Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

Effect of abutment design on fracture resistance of resin-matrix ceramic crowns for dental implant restoration: an in vitro study.

BACKGROUND: The purpose of this study is to investigate the performance and fracture resistance of different resin-matrix ceramic materials for use in implant-supported single crowns with respect to the abutment design (crown thickness: 1 mm, 2 and 3 mm). METHODS: Forty-eight abutments and crowns were fabricated on implants in the right lower first molar. Two resin-matrix ceramic materials for dental crowns were selected for study: (1) a glass-ceramic in a resin interpenetrating matrix (Vita Enamic, Vita, Germany) and (2) a resin-based composite with nanoparticle ceramic filler (Lava Ultimate, 3 M ESPE, USA). Three types of abutments were designed: 1 mm thick crown + custom titanium abutment, 2 mm thick crown + custom titanium abutment and 3 mm thick crown + prefabricated titanium abutment. The experiment was divided into 6 groups (n = 8) according to the crown materials and abutment designs. After 10,000 thermocycles, fracture resistance was measured using a universal testing machine. The statistical significance of differences between various groups were analysed with ANOVA followed by a post hoc Tukey's honestly significant difference test. The surfaces of the fractured specimens were examined with scanning electron microscopy (SEM). RESULTS: Two-way ANOVA revealed that the abutment design (F = 28.44, P = 1.52 × 10- 8<0.001) and the crown materials (F = 4.37, P = 0.043 < 0.05) had a significant effect on the fracture resistance of implant crown restoration. The Lava Ultimate-2 mm group showed the highest fracture resistance of 2222.74 ± 320.36 N, and the Vita Enamic-3 mm group showed the lowest fracture resistance of 1204.96 ± 130.50 N. Most of the 1 and 2 mm groups had partial crown fractures that could be repaired directly with resin, while the 3 mm group had longitudinal fracture of the crown, and the crowns were detached from the abutments. CONCLUSION: Based on the in vitro data of this study, the fracture resistance of the 2 mm thick resin-matrix ceramic crown design was higher than that of the 1 and 3 mm groups. The 2 mm thick resin-matrix ceramic crown and personalized abutment are an option to replace zirconia for implant crown restoration.

Er:YAG laser removal of zirconia crowns on titanium abutment of dental implants: an in vitro study.

BACKGROUND: This research aimed to explore feasibility and the time required when erbium-doped yttrium aluminum garnet (Er:YAG) laser as a non-invasive treatment modality to retrieve different thicknesses of zirconia material bonded by two dental cements from titanium implant abutments. METHODS: Prepared 80 titanium blocks (length: 20 mm, width: 10 mm, height: 10 mm) and square zirconia sheets (length: 10 mm) with different thicknesses (1 mm, 2 mm, 3 mm, and 4 mm) were 20 pieces each. Resin modified glass ionomer cement (RelyX Luting 2; RXL) and resin cement (Clearfil SA luting; CSL) were used to bond zirconia sheet and titanium block. Specimens were kept in 100% humidity for 48 h. Er:YAG laser was used to retrieve the zirconia sheet and recorded the time. Universal testing machine was used to measure the residual adhesion of the samples that did not retrieve after 5 min of laser irradiation. Shear bond strength (MPa) and the time data (s) were analyzed using Kruskal-Wallis Test. The bonding surface and the irradiation surface of the zirconia sheet was examined with the scanning electron microscopy (SEM). RESULTS: Within 5 min of laser irradiation, RXL group: 1 mm group all fell off, 2 mm group had 3 specimens did not fall off, there was no statistical difference in the average time between the two groups; CSL group: half of the 1 mm group fell off. Shear bond strength test results: there was no statistical difference between 1 and 2 mm in RXL group and 1 mm in CSL group, there was no statistical difference between 3 mm in RXL group and 2 mm in CSL group, and there were significant differences statistically in comparison between any two groups in the rest. SEM inspection showed that the bonding surface and the irradiation surface of the zirconia sheet had changes. CONCLUSION: In this vitro study, the following could be concluded: it is faster to remove zirconia crowns with thickness less than 2 mm from titanium abutment when luted with RelyX Luting 2 compared to Clearfil SA luting.

Combination of Optimization and Metalated-Ligand Exchange: An Effective Approach to Functionalize UiO-66(Zr) MOFs for CO2 Separation.

The strategy to functionalize water-stable metal-organic frameworks (MOFs) in order to improve their CO2 uptake capacities for efficient CO2 separation remains limited and challenging. We herein present an effective approach to functionalize a prominent water-stable MOF, UiO-66(Zr), by a combination of optimization and metalated-ligand exchange. In particular, by systematic optimization, we have successfully obtained UiO-66(Zr) of the highest BET surface area reported so far (1730 m(2) g(-1) ). Moreover, it shows a hybrid Type I/IV N2 isotherm at 77 K and a mesopore size of 3.9 nm for the first time. The UiO-66 MOF underwent a metalated-ligand-exchange (MLE) process to yield a series of new UiO-66-type MOFs, among which UiO-66-(COONa)2 -EX and UiO-66-(COOLi)4 -EX MOFs have both enhanced CO2 working capacity and IAST CO2 /N2 selectivity. Our approach has thus suggested an alternative design to achieve water-stable MOFs with high crystallinity and gas uptake for efficient CO2 separation.

