Integrated transcriptome and metabolome analyses revealed regulatory mechanisms of flavonoid biosynthesis in Radix Ardisia.

Background: Radix Ardisia (Jab Bik Lik Jib) is a common Miao medicine and is widely distributed in the Guizhou region of southern China. The botanical origin of Radix Ardisia includes the dry root and rhizome of Ardisia Crenata Sims (ACS) or Ardisia Crispa (Thunb.) A.DC. (AC), which are closely related species morphologically. However, the secondary metabolites in their roots are different from one another, especially the flavonoids, and these differences have not been thoroughly explored at the molecular level. This project preliminarily identified regulatory molecular mechanisms in the biosynthetic pathways of the flavonoids between ACS and AC using a multi-omics association analysis. Methods: In this study, we determined the total levels of saponin, flavonoid, and phenolic in Radix Ardisia from different origins. Integrated transcriptome and metabolome analyses were used to identify the differentially expressed genes (DEGs) and differentially expressed metabolites (DEM). We also performed conjoint analyses on DEGs and DEMs to ascertain the degree pathways, and explore the regulation of flavonoid biosynthesis. Results: The total flavonoid and phenolic levels in ACS were significantly higher than in AC (P < 0.05). There were 17,685 DEGs between ACS vs. AC, 8,854 were upregulated and 8,831 were downregulated. Based on this, we continued to study the gene changes in the flavonoid biosynthesis pathway, and 100 DEGs involving flavonoid biosynthesis were differentially expressed in ACS and AC. We validated the accuracy of the RNA-seq data using qRT-PCR. Metabolomic analyses showed that 11 metabolites were involved in flavonoid biosynthesis including: Naringenin, Luteolin, Catechin, and Quercetin. A conjoint analysis of the genome-wide connection network revealed the differences in the types and levels of flavonoid compounds between ACS and AC. The correlation analysis showed that Naringenin, Luteolin, Catechin, and Quercetin were more likely to be key compounds in the flavonoid biosynthesis pathway also including 4CL, AOMT, CHS, CHI, DFR, F3'5'H, FLS, and LAR. Conclusions: This study provides useful information for revealing the regulation of flavonoid biosynthesis and the regulatory relationship between metabolites and genes in the flavonoid biosynthesis pathway in Radix Ardisia from different origins.

Hyperoside suppresses osteoclasts differentiation and function through downregulating TRAF6/p38 MAPK signaling pathway.

Hyperoside (HP), as a natural product, can promote proliferation and differentiation of osteoblasts and presents a protective effect on ovariectomized (OVX) mice. However, the inhibitory effect of HP on osteoclasts (OCs) and the potential mechanism remain to be elucidated. In this study, it was found that HP could effectively inhibit the differentiation and bone resorption of OCs, and its intrinsic molecular mechanism was related to the inhibition of TRAF6/p38 MAPK signaling pathway. Therefore, HP could be a promising natural compound for lytic bone diseases.

[Protective effects of Lonicerae Japonicae Flos against acute alcoholic liver injury in rats based on network pharmacology].

