Helicobacter pylori PldA modulates TNFR1-mediated p38 signaling pathways to regulate macrophage responses for its survival.

Helicobacter pylori, a dominant member of the gastric microbiota was associated with various gastrointestinal diseases and presents a significant challenge due to increasing antibiotic resistance. This study identifies H. pylori's phospholipase A (PldA) as a critical factor in modulating host macrophage responses, facilitating H. pylori 's evasion of the immune system and persistence. PldA alters membrane lipids through reversible acylation and deacylation, affecting their structure and function. We found that PldA incorporates lysophosphatidylethanolamine into macrophage membranes, disrupting their bilayer structure and impairing TNFR1-mediated p38-MK2 signaling. This disruption results in reduced macrophage autophagy and elevated RIP1-dependent apoptosis, thereby enhancing H. pylori survival, a mechanism also observed in multidrug-resistant strains. Pharmacological inhibition of PldA significantly decreases H. pylori viability and increases macrophage survival. In vivo studies corroborate PldA's essential role in H. pylori persistence and immune cell recruitment. Our findings position PldA as a pivotal element in H. pylori pathogenesis through TNFR1-mediated membrane modulation, offering a promising therapeutic target to counteract bacterial resistance.

Real-Time Tracking of Laryngeal Motion via the Surface Depth-Sensing Technique for Radiotherapy in Laryngeal Cancer Patients.

Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left-right, cranio-caudal, and anterior-posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were -0.7 ± 1.0 mm (-18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left-right, cranio-caudal, and anterior-posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer.

Effectiveness of N-acetylcysteine in Treating Clinical Symptoms of Substance Abuse and Dependence: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Treatment with N-acetylcysteine (NAC) is believed to reduce the clinical symptoms among individuals with substance abuse or dependence. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness of NAC in treating substance abuse and dependence. METHODS: PubMed, EMBASE, ClinicalTrials.gov registry, and the Cochrane Library were searched for trials published before June 2020. RESULTS: A total of 16 trials were analyzed. The treatment effectiveness domains assessed in this study were craving and depressive symptoms, withdrawal syndrome, adverse events, and smoking frequency. Standardized mean difference (SMD), weighted mean difference (WMD), and odds ratio (OR) were used for evaluation where appropriate. A significant decrease in craving symptoms was observed in the NAC treatment group compared with the control group (SMD, -0.67; 95% confidence interval [CI], -1.21 to 0.21). When withdrawal and depressive symptoms were considered as a single domain, the NAC treatment group demonstrated a significantly higher overall improvement than the control group (SMD, -0.35; 95% CI, -0.64 to -0.06). No between-group differences in term of the OR of adverse events (OR, 1.18; 95% CI, 0.68 to 2.06) and a non-significant trend toward reduction in smoking frequency was observed in the NAC treatment group compared with the control group (WMD, -3.09; 95% CI, -6.50 to 0.32). CONCLUSION: NAC provides certain noticeable benefits in attenuating substance craving and might help alleviate depressive symptoms and withdrawal syndrome. Precautious measures should be considered when using NAC although no difference in adverse effects was found between NAC treatment and control group.