Use of an intraoral scanner and CAD-CAM for simultaneous restoration with a personalized titanium post-core and a zirconia crown.

Customized posts-and-cores have been widely used for improved fitness within a prepared post space. However, in comparison to direct restoration, they necessitate an increased number of appointments for patients. A 24-year-old man presented with a maxillary left canine that had fractured due to trauma 10 months previously. For this case, a digital process was used for simultaneous restoration with a personalized titanium post-and-core and a zirconia crown achieved with an intraoral scanner (IOS) and computer-aided design/computer-aided manufacturing (CAD-CAM). This workflow allowed the restoration to be completed in 2 visits, facilitating more effective and predictable treatment, with reduced time and cost for the patient.

The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice.

Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.

Border fences reduce potential for transboundary migration of Marco Polo Sheep (Ovis ammon polii) in the Pamir Plateau.

Border fences have severely impeded the transboundary migration of a number of large mammals worldwide, with central Asia being one of the most impacted. The Marco Polo sheep (Ovis ammon polii), an iconic species of Pamir, is threatened in its transboundary movement by increasing border fencing among their five distributed countries, including Tajikistan, Kyrgyzstan, China, Afghanistan, and Pakistan. In this study, by building ensemble species distribution models, we found that eastern Tajikistan had the largest suitable Macro Polo sheep habitat (about 42 % of the total suitable habitat), followed by China (about 32 %). We used least-cost paths to identify 51 ecological corridors including 5 transboundary ecological corridors, which may be important to maintain connectivity in both domestic and transboundary regions. To assess the potential barrier effect of border fences, we assessed four scenarios (30, 40, 50 and 60°) corresponding to the upper limit of the slope for the construction of fences. In areas too steep for fencing, these could be used by wild sheep to cross barriers or borders and may represent migration or movement routes, defined as natural passages. In the most pessimistic Scenario 60, only 25 migratory passages along the border fences were identified, compared to 997 in the most optimistic scenario (Scenario 30), indicating a strong negative effect of intensive border fencing on the transboundary movement of Marco Polo sheep. The establishment of transnational conservation parks, and ensuring permeability is maintained in key areas, could have a positive impact on the connectivity and persistence of Marco Polo sheep populations, and provide important lessons for other large migratory mammals in transboundary regions.

Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target.

A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.

Analysis of the Vulvar Skin Microbiota in Asymptomatic Women and Patients With Vulvar Lichen Sclerosus Based on 16S rRNA Sequencing.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease that brings life-long and psychological distress to patients. It remains unclear whether this condition is related to changes in the skin microbial community. The aim of this study was to evaluate the compositional characteristics of the vulvar skin microbiota between VLS patients and asymptomatic postmenopausal women. We included 60 cases of postmenopausal patients in the outpatient vulvar clinic of Peking University First Hospital from August 2020 to October 2020. Thirty-one patients were diagnosed with VLS by vulvar skin biopsy (VLS group), while 29 women were asymptomatic volunteers (control group). DNA was extracted from vulvar skin swabs of the VLS and control groups. The V3-V4 fragments of 16S rRNA were targeted for high-throughput sequencing and gene sequence analysis. The sequencing results were analysed by α diversity, ß diversity, species composition, LEfSe analysis to compare the compositional differences of the vulvar skin microbiota between the two groups. Our study revealed that at the phylum level, patients with VLS had a lower relative abundance of Firmicutes (p < 0.0001) and a higher relative abundance of Proteobacteria than the control group (p < 0.0001). At the genus level, Lactobacillus spp. accounted for the largest proportion of the microflora in the asymptomatic controls, while the proportion of Prevotella spp. in the VLS group was the highest. In the VLS group, the relative abundance of Finegoldia spp., Ralstonia spp., Peptoniphilus spp., Anaerococcus spp., Campylobacter spp., Providencia spp. Kelbsiella spp., Ezakiella spp., and Escherichia-Shigella spp. was significantly increased compared with the control group. Although there was no significant difference in the α diversity of the vulvar skin microbiota, the ß diversity differed significantly between the two groups.

[The significance of TGF-beta expression in scar in adenosine receptor A(2A) knockout mice].

OBJECTIVE: To discuss the mechanism of scar hypertrophy in adenosine receptor A(2A) (A(2A) R) knockout mice. METHODS: Animal models of hypertrophic scar were established in 12 A(2A) R knockout mice and 12 wild-type mice as control. The thickness and the size of transverse section of the hypertrophic scar were observed by H-E staining. The hydroxyproline (HYP) in the scar was measured colorimetrically. The TGF-beta expression was tested by Western blotting method. RESULTS: The hypertrophic scar in wild-type mice was more severe than that in knockout mice. Compared with self-control, the increase of the thickness and the size of transverse section of hypertrophic scar was markedly higher in wild-type group than in the knockout group (P < 0.01). There was significant difference in HYP content between the two groups (P < 0.01). Compared with self-control, the increase of TGF-beta expression in wild-type group was much more than that in knockout group (P < 0.01). CONCLUSIONS: The TGF-beta expression decreases in the A(2A) R knockout mice. The scar hypertrophy is also much less in the A(2A) R knockout mice.