Explore the vast range of titles available.

Long noncoding RNAs (lncRNAs) have been investigated in multiple human cancers including gastric cancer (GC). Our research aims to explore the role of H19 in aerobic glycolysis, proliferation, and immune escape of GC cells. The expression of H19 in GC samples was analyzed using Gene Expression Profiling Interactive Analysis, Gene Expression Omnibus data, and real‐time quantitative PCR analysis. Relative quantification of glucose consumption and lactate production from cell supernatant were applied to assess the aerobic glycolysis of GC cells. Subcellular fractionation, luciferase reporter, and western blot assays certified the binding between genes. Cell Counting Kit‐8 and colony formation assays were used to determine GC cell proliferation. Flow cytometry, ELISA, and real‐time quantitative PCR assays were applied to analyze the immunosuppressive effect of H19. H19 was highly expressed in samples of patients with GC, and associated with tumor growth in vivo. H19 knockdown suppressed glucose consumption, lactate production, and proliferation of GC cells by regulating the microRNA (miR)‐519d‐3p/lactate dehydrogenase A (LDHA) axis. Both miR‐519d‐3p depletion and LDHA overexpression could reverse the H19 knockdown‐induced decrease in aerobic glycolysis and proliferation. Moreover, conditioned medium from stable knockdown H19 GC cells modulated the activity of immune cells including γδT cells, Jurkat cells, and tumor‐associated macrophages in a miR‐519d‐3p/LDHA/lactate axis‐dependent manner. The H19/miR‐519d‐3p/LDHA axis mainly contributed to aerobic glycolysis, proliferation, and immune escape of GC cells. Our results showed that H19 modulated aerobic glycolysis, proliferation, and immune escape of gastric cancer cells through the miR‐519d‐3p/LDHA axis.

Background Gastric cancer is a common cancer in China. This project investigated the disease burden of gastric cancer from 1990 to 2019 in China and globally. Methods The global age‐standardized rates (ASRs) were extracted from the Global Burden of Disease. Moreover, the estimated annual percentage changes (eAPCs) in the ASRs of incidence (ASIR), mortality (ASMR), and disability‐adjusted life‐years (DALYs) were calculated to determine the trends by countries and regions. Results In China, the ASIR declined from 37.56 to 30.64 per 100,000 and the ASMR declined from 37.73 to 21.72 per 100,000. The global ASIR decreased from 22.44 to 15.59 and the ASMR declined from 20.48 to 11.88 per 100,000 persons from 1990 to 2019. The ASIR was the lowest in Malawi (3.28 per 100,000) and the highest in Mongolia (43.7 per 100,000), whereas the ASMR was the lowest in the United States of America (3.40 per 100,000) and the highest in Mongolia (40.04 per 100,000) in 2019. The incidence of early‐onset gastric cancer increased in China. The DALYs attributed to gastric cancer presented a slight decrease during the period. China had a higher mortality/incidence ratio (0.845) and 5‐year prevalence (27.6/100,000) than most developed countries. Conclusion China presented a steady decline in the incidence and mortality rates for gastric cancer. The global ASIR, ASMR, and DALYs showed a slight rise decrease. Different patterns of gastric cancer rates and temporal trends have been identified in different geographical regions, indicating that specific strategies are needed to prevent the increase in some countries. This is a report of epidemiologic characterization of gastric cancer in China and globally. This research offers an overview of differential patterns of gastric cancer rates and temporal trends, providing policy‐makers with information needed to forestall the increase in gastric cancer.

