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Background: To examine the cardiovascular disease (CVD) risks associated with metabolic dysfunction‐associated steatotic liver disease (MASLD) and different numbers of cardiometabolic risk factors (CMRFs) in patients with inflammatory bowel disease (IBD) based on a long‐term prospective cohort. Methods: Prevalent IBD patients at baseline who were free of CVD, cancer, alcoholic liver disease, cancer and hepatitis B/C virus seropositive were included (N = 4204). MASLD, MASLD subtypes [pure MASLD, MASLD with increased alcohol intake (MetALD)], lean/non‐lean MASLD and CMRFs at baseline were defined according to the latest criteria proposed by AASLD and EASL. The primary outcome was incident CVD, including ischaemic heart disease (IHD), heart failure (HF) and stroke. Multivariable Cox proportional hazard models were used to estimate the relationship. Results: Overall, 1528 (36.4%) were diagnosed with MASLD at baseline. During a median of 13.1‐year follow‐up, 503 incident CVDs were identified. Compared with IBD‐only, IBD‐MASLD patients had an increased risk of CVD (HR = 1.77, 95%CI: 1.26–2.49), especially in those with MetALD (HR = 2.34, 1.34–4.11) and lean MASLD (HR = 2.30, 1.13–4.66). As the number of CMRFs increased, the risks of CVD were significantly increased (ptrend <0.001), with a 116% and 92% excess risk in MASLD with 3 CMRFs (HR = 2.16, 1.48–3.15) and ≥4 CMRFs (HR = 1.92, 1.27–2.91). Similar excess risk of incident IHD and HF was observed in IBD‐MASLD, either pure MASLD or MetALD, as well as lean/non‐lean MASLD. Conclusions: MASLD is associated with increased CVD risk in IBD patients, with greater risk as number of CMRFs increased and evidently higher risk in MetALD and lean MASLD patients. [ABSTRACT FROM AUTHOR]

Fast‐switching high‐efficiency liquid crystal grating is a key component in holographic true‐3D display systems. In this paper, we present our research and development of a 10.7" liquid crystal grating with 2‐3 millisecond switching time, close‐to‐ideal deflection efficiency, and >100 polarization contrast. The high performance is achieved by optimizing the design and process of the liquid crystal grating panel as well as the optical module stack. Several key design principles are analyzed and verified. Based on the developed liquid crystal grating, a 10.4" full‐color naked‐eye holographic 3D display prototype is successfully realized. [ABSTRACT FROM AUTHOR]

Polymer-dispersed liquid crystal (PDLC) films are widely used in intelligent opto-electronic field owing to their electrically switchable properties. Previous studies have focused on the improvement of electro-optical properties of PDLC film in visible light bands; yet, the application of PDLC in other bands has few research. In this paper, vinylferrocene was introduced into PDLC films containing polyhedral oligomeric silsesquioxane (POSS) to improve UV-shielding properties. Scanning electron microscopy (SEM) studies revealed that vinylferrocene was uniformly dispersed in the polymer network. The structure could improve the electro-optical properties of PDLC film. The effect of temperature on PDLC film was studied. When the temperature reached 35°C, the PDLC composite film polymer network had better electro-optical properties. The PDLC composite films can effectively shield 86.73% UV light at on-state and 93.37% at off-state. The unique UV-shielding properties make this PDLC film a great application potential in smart windows. This PDLC combined with POSS and vinylferrocene film also exhibits large-area processability, which can further expand its application. [ABSTRACT FROM AUTHOR]

