Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Background: The etiological underpinnings of gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) remain elusive, coupled with a scarcity of effective therapeutic interventions for IPF. Angelicae sinensis radix (ASR, also named Danggui) is a Chinese herb with potential anti-fibrotic properties, that holds promise as a therapeutic agent for IPF.Objective: This study seeks to elucidate the causal interplay and potential mechanisms underlying the coexistence of GERD and IPF. Furthermore, it aims to investigate the regulatory effect of ASR on this complex relationship.Methods: A two-sample Mendelian randomization (TSMR) approach was employed to delineate the causal connection between gastroesophageal reflux disease and IPF, with Phennoscanner V2 employed to mitigate confounding factors. Utilizing single nucleotide polymorphism (SNPs) and publicly available microarray data, we analyzed potential targets and mechanisms related to IPF in GERD. Network pharmacology and molecular docking were employed to explore the targets and efficacy of ASR in treating GERD-related IPF. External datasets were subsequently utilized to identify potential diagnostic biomarkers for GERD-related IPF.Results: The IVW analysis demonstrated a positive causal relationship between GERD and IPF (IVW: OR = 1.002, 95%CI: 1.001, 1.003; p < 0.001). Twenty-five shared differentially expressed genes (DEGs) were identified. GO functional analysis revealed enrichment in neural, cellular, and brain development processes, concentrated in chromosomes and plasma membranes, with protein binding and activation involvement. KEGG analysis unveiled enrichment in proteoglycan, ERBB, and neuroactive ligand-receptor interaction pathways in cancer. Protein-protein interaction (PPI) analysis identified seven hub genes. Network pharmacology analysis demonstrated that 104 components of ASR targeted five hub genes (PDE4B, DRD2, ERBB4, ESR1, GRM8), with molecular docking confirming their excellent binding efficiency. GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF (ESR1: AUCGERD = 0.762, AUCIPF = 0.725; GRM8: AUCGERD = 0.717, AUCIPF = 0.908). GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF, validated in external datasets.Conclusion: This study establishes a causal link between GERD and IPF, identifying five key targets and two potential diagnostic biomarkers for GERD-related IPF. ASR exhibits intervention efficacy and favorable binding characteristics, positioning it as a promising candidate for treating GERD-related IPF. The potential regulatory mechanisms may involve cell responses to fibroblast growth factor stimulation and steroidal hormone-mediated signaling pathways

A unique subseafloor microbiosphere in the Mariana Trench driven by episodic sedimentation

Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere. Currently, the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown. Here, analyses of carbon isotope composition in a ~ 750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition, with anomalous 14C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology. Microbial community composition and diverse enzyme activities in the upper ~ 27 cm differed from those at lower depths, probably due to sudden sediment deposition and differences in redox condition and organic matter availability. At lower depths, microbial population numbers, and composition remained relatively constant, except at some discrete depths with altered enzyme activity and microbial phyla abundance, possibly due to additional sudden sedimentation events of different magnitude. Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth’s deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations. Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere

Estimates of entropy numbers in probabilistic setting

In this paper, we define the entropy number in probabilistic setting and determine the exact order of entropy number of finite-dimensional space in probabilistic setting. Moreover, we also estimate the sharp order of entropy number of univariate Sobolev space in probabilistic setting by discretization method

Spatial-temporal evolution of overweight and obesity among Chinese adolescents from 2016 to 2020

Summary: This study examines the spatial-temporal evolution of overweight and obesity among Chinese adolescents aged 14–17. Data from five national surveys conducted between 2016 and 2020 were analyzed to determine distribution patterns and trends. Results showed that overweight and obesity exhibit spatial clustering, with greater severity in the north and less severity in the south. The issue has spread from the northeast to the southwest of Mainland China. Using a local autocorrelation model, the regions were divided into a northern disease cold spot area (Inner Mongolia) and a southern disease hot spot area (Guangxi). Over the past five years, overweight rates among Chinese adolescents have not been effectively curbed, but obesity has shown some success in control and reversal until 2019. Future efforts should focus on the spatial-temporal pattern of disease spread, targeting hotspot areas and abnormal values for regional synergy and precise prevention and control

Intracranial vessel wall segmentation with deep learning using a novel tiered loss function incorporating class inclusion.

PURPOSE: To develop an automated vessel wall segmentation method on T1-weighted intracranial vessel wall magnetic resonance images, with a focus on modeling the inclusion relation between the inner and outer boundaries of the vessel wall. METHODS: We propose a novel method that estimates the inner and outer vessel wall boundaries simultaneously, using a network with a single output channel resembling the level-set function height. The network is driven by a unique tiered loss that accounts for data fidelity of the lumen and vessel wall classes and a length regularization to encourage boundary smoothness. RESULTS: Implemented with a 2.5D UNet with a ResNet backbone, the proposed method achieved Dice similarity coefficients (DSC) in 2D of 0.925 ± 0.048, 0.786 ± 0.084, Hausdorff distance (HD) of 0.286 ± 0.436, 0.345 ± 0.419 mm, and mean surface distance (MSD) of 0.083 ± 0.037 and 0.103 ± 0.032 mm for the lumen and vessel wall, respectively, on a test set; compared favorably to a baseline UNet model that achieved DSC 0.924 ± 0.047, 0.794 ± 0.082, HD 0.298 ± 0.477, 0.394 ± 0.431 mm, and MSD 0.087 ± 0.056, 0.119 ± 0.059 mm. Our vessel wall segmentation method achieved substantial improvement in morphological integrity and accuracy compared to benchmark methods. CONCLUSIONS: The proposed method provides a systematic approach to model the inclusion morphology and incorporate it into an optimization infrastructure. It can be applied to any application where inclusion exists among a (sub)set of classes to be segmented. Improved feasibility in result morphology promises better support for clinical quantification and decision