As artificial intelligence–generated content (AIGC) becomes increasingly integrated into creative practices, its application in public art—particularly in urban sculpture—raises fundamental questions regarding aesthetic cognition, emotional engagement, and artistic acceptance. This study proposes and empirically tests a conceptual model to explain how general audiences perceive and evaluate AIGC-generated urban sculptures. Drawing upon Leder et al.’s aesthetic appreciation framework and theories of human–AI trust, we develop a structural equation model (SEM) comprising seven latent constructs: visual aesthetic features, cognitive mastery, emotional arousal, perceived artistic value, trust in AIGC, artistic acceptance intention, and familiarity control. A total of 24 AI-generated sculpture stimuli were produced using Midjourney v6 and evaluated along five aesthetic dimensions through expert visual content analysis. Questionnaire data were collected from 326 respondents across sculpture parks, art plazas, and university campuses in China. SEM results reveal that both cognitive mastery and emotional arousal significantly mediate the relationship between aesthetic features and perceived artistic value. Moreover, trust in AIGC and perceived artistic value jointly predict acceptance intentions, highlighting the intertwined roles of perceptual, affective, and attitudinal factors in the legitimation of AI-generated art. This research extends classical aesthetic theory to non-human creative contexts and provides practical implications for the design, deployment, and public communication of algorithmically generated urban artworks. By demonstrating that audiences can cognitively and emotionally resonate with AI-generated sculptures—contingent on visual coherence, symbolic richness, and technological trust—this study offers a novel empirical foundation for future investigations into the cultural and spatial integration of artificial creativity. However, the ecological validity of the study is inherently limited, as the stimuli consisted of digital renderings rather than physical public sculptures. Therefore, the findings represent preliminary insights into audience responses to conceptual AIGC artworks.

Ginger nut, AGA soil, and shell lime are the primary building limes used in traditional Chinese architectural sites. They have been widely researched and developed for restoring rock and soil heritage over the last decade. Previous studies have shown that these materials are compatible with weathered rock in terms of mechanical properties and environmental adaptability. In this study, metakaolinite was added to Chinese hydraulic limes to improve the mortar abilities. The basic properties and weather abilities of the mortars were evaluated. The characteristics of carbonation and hydration were analyzed over 900 days. The results indicated that the early strength improved and the contracting rate reduced when metakaolinite was added. The shell lime mortar was improved considerably compared with the modified ginger nut and AGA soil. The lime mortar content was determined using the X-ray diffraction results. The carbonation and hydration characteristics revealed that the metakaolinite aided the generation of hydraulic products (Ca2Al2SiO7·nH2O and β-CaSiO3·nH2O), particularly in the early stage. The microstructures were observed by scanning electron microscopy, which revealed more uniform and consolidated structures when metakaolinite was added.

Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery. Transcription factors are crucial in disease but hard to target with traditional drugs. Here, authors present BlockerSELEX, a strategy to develop inhibitory aptamers that block transcription factor interactions, which disrupts interactions between key proteins, showing potential for new nucleic acid therapies.

Abstract Background: Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. Methods: We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177+ neutrophils, and CD40L+ T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan–Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results: We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X1 + 0.758X2 + 1.347X3 − 7.745 (X1, X2, and X3 represent the proportions of CD177+ neutrophils, eosinophils, and CD40L+ T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <−0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905–0.979) with a sensitivity of 92.5% and a specificity of 83.6% (P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781–0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748–0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing (P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions: ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. Registration: Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Aims: Genetic variants increase the susceptibility to anti-drug antibodies (ADA) in response to anti-TNF therapy in chronic inflammatory diseases. However, little is known about genetic variants in Chinese populations. This study aimed to identify genetic variants contributing to the risk of the development of antibodies to infliximab (ATI) in Chinese patients with Crohn’s disease (CD). Methods: CD patients (n = 104) treated with infliximab (IFX) during the maintenance therapy were enrolled in this cross-sectional study. ATI was assessed by an in-house developed drug-tolerant ELISA method. ATI titers of 1:20 and ≥1:60 were considered a low titer and a high titer, respectively. Thirteen types of single nucleotide polymorphisms (SNPs) within 13 genes involved in the immune process, the susceptibility to chronic inflammatory diseases, cytokines and apoptosis pathways were investigated. Results: The median trough levels of infliximab (TLI) in patients with clinical remission (CR) were higher than those in patients without CR (3.80 vs. 1.50 μg/mL, p < .001). The median TLI in patients with high-titer ATI was significantly lower than that in ATI-negative patients (1.15 vs. 4.48 μg/mL, p < .001) or those with low-titer ATI (1.15 vs. 2.95 μg/mL, p = .03). The HLA-DQA1*05 rs2097432 GG and GA genotypes were more frequent in patients with ATI (GG and AG vs. AA, 27/38 = 71.05% vs. 29/66 = 43.94%, OR 2.94, 95% CI 1.19–7.30, p = .02). Patients carrying the CC and AC genotypes of rs396991 in FCGR3A were associated with a higher frequency of ATI formation (CC and AC vs. AA, 37/57 = 64.91% vs. 19/47 = 40.43%, OR 2.94, 95% CI 1.24–6.96, p = .01). According to the number of variants in rs2097432 and rs393991, patients with two variants had a higher proportion of producing ATI (two variants vs. no variant, 17/21 = 80.95% vs. 9/30 = 30.00%, OR 9.92, 95% CI 2.59–37.87, p = .001; single variant vs. no variant, 30/53 = 56.60% vs. 9/30 = 30.00%, OR 3.04, 95% CI 1.18–7.88, p = .02). No association was found between other SNPs and ATI production. Conclusion: Rs2097432 in HLA-DQA1*05 and rs396991 in FCGR3A are associated with ATI production in Chinese patients with CD. A pharmacogenomic strategy could help with the clinical management of CD.

