Comprehensive 16S rRNA and metagenomic data from the gut microbiome of aging and rejuvenation mouse models.

The gut microbiota is associated with the health and longevity of the host. A few methods, such as fecal microbiota transplantation and oral administration of probiotics, have been applied to alter the gut microbiome and promote healthy aging. The changes in host microbiomes still remain poorly understood. Here, we characterized both the changes in gut microbial communities and their functional potential derived from colon samples in mouse models during aging. We achieved this through four procedures including co-housing, serum injection, parabiosis, and oral administration of Akkermansia muciniphila as probiotics using bacterial 16 S rRNA sequencing and shotgun metagenomic sequencing. The dataset comprised 16 S rRNA sequencing (36,249,200 paired-end reads, 107 sequencing data) and metagenomic sequencing data (307,194,369 paired-end reads, 109 sequencing data), characterizing the taxonomy of bacterial communities and their functional potential during aging and rejuvenation. The generated data expand the resources of the gut microbiome related to aging and rejuvenation and provide a useful dataset for research on developing therapeutic strategies to achieve healthy active aging.

Ageing and rejuvenation models reveal changes in key microbial communities associated with healthy ageing.

BACKGROUND: The gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging. RESULTS: Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy. CONCLUSIONS: In conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing. Video abstract.

Small heterodimer partner deficiency exacerbates binge drinking­induced liver injury via modulation of natural killer T cell and neutrophil infiltration.

Binge drinking among alcohol consumers is a common occurrence, and may result in the development of numerous diseases, including liver disorders. It has previously been reported that natural killer T (NKT) cells induce alcohol­associated liver injury by promoting neutrophil infiltration. In the present study, the role of the orphan nuclear receptor small heterodimer partner (SHP), which is encoded by the NR0B2 gene, in acute binge drinking­induced liver injury was investigated. SHP­knockout (KO) and wild­type (WT) control mice were intragastrically administered single doses of alcohol. The plasma concentrations of alanine aminotransferase and aspartate aminotransferase in SHP­KO mice following alcohol treatment were significantly increased compared with WT mice. However, results of oil red O staining and 2',7'­dichlorodihydrofluorescein diacetate staining indicated that levels of acute binge drinking­associated hepatic lipid accumulation and oxidative stress were not significantly different between WT and SHP­KO alcohol­treated mice. Notably, tumor necrosis factor­α mRNA expression in the liver of SHP­KO mice was significantly increased following alcohol administration, compared with WT mice. Furthermore, the mRNA expression levels of C­C motif chemokine ligand 2, C­X­C motif chemokine ligand 2 and interleukin­4, which are all potent chemoattractants of NKT cells, as well as neutrophil expression levels, were significantly increased in the livers of SHP­KO mice compared with WT mice following alcohol administration, as determined by reverse transcription­quantitative polymerase chain reaction and flow cytometry. Enhanced infiltration of NKT cells, determined by flow cytometry, was also demonstrated in the livers of SHP­KO mice following alcohol administration, compared with WT mice. The results of the present study indicate that SHP may be involved in liver­associated protective mechanisms, with regards to the attenuation of damage caused by acute binge drinking, via regulation of NKT cell and neutrophil migration to the liver. The modulation of SHP may be a novel therapeutic strategy for the treatment of acute binge drinking­induced liver injury.

An injectable collagen/poly(γ-glutamic acid) hydrogel as a scaffold of stem cells and α-lipoic acid for enhanced protection against renal dysfunction.

Mesenchymal stem cells (MSCs) can ameliorate renal injury and accelerate repair of acute kidney injury. Herein, we developed a collagen/poly(γ-glutamic acid) (γ-PGA) hydrogel as an injectable scaffold for the delivery of mouse MSCs (mMSCs) and anti-oxidant drugs into injured sites. By the introduction of γ-PGA into conventional collagen, the viscosity of collagen was reduced at ambient temperature for easy handling, while the elastic and viscous moduli of collagen were increased and a new porous structure was generated near body temperature. When in situ gel-forming collagen/γ-PGA hydrogels loaded with mMSCs and α-lipoic acid (LA) were administered to a mouse model of renal dysfunction, they significantly attenuated the level of blood urea nitrogen and creatinine, which resulted from the increased retention of therapeutic mMSCs and the controlled release of anti-oxidant drugs at the injured site. These findings suggested that this novel type of hydrogel could be applied as an injectable scaffold for use in regenerative medicine.

Anti-atherogenic effect of Humulus japonicus in apolipoprotein E-deficient mice.

