Search

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

Juan Guo,1,* Zhiyu Pan,1,* Lvyuan Fan,1 Yilin Zhong,1 Rui Pang,2 Yubin Su1 1Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yubin Su, Email suyb7@jnu.edu.cnBackground: The issue of methicillin-resistant Staphylococcus aureus (MRSA) resistant to many antibiotics and causing serious infectious diseases is a growing healthcare concern.Purpose: In recent years, exogenous administration of metabolites in combination with antibiotics can re-sensitize resistant bacteria to antibiotics; however, their effects vary, and their underlying mechanism of action remains elusive.Methods: We assessed the bactericidal effects of the three amino acids in combination with gentamicin in vitro and in vivo. Subsequently, we explored the role of these amino acids on the metabolomics of MRSA using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, we performed the downstream analyses using MetaboAnalyst and Interactive Pathways Explorer.Results: Exogenous threonine showed the best bactericidal efficacy with gentamicin, followed by glycine, wherein serine had no effect. Amino acid treatments mainly up-regulated the metabolites, increased the amino acid abundance, and significantly activated metabolisms; these effects were consistent with the bactericidal efficacy of the three amino acids. Most amino acids participated in the tricarboxylic acid cycle, and threonine supplem

In women, ovarian cancer is a common gynecological cancer associated with poor prognosis, reoccurrence and chemoresistance. Scoulerine, a benzylisoquinoline alkaloid, has been reported effective against several carcinomas. Thus, we investigated the impact of scoulerine on ovarian cancer cells (OVCAR3). Cell viability was assessed by MTT assay, migration was determined by Boyden Chamber assay, while the invasion was monitored by Boyden Chamber assay using the matrigel. The stemness properties of OVCAR3 cells were observed by tumorsphere assay. Epithelial to mesenchymal transition (EMT) and stemness-related protein markers were monitored by real-time PCR analysis and immunoblotting. Scoulerine inhibits the viability of OVCAR3 cells with the IC50 observed at 10 µmol L–1 after 48 h treatment. Scoulerine inhibited the colony-forming ability, migration and invasiveness of OVCAR3 cells in a dose-dependent fashion. Scoulerine treatment also drastically reduced the spheroid-forming ability of OVCAR3 cells. The mesenchymal and stemness-related markers like N-cadherin, vimentin, CD-44, Oct-4, Sox-2 and Aldh1A1 were downregulated, whereas the epithelial markers like E-cadherin and CD-24 were upregulated in scoulerine-treated cells. The upstream PI3K/Akt/mTOR-axis was downregulated in scoulerine-treated cells. We concluded that scoulerine successfully perturbs the cancerous properties of OVCAR3 cells by targeting the PI3K/Akt/mTOR axis. In vivo studies revealed a substantial decrease in tumor mass and volume after scoulerine treatment. Furthermore, scoulerine treatment was found to decrease oxidative stress factors in ovarian cancer mice model. Scoulerine is a potential anticancer agent against ovarian cancer and can be considered as a lead molecule for this malignancy, provided further investigations are performed.

Artificial photosynthesis is a desirable critical technology for the conversion of CO2 and H2O, which are abundant raw materials, into fuels and chemical feedstocks. Similar to plant photosynthesis, artificial photosynthesis can produce CO, CH3OH, CH4, and preferably higher hydrocarbons from CO2 using H2O as an electron donor and solar light. At present, only insufficient amounts of CO2-reduction products such as CO, CH3OH, and CH4 have been obtained using such a photocatalytic and photoelectrochemical conversion process. Here, we demonstrate that photocatalytic CO2 conversion with a Ag@Cr-decorated mixture of CaGa4O7-loaded Ga2O3 and the CaO photocatalyst leads to a satisfactory CO formation rate (>835 µmol h−1) and excellent selectivity toward CO evolution (95%), with O2 as the stoichiometric oxidation product of H2O. Our photocatalytic system can convert CO2 gas into CO at >1% CO2 conversion (>11531 ppm CO) at ambient temperatures and pressures.

Spin-crossover (SCO) molecules are thought to be ideal systems for molecular spintronics when SCO can be precisely controlled at the single-molecule level. This is demonstrated here in the single-molecule junctions of Fe-porphyrin formed in a scanning tunneling microscope. Experimentally, we find that the junctions feature a zero bias resonance in molecular conductance associated with the. Fe spin center. When mechanically stretching or squeezing the junctions by adjusting the tip height, the line shape of the zero-bias resonance varies reversibly. First-principles calculations reveal that widening the junction gap by 2 A transforms the macrocyclic core hosting the Fe center from a saddle to a planar conformation. This conformational Change shortens the Fe-N bonds by 3%, which changes the Fe spin state from S = 2 to S = 1.

