Polyvinylpyrrolidone-Coated Cubic Hollow Nanocages of PdPt3 and PdIr3 as Highly Efficient Self-Cascade Uricase/Peroxidase Mimics.

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.

Nicotinamide mononucleotide based hyaluronic acid methacryloyl hybrid hydrogel regulating stem cells fate for bone regeneration via SIRT1/RUNX2 signaling.

Efficient bone reconstruction, especially of the critical size after bone damage, remains a challenge in the clinic. Bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation is considered as a promising strategy for bone repair. Nicotinamide adenine dinucleotide (NAD+) regulating BMSC fate and cellular function enhance osteogenesis, but is hardly delivered and lack of targeting. Herein, a novel and biocompatible scaffold was fabricated to locally deliver a precursor of NAD+, nicotinamide mononucleotide (NMN) to the bone defect site, and its bone repair capability and healing mechanism were clarified. NMN-based hyaluronic acid methacryloyl hybrid hydrogel scaffold (denoted as NMN/HAMA) was prepared via photopolymerization. In vitro RT-qPCR analysis, western blotting, Elisa and alizarin red S staining assays demonstrated that the NMN/HAMA hybrid hydrogel regulated BMSCs cellular function in favour of osteogenic differentiation and mineralization by upregulating the mRNA and proteins expression of the osteogenic genes type I pro-collagen (Col-1), bone morphogenic protein 4 (BMP4), and runt-related transcription factor 2 (RUNX2) via the SIRT1 pathway. Implantation of such hybrid hydrogels significantly enhanced bone regeneration in rodent critical calvarial defect models. Furthermore, restoration of the bone defect with NMN administration was inhibited in Prx1 Cre+; SIRT1flox/flox mice, confirming that the NMN/HAMA hybrid hydrogel scaffold promoted bone regeneration via the SIRT1-RUNX2 pathway. These results imply that NMN-based scaffold may be a promising and economic strategy for the treatment of bone defects.

dupA + H. pylori reduces diversity of gastric microbiome and increases risk of erosive gastritis.

Helicobacter pylori is believed to induce gastropathy; however, the exact pathogenic molecules involved in this process have not been elucidated. Duodenal ulcer promoting gene A (DupA) is a virulence factor with a controversial role in gastric inflammation and carcinogenesis. To explore and confirm the function of DupA in gastropathy from the perspective of the microbiome, we investigated the microbial characteristics of 48 gastritis patients through 16S rRNA amplicon sequencing. In addition, we isolated 21 H. pylori strains from these patients and confirmed the expression of dupA using PCR and qRT-PCR. Bioinformatics analysis identified diversity loss and compositional changes as the key features of precancerous lesions in the stomach, and H. pylori was a characteristic microbe present in the stomach of the gastritis patients. Co-occurrence analysis revealed that H. pylori infection inhibits growth of other gastric inhabiting microbes, which weakened the degradation of xenobiotics. Further analysis showed that dupA+ H. pylori were absent in precancerous lesions and were more likely to appear in erosive gastritis, whereas dupA- H. pylori was highly abundant in precancerous lesions. The presence of dupA in H. pylori caused less disturbance to the gastric microbiome, maintaining the relatively richness of gastric microbiome. Overall, our findings suggest that high dupA expression in H. pylori is correlated with a high risk of erosive gastritis and a lower level of disturbance to the gastric microbiome, indicating that DupA should be considered a risk factor of erosive gastritis rather than gastric cancer.

Microbiota analysis with next-generation 16S rDNA gene sequencing in recurrent common bile duct stones.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the main remedy for gallstones, but the postoperative recurrence rate is high. Recent research has indicated that the biliary microbiome takes part in the pathogenesis of cholelithiasis. However, it is not yet known whether biliary microbiome dysbiosis is relevant to recurrent cholelithiasis. Methods: Thus, we investigated the bacterial communities of the biliary microbiomes of patients with recurrent common bile duct (CBD) stones and analyzed the relationship between recurrent CBD stones and biliary microbiota. The bile specimens of 5 patients with recurrent CBD stones (FF) and 45 patients with primary CBD stones (YF) were collected during the ERCP process. The microbiota was analyzed using 16S ribosomal DNA (rDNA) high-throughput sequencing. We also identified the link between recurrent CBD stones and biliary microbiota. Results: Our results showed that at the phylum level, proteobacteria and firmicutes were the main two genera groups, and proteobacteria was high in FF patients. Additionally, synergistetes were high, but Bacteroidetes and actinobacteria were low in FF patients. The microbiomes in the bile of the YF patients were more evenly distributed than those in the bile of the FF patients. We also discovered that FF patients had decreased microbial bile diversity. At the genus level, klebsiella dominated in the FF patients, while Escherichia-shigella dominated in the YF patients. Additionally, klebsiella was higher in the FF patients than the YF patients. Conclusions: The observed differences in the genera between the recurrent CBD stone FF patients and the YF patients provide novel insights into the link between biliary microbiota changes and recurrent CBD stones.

Application of three-dimensional visualization technology in the anatomical variations of hilar bile ducts in Chinese population.

This study aimed to establish three-dimensional models of the biliary tract of Chinese people using the Hisense computer-aided surgery (CAS) system and to explore the branching patterns and variation types of the biliary system under the study of 3D reconstruction of the biliary tract. Three-dimensional models of the biliary tract were reconstructed in 50 patients using the Hisense CAS system. The branching patterns of intrahepatic bile ducts were observed. The biliary tract was classified according to the confluence of the right posterior sectoral duct (RPSD), right anterior sectoral duct (RASD) and left hepatic duct (LHD), and the presence or absence of accessory hepatic ducts. The 3D models of the bile ducts were successfully reconstructed in 50 Chinese patients. The branching patterns of the bile ducts were classified into seven types. The anatomy of the bile ducts was typical in 54% of cases (n = 27), showed triple confluence in 10% (n = 5), and crossover anomaly in 14% (n = 7), which means anomalous drainage of the RPSD into the LHD, anomalous drainage of the RPSD into the common hepatic duct (CHD) in 10% (n = 5), anomalous drainage of the RPSD into the cystic duct (CD) in 2% (n = 1), absence of left main hepatic duct in 1% (n = 1), presence of accessory duct in 8% (n = 4). Among them, there were three cases of accessory hepatic ducts coexisting with other variation types. By using the Hisense CAS system to establish 3D models of the biliary tract of the Chinese people, we established the branching model of the second-order bile ducts, which has important value for the classification of the biliary system and its variation types.