BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Gastric cancer (GC) is a globally prevalent malignancy with a particularly heavy burden in China. Helicobacter pylori ( H. pylori ) is a Group I carcinogen for GC, with a higher seroprevalence rate indicating a higher GC incidence. However, only approximately 3% of the individuals with H. pylori infection eventually develop GC, and about 2.6% still progress to GC even 10-20 years after the eradication of H. pylori . Thus, the pathogenic mechanism of H. pylori for GC must be elucidated, and high-risk individuals precisely identified. Furthermore, GC can occur even in individuals who have never been infected with H. pylori . As H. pylori infection rates decline, the proportion of H. pylori -negative GC cases is increasing annually, gaining significant research attention. In this review, potential pathogenic mechanisms of H. pylori infection are explored from the aspects of H. pylori virulence factors and host factors (genetic susceptibility and immune microenvironment). Possible risk factors for H. pylori -negative GC include infections by other microorganisms (e.g., bacteria, fungi, and viruses), autoimmune gastritis, bile reflux, genetic mutations, and environmental factors. We aim to review the potential mechanisms for GC with varying H. pylori infection statuses, identify the high-risk individuals, and pose questions that need to be addressed. In the future, as the prevalence of H. pylori infection gradually decreases, GC prevention and management must evolve to address host-specific factors and the growing challenge of H. pylori -negative GC by integrating multidisciplinary perspectives.
Stomach Neoplasms/genetics* ; Humans ; Helicobacter Infections/complications* ; Helicobacter pylori/pathogenicity* ; Risk Factors

Panax quinquefolium, also known as American ginseng, is a perennial herb in the Araliaceae family. It has the effects of replenishing Qi and nourishing Yin, clearing heat and generating saliva. Additionally, it has protective effects on the nerves, improves myocardial ischemia and hypoxia, regulates metabolism, enhances the body's immunity, and is known as "green gold". However, with the development of the industry and the expansion of planting scales, P. quinquefolium faces serious disease issues that are difficult to prevent and control. Among these, root rot, often referred to as "plant cancer", is one of the most destructive plant diseases affecting the yield and quality of P. quinquefolium. P. quinquefolium root rot is caused by the fungi Fusarium(genus) and Ilyonectria(genus), which severely affect the root system and limit the production and quality of P. quinquefolium, thus restricting the development of the P. quinquefolium industry. In recent years, research on P. quinquefolium root rot has attracted significant attention and made some progress. However, the mechanisms of interaction between the root rot pathogens and the host plant remain unclear. This paper reviews the research progress on the pathogens, infection cycle, disease prevalence, pathogenesis, and biological control of P. quinquefolium root rot to provide prospects for future research, aiming to provide references for the in-depth study and effective control of root rot, and to promote the green and healthy development of the P. quinquefolium industry.
Panax/microbiology* ; Plant Diseases/prevention & control* ; Plant Roots/microbiology* ; Fusarium/pathogenicity*

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Salmonellosis represents a global epidemic, and the emergence of extensively drug-resistant (XDR) Salmonella and its sustained transmission worldwide constitutes a significant public health concern. Flagellum-mediated motility serves as a crucial virulence trait of Salmonella that guides the pathogen toward the epithelial surface, enhancing gut colonization. Artemisia argyit essential oil, a traditional herb extract, demonstrates efficacy in treating inflammation-related symptoms and diseases; however, its effects on flagellum assembly and expression mechanisms in anti-Salmonella activity remain inadequately explored. This study aimed to elucidate the mechanism by which Artemisia argyit essential oil addresses Salmonella infections. Network pharmacological analysis revealed that Traditional Chinese Medicine (TCM) Artemisia argyit exhibited anti-Salmonella infection potential and inhibited flagellum-dependent motility. The application of Artemisia argyit essential oil induced notable motility defects through the downregulation of flagellar and fimbriae expression. Moreover, it significantly reduced Salmonella-infected cell damage by interfering with flagellum-mediated Salmonella colonization. In vivo studies demonstrated that Artemisia argyit essential oil administration effectively alleviated Salmonella infection symptoms by reducing bacterial loads, inhibiting interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) production, and diminishing pathological injury. Gas chromatography-mass spectrometry (GC-MS) analysis identified forty-three compounds in Artemisia argyit essential oil, with their corresponding targets and active ingredients predicted. Investigation of an in vivo model of Salmonella infection using the active ingredient demonstrated that alpha-cedrene ameliorated Salmonella infection. These findings suggest the potential application of Artemisia argyit essential oil in controlling Salmonella, the predominant food-borne pathogen.
Artemisia/chemistry* ; Oils, Volatile/chemistry* ; Animals ; Flagella/drug effects* ; Salmonella Infections/microbiology* ; Humans ; Mice ; Anti-Bacterial Agents/pharmacology* ; Salmonella/pathogenicity*