The porphyrin macrocyclic core features dynamic conformational transformations in free space because of its structural flexibility. Once attached to a substrate, the molecule substrate interaction often restricts this flexibility and stabilizes the porphyrin in a specific conformation. Here using molecular dynamic and density-functional theory simulations and scanning tunneling microscopy and spectroscopy, we investigated the conformation relaxation and stabilization processes of two porphyrin derivatives (5,15-dibromopheny1-10,20-diphenylporphyrin, Br2TPP, and 5,15-diphenylporphyrin, DPP) adsorbed on Au(111) and Pb(111) surfaces. We found that Br2TPP adopts either dome or saddle conformations on Au(111) but only the saddle conformation on Pb(111), whereas DPP deforms to a ruffled conformation on Au(111). We also resolved the structural transformation pathway of Br2TPP from the free-space conformations to the surface-anchored conformations. These findings provide unprecedented insights revealing the conformation adaptation process. We anticipate that our results may be useful for controlling molecules. the conformation of surface-anchored porphyrin molecules. © 2017 American Chemical Society.

Spin-crossover (SCO) molecules are thought to be ideal systems for molecular spintronics when SCO can be precisely controlled at the single-molecule level. This is demonstrated here in the single-molecule junctions of Fe-porphyrin formed in a scanning tunneling microscope. Experimentally, we find that the junctions feature a zero bias resonance in molecular conductance associated with the. Fe spin center. When mechanically stretching or squeezing the junctions by adjusting the tip height, the line shape of the zero-bias resonance varies reversibly. First-principles calculations reveal that widening the junction gap by 2 A transforms the macrocyclic core hosting the Fe center from a saddle to a planar conformation. This conformational Change shortens the Fe-N bonds by 3%, which changes the Fe spin state from S = 2 to S = 1.

The porphyrin macrocyclic core features dynamic conformational transformations in free space because of its structural flexibility. Once attached to a substrate, the molecule substrate interaction often restricts this flexibility and stabilizes the porphyrin in a specific conformation. Here using molecular dynamic and density-functional theory simulations and scanning tunneling microscopy and spectroscopy, we investigated the conformation relaxation and stabilization processes of two porphyrin derivatives (5,15-dibromopheny1-10,20-diphenylporphyrin, Br2TPP, and 5,15-diphenylporphyrin, DPP) adsorbed on Au(111) and Pb(111) surfaces. We found that Br2TPP adopts either dome or saddle conformations on Au(111) but only the saddle conformation on Pb(111), whereas DPP deforms to a ruffled conformation on Au(111). We also resolved the structural transformation pathway of Br2TPP from the free-space conformations to the surface-anchored conformations. These findings provide unprecedented insights revealing the conformation adaptation process. We anticipate that our results may be useful for controlling molecules. the conformation of surface-anchored porphyrin molecules. © 2017 American Chemical Society.

Spin-crossover (SCO) molecules are thought to be ideal systems for molecular spintronics when SCO can be precisely controlled at the single-molecule level. This is demonstrated here in the single-molecule junctions of Fe-porphyrin formed in a scanning tunneling microscope. Experimentally, we find that the junctions feature a zero bias resonance in molecular conductance associated with the. Fe spin center. When mechanically stretching or squeezing the junctions by adjusting the tip height, the line shape of the zero-bias resonance varies reversibly. First-principles calculations reveal that widening the junction gap by 2 A transforms the macrocyclic core hosting the Fe center from a saddle to a planar conformation. This conformational Change shortens the Fe-N bonds by 3%, which changes the Fe spin state from S = 2 to S = 1.

The porphyrin macrocyclic core features dynamic conformational transformations in free space because of its structural flexibility. Once attached to a substrate, the molecule substrate interaction often restricts this flexibility and stabilizes the porphyrin in a specific conformation. Here using molecular dynamic and density-functional theory simulations and scanning tunneling microscopy and spectroscopy, we investigated the conformation relaxation and stabilization processes of two porphyrin derivatives (5,15-dibromopheny1-10,20-diphenylporphyrin, Br2TPP, and 5,15-diphenylporphyrin, DPP) adsorbed on Au(111) and Pb(111) surfaces. We found that Br2TPP adopts either dome or saddle conformations on Au(111) but only the saddle conformation on Pb(111), whereas DPP deforms to a ruffled conformation on Au(111). We also resolved the structural transformation pathway of Br2TPP from the free-space conformations to the surface-anchored conformations. These findings provide unprecedented insights revealing the conformation adaptation process. We anticipate that our results may be useful for controlling molecules. the conformation of surface-anchored porphyrin molecules. © 2017 American Chemical Society.