This study aims to explore underlying mechanism of Lonicerae Japonicae Flos(LJF) in protecting rats against acute alcoholic liver injury(ALI) based on mitogen-activated protein kinase(MAPK) pathway. First, the targets of LJF in preventing ALI were predicted by network pharmacology and the component-target-pathway network was constructed, so that the key targets of LJF components acting on MAPK pathway were screened. Second, male SD rats were randomized into the control(KB) group, model(MX) group, positive(YX) group, and LJF high-(GJ), medium-(ZJ), and low-(DJ) dose groups. Each administration group was given(ig) corresponding drugs for 7 days and KB group and MX group received(ig) equal volume of distilled water every day. Except for KB group, rats were given Chinese spirit(56%, 3 days) for ALI modeling. The levels of aspartate transaminase(AST), alanine transaminase(ALT), interleukin-6(IL6) and tumor necrosis factor-α(TNF-α) in serum and malondialdehyde(MDA), glutathione(GSH), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in liver tissue of rats in each group were detected. Furthermore, we employed quantitative real-time PCR(qRT-PCR) to probe the effects of LJF on the key targets of MAPK pathway in ALI rats. A total of 28 active components of LJF were screened from TCMSP database, and 317 intersected with ALI-related targets. According to Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, the 317 targets involved 226 pathways, which were mainly liver disease, inflammation, immunity, apoptosis and other related pathways. According to the MAPK pathway-target-active component network, the key active components of LJF, such as chlorogenic acid, hederagenol, and hyperoside, acted on 25 key targets of MAPK pathway. The results of in vivo experiments showed decreased levels of AST, ALT, and MDA in DJ, ZJ, and GJ groups(P<0.01 or P<0.05), reduced levels of IL6 in DJ and GJ groups(P<0.01 or P<0.05), and improved levels of SOD and GSH in ZJ and GJ groups(P<0.01 or P<0.05). The results of qRT-PCR demonstrated that the expression levels of mitogen-activated protein kinase kinase 4(MAPK2 K4) and mitogen-activated protein kinase 3(MAPK3) were decreased in DJ, ZJ, and GJ groups(P<0.01). The network pharmacology and experimental verification showed that the active components in LJF can reduce the inflammatory factor level and enhance the activities of SOD and GSH-Px by inhibiting the expression of key targets of MAPK pathway, thus alleviating and preventing liver damage caused by alcohol.

Synthesis of in-plane and stacked graphene/hexagonal boron nitride heterostructures by combining with ion beam sputtering deposition and chemical vapor deposition.

Graphene/hexagonal boron nitride (h-BN) heterostructures have attracted a great deal of attention in recent years due to their unique and complementary properties for use in a wide range of potential applications. However, it still remains a challenge to synthesize large-area high quality samples by a scalable growth method. In this work, we present the synthesis of both in-plane and stacked graphene/h-BN heterostructures on Cu foils by sequentially depositing h-BN via ion beam sputtering deposition (IBSD) and graphene with chemical vapor deposition (CVD). Due to a significant difference in the growth rate of graphene on h-BN and Cu, the in-plane graphene/h-BN heterostructures were rapidly formed on h-BN domain/Cu substrates. The large-area vertically stacked graphene/h-BN heterostructures were obtained by using the continuous h-BN film as a substrate. Furthermore, the well-designed sub-bilayered h-BN substrates provide direct evidence that the monolayered h-BN on Cu exhibits higher catalytic activity than the bilayered h-BN on Cu. The growth method applied here may have great potential in the scalable preparation of large-area high-quality graphene/h-BN heterostructures.

Theoretical evaluation of flotation performance of carboxyl hydroxamic acids with different number of polar groups on the surfaces of diaspore (010) and kaolinite (001).

The adsorption behaviors of three carboxyl hydroxamic acids on diaspore (010) and kaolinite (001) have been studied by density functional theory (DFT) and molecular dynamics (MD) method. The results indicated that carboxyl hydroxamic acids could adsorb on diaspore surface by ionic bonds and hydrogen bonds, and adsorb on kaolinite surface by hydrogen bonds. The models of carboxyl hydroxamic acids adsorbed on diaspore and kaolinite surfaces are proposed.

[Circumcision with the Chinese Shang Ring in children: outcomes of 824 cases].

OBJECTIVE: To observe the clinical effects of using the Chinese Shang Ring in circumcision children with either phimosis or redundant prepuce, and to investigate its superiority over the similar devices available. METHODS: A total of 824 children with phimosis or redundant prepuce underwent circumcision with the Shang Ring. The clinical data were assessed concerning the duration of the procedure, incidence of post-operative complications, time of recovery and appearance of the penis. RESULTS: The procedure duration was (2.6 +/-1.2) min, and the complications included infection in 4 (0.6%), edema in 21 (3.2%), delayed removal of the ring in 10 (1.5%), redundant and asymmetric mucosa attributable to performance in 6 (0.9%) of the cases. The wounds healed and the rings were removed at 13.4 +/- 5.8 days after circumcision, with well-smoothed incision and good cosmetic results. CONCLUSION: Child circumcision with the Chinese Shang Ring is easy and simple in performance, with less operative time, fewer complications and better cosmetic results.