Background Genetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis. Methods A GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets. Results At the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis. Conclusion In this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.

Earthquake has crucial effect in stability of the rock mass in Grotto Temple. However, only a few studies begin with the mountain of Grotto Temple and explore the interactions between rock mass stability of the mountain and that of temple. Firstly, the mechanical and displacement characteristics of North Grotto Temple (NGT) were analyzed, with a particular focus on effects of seismic waves, utilizing the finite difference modelling software FLAC 3D. Subsequently, mechanical properties, displacement nephogram, displacement response characteristics, and acceleration response characteristics of the mountain under seismic conditions were analysed. The simulation results indicate that there was no abrupt displacement at the location of NGT, but the stress changes were complex. Significant stress concentration effects were observed on slope and cliff faces, especially at the site of NGT, leading to relatively large displacements in that area. The phenomena of amplified peak displacement and peak acceleration were particularly pronounced. Additionally, strong shear stresses were observed near contact surfaces, suggesting potential shear sliding failure along these interfaces. This study not only provides theoretical basis for conservation, reinforcement, and monitoring of NGT, but also offers new research perspectives on the stability of rock masses in cave temples.

Background The immune landscape associated with different subtypes of intestinal metaplasia (IM) and early gastric cancer (EGC) remains unclear. This study aimed to investigate the immune landscape of complete intestinal metaplasia (CIM), incomplete intestinal metaplasia (IIM), and EGC, as well as the underlying mechanisms of EGC progression. Methods Gastric biopsy samples were collected from five patients with CIM, six patients with IIM, and four patients with EGC, followed by single-cell RNA sequencing. Multiplex immunohistochemical staining was employed to validate the samples from the aforementioned patients. To elucidate the potential mechanisms involved, in vitro coculture experiments were conducted using FOLR2 + /FOLR2 − macrophages and CD8 + T cells. Flow cytometry was utilized to investigate the biological functions of FOLR2 + macrophages in the progression of EGC. Results Five subpopulations of macrophages were identified in CIM, IIM and EGC samples. FOLR2 + macrophages possess antitumor immune potential, and the proportion of FOLR2 + macrophage gradually decreased from the CIM stage to the IIM and EGC stages. FOLR2 + macrophages were significantly positively correlated with CD8 + T cells and activated the cytotoxicity of CD8 + T cells via antigen cross-presentation. Additionally, during the progression of EGC, epithelial cells progressively upregulated APP expression, thus inducing necroptosis of FOLR2 + macrophages via the APP‒TNFRSF21 axis. Conclusions Our work provides an understanding of the potential mechanisms underlying the malignant transformation of IM mediated by FOLR2 + macrophages. Graphical Abstract