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Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis
Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate‐induced colitis in mice. Based on flow cytometry, colitis‐associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell‐null Rag1−/− mice or upon anti‐IL‐17‐A antibody‐treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA‐driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti‐colitis effect in RAR‐α ‐mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA‐SAA1/2‐Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity. By improving retinoic acid synthesis, a novel probiotic L. intestinalis exerts a protective effect against colitis. Retinoic acid triggers epithelial gene alteration, including SAA1, SAA2, and C/EBPA, to downregulate RORγt+ Th17 cells. L. intestinalis and its associated metabolite, retinoic acid, have potential therapeutic effects for suppressing colonic inflammation.
Journal Article
Escape : designing the modern guest house
A book showcasing guest house design which merges practicality with motifs of nature and art, to create the perfect combination of user convenience, comfort, and a unique experience Guest houses can be found in nearly every corner of the world as urban and rural dwellers open their homes, or build new ones, to host visitors. These guest houses take a multitude of forms, styles, and even names BandB in Britain, 'pension' in France, 'minshuku' in Japan, as well as being referred to as apartment hotels, boutique hotels, or hostels in some cases - but their primary goal is to satisfy the accommodation requirements and desired experience of the guests. In contrast to the ordinary hotel, guest houses combine unique and attractive features with thematic concepts that are intended to appeal to a visitor's individuality. Hosts provide guests with more than just accommodation options; they seek to generate an environment that offers a cultural experience by means of personalised interaction and service. On a conceptual level, the guest house addresses architecture and interior design as critical methods of contributing to an alternative or ideal lifestyle. \"Escape: Designing the Modern Guest House\" showcases 43 distinctive projects from around the world. These exclusive works have visual and spatial impact, representing the essence of new guest house design. This book highlights some of the most outstanding architectural strategies of recent years, displaying variations on spatial experience through the interplay of design elements. It provides strong reference material for design professionals and students in architecture, interior design, and related fields, as well as those looking to revamp their guest house accommodation with a contemporary 21st-century focus. Features guest houses in Italy, Taiwan, Japan, Vietnam, Thailand, USA, Chile, China, Portugal, South Korea, Spain, France, and Greece.
Book
An ALE meta-analysis on the effects of neural changes due to exercise on executive function in a healthy population
Executive function plays an important role throughout an individual’s life, and current research has shown that physical activity is an effective way to promote the development of executive function. Further research into the mechanisms in the brain that promote executive function has focused on populations with diseases, and no consistent conclusions have been drawn for healthy populations. Moreover, the differential effects of different exercise doses and sample characteristics on executive function brain activation remain unclear. In this study, we used an activation likelihood estimation (ALE) meta-analysis integrating 20 task-based and resting-state functional magnetic resonance imaging (fMRI) studies to investigate the mechanisms in the brain underlying the effects of different exercise interventions on executive functions in healthy populations. The results showed that exercise interventions significantly altered brain activation patterns during cognitive tasks, particularly in the frontal, precuneus, thalamus and cingulate regions. We examined exercise interventions in various sub-groups, showing patterns of effects in different age groups, exercise types and exercise durations.
Journal Article
Population aging and trends of pulmonary tuberculosis incidence in the elderly
Background
To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly.
Methods
We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (< 60 years) through logistic model and Join-point regression model.
Results
Among the total PTB cases, 77,192(32.2%) were elderly. Compared with non-elderly patients, newly active elderly PTB patients account for a greater proportion of male cases (OR 1.688, 95% CI 1.656–1.722), rural population cases (OR 3.411, 95% CI 3.320–3.505) and bacteriologically confirmed PTB cases (OR 1.213, 95%CI 1.193–1.234). The annual reported incidence of total, elderly, pulmonary bacteriologically confirmed cases were 35.21, 68.84, 35.63 (per 100,000), respectively. The annual reported incidence of PTB in the whole population, the elderly group and the non-elderly group has shown a slow downward trend since 2008. The joinpoint regression model showed that the overall reported incidence of PTB in the elderly significantly decreased from 2007 to 2017 (APC = -5.3,
P
< 0.05). The reported incidence of bacteriologically confirmed PTB among elderly patients declined rapidly from 2005 to 2014(2005–2010 APC = -7.2%,
P
< 0.05; 2010–2014 APC = -22.6%,
P
< 0.05; 2014–2017 APC = -9.0%,
P
= 0.1). The reported incidence of clinically diagnosed PTB among elderly patients from 2005 to 2017 (11.48–38.42/100,000) increased by about 235%. It rose significantly from 2007 to 2014 (APC = 9.4,
P
<0.05).
