Intestinal lysozyme1 deficiency alters microbiota composition and impacts host metabolism through the emergence of NAD+-secreting ASTB Qing110 bacteria.

The intestine plays a pivotal role in nutrient absorption and host defense against pathogens, orchestrated in part by antimicrobial peptides secreted by Paneth cells. Among these peptides, lysozyme has multifaceted functions beyond its bactericidal activity. Here, we uncover the intricate relationship between intestinal lysozyme, the gut microbiota, and host metabolism. Lysozyme deficiency in mice led to altered body weight, energy expenditure, and substrate utilization, particularly on a high-fat diet. Interestingly, these metabolic benefits were linked to changes in the gut microbiota composition. Cohousing experiments revealed that the metabolic effects of lysozyme deficiency were microbiota-dependent. 16S rDNA sequencing highlighted differences in microbial communities, with ASTB_g (OTU60) highly enriched in lysozyme knockout mice. Subsequently, a novel bacterium, ASTB Qing110, corresponding to ASTB_g (OTU60), was isolated. Metabolomic analysis revealed that ASTB Qing110 secreted high levels of NAD+, potentially influencing host metabolism. This study sheds light on the complex interplay between intestinal lysozyme, the gut microbiota, and host metabolism, uncovering the potential role of ASTB Qing110 as a key player in modulating metabolic outcomes. IMPORTANCE: The impact of intestinal lumen lysozyme on intestinal health is complex, arising from its multifaceted interactions with the gut microbiota. Lysozyme can both mitigate and worsen certain health conditions, varying with different scenarios. This underscores the necessity of identifying the specific bacterial responses elicited by lysozyme and understanding their molecular foundations. Our research reveals that a deficiency in intestinal lysozyme1 may offer protection against diet-induced obesity by altering bacterial populations. We discovered a strain of bacterium, ASTB Qing110, which secretes NAD+ and is predominantly found in lyz1-deficient mice. Qing110 demonstrates positive effects in both C. elegans and mouse models of ataxia telangiectasia. This study sheds light on the intricate role of lysozyme in influencing intestinal health.

Identifying spatial heterogeneity of COVID-19 transmission clusters and their built-environment features at the neighbourhood scale.

The identification of high-risk areas for infectious disease transmission and its built-environment features are crucial for targeted surveillance and early prevention efforts. While previous research has explored the association between infectious disease incidence and urban built environment, the investigation of spatial heterogeneity of built-environment features in high-risk areas has been insufficient. This paper aims to address this gap by analysing the spatial heterogeneity of COVID-19 clusters in Shanghai at the neighbourhood scale and examining associated built-environment features. Using a spatiotemporal clustering algorithm, the study analysed 1395 reported cases in Shanghai from March 6 to March 17, 2022. Both global Poisson regression (GPR) and geographically weighted Poisson regression (GWPR) models were applied to examine the association between built-environment variables and the size of COVID-19 clusters. Our findings suggest that larger COVID-19 clusters emerging in the suburbs compared with the downtown and multiple built-environment features are significantly associated with this pattern. Specifically, neighbourhoods with a higher proportion of commercial, public service and industrial land, higher centrality of metro stations, and proximity to hospitals are positively associated with larger COVID-19 clusters, while neighbourhoods with higher land use mix and green/open spaces density are associated with smaller COVID-19 clusters. Moreover, we identified that metro stations with high centrality present the highest risk in the downtown, while commercial and public service places exhibit the highest risk in the suburbs. By highlighting the overlooked spatial heterogeneity of built-environment features for high-risk areas, this study aims to provide valuable guidance for public health departments in implementing place-based interventions to effectively prevent the spread of potential epidemics.

Current status and progress of the development of prostate cancer vaccines.

At present, common treatments of prostate cancer mainly include surgery, radiotherapy, chemotherapy and hormone therapy. However, patients have high recurrence rate after treatment, and are prone to castration-resistant prostate cancer. Tumor vaccine is based on tumor specific antigen (TSA) and tumor associated antigen (TAA) to activate specific immune response of the body to cancer cells. With continuous maturity of tumor vaccine technology, different forms of prostate cancer vaccines have been developed, such as cellular vaccines, extracellular-based anti-tumor vaccines, polypeptide vaccines, and nucleic acid vaccines. In this review, we summarize current status and progress in the development of prostate cancer vaccines.

Examining the association between the built environment and active travel using GPS data: A study of a large residential area (Daju) in Shanghai.