The culture and inheritance of Huizhou architecture: taking the design practice of INK Weiping tourism cultural street as an example

This article uses the design analysis and insights of the Weiping Tourism Cultural Street, which the author participated in and practice to discuss how Huizhou culture can be protected and inherited in tourism cultural projects. Through the planning of the buildings of the project and the site planning of the surrounding environment, the formation of public spaces such as traditional streets, traditional theaters, as well as the influence of Huizhou culture on the space and architectural style and details of the building, the article interprets in detail the application of Huizhou architectural design and its traditional cultural connotations in cultural tourism development projects. At the same time, the article also discusses and summarizes the problems encountered in the protection and inheritance of Huizhou culture in the design and development process of the project, which has an enlightening effect on the better integration of the current practice of new Huizhou architecture with the current social and economic environment

Knowledge, attitude, and practice of body shape and fitness among university students in China

Abstract Background Body shape and fitness (BSF) is critical for overall well-being, while university students in China are subjected to stress, peer pressure, performance anxiety, busy schedules, and lack of sleep, which can easily lead to poor BSF. This study aimed to explore the knowledge, attitude, and practice of BSF and related factors among university students in China. Methods This web-based cross-sectional study was conducted on students of 15 universities in China between September 1st and November 30th, 2022. The KAP scores were evaluated using a 38-item questionnaire, including social demography, knowledge, attitude, and practice. Univariable and multivariable regression analyses were performed to identify the factors associated with KAP. Results A total of 995 valid questionnaires were collected. There were 431 (43.3%) males and 564 (56.7%) females. Most participants were sophomores (51.2%) and freshmen (36.3%). Most participants had a BMI of 18–24 kg/m2 (66.1%). The students scored highly on BSF-related knowledge (8.30 ± 1.49), moderately on attitude (37.20 ± 4.46), and low on practice (19.64 ± 4.62). Multivariate logistic regression analysis showed that attitude score (P = 0.001), sex (P = 0.001), grade (P = 0.011), body mass index (BMI) (P < 0.050), parent’s education level (P = 0.005), monthly allowance (P < 0.050), and sleep quality and habits (P = 0.016) were independently associated with practice scores. Conclusions University students in China were found to have good knowledge, moderate attitude, and poor practice toward BSF. Attitude, sex, grade, BMI, parents’ education, monthly living expenses, and sleep quality and habits affected their practice. More BSF-related courses or activities are required to motivate students, especially females

The Role of Reactive Oxygen Species and Nitric Oxide in the Inhibition of Trichophyton rubrum Growth by HaCaT Cells

Trichophyton rubrum (T. rubrum) is one of the most important agents of dermatophyte infection in humans. The aim of this experiment was to evaluate the effect of HaCaT cells on T. rubrum, investigate the responsible mechanism of action, and explore the role of reactive oxygen species (ROS) and nitric oxide (NO) in the inhibition of T. rubrum growth by HaCaT cells. The viability of fungi treated with HaCaT cells alone and with HaCaT cells combined with pretreatment with the NADPH oxidase inhibitor (DPI) or the nitric oxide synthase (NOS) inhibitor L-NMMA was determined by enumerating the colony-forming units. NOS, ROS, and NO levels were quantified using fluorescent probes. The levels of the NOS inhibitor asymmetric dimethylarginine (ADMA) were determined by enzyme-linked immunosorbent assay (ELISA). Micromorphology was observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, fungal keratinase activity was assessed by measuring dye release from keratin azure. In vitro fungal viability, keratinase activity, and ADMA content decreased after HaCaT cell intervention, whereas the levels of ROS, NO, and NOS increased. The micromorphology was abnormal. Fungi pretreated with DPI and L-NMMA exhibited opposite effects. HaCaT cells inhibited the growth and pathogenicity of T. rubrum in vitro. A suggested mechanism is that ROS and NO play an important role in the inhibition of T. rubrum growth by HaCaT cells

MRA-free intracranial vessel localization on MR vessel wall images.

Analysis of vessel morphology is important in assessing intracranial atherosclerosis disease (ICAD). Recently, magnetic resonance (MR) vessel wall imaging (VWI) has been introduced to image ICAD and characterize morphology for atherosclerotic lesions. In order to automatically perform quantitative analysis on VWI data, MR angiography (MRA) acquired in the same imaging session is typically used to localize the vessel segments of interest. However, MRA may be unavailable caused by the lack or failure of the sequence in a VWI protocol. This study aims to investigate the feasibility to infer the vessel location directly from VWI. We propose to synergize an atlas-based method to preserve general vessel structure topology with a deep learning network in the motion field domain to correct the residual geometric error. Performance is quantified by examining the agreement between the extracted vessel structures from the pair-acquired and alignment-corrected angiogram, and the estimated output using a cross-validation scheme. Our proposed pipeline yields clinically feasible performance in localizing intracranial vessels, demonstrating the promise of performing vessel morphology analysis using VWI alone