absorption spectroscopy in the detection of ocean nutrient through researching the evaporation of sodium nitrate solution. The silicon dioxide (SiO2) with highly dispersion was prepared by Stober method, The silver/silica (Ag/SiO2) composite materials were prepared by mixing ammonia solution and silicon dioxide aqueous solution. Three kinds of composite materials with different surface morphology were fabricated through optimizing the experimental parameter and changing the experimental process. The surface morphology, crystal orientation and surface plasmon resonance were investigated by means of the scanning electronic microscope (SEM), X-ray diffraction (XRD), UV-Visible absorption spectrum and infrared ab- sorption spectroscopy. The SEM images showed that the sample A was purified SiO2, sample B and sample C were mixture of silver nanoparticle and silicon dioxide, while sample D was completed nanoshell structure. The absorption spectroscopy showed that there was surface plasmon resonance in the UV-visible region, while there was possibility of surface plasmon resonance in the Infrared absorption region. The effect of Ag/SiO2 composite material on the infrared absorption spectra of sodium nitrite solution was investigated through systematically analyzing the infrared absorption spectroscopy of sodium nitrate solution during its evaporation, i. e. the peak integration area of nitrate and the peak integration area of water molecule. The experimental results show that the integration area of nitrate was enhanced greatly during the evaporation process while the integration area of water molecule decreased continuously. The integration area of nitrate comes from the anti-symmetric stretch vibration and the enhancement of the vibration is attributed to the interface effect of Ag/SiO2 which is consistent with Jensen T.R's result.

Postischemic Long-Term Treatment with Qiangli Tianma Duzhong Capsule Improves Brain Functional Recovery via the Improvement of Hemorrheology and the Inhibition of Platelet Aggregation in a Rat Model of Focal Cerebral Ischemia.

Qiangli Tianma Duzhong capsule (TMDZ), a Chinese herbal drug, is clinically used to improve functional outcome in patients with ischemic stroke in China. This study was conducted to establish whether postischemic long-term treatment with TMDZ could reduce the loss of injured hemisphere and confer the improvements of neurological outcome in chronic survival of rats with 2 h middle cerebral artery occlusion (MCAO)/reperfusion brain injury and its primary mechanisms. We found that TMDZ (44.5, 89, or 178 mg/kg), administered per os 6 h after the onset of ischemia and for 28 consecutive days, significantly improved the behavior deficits, beginning on day 7, and further improved later. TMDZ treatment also markedly reduced the tissue loss of the injured hemisphere and improved histopathology. In the meantime, TMDZ treatment could improve hemorrheology and inhibit platelet aggregation. These results provide the first evidence that post-ischemic long-term treatment with TMDZ confers the improvements of neurological outcome and the loss of injured hemisphere in an animal ischemic stroke model, and its mechanisms might be associated with the improvements of hemorrheology and the inhibition of platelet aggregation.

The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis.

Cultured lung endothelial cells (LEC) respond to VEGF or arachidonic acid with increases in cell proliferation, the formation of tube-like structures, and the activation of Akt and ERK1/2 mediated growth pathways. LECs express a VEGF inducible Cyp2c44 epoxygenase and its 11,12- and 14,15-EET metabolites increase cell proliferation, tubulogenic activity, and the phosphorylation states of the ERK1/2 and Akt kinases. Ketoconazole, an epoxygenase inhibitor, blocks the cellular responses to VEGF. LECs expressing a Cyp2c44 epoxygenase small interference RNA show reductions in Cyp2c44 mRNA levels, and in their VEGF-stimulated proliferative and tubulogenic capacities; effects that are associated with decreases in VEGF-induced phosphorylation of the ERK1/2 and Akt kinases. We conclude that the Cyp2c44 arachidonic acid epoxygenase is a component of the signaling pathways associated with VEGF-stimulated angiogenesis, and suggest a role for EETs in the growth factor-induced changes in the activation states of the ERK1/2 and Akt kinase pathways.

[Seperation and structure elucidation of alkaloids from Chinese drug buzhaye, Folium Microcos].

From the chloroform extracts of the dried Folium Microcos, four compounds were isolated by using repeated column chromatography on silica gel and recrystallization and their structures were elucidated by physicochemical properties and UV, MS and NMR, separately. They are N-methyl-6alpha-(deca-1', 3', 5'-trienyl)-3beta-methoxy-2beta-methylpiperidine, 6-(deca-1', 3', 5'-trienyl)-3-methoxy-2-methylpiperidine, N-methyl-6-(deca-1', 3', 5'-trienyl)-2, 3-dimethylpiperidine and N-methyl-6-(deca-1', 3', 5'-trienyl)-2-methylpiperidine, named as micropiperidine A, micropiperidine B, micropiperidine C and micropiperidine D, respectively. The latter three are new compounds.

Pharmacodynamics and potential toxicity of intranasally administered dipyrone.

Dipyrone is a non-narcotic analgesic and antipyretic drug used in both pediatric and adult patients. Dipyrone solution can be used intranasally as an antipyretic agent for infants. However, dipyrone is not stable in liquid state. Therefore, a stable dipyrone formulation was developed and the antipyretic effect of the formulation was studied after intranasal administration in rabbits and rats, respectively. To guarantee dose accuracy in animal studies, effect of dose volume on the distribution of dipyrone solution in rabbit nasal cavities were studied, using gentian violet as an indicator. Animal fever model and intranasal administration methods were established. In addition, the potential toxicity of the dipyrone formulation was studied. It was shown that the nasal volume of rabbits is large enough to hold 100 microl solution. After intranasal administration, improved pharmacodynamics was obtained with the new developed dipyrone formulation compared to the normal dipyrone solution, and significantly decreased body temperature was observed 10 min after dosing. The toxicity was negligible. In conclusion, the dipyrone formulation is effective and safe for clinical medication.