Humulus japonicus (HJ) is used as a traditional medicine in Korea owing to its multiple properties including anti-mycobacterial, antioxidant and antihypertensive effects. The present study aimed to examine the anti­inflammatory and anti-atherogenic effects of a methanol extract of HJ. In lipopolysaccharide-stimulated RAW 264.7 cells, HJ significantly suppressed the mRNA expression and secretion of pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1ß and IL-6)], and the release of inflammatory mediators such as nitrite and prostaglandin E2, together with a concomitant decrease in the mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. To examine whether HJ is capable of inhibiting experimental atherogenesis in an animal model, we randomly divided apolipoprotein E-deficient (apoE-/-) mice into three groups: mice fed an atherogenic diet plus vehicle (0.5% carboxymethyl cellulose) as the control vehicle group, and mice fed an atherogenic diet plus either 100 (HJ100) or 500 mg/kg (HJ500) of HJ as the experimental groups. After 12 weeks of HJ administration, lipid accumulation and the formation of atherosclerotic lesions in the aorta (en face) and the aortic sinus markedly decreased in the HJ500 group compared with the corresponding values in the vehicle control group. Moreover, monocyte and macrophage infiltration in the aortic sinus was markedly reduced in the HJ500 group. Reverse transcription-quantitative polymerase chain reaction analysis of the whole aorta showed that the mRNA levels of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, CD68 and IL-18 were significantly decreased in the HJ500 group. Collectively, these findings suggest that HJ may suppress atherosclerosis by inhibiting lipid accumulation and the expression of pro-atherogenic factors, and it may be effective at preventing the development of atherosclerosis.

Analysis of the mouse gut microbiome using full-length 16S rRNA amplicon sequencing.

Demands for faster and more accurate methods to analyze microbial communities from natural and clinical samples have been increasing in the medical and healthcare industry. Recent advances in next-generation sequencing technologies have facilitated the elucidation of the microbial community composition with higher accuracy and greater throughput than was previously achievable; however, the short sequencing reads often limit the microbial composition analysis at the species level due to the high similarity of 16S rRNA amplicon sequences. To overcome this limitation, we used the nanopore sequencing platform to sequence full-length 16S rRNA amplicon libraries prepared from the mouse gut microbiota. A comparison of the nanopore and short-read sequencing data showed that there were no significant differences in major taxonomic units (89%) except one phylotype and three taxonomic units. Moreover, both sequencing data were highly similar at all taxonomic resolutions except the species level. At the species level, nanopore sequencing allowed identification of more species than short-read sequencing, facilitating the accurate classification of the bacterial community composition. Therefore, this method of full-length 16S rRNA amplicon sequencing will be useful for rapid, accurate and efficient detection of microbial diversity in various biological and clinical samples.

New class of scorpionate: tris(tetrazolyl)-iron complex and its different coordination modes for alkali metal ions.

We report formation of a new metallascorpionate ligand, [FeL3](3-) (IPtz), containing a Fe core and three 5-(2-hydroxyphenyl)-1H-tetrazole (LH2) ligands. It features two different binding sites, oxygen and nitrogen triangles, which consist of three oxygen or nitrogen donors from tetrazole. The binding affinities of the complex for three alkali metal ions were studied using UV spectrophotometry titrations. All three alkali metal ions show high affinities and binding constants (>3 × 10(6) M(-1)), based on the 1:1 binding isotherms to IPtz. The coordination modes of the alkali metals and IPtz in the solid were studied using X-ray crystallography; two different electron-donor sites show different coordination numbers for Li(+), Na(+), and K(+) ions. The oxygen triangles have the κ(2) coordination mode with Li(+) and κ(3) coordination mode with Na(+) and K(+) ions, whereas the nitrogen triangles show κ(3) coordination with K(+) only. The different binding affinities of IPtz in the solid were manipulated using multiple metal precursors. A Fe-K-Zn trimetallic complex was constructed by assembly of an IPtz ligand, K, and Zn precursors and characterized using X-ray crystallography. Oxygen donors are coordinated with the K ion via the κ(3) coordination mode, and nitrogen donors are coordinated with Zn metal by κ(3) coordination. The solid-state structure was confirmed to be a honeycomb coordination polymer with a one-dimensional infinite metallic array, i.e., -(K-K-Fe-Zn-Fe-K)n-.

Preparation of ansa-metallocenes for production of poly(α-olefin) lubricants.

An ansa-zirconocene bearing methyl substituents at all positions adjacent to the bridgehead [(-C(Ph)HC(Ph)H-)(η(5)-2,5-Me2C5H2)2ZrCl2] (4) was prepared in high yields (78%) through the reductive dimerization of 1,4-dimethyl-6-phenylfulvene utilizing ZrCl2·DME generated in situ. The structure of 4 was subsequently confirmed using X-ray crystallography. 4 exhibited excellent catalytic performance with regard to 1-decene oligomerization, which was carried out with the intention of preparing lubricant base stocks. High activities (21 × 10(6) g mol(-1) Zr h(-1) activity; TON = 150 000; TOF = 42 s(-1)) were observed at temperatures as high as 120 °C and the oligomer distribution was appropriate for lubricant application. The simulated distillation (SIMDIS) data confirmed that a wide range of oligomers were formed, ranging from the dimer (2-mer) to 20-mer. A minimal amount of the dimer and oligomers larger than the 10-mer was formed (13 and 25 wt%, respectively). Alternatively, a typical unbridged complex such as (η(5)-nBuC5H4)2ZrCl2 primarily produced dimers (54 wt%), whereas the ansa-zirconocene (EBI)ZrCl2 primarily produced oligomers larger than 10-mer (62 wt%). The methyl substituents at the positions adjacent to the bridgehead in 4 played a significant role in the catalytic performance.