Background To investigate prospective association of coffee and tea intake with incident irritable bowel syndrome (IBS) in a long-term cohort. Methods Participants free of IBS, coeliac disease, inflammatory bowel disease and any cancer at baseline from UK Biobank were included. Coffee and tea intake was measured separately via baseline touchscreen questionnaire, with four categories for each intake (0, 0.5–1, 2–3 and ≥4 cups/day). Primary outcome was incident IBS. Cox proportional hazard model was used to estimate associated risk. Results Among 425 387 participants, 83 955(19.7%) and 186 887(43.9%) consumed ≥4 cups/day of coffee and tea at baseline, respectively. During median 12.4-year follow-up, incident IBS was identified in 7736 participants. Compared with no coffee intake, consumption of 0.5–1, 2–3 and ≥4 cups/day was associated with lower IBS risk [hazard ratio (HR)=0.93, 95% CI: 0.87–0.99; 0.91, 0.85–0.97; 0.81, 0.76–0.88; P trend < 0.001]. Specifically, decreased risk was evident in individuals who consumed instant (HR = 0.83, 0.78–0.88) or ground coffee (HR = 0.82, 0.76–0.88) compared with no coffee drink. Regarding tea intake, protective association was only found in individuals who consumed 0.5–1 cup/day (HR = 0.87, 0.80–0.95), whereas no significant association was detected in those who consumed 2–3 (HR = 0.94, 0.88–1.01) or ≥4 cups/day (HR = 0.95, 0.89–1.02) compared with no-tea intake (P trend = 0.848). Conclusions Higher intake of coffee, particularly instant and ground coffee, is associated with lower risk of incident IBS, with significant dose–response relationship. Moderate-tea intake (0.5–1 cup/day) is associated with lower IBS risk. [ABSTRACT FROM AUTHOR]

Purpose: Early diagnosis is crucial for optimal prognosis of gastric cancer (GC). Hereby, we aimed to identify novel serum autoantibody-based biomarkers for precancerous lesion (PL) and early GC. Methods: We performed serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (Nano-LC-Q-TOF-MS/MS) to screen for GC-associated autoantibodies. The identified autoantibodies were analyzed for potential detection value for PL and GC by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves analysis was conducted to evaluate the accuracy of the biomarkers. Results: We identified seven candidates, such as mRNA export factor (RAE1), Nucleophosmin 1 (NPM1), phosphoglycerate kinase 1 (PGK1), and ADP-ribosylation factor 4 (ARF4). Antibodies against all seven proteins were present at higher levels in sera from 242 patients (51 PL, 78 early GC, 113 advanced GC) compared with sera from 122 healthy individuals. RAE1-specific autoantibody discriminated best between patients at different GC stages, with area under the curve (AUC) values of 0.710, 0.745, and 0.804 for PL, early GC, and advanced GC, respectively. Two predictive models composed of gender, RAE1, PGK1, NPM1, and ARF4 autoantibodies (Model 2 for PL) and of age, gender, RAE1, PGK1, and NPM1 autoantibodies (Model 3 for early GC) had improved diagnostic efficiencies, with AUCs of 0.803 and 0.857, sensitivities of 66.7% and 75.6%, and specificities of 78.7% and 87.7%, respectively. Conclusion: The identified serum tumor-associated autoantibodies (TAAbs) may have good potential for early detection of GC and PL. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS)-guided natural orifice transluminal gallbladder polypectomy provides a minimally invasive alternative to cholecystectomy. The study aimed to investigate the feasibility and safety of protocol for gallbladder endoscopic mucosal resection (gEMR) under EUS guidance using a porcine model. Fifteen Bama mini pigs were randomly divided into the control (CG, n = 3) and experimental (EG, n = 12) groups. EUS-guided fine needle aspiration was performed in the CG and used to establish a gallbladder pathway for polyp resection under EUS guidance in the EG. Procedural safety was evaluated using routine blood and biochemical tests, microbial bile cultures, histopathological tests, and enzyme-linked immunosorbent assays for inflammatory adhesion factors. EUS-guided metal stents were successfully deployed in all 12 pigs. Two cases of stent displacement occurred postoperatively, and one pig died of infectious peritonitis on the first day after stent implantation. In 11 surviving experimental animals, mature gallbladder paths were formed at 7–14 days after gastro-cholecystostomy, through which gEMR of gallbladder polyps was successfully performed. There were no significant changes in levels of inflammatory and adhesion factors during the postoperative process. EUS-gEMR may be a safe and effective minimally invasive treatment approach for gallbladder polyps. [ABSTRACT FROM AUTHOR]