Automobile dependence and physical inactivity have become common health challenges for residents in large suburban residential areas. Limited literature has examined the associations between the built environment and active travel in such residential areas and the differences in these associations among residents from different neighborhoods. To avoid inaccurate results potentially derived from residence-based measures, we adopt a mobility-based approach for environmental exposure assessment. Using GPS data from 530 trips made by 98 participants in a large residential area in Shanghai, we investigate the relationships between neighborhood types, pollution perceptions, built environment features and active travel. The results indicate that residents in affordable and relocation housing make fewer active trips than those in market-rate housing, while the built environment seems to mitigate this difference. Sports facilities promote active travel while commercial facilities and road intersections discourage it. We identify significant interactions between the percentage of green space and neighborhood type, as well as floor area ratio and air pollution perception. Interventions promoting active travel include active-travel-friendly design for commercial facilities and road intersections, the provision of more sports facilities, a careful increase in floor area ratio, and the provision of more green space that is attractive to residents from different neighborhoods.

EZH2 identifies the precursors of human natural killer cells with trained immunity.

OBJECTIVE: Trained immunity of natural killer (NK) cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation. However, the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown. We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12, IL-15, and IL-18, and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity. On the basis of our hypothesis, we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention. METHODS: Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets. Single-cell RNA sequencing (scRNA-seq) plus TotalSeq™ technology was used to track the heterogeneity of NK cells during the induction of trained immunity. RESULTS: Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity. Therefore, we used scRNA-seq plus TotalSeq™ technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57-NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+ NK cells. Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells. We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57-NKG2A+EZH2+ NK cells had faster cell cycles and an enhanced trained phenotype, and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells. These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity. CONCLUSIONS: Our work revealed human NK heterogeneity in the induction of trained immunity, identified the precursor subset for trained NK cells, and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.

Diagnostic Value of the Fimbriae Distribution Pattern in Localization of Urinary Tract Infection.

Urinary tract infections (UTIs) are one of the most common infectious diseases. UTIs are mainly caused by uropathogenic Escherichia coli (UPEC), and are either upper or lower according to the infection site. Fimbriae are necessary for UPEC to adhere to the host uroepithelium, and are abundant and diverse in UPEC strains. Although great progress has been made in determining the roles of different types of fimbriae in UPEC colonization, the contributions of multiple fimbriae to site-specific attachment also need to be considered. Therefore, the distribution patterns of 22 fimbrial genes in 90 UPEC strains from patients diagnosed with upper or lower UTIs were analyzed using PCR. The distribution patterns correlated with the infection sites, an XGBoost model with a mean accuracy of 83.33% and a mean area under the curve (AUC) of the receiver operating characteristic (ROC) of 0.92 demonstrated that fimbrial gene distribution patterns could predict the localization of upper and lower UTIs.

Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC.

Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract infections, is associated with prostate and bladder cancers. Cytotoxic necrotizing factor 1 (CNF1) is a key UPEC toxin; however, its role in bladder cancer is unknown. In the present study, we found CNF1 induced bladder cancer cells to secrete vascular endothelial growth factor (VEGF) through activating Ras homolog family member C (RhoC), leading to subsequent angiogenesis in the bladder cancer microenvironment. We then investigated that CNF1-mediated RhoC activation modulated the stabilization of hypoxia-inducible factor 1α (HIF1α) to upregulate the VEGF. We demonstrated in vitro that active RhoC increased heat shock factor 1 (HSF1) phosphorylation, which induced the heat shock protein 90α (HSP90α) expression, leading to stabilization of HIF1α. Active RhoC elevated HSP90α, HIF1α, VEGF expression, and angiogenesis in the human bladder cancer xenografts. In addition, HSP90α, HIF1α, and VEGF expression were also found positively correlated with the human bladder cancer development. These results provide a potential mechanism through which UPEC contributes to bladder cancer progression, and may provide potential therapeutic targets for bladder cancer.

Spatial Analysis of Built Environment Risk for Respiratory Health and Its Implication for Urban Planning: A Case Study of Shanghai.

Urban planning has been proven and is expected to promote public health by improving the built environment. With a focus on respiratory health, this paper explores the impact of the built environment on the incidence of lung cancer and its planning implications. While the occurrence of lung cancer is a complicated and cumulative process, it would be valuable to discover the potential risks of the built environment. Based on the data of 52,009 lung cancer cases in Shanghai, China from 2009 to 2013, this paper adopts spatial analytical methods to unravel the spatial distribution of lung cancer cases. With the assistance of geographic information system and Geo-Detector, this paper identifies certain built environments that are correlated with the distribution pattern of lung cancer cases in Shanghai, including the percentage of industrial land (which explains 28% of the cases), location factors (11%), and the percentages of cultivated land and green space (6% and 5%, respectively). Based on the quantitative study, this paper facilitates additional consideration and planning intervention measures for respiratory health such as green buffering. It is an ecological study to illustrate correlation that provides approaches for further study to unravel the causality of disease incidence and the built environment.