Inhibiting pyroptosis: novel immune evasion strategies for pathogens.

Pyroptosis is a type of programmed cell death mediated by the Gasdermin family. It is triggered in response to pathogen infection or other danger signals. The activation of Gasdermins leads to pyroptosis and the release of large amounts of inflammatory cytokines. Pyroptosis plays a crucial role in combating pathogen infections, as it helps to eliminate infected cells and activate the immune system. However, pathogens have already developed sophisticated strategies to evade or inhibit pyroptosis, allowing them to persist and facilitate infection. This review provides an overview of the discovery of pyroptosis and its importance in anti-infectious immunity. We also discuss several new strategies for inhibiting pyroptosis by pathogens. A thorough learning of the occurrence and regulation of pyroptosis may reveal the pathogenesis of related infectious diseases and contribute to developing effective anti-infective therapeutic strategies.

Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis.

BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.

The Expression and Function of Notch Involved in Ovarian Development and Fecundity in Basilepta melanopus.

Basilepta melanopus is a pest that severely affects oil tea plants, and the Notch signaling pathway plays a significant role in the early development of insect ovaries. In this study, we explored the function of the notch gene within the Notch signaling pathway in the reproductive system of B. melanopus. The functional domains and expression patterns of Bmnotch were analyzed. Bmnotch contains 45 epidermal growth factor-like (EGF-like) domains, one negative regulatory region, one NODP domain and one repeat-containing domain superfamily. The qPCR reveals heightened expression in early developmental stages and specific tissues like the head and ovaries. The RNA interference (RNAi)-based suppression of notch decreased its expression by 52.1%, exhibiting heightened sensitivity to dsNotch at lower concentrations. Phenotypic and mating experiments have demonstrated that dsNotch significantly impairs ovarian development, leading to reduced mating frequencies and egg production. This decline underscores the Notch pathway's crucial role in fecundity. The findings advocate for RNAi-based, Notch-targeted pest control as an effective and sustainable strategy for managing B. melanopus populations, signifying a significant advancement in forest pest control endeavors.

Global, regional, and national trends in metabolic risk factor-associated mortality among the working-age population from 1990-2019: An age-period-cohort analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.