CO2/ethylene oxide copolymerization and ligand variation for a highly active salen-cobalt(III) complex tethering 4 quaternary ammonium salts.

A cobalt(III) complex (1) of a salcy-type ligand tethering 4 quaternary ammonium salts, which is thought to act as a highly active catalyst for CO2/propylene oxide (PO) copolymerization, also shows high activity (TOF, 25,900 h(-1); TON, 518,000; 2.72 kg polymer per g cat) and selectivity (>98%) for CO2/ethylene oxide (EO) copolymerization that results in high-molecular-weight polymers (M(n), 200,000-300,000) that have strictly alternating repeating units. The related cobalt(III) complexes 11-14 were prepared through variations of the ligand framework of 1 by replacing the trans-1,2-diaminocyclohexane unit with 2,2-dimethyl-1,3-propanediamine, trans-1,2-diaminocyclopentane, or 1,1'-binaphthyl-2,2'-diamine or by replacing the aldimine bond with ketimine. These ligand frameworks are thought to favour the formation of the cis-ß configuration in complexation, and the formation of the cis-ß configuration in 11-14 was confirmed through NMR studies or X-ray crystallographic studies of model complexes not bearing the quaternary ammonium salts. Complexes 11, 13, and 14, which adopt the cis-ß configuration even in DMSO did not show any activity for CO2/PO copolymerization. Complex 12, which was constructed with trans-1,2-diaminocyclopentane and fluctuated in DMSO between the coordination and de-coordination of the acetate ligand as observed for 1, showed fairly high activity (TOF, 12,400 h(-1)). This fluctuating behaviour may play a role in polymerization. However, complex 12 did not compete with 1 in terms of activity, selectivity, and the catalyst cost.

Synthesis, X-ray structures, and controlled ring opening polymerization behavior of L-lactide using titanium complexes chelated by tetradentate diamine-diethanolate ligand.

The synthesis and characterization of LTi(O-i-Pr)(2) (1) and LTiCl(2) (2) complexes containing a new [ONNO]-type tetradentate diamine-diethanolate ligand such as (HOCMe(2)CH(2)NMeCH(2)CH(2)NMeCH(2)CMe(2)OH) (LH(2)) was achieved. Single-crystal X-ray analyses revealed that monomeric complexes 1 and 2 had pseudo-C(2) and pseudo-C(1) symmetric distorted octahedral geometry, respectively. Interestingly, complex 1 has fac-fac geometry for tetradentate L around a Ti centre in both solid and solution, whereas complex 2 has different geometry in solid (mer-fac, C(1)) and solution (fac-fac, C(2)). They are effective catalysts for the controlled ring opening polymerization of L-lactide, as shown by the linearity of the number average of the molecular weight of polylactides versus conversion, as well as narrow PDI values.

4-{[(1S,2R)-2-Hy-droxy-indan-1-yl]amino}-pent-3-en-2-one.

In the mol-ecule of the title compound, C(14)H(17)NO(2), the dihedral angle formed by the mean planes through the indan ring system and the amino-pentenone fragment is 83.26 (13)°. An intra-molecular N-H⋯O hydrogen bond is observed. In the crystal, mol-ecules are linked into one-dimensional chains extending along the [010] direction via O-H⋯O and C-H⋯O hydrogen bonds.

(1S,2R)-1-[(E)-(Thio-phen-2-yl-methyl-idene)amino]-indan-2-ol.

In the title compound, C(14)H(13)NOS, the dihedral angle formed by the mean planes through the indane ring system and the thio-phene ring is 85.04 (11)°. The imine bond is located in the thio-phene plane [the S-C-C-N torsion angle is 0.00 (3)°] and an intra-molecular O-H⋯N hydrogen bond is observed.

Bis(µ-trimethyl-silanolato-κO:O)bis-{[2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentyl-phenolato-κN,O]zinc}.

The binuclear title complex, [Zn(2)(C(22)H(28)N(3)O)(2)(C(3)H(9)OSi)(2)], has a crystallographic imposed centre of symmetry. The Zn(II) atom is coordinated by three O and one N atom from one 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentyl-phenolate ligand and two bridging trimethyl-silanolate anions in a distorted tetra-hedral geometry. The dihedral angle between the benzotriazole ring system and the benzene ring is 19.83 (5)°. The tert-pentyl groups are disordered over two orientations with refined site-occupancy ratios of 0.858 (4):0.142 (4) and 0.665 (6):0.335 (6).