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

The protein kinase A/protein kinase G/protein kinase C-family (AGC kinase family) of eukaryotes is involved in regulating numerous biological processes. The 3-phosphoinositide- dependent protein kinase 1 (PDK1), is a conserved serine/threonine kinase in eukaryotes. To understand the roles of PDK1 homologous genes in cell death and immunity in tetraploid Nicotiana tabacum, the previuosly generated transgenic CRISPR/Cas9 lines, in which 5-7 alleles of the 4 homologous PDK1 genes (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out, were used in this study. Our results showed that the hypersensitive response (HR) triggered by transient overexpression of active Pto (Pto^Y207D) or soybean GmMEKK1 was significantly delayed, whereas the resistance to Pseudomonas syrangae pv. tomato DC3000 (Pst DC3000) and tobacco mosaic virus (TMV) was significantly elevated in these partial knockout lines. The elevated resistance to Pst DC3000 and TMV was correlated with the elevated activation of NtMPK6, NtMPK3, and NtMPK4. Taken together, our results indicated that NtPDK1s play a positive role in cell death but a positive role in disease resistance, likely through negative regulation of the MAPK signaling cascade.
Nicotiana/virology* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plants, Genetically Modified/genetics* ; Gene Knockout Techniques ; Plant Proteins/genetics* ; CRISPR-Cas Systems ; Protein Serine-Threonine Kinases/genetics* ; 3-Phosphoinositide-Dependent Protein Kinases/genetics* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Tobacco Mosaic Virus/pathogenicity*

In recent years, the spread of clubroot disease caused by Plasmodiophora brassicae infection has seriously affected the yield and quality of Brassica juncea (L.) Czern.. The cascade of mitogen-activated protein kinases (MAPKs), a highly conserved signaling pathway, plays an important role in plant responses to both biotic and abiotic stress conditions. To mine the MAPK genes related to clubroot disease resistance in B. juncea, we conducted a genome-wide analysis on this vegetable, and we analyzed the phylogenetic evolution and gene structure of the MAPK gene family in mustard. The 66 BjuMAPK genes identified by screening the whole genome sequence of B. juncea were unevenly distributed on 17 chromosomes. At the genomic scale, tandem repeats led to an increase in the number of MAPK genes in B. juncea. It was found that members of the same subfamily had similar gene structures, and there were great differences among different subfamilies. These predicted cis-acting elements were related to plant hormones, stress resistance, and plant growth and development. The expression of BjuMAPK02, BjuMAPK15, BjuMAPK17, and BjuMAPK19 were down-regulated or up-regulated in response to P. brassicae infection. The above results lay a theoretical foundation for further studying the functions of BjuMAPK genes in B. juncea in response to the biotic stress caused by clubroot disease.
Mustard Plant/parasitology* ; Plasmodiophorida/pathogenicity* ; Plant Diseases/genetics* ; Mitogen-Activated Protein Kinases/metabolism* ; Phylogeny ; Disease Resistance/genetics* ; Gene Expression Regulation, Plant ; Genome, Plant ; Plant Proteins/genetics*

In recent years, potato scab caused by pathogenic Streptomyces spp. has become widespread globally, with increasing damage severely compromising the commercial value and storability of tubers. The pathogens are transmitted through the soil and seeds of potato, while existing control technologies have demonstrated limited efficacy in preventing the colonization and spread of pathogens, which pose a critical bottleneck in the sustainable development of the potato industry. This study systematically examines the pathogen characteristics and pathogenic mechanisms, evaluates the impacts of soil nutrients and microbial community structure on disease severity, and analyzes limitations in current chemical control, biological control, and disease-resistant variety breeding approaches. We propose an integrated control strategy of disease-resistant varieties, phosphorus fertilizer reduction, fertilizer efficiency enhancement, and phosphorus-soluble antagonistic fungicides, aiming to provide novel research perspectives for achieving effective prevention and control of potato scab.
Solanum tuberosum/microbiology* ; Plant Diseases/prevention & control* ; Streptomyces/pathogenicity* ; Disease Resistance ; Fungicides, Industrial/pharmacology* ; Fertilizers ; Soil Microbiology