A new sight to acute pancreatitis through paracolic gutter exudation, a multicenter retrospective study.

Objectives: Paracolic gutter exudation (PGE) may influence the severity of acute pancreatitis, but no study has explored it extensively. The objective of this study was to evaluate PGE for assessing the severity of disease. Methods: We performed a retrospective analysis of 488 patients from three tertiary hospitals in Guangxi, China. General clinical information, severity, and clinical courses were recorded. The PGE score were classified as follows: 0 for no exudation, 1 for unilateral exudation, and 2 for bilateral exudation. We used ROC curves to assess the predictive value of the PGE score, and logistic regression analysis to determine risk factors associated with death, ICU admission, and the occurrence of MODS. Results: This study included 352 patients with moderately severe acute pancreatitis (MSAP) and 136 patients with severe acute pancreatitis (SAP). Patients who had PGE experienced higher total hospitalization costs, longer hospital stays, a higher incidence of SAP, higher mortality rates, higher ICU admission rates, a higher incidence of MODS, and higher incidence of infections than those without (P < 0.05). Diagnostic efficacy in predicting severity in patients with MSAP and SAP increased after BISAP, MCTSI, modified Marshall, and SOFA scores combined with PGE score respectively. The PGE score of >1 is an independent risk factor for ICU admission and MODS occurrence. (P < 0.05). Conclusion: The PGE provides reliable and objective information for assessing severity and clinical course of patients with MSAP and SAP.

Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study.

BACKGROUND & AIMS: Previous studies confirm vonoprazan-amoxicillin effectiveness for Helicobacter pylori. This study aims to investigate vonoprazan with varying amoxicillin dose and duration. METHODS: This multicenter, prospective, randomized controlled, noninferiority trial enrolled patients with treatment naive H pylori infection from 5 clinical centers. Eligible participants were randomly assigned to H-VA-10 (vonoprazan 20 mg twice a day (b.i.d.) + amoxicillin 750 mg 4 times a day, 10 days), L-VA-10 (vonoprazan 20 mg b.i.d. + amoxicillin 1000 mg b.i.d, 10 days), and H-VA-14 (vonoprazan 20 mg b.i.d + amoxicillin 750 mg 4 times a day, 14 days) in a 1:1:1 ratio. The eradication rate was assessed using the 13C-urea breath test at least 28 days after treatment. RESULTS: Of the 623 eligible patients, 516 patients were randomized. In both the intention-to-treat and per-protocol analyses, eradication rates were comparable between H-VA-10 and H-VA-14 groups (86.6% vs 89.5% and 90.9% vs 94.5%, P = .021 and .013 for noninferiority, respectively). However, eradication rates were significantly lower in the L-VA-10 group than the H-VA-14 group (79.7% vs 89.5% and 82.0% vs 94.5%, P = .488 and .759, respectively). Rates of study withdrawal, loss to follow-up, and adverse events were similar across study groups. CONCLUSIONS: H-VA-10 and H-VA-14 regimens provide satisfactory efficacy for H pylori infection, and the L-VA-10 regimen was inferior. CLINICALTRIALS: gov number: NCT05719831.

Electrode-Less MnO2 -Metal Batteries with Deposition and Stripping Chemistry.

Electrode materials are key components in typical batteries, where the electrodes are generally fabricated onto current collectors in solid forms and are isolated by a separator. However, the preparation of the electrodes increases the fabrication complexity, which speeds down their large-scale production. Here, series of static electrode-less MnO2 -metal batteries are presented that are facilely fabricated by using carbon current collectors and electrolytes. The MnO2 -metal batteries are operated in dual-deposition/stripping chemistries of Mn2+ /MnO2 on the cathode and M/Mx+ on the anode. The MnO2 -Cd/Zn/Cu batteries exhibit remarkable rates up to 200 C, excellent reversibility of 15 000 cycles, and realistic gravimetric and volumetric energy densities of 93.7 Wh kg-1 and 134 Wh L-1 , respectively. Impressively, the MnO2 -Cd battery can achieve over 160 000 cycles in the high current pulse test, showing promises in the applications of electrical vehicle's start-stop and large-scale energy storage.