Purpose: Tumor microenvironment (TME) affects the progression of rectal cancer (RC), and the clinical relevance of its immune elements was widely reported. Here we aim to delineate the complete TME landscape, including non-immune features, to improve our understanding of RC heterogeneity and provide a better strategy for precision medicine. Methods: Single-cell analysis of GSE161277 using Seurat and Cellcall was performed to identify cell-cell interactions. The ssGSEA was employed to quantify the TME elements in TCGA patients, which were further clustered into subtypes by hclust. WGCNA and LASSO were combined to construct a degenerated signature for prognosis, and its performance was validated in two GEO datasets. Results: We proposed a subtyping strategy based on the abundance of both immune and non-immune components, which divided all RC patients into 4 subtypes (Immune-, Canonical-, Dormant- and Stem-like). Different subtypes exhibited distinct mutation landscapes, biological features, immune characteristics, immunotherapy responses and prognoses. Next, WGCNA and LASSO regression were combined to construct a 10-gene signature based on differentially expressed genes among different subtypes. Subgroups divided by this signature also exhibited different clinical parameters and responses to immune checkpoint blockades. Diverse machine learning algorithms were applied to achieve higher accuracy for survival prediction and a nomogram was further established in combination with M stage and age to provide an accurate and visual prediction of prognosis. Conclusions: We identified four TME-based RC subtypes with distinct biological and clinical features. Based on those subtypes, we also proposed a degenerated 10-gene signature to predict the prognosis and immunotherapy response. [ABSTRACT FROM AUTHOR]

Human coronaviruses (HCoVs) were first described in 1960s for patients experiencing common cold. Since then, increasing number of HCoVs have been discovered, including those causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the circulating coronavirus disease 2019 (COVID‐19), which can cause fatal respiratory disease in humans on infection. HCoVs are believed to spread mainly through respiratory droplets and close contact. However, studies have shown that a large proportion of patients with HCoV infection develop gastrointestinal (GI) symptoms, and many patients with confirmed HCoV infection have shown detectable viral RNA in their faecal samples. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal HCoV infection. These data highlight the nature of HCoV GI infection and its potential faecal‐oral transmission. Here, we summarise the current findings on GI manifestations of HCoVs. We also discuss how HCoV GI infection might occur and the current evidence to establish the occurrence of faecal‐oral transmission. [ABSTRACT FROM AUTHOR]

The emerging Color Filter on Touch (CFOT) technology significantly reduces OLED module transmittance and hence obstructs the use of traditional optical fingerprint on display (FOD). In this work, we demonstrate the integration of pinhole‐based FOD with CFOT OLED, achieving high performance FOD and display simultaneously. [ABSTRACT FROM AUTHOR]

Background: The relationship between non-alcoholic fatty liver degree as well as non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) remains poorly understood. We aimed to investigate the prospective association of non-alcoholic fatty liver degree as well as NAFLD with incident IBS in a large-scale population-based cohort.Methods: Participants free of IBS, coeliac disease, inflammatory bowel disease, alcoholic liver disease, and any cancer at baseline from the UK Biobank were included. Non-alcoholic fatty liver degree was measured by a well-validated fatty liver index (FLI), with FLI ≥ 60 as an indicator of NAFLD. Primary outcome was incident IBS. Cox proportional hazard model was used to investigate the associated risk of incident IBS.Results: Among 396,838 participants (mean FLI was 48.29 ± 30.07), 153,203(38.6%) were with NAFLD diagnosis at baseline. During a median of 12.4-year follow-up, 7129 cases of incident IBS were identified. Compared with non-NAFLD, NAFLD patients showed a 13% higher risk of developing IBS (HR = 1.13, 95%CI: 1.05-1.17) after multivariable adjustment. Compared with the lowest, the highest FLI quartile was associated with a significantly increased risk of IBS (HRQ4 VS Q1 = 1.21, 1.13-1.30, Ptrend < 0.001). Specifically, the positive association between non-alcoholic fatty liver degree and IBS was also observed by per SD change of FLI (adjusted HR = 1.08, 1.05-1.10). Further sensitivity analysis and subgroup analysis indicated similar results, with the positive association particularly observed in females, but not in males.Conclusions: High degree of non-alcoholic fatty liver as well as non-alcoholic fatty liver disease is associated with increased risk of incident IBS. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Chromatic dispersion of reflection makes different shapes of patterns on the display and particularly obvious under the sunlight. This will seriously affect the use of the display outdoors. We have investigated the chromatic dispersion on CFOT and regard the origin of it is identified as the diffraction of the OLED pixels. The simulation results are consistent with the experimental results, and several important factors affecting the diffraction are given in this paper. According to the influencing factors, several corresponding countermeasures are proposed. [ABSTRACT FROM AUTHOR]