Conclusions
Compared with the non-elderly population, the reported incidence of PTB in the elderly population is higher. The main burden of PTB will shift to the elderly, men, rural population, and clinically diagnosed patients. With the intensification of aging, more researches on elderly PTB prevention and treatment will facilitate the realization of the global tuberculosis (TB) control targets.
Journal Article
Entrepreneurs in contemporary China : wealth, connections, and crisis
\"By drawing on extensive interviews with business founders and CEOs this book explores the complexities and dynamics of business and social relations responsible for present-day China's economic vibrancy. It makes an original contribution both through its empirical richness and theoretical innovations on trust, social networks, crisis and gender\"-- Provided by publisher.
Book
A compendium of mitochondrial molecular characteristics provides novel perspectives on the treatment of rheumatoid arthritis patients
Rheumatoid arthritis (RA) is an autoimmune disease that exhibits a high degree of heterogeneity, marked by unpredictable disease flares and significant variations in the response to available treatments. The lack of optimal stratification for RA patients may be a contributing factor to the poor efficacy of current treatment options. The objective of this study is to elucidate the molecular characteristics of RA through the utilization of mitochondrial genes and subsequently construct and authenticate a diagnostic framework for RA. Mitochondrial proteins were obtained from the MitoCarta database, and the R package limma was employed to filter for differentially expressed mitochondrial genes (MDEGs). Metascape was utilized to perform enrichment analysis, followed by an unsupervised clustering algorithm using the ConsensuClusterPlus package to identify distinct subtypes based on MDEGs. The immune microenvironment, biological pathways, and drug response were further explored in these subtypes. Finally, a multi-biomarker-based diagnostic model was constructed using machine learning algorithms. Utilizing 88 MDEGs present in transcript profiles, it was possible to classify RA patients into three distinct subtypes, each characterized by unique molecular and cellular signatures. Subtype A exhibited a marked activation of inflammatory cells and pathways, while subtype C was characterized by the presence of specific innate lymphocytes. Inflammatory and immune cells in subtype B displayed a more modest level of activation (Wilcoxon test P < 0.05). Notably, subtype C demonstrated a stronger correlation with a superior response to biologics such as infliximab, anti-TNF, rituximab, and methotrexate/abatacept (P = 0.001) using the fisher test. Furthermore, the mitochondrial diagnosis SVM model demonstrated a high degree of discriminatory ability in distinguishing RA in both training (AUC = 100%) and validation sets (AUC = 80.1%). This study presents a pioneering analysis of mitochondrial modifications in RA, offering a novel framework for patient stratification and potentially enhancing therapeutic decision-making.
Journal Article
Activation of CTNNB1 by deubiquitinase UCHL3-mediated stabilization facilitates bladder cancer progression
Background
The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Recent studies have suggested that CTNNB1 hyperactivation is closely related to the occurrence and development of bladder cancer (BCa). As a member of the deubiquitinating enzyme (DUB) family, ubiquitin C-terminal hydrolase L3 (UCHL3) is abnormally expressed in various cancers. In this study, we discovered that UCHL3 is a novel oncogene in bladder cancer, suggesting it is a promising target against bladder cancer.
Methods
We utilized CRISPR‒Cas9 technology to construct cell lines with UCHL3 stably overexpressed or knocked out. The successful overexpression or knockout of UCHL3 was determined using Western blotting. Then, we performed CCK-8, colony formation, soft agar and Transwell migration assays to determine the impact of the UCHL3 gene on cell phenotype. RNA-seq was performed with UCHL3-depleted T24 cells (established via CRISPR–Cas9-mediated genomic editing). We analyzed differences in WNT pathway gene expression in wild-type and UCHL3-deficient T24 cell lines using a heatmap and by gene set enrichment analysis (GSEA). Then, we validated the effect of UCHL3 on the Wnt pathway using a dual fluorescence reporter. We then analyzed the underlying mechanisms involved using Western blots, co-IP, and immunofluorescence results. We also conducted nude mouse tumor formation experiments. Moreover, conditional UCHL3-knockout mice and bladder cancer model mice were established for research.
Results
We found that the overexpression of UCHL3 boosted bladder cancer cell proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed tumor tumorigenesis in vitro and in vivo. UCHL3 was highly associated with the Wnt signaling pathway and triggered the activation of the Wnt signaling pathway, which showed that its functions depend on its deubiquitination activity. Notably, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer cells and associated with indicators of advanced clinicopathology.
Conclusion
In summary, we found that UCHL3 is amplified in bladder cancer and functions as a tumor promoter that enhances proliferation and migration of tumor cells in vitro and bladder tumorigenesis and progression in vivo. Furthermore, we revealed that UCHL3 stabilizes CTNNB1 expression, resulting in the activation of the oncogenic Wnt signaling pathway. Therefore, our findings strongly suggest that UCHL3 is a promising therapeutic target for bladder cancer.
Journal Article