Effects of a derivative of reutericin 6 and gassericin A on the biofilm of Streptococcus mutans in vitro and caries prevention in vivo.

It is known that Streptococcus mutans (S. mutans) is the leading cariogenic pathogen. Recently, an increasing number of antimicrobial peptides (AMPs) have been brought into consideration as anti-caries agents. Here, we designed and synthesized an AMP derived from reutericin 6 and/or gassericin A, named LN-7, and explored its effect on biofilm of S. mutans UA159 in vitro and development of dental caries in vivo. Antibacterial assays showed that LN-7 was more active against S. mutans (3.2 µM) than many peptide-based agents, capable of killing other types of Streptococci in oral cavity. In addition, LN-7 presented fast killing kinetics, with more than 97% S. mutans killed within 5 min. The mechanism of the antimicrobial activity mainly lies on the disruption of bacterial membrane. Effects of LN-7 on the biofilm formation and the viability of preformed biofilm were quantified by crystal violet staining, which showed that LN-7 could effectively inhibit the biofilm accumulation of S. mutans. Moreover, the biofilm of S. mutans treated with LN-7 displayed notable changes in bacterial viability and morphology, observed by confocal laser scanning microscopy and scanning electron microscopy. In addition, topical oral treatment with LN-7 could suppress the development of dental caries in vivo, reducing the occurrence of severe dental lesion in a rodent model. These results reveal a new peptide-based agent as a topical treatment for dental caries, opening the door to clinical studies to explore its potential for caries prevention.

[Design, screening and antimicrobial activity of novel peptides against Streptococcus mutans].

OBJECTIVE: To construct antimicrobial peptides with potent antimicrobial activity, low cytotoxicity and efficient killing rate of Streptococcus mutans for prevention and treatment of dental caries. METHODS: We exploited the existing design strategies to modify reutericin 6 or gassericin A produced by Lactobacillus species in the oral cavity based on their cationicity, amphipathicity and α-helical structure. We examined their antimicrobial activities using bacterial susceptibility assay, their cytotoxicity through cytotoxicity assay and their killing rate of Streptococcus mutans with time-kill assay. We further evaluated the candidate derivatives for their killing rate against Streptococcus mutans, their antimicrobial activity against different oral pathogens and the development of drug resistance. RESULTS: We constructed 6 AT-1 derivatives, among which AT-7 showed an MIC of 3.3 µmol/L against Streptococcus mutans, Porphyromonas gingivalis and Actinomyces viscosus with a killing rate of 88.7% against Streptococcus mutans within 5 min. We did not obtain de novo strains of Streptococcus mutans resistant to AT- 7 after induction for 10 passages. CONCLUSIONS: Hydrophobicity and imperfect amphipathic structure are two key parameters that define the antimicrobial potency of the antimicrobial peptides. The imperfectly amphipathic peptide AT-7 shows the potential for clinical application in dental caries treatment.

Helicobacter pylori inhibited cell proliferation in human periodontal ligament fibroblasts through the Cdc25C/CDK1/cyclinB1 signaling cascade.