Using cryogenic scanning tunneling microscopy, we measured the electronic states and Kondo resonance of single Fe(II)-porphyrin molecules adsorbed on a Au(111) surface with intramolecular resolution. We found that the Fe(II) ion introduces a spin-polarized molecular state near the Fermi level. Tunneling spectroscopy revealed that this state gives rise to Kondo resonance exhibiting characteristics different from those of the Fe(II) spin state. Spin-polarized density functional theory calculations revealed that the molecule was weakly adsorbed on the surface, yet still switches its spin configuration from S = 1 to 2. The spin switching was found to be driven by three effects: a structural distortion of the macrocyclic ring from planar to saddle shaped, a weak chemical bonding between the Fe and the Au surface atom underneath, and weakened Fe-N bonds due to Au(111)-molecule charge transfer.

We apply supramolecular assembly to control the adsorption configuration of Co-porphyrin molecules on Au(111) and Cu(111) surfaces. By means of cryogenic scanning tunneling microscopy, we reveal that the Kondo effect associated with the Co center is absent or present in different supramolecular systems. We perform first-principles calculations to obtain spin-polarized electronic structures and compute the Kondo temperatures using the Anderson impurity model. The switching behavior is traced to varied molecular adsorption heights in different supramolecular structures. These findings unravel that a competition between intermolecular interactions and molecule-substrate interactions subtly regulates the molecular Kondo effect in supramolecular systems. © 2015 American Chemical Society.

We apply supramolecular assembly to control the adsorption configuration of Co-porphyrin molecules on Au(111) and Cu(111) surfaces. By means of cryogenic scanning tunneling microscopy, we reveal that the Kondo effect associated with the Co center is absent or present in different supramolecular systems. We perform first-principles calculations to obtain spin-polarized electronic structures and compute the Kondo temperatures using the Anderson impurity model. The switching behavior is traced to varied molecular adsorption heights in different supramolecular structures. These findings unravel that a competition between intermolecular interactions and molecule-substrate interactions subtly regulates the molecular Kondo effect in supramolecular systems. © 2015 American Chemical Society.

Using cryogenic scanning tunneling microscopy, we measured the electronic states and Kondo resonance of single Fe(II)-porphyrin molecules adsorbed on a Au(111) surface with intramolecular resolution. We found that the Fe(II) ion introduces a spin-polarized molecular state near the Fermi level. Tunneling spectroscopy revealed that this state gives rise to Kondo resonance exhibiting characteristics different from those of the Fe(II) spin state. Spin-polarized density functional theory calculations revealed that the molecule was weakly adsorbed on the surface, yet still switches its spin configuration from S = 1 to 2. The spin switching was found to be driven by three effects: a structural distortion of the macrocyclic ring from planar to saddle shaped, a weak chemical bonding between the Fe and the Au surface atom underneath, and weakened Fe-N bonds due to Au(111)-molecule charge transfer.

We apply supramolecular assembly to control the adsorption configuration of Co-porphyrin molecules on Au(111) and Cu(111) surfaces. By means of cryogenic scanning tunneling microscopy, we reveal that the Kondo effect associated with the Co center is absent or present in different supramolecular systems. We perform first-principles calculations to obtain spin-polarized electronic structures and compute the Kondo temperatures using the Anderson impurity model. The switching behavior is traced to varied molecular adsorption heights in different supramolecular structures. These findings unravel that a competition between intermolecular interactions and molecule-substrate interactions subtly regulates the molecular Kondo effect in supramolecular systems. © 2015 American Chemical Society.

Using cryogenic scanning tunneling microscopy, we measured the electronic states and Kondo resonance of single Fe(II)-porphyrin molecules adsorbed on a Au(111) surface with intramolecular resolution. We found that the Fe(II) ion introduces a spin-polarized molecular state near the Fermi level. Tunneling spectroscopy revealed that this state gives rise to Kondo resonance exhibiting characteristics different from those of the Fe(II) spin state. Spin-polarized density functional theory calculations revealed that the molecule was weakly adsorbed on the surface, yet still switches its spin configuration from S = 1 to 2. The spin switching was found to be driven by three effects: a structural distortion of the macrocyclic ring from planar to saddle shaped, a weak chemical bonding between the Fe and the Au surface atom underneath, and weakened Fe-N bonds due to Au(111)-molecule charge transfer.