The emerging Color Filter on Touch (CFOT) technology significantly reduces OLED module transmittance and hence obstructs the use of traditional optical fingerprint on display (FOD). In this work, we demonstrate the integration of pinhole‐based FOD with CFOT OLED, achieving high performance FOD and display simultaneously. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a frequently-encountered chronic gastrointestinal disorder characterized by recurrent abdominal pain accompanied by changes in fecal morphology and bowel habits [[1]]. Therefore, investigating the changes in microbiota and metabolites obtained from the mucosa of IBS patients may provide a deeper understanding of the pathogenesis of IBS [[1]]. IBS is usually classified into four types: predominant-diarrhea (IBS-D), constipation-predominant (IBS-C), mixed bowel habits (IBS-M), and unclassified (IBS-U) [[5]]. [Extracted from the article]

Rho GTPases are molecular switches that play an important role in regulating the behavior of a variety of tumor cells. RhoA GTPase-activating protein 26 (ARHGAP26) is a GTPase-activating protein and inhibits the activity of Rho GTPases by promoting the hydrolytic ability of Rho GTPases. It also affects tumorigenesis and progression of various tumors through several methods, including formation of abnormal fusion genes and circular RNA. This review summarizes the biological functions and molecular mechanisms of ARHGAP26 in different tumors, proposes the potential clinical value of ARHGAP26 in cancer treatment, and discusses current issues that need to be addressed. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the role of HOXC11 in progression and prognosis in colon adenocarcinoma (COAD) patients. The COAD patient data were downloaded from "The Cancer Genome Atlas (TCGA)" database. The Wilcoxon rank-sum test or Kruskal-Wallis test was used to analyze the correlation between HOXC11 expression and clinicopathologic characteristics. The significance of difference in overall survival between different groups was determined by log-rank test. The HOXC11 expression was verified from mRNA and protein level by conducting real-time quantitative PCR, Western blot, and immunohistochemistry analysis. Significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened after gene set enrichment analysis. As a result, high HOXC11 expression was closely related to the occurrence of COAD based on the data in TCGA, which was then successfully validated in cell lines and clinical tissues. Enhanced HOXC11 expression was significantly associated with tumor-node-metastasis (TNM) and M stage. Prognosis of highly expressed HOXC11 COAD patients was significantly worse than those with low HOXC11 expression. GRAFT_VERSUS_HOST_DISEASE and other signaling pathways were significantly activated in high HOXC11 expression COAD patients. In conclusion, high expression of HOXC11 was closely associated with the progression of COAD, and HOXC11 was a promising prognostic biomarker in COAD patients. [ABSTRACT FROM AUTHOR]

Exosomes are single-membrane, secreted organelles with a diameter of 30–200 nm, containing diverse bioactive constituents, including DNAs, RNAs, proteins, and lipids, with prominent molecular heterogeneity. Extensive studies indicate that exosomal RNAs (e.g., microRNAs, long non-coding RNAs, and circular RNAs) can interact with many types of cancers, associated with several hallmark features like tumor growth, metastasis, and resistance to therapy. Pancreatic cancer (PaCa) is among the most lethal cancers worldwide, emerging as the seventh foremost cause of cancer-related death in both sexes. Hence, revealing the specific pathogenesis and improving the clinical diagnosis and treatment process are urgently required. As the study of exosomes has become an active area of research, the functional connections between exosomes and PaCa have been deeply investigated. Among these, exosomal RNAs seem to play a significant role in the development, diagnosis, and treatment of PaCa. Exosomal RNAs delivery ultimately modulates the various features of PaCa, and many scholars have interpreted how exosomal RNAs contribute to the proliferation, angiogenesis, migration, invasion, metastasis, immune escape, and drug resistance in PaCa. Besides, recent studies emphasize that exosomal RNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets for PaCa. In this review, we will introduce these recent insights focusing on the discoveries of the relationship between exosomal RNAs and PaCa, and the potentially diagnostic and therapeutic applications of exosomes in PaCa. [ABSTRACT FROM AUTHOR]

Background: Plasma miRNAs are emerging biomarkers for colon cancer (CC) diagnosis. However, the lack of robust internal references largely limits their clinical application. Here we propose a ratio-based, normalizer-free algorithm to quantitate plasma miRNA for CC diagnosis. Methods: A miRNA-pair matrix was established by pairing differentially expressed miRNAs in the training group from GSE106817. LASSO regression was performed to select variables. To maximize the performance, four algorithms (LASSO regression, random forest, logistic regression, and SVM) were tested for each biomarker combination. Data from GSE106817 and GSE112264 were used for internal and external verification. RT-qPCR data acquired from another cohort were also used for external validation. Results: After validation through four algorithms, we obtained a 4-miRNA pair model (miR-1246 miR-451a; miR-1246 miR-4514; miR-654-5p miR-575; miR-4299 miR-575) that showed good performance in differentiating CC from normal controls with a maximum AUC of 1.00 in internal verification and 0.93 in external verification. Tissue validation showed a maximum AUC of 0.81. Further external validation using RT-qPCR data exhibited good classifier ability with an AUC of 0.88. Conclusion: We established a cross-platform prediction model robust against sample-specific disturbance, which is not only well-performed in predicting CC but also promising in the diagnosis of other diseases. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) and its G-protein-coupled receptors (Lpar1–Lpar6) mediate a plethora of activities associated with cancer growth and progression. However, there is no systematic study about whether and how LPA promotes esophageal squamous cell carcinoma (ESCC). Here, we show that autotaxin (ATX), a primary LPA-producing enzyme, is highly expressed in ESCC, and overexpressed ATX is associated with the poor outcome of ESCC patients. Meanwhile, the expression of Lpar1 was much higher in ESCC cells compared with Het-1a (human esophagus normal epithelial cells). Functional experiments showed that LPA remarkably increased the proliferation and migration of ESCC cells. Furthermore, Lpar1 knockdown abolished the effect of LPA on ESCC cell proliferation and migration. Mechanistic studies revealed that LPA promoted ESCC cell lines proliferation and migration through PI3K/Akt pathway. Treatment of KYSE30 cell xenografts with Lpar1 inhibitor BMS-986020 significantly repressed tumor growth. Our results shed light on the important role of LPA in ESCC, and Lpar1 might be a potential treatment target for ESCC. [ABSTRACT FROM AUTHOR]

The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is associated with the invasion and metastasis of tumor cells. Epithelial cell transforming 2 (ECT2) is a guanine nucleotide exchange factor (GEF) of the Rho family of GTPases. It has also been reported that upregulation of ECT2 in pancreatic cancer, but the role and mechanism of ECT2 have not been previously determined. We found that ECT2 was significantly elevated in PDAC tissues and cells, correlated with more advanced AJCC stage, distant metastases, and overall survival of patients with PDAC. Inhibition and overexpression tests showed that ECT2 promoted proliferation, migration and invasion in vitro , and promoted tumor growth and metastasis in vivo. We determined that ECT2 was involved in the post-translational regulation of Grb2. ECT2 inhibited the degradation of Grb2 through deubiquitination. Furthermore, knockdown of ECT2 downregulated EGFR levels by accelerating EGFR degradation. EGF stimulation facilitated the formation of ECT2-Grb2 complex. Overall, our findings indicated that ECT2 could be used as a promising new therapeutic candidate for PDAC. [ABSTRACT FROM AUTHOR]