PURPOSE: Several studies have shown that the oral cavity is a secondary location for Helicobacter pylori colonization and that H. pylori is associated with the severity of periodontitis. This study investigated whether H. pylori had an effect on the periodontium. We established an invasion model of a standard strain of H. pylori in human periodontal ligament fibroblasts (hPDLFs), and evaluated the effects of H. pylori on cell proliferation and cell cycle progression. METHODS: Different concentrations of H. pylori were used to infect hPDLFs, with 6 hours of co-culture. The multiplicity of infection in the low- and high-concentration groups was 10:1 and 100:1, respectively. The Cell Counting Kit-8 method and Ki-67 immunofluorescence were used to detect cell proliferation. Flow cytometry, quantitative real-time polymerase chain reaction, and western blots were used to detect cell cycle progression. In the high-concentration group, the invasion of H. pylori was observed by transmission electron microscopy. RESULTS: It was found that H. pylori invaded the fibroblasts, with cytoplasmic localization. Analyses of cell proliferation and flow cytometry showed that H. pylori inhibited the proliferation of periodontal fibroblasts by causing G2 phase arrest. The inhibition of proliferation and G2 phase arrest were more obvious in the high-concentration group. In the low-concentration group, the G2 phase regulatory factors cyclin dependent kinase 1 (CDK1) and cell division cycle 25C (Cdc25C) were upregulated, while cyclin B1 was inhibited. However, in the high-concentration group, cyclin B1 was upregulated and CDK1 was inhibited. Furthermore, the deactivated states of tyrosine phosphorylation of CDK1 (CDK1-Y15) and serine phosphorylation of Cdc25C (Cdc25C-S216) were upregulated after H. pylori infection. CONCLUSIONS: In our model, H. pylori inhibited the proliferation of hPDLFs and exerted an invasive effect, causing G2 phase arrest via the Cdc25C/CDK1/cyclin B1 signaling cascade. Its inhibitory effect on proliferation was stronger in the high-concentration group.

Rational design of peptides with enhanced antimicrobial and anti-biofilm activities against cariogenic bacterium Streptococcus mutans.

Streptococcus mutans (S. mutans) is known to be a leading cariogenic pathogen in the oral cavity. Antimicrobial peptides possess excellent properties to combat such pathogens. In this study, we compared the antimicrobial activity of novel linear reutericin 6- and/or gassericin A-inspired peptides and identified LR-10 as the leading peptide. Antibacterial assays demonstrate that LR-10 is more active against S. mutans (3.3 µM) than many peptide-based agents without resistance selection, capable of killing many oral pathogens, and tolerant of physiological conditions. LR-10 also presented a faster killing rate than chlorhexidine and erythromycin, and appeared to display selective activity against S. mutans within 10 s. S. mutans is usually encased in plaque biofilms. Biofilm inhibitory assays indicated that LR-10 had excellent inhibitory effect on the biofilm formation of S. mutans and biofilm-encased cells in vitro at low concentrations (6.5 µM). Consistent with most peptides, LR-10 kills S. mutans mainly by disrupting the cell membranes. Notably, both hemolytic activity assays and cytotoxicity tests indicated that LR-10 could keep biocompatible at the effective concentrations. Hence, LR-10 could be a good candidate for clinical treatment of dental caries.

Daphnetin inhibits RANKL-induced osteoclastogenesis in vitro.

Osteoporosis is a common orthopedic disease which is associated with hyper-activated osteoclastogenesis. Daphnetin is a natural coumarin derivative isolated from Genus Daphne, which possesses antiarthritis effect. However, the role of daphnetin in osteoclastogenesis has not been illustrated. This study aimed to investigate the effects of daphnetin on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro. Our results showed that the osteoclast formation was significantly suppressed by daphnetin treatment in bone marrow-derived macrophages (BMMs), which was illustrated by reduced number of tartrate-resistant acid phosphatase positive multinucleated osteoclasts and decreased expression levels of tumor necrosis factor receptor-associated factors (TRAF6), c-Fos, nuclear factor of activated T cells c1, and cathepsin K. RANKL caused significant induction effects in reactive oxygen species (ROS) generation and nicotinamide adenine dinucleotide phosphate oxidase activity, whereas the induction was dramatically reduced after pretreatment with daphnetin. In addition, daphnetin prevented the RANKL-induced activation of NF-κB and Akt/GSK-3ß pathways in BMMs. These findings indicated that daphnetin exhibited an inhibitory effect on RANKL-induced osteoclastogenesis in vitro. The effect of daphnetin might be mediated by inhibiting ROS signal transduction, as well as preventing the activation of NF-κB and Akt/GSK-3ß signaling pathways. These findings indicated that daphnetin might be considered as a new therapeutic approach for the osteoporosis treatment.