An ortho-rhom-bic polymorph of 1-benzyl-1H-benzimidazole.

The title compound, C(14)H(12)N(2), in contrast to the previously reported monoclinic polymorph [Lei et al. (2009 ▶). Acta Cryst. E65, o2613], crystallizes in the ortho-rhom-bic crystal system. The dihedral angle between the imidazole ring system and the phenyl ring is 76.78 (16)°. Weak C-H⋯N and C-H⋯π inter-actions are observed in the crystal structure.

1-(Butan-2-yl-idene)-2-(2-nitro-phen-yl)hydrazine.

Crystals of the title compound, C(10)H(13)N(3)O(2), were obtained from a condensation reaction of butan-2-one and 1-(2-nitro-phen-yl)hydrazine. The mol-ecule exhibits a nearly coplanar structure, except for the methyl and methyl-ene H atoms, the largest deviations from the mean plane defined by all non-H atoms, except for the nitro group, being 0.120 (2) Šfor one of the nitro O atoms. Intra-molecular N-H⋯O hydrogen bonding helps to establish the mol-ecular configuration.

1-[4-(2-Fur-yl)but-3-en-2-yl-idene]-2-(2-nitro-phen-yl)hydrazine.

In the title Schiff base compound, C(14)H(13)N(3)O(3), the furan and benzene rings are oriented at a dihedral angle of 10.24 (13)°. Intra-molecular N-H⋯O hydrogen bonding is observed between the imino and nitro groups.

N'-(2-Furylmethyl-ene)nicotinohydrazide.

The asymmetric unit of the title compound, C(11)H(9)N(3)O(2), contains two independent mol-ecules: the dihedral angles between the pyridine ring and the furyl ring are 17.00 (16) and 34.12 (15)°. The crystal structure involves inter-molecular C-H⋯O, N-H⋯N and N-H⋯O hydrogen bonds.

{4-Bromo-2-[2-(piperidin-1-ium-1yl)ethyl-iminometh-yl]phenolato}diiodido-zinc(II).

In the title complex, [ZnI(2)(C(14)H(19)BrN(2)O)], the Zn(II) atom is four-coordinated by the imine N and phenolate O atoms of the Schiff base ligand and by two iodide ions in a distorted tetra-hedral coordination. In the crystal structure, mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds, forming chains running along the b axis.

Diiodido[N'-(2-methoxy-benzyl-idene)-N,N-dimethyl-ethane-1,2-diamine]zinc(II).

In the title complex, [Zn(C(12)H(18)N(2)O)I(2)], the Zn(II) ion is four-coordinated by the imine N and amine N atoms of the Schiff base ligand and by two iodide ions in a distorted tetra-hedral coordination.

1-(But-2-enyl-idene)-2-(2-nitro-phen-yl)hydrazine.

The mol-ecule of the title Schiff base compound, C(10)H(11)N(3)O(2), adopts an E geometry with respect to the C=N double bond. The mol-ecule is roughly planar, with the largest deviation from the mean plane being 0.111 (2) Å, The enyl-idene-hydrazine group is, however, slightly twisted with respect to the phenyl ring, making a dihedral angle of 6.5 (3)°. An intra-molecular N-H⋯O hydrogen bond may be responsible for the planar conformation. An inter-molecular N-H⋯O hydrogen bond links two mol-ecules around an inversion center, building a pseudo dimer.

1-(2-Furylmethyl-ene)-2-(2-nitro-phen-yl)hydrazine.

The title Schiff base compound, C(11)H(9)N(3)O(3), was obtained from a condensation reaction of furan-2-carbaldehyde and 2-nitro-phenyl-hydrazine. The mol-ecule is roughly planar, the largest deviation from the mean plane defined by all non-H atoms being 0.097 (4). An in ntra-molecular N-H⋯O hydrogen bond might influence the planar conformation of the mol-ecule. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules, forming a chain.

2-Eth-oxy-4-{[(2-nitro-phen-yl)hydrazono]meth-yl}phenol.

The title compound, C(15)H(15)N(3)O(4), a Schiff base, was obtained from a condensation reaction of 3-eth-oxy-4-hydroxy-benzaldehyde and 2-nitro-phenyl-hydrazine. The mol-ecule is approximately planar, the largest deviation from the mean plane being 0.1449 (16) Å. An intramolecular N-H⋯O inter-action is also present. In the crystal, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules, forming chain parallel to the b axis.

{4-Bromo-2-[3-(diethyl-ammonio)propyl-imino-meth-yl]phenolato}diiodidozinc(II) methanol solvate.

In the title complex, [ZnI(2)(C(14)H(21)BrN(2)O)]·CH(3)OH, the asymmetric unit consists of a mononuclear zinc(II) complex mol-ecule and a methanol solvent mol-ecule. The compound was derived from the zwitterionic form of the Schiff base 4-bromo-2-[3-(diethyl-amino)propyl-imino-meth-yl]phenol. The Zn(II) atom is four-coordinated by the imine N and phenolate O atoms of the Schiff base ligand and by two iodide ions in a distorted tetra-hedral coordination. In the crystal structure, the methanol mol-ecules are linked to the Schiff base mol-ecules through N-H⋯O and O-H⋯O hydrogen bonds. One I atom is disordered over two positions in a 0.702 (19):0.298 (19) ratio.

Diiodido{4-nitro-2-[2-(piperidin-1-yl)ethyl-imino-meth-yl]phenolato}zinc(II).

In the title complex, [ZnI(2)(C(14)H(19)N(3)O(3))], the Zn(II) atom is four-coordinated by the imine N and phenolate O atoms of the Schiff base ligand, and by two iodide ions in a distorted tetra-hedral coordination. In the crystal structure, mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds, forming dimers.

[µ-1,1'-(Butane-1,4-di-yl)di-1H-benz-imidazole-κN:N]bis-{[N,N'-bis(car-boxy-meth-yl)ethyl-enediamine-N,N'-di-acetato-κO,O',O'',N,N']mercury(II)} methanol disolvate.

The binuclear title complex, [Hg(2)(C(10)H(14)N(2)O(8))(2)(C(18)H(18)N(4))]·2CH(3)OH, lies on an inversion center with the unique Hg(II) ion coordinated in a disorted octa-hedral environment with one Hg-N bond significantly shorter than the other two. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link complex and solvent mol-ecules into a three-dimensional network.

N'-[4-(2-Fur-yl)but-3-en-2-yl-idene]-iso-nicotino-hydrazide.

The mol-ecule of the title Schiff base compound, C(14)H(13)N(3)O(2), is not perfectly planar; the furyl and pyridine rings are twisted with respect to each other along the C(4)N(2)C(2) organic chain, making a dihedral angle of 13.3 (1)°. The occurence of N-H⋯O hydrogen bonds builds up a chain developing parallel to the c axis.

But-2-enal 2,4-dinitro-phenyl-hydrazone.

In the title compound, C(10)H(10)N(4)O(4), the but-2-enal chain is almost planar, the largest deviation from the mean plane being 0.013 (1) Å, and this plane makes a dihedral angle of 9.95 (24)° with the benzene ring,. Of the two nitro groups, one is twisted with respect to the benzene ring, making a dihedral angle of 5.7 (1)°, whereas the other is nearly in the plane of the benzene ring, with a twist angle of only 0.7 (1)°. This difference is related to the occurence of an intra-molecular N-H⋯O hydrogen bond with the O atom of the less twisted nitro group. The NH group is also involved in a weak inter-action with the same O atom of a symmetry-related mol-ecule, thus forming a pseudo inversion dimer.