Background: Chronic stress is associated with activation of the HPA axis, elevation in pro‐inflammatory cytokines, decrease in intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It is unknown whether epigenetic regulatory pathways play a role in chronic stress–induced intestinal barrier dysfunction and visceral hyperalgesia. Methods: Young adult male rats were subjected to water avoidance stress ± H3K9 methylation inhibitors or siRNAs. Visceral pain response was assessed. Differentiated Caco‐2/BBE cells and human colonoids were treated with cortisol or IL‐6 ± antagonists. Expression of TJ, IL‐6, and H3K9 methylation status at gene promoters was measured. Transepithelial electrical resistance and FITC‐dextran permeability were evaluated. Key Results: Chronic stress induced IL‐6 up‐regulation prior to a decrease in TJ proteins in the rat colon. The IL‐6 level inversely correlated with occludin expression. Treatment with IL‐6 decreased occludin and induced visceral hyperalgesia. Chronic stress and IL‐6 increased H3K9 methylation and decreased transcriptional GR binding to the occludin gene promoter, leading to down‐regulation of protein expression and increase in paracellular permeability. Intrarectal administration of a H3K9 methylation antagonist prevented chronic stress–induced visceral hyperalgesia in the rat. In a human colonoid model, cortisol decreased occludin expression, which was prevented by the GR antagonist RU486, and IL‐6 increased H3K9 methylation and decreased TJ protein levels, which were prevented by inhibitors of H3K9 methylation. Conclusions & Inferences: Our findings support a novel role for methylation of the repressive histone H3K9 to regulate chronic stress, pro‐inflammatory cytokine–mediated reduction in colon TJ protein levels, and increase in paracellular permeability and visceral hyperalgesia. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is closely associated with the occurrence and development of gastric diseases. Therefore, eliminating H. pylori infection should help to prevent gastric diseases. Vitamin D3 (VitD3, 1,25(OH)2D3) was previously observed to exhibit anti- H. pylori infection activity in clinic, but these results were reported in heterogeneous in vivo studies without elucidation of the underlying mechanisms. In the present study, we established H. pylori infection models in both wild-type and VDR knockdown (VDR-KD) mice, which were used to demonstrate that VitD3 inhibits H. pylori infection by enhancing the expression of VitD receptor (VDR) and cathelicidin antimicrobial peptide (CAMP). Furthermore, VDR-KD mice that exhibited lower VDR expression were more susceptible to H. pylori infection. In cultured mouse primary gastric epithelial cells, we further demonstrated that the VitD3/VDR complex binds to the CAMP promoter region to increase its expression. These data provide a mechanistic explanation of the anti- H. pylori infection activity of VitD3 at the molecular level in mice and suggest a new avenue for the clinical management of H. pylori eradication therapy. [ABSTRACT FROM AUTHOR]

Previously, abnormal extracellular vesicle (EV) sorting of miR-193a was identified in colorectal cancer (CRC) progression. Although a reduced level of miR-193a-5p in plasma/serum has been reported in many different types of cancer, the EV-derived miR-193a-5p level in CRC and its potential application as a minimally invasive biomarker are still unknown. Here, we evaluated the circulating EV-derived miR-193a-5p expression levels in a cohort of 101 participants by real-time quantitative polymerase chain reaction (RT-qPCR). We found that plasma EV-miR-193a-5p decreased significantly in CRC patients as compared with precancerous colorectal adenoma (CA) and non-cancerous control (NC) individuals. The circulating EV-miR-193a-5p showed an area under the receiver operating characteristic curve (AUC) of 0.740 in distinguishing CRC from CA and an AUC of 0.759 in distinguishing CRC from NC. Furthermore, the suppression on CRC cells of miR-193a-5p was verified by transwell, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium), EdU, RT-qPCR, and western blotting. Bioinformatic analysis predicted 32 genes, which were the most likely miR-193a-5p targeted and mainly focused on tumor progression. Among them, we revealed that miR-193a-5p could inhibit CRC migration and invasion via targeting tumor-associated genes like CUT-like homeobox 1 (CUX1) and intersectin 1 (ITSN1). In conclusion, miR-193a-5p could suppress CRC development, and decreased plasma EV-miR-193a-5p could be a promising biomarker for human CRC detection. [ABSTRACT FROM AUTHOR]

Background. Bismuth-containing quadruple therapy achieves higher eradication rate of Helicobacter pylori. High level of bismuth in blood may result in damage of many organs. Wei Bi Mei is a new bismuth-containing drug combining chemicals and Chinese medicine portions. The present research is to study the pharmacokinetics of bismuth to evaluate the safety and rational use of Wei Bi Mei granules. Material and Methods. Seven healthy Chinese adult subjects were enrolled in this research, which included a single-dose study and a multiple-dose study. Wei Bi Mei granules were administered orally to the subjects at corresponding time. Blood and urine were collected. All samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Results. For single-dose Wei Bi Mei granules administration, the mean time to peak concentration (tmax) of bismuth was 2.29 ± 0.76 h, and the mean peak concentration (Cmax) of bismuth was 0.85 ± 0.55 ng/mL. For multiple-dose Wei Bi Mei granules administration, the Cmax was 2.25 ± 1.18 ng/mL at day two, and the volume of distribution (Vd) was (22.97 ± 9.82) × 103 L. The urinary excretion of bismuth was the fastest during the first two days, with a mean excretion rate of 3.84 ± 1.23 ng/h. The bismuth concentration in urine was significantly reduced at day 16. Conclusion. Bismuth has a washout period of approximately two months. The concentration of bismuth in blood was far less than the "safe level." Thus, Wei Bi Mei is a highly safe therapeutic medicine, with a good clinical application value. Wei Bi Mei should be recommended more widely for use in bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection. [ABSTRACT FROM AUTHOR]

Background: Circulating small extracellular vesicles (sEVs) and its associated proteins are of great interest in the early detection of many diseases. However, there is no gold standard for plasma sEVs isolation, especially for proteomic profiling which could be largely affected by contamination such as lipoproteins and plasma proteins. Previous studies suggested combinations of different sEVs isolation methods could improve the yield and purity of the isolated fractions. Nevertheless, there is no systematic evaluation of size-exclusion chromatography (SEC), ultracentrifugation (UC), and their combination in a proteomic perspective. Results: Plasma samples were collected from healthy individuals, and sEVs were separated by one-step SEC, one-step UC, and combining SEC with UC, respectively. Here we exhibited that the purity of sEVs was improved by SEC in contrast to traditional UC. Furthermore, by conducting a SEC procedure followed by UC, we separated sEVs with the highest purity. In the proteomic analysis, 992 protein species were identified in the plasma sEVs isolated by our novel separation method, of which several proteins are sEVs-associated proteins but hitherto never been identified in the previous studies and database, much more than plasma sEVs isolated by UC (453) or SEC (682) alone. As compared to Vesiclepedia and Exocarta databases, plasma sEVs isolated by the new procedure kept 584 previously identified sEVs-associated proteins and 360 other proteins that have not been detected before. Detailed analysis suggested that more kinds of sEVs biomarkers, such as CD9, ALIX, and FLOT1, could be identified in plasma sEVs isolated by the novel isolation method as compared to one-step UC/SEC. Furthermore, the lower abundance ranks of common contaminants, such as lipoproteins and IgG chains, in the sEVs fractions obtained by our new method as compared to one-step UC/SEC also demonstrated the purity of sEVs had been improved. Conclusions: Combining SEC with UC could significantly improve the performance of mass spectrometry-based proteomic profiling in analyzing plasma-derived sEVs. [ABSTRACT FROM AUTHOR]

Tumors are surrounded by complex environmental components, including blood and lymph vessels, fibroblasts, endothelial cells, immune cells, cytokines, extracellular vesicles, and extracellular matrix. All the stromal components together with the tumor cells form the tumor microenvironment (TME). In addition, extracellular physical and chemical factors, including extracellular pH, hypoxia, elevated interstitial fluid pressure, and fibrosis, are closely associated with tumor progression, metastasis, immunosuppression, and drug resistance. Cellular and extracellular components in TME contribute to nearly all procedures of carcinogenesis. By summarizing the recent work in this field, we make a comprehensive review on the role of cellular and extracellular components in the process of carcinogenesis and their potential application in early diagnosis of cancer. We hope that a systematic review of the diverse aspects of TME will help both research scientists and clinicians in this field. [ABSTRACT FROM AUTHOR]

Early diagnosis of colon cancer (CC) is clinically important, as it can significantly improve patients' survival rate and quality of life. Although the potential role for small extracellular vesicles (sEVs) in early detection of many diseases has been repeatedly mentioned, systematic screening of plasma sEVs derived early CC specific biomarkers has not yet been reported. In this work, plasma sEVs enriched fractions were derived from 15 early-stage (TisN0M0) CC patients and 10 normal controls (NC). RNA sequencing identified a total number of 95 sEVs enriched fraction derived miRNAs with differential expression between CC and NC, most of which (60/95) was in well accordance with tissue results in the Cancer Genome Atlas (TCGA) dataset. Among those miRNAs, we selected let-7b-3p, miR-139-3p, miR-145-3p, and miR-150-3p for further validation in an independent cohort consisting of 134 participants (58 CC and 76 NC). In the validation cohort, the AUC of 4 individual miRNAs ranged from 0.680 to 0.792. A logistic model combining two miRNAs (i.e. let-7b-3p and miR-145-3p) achieved an AUC of 0.901. Adding the 3rd miRNA into this model can further increase the AUC to 0.927. Side by side comparison revealed that sEVs miRNA profile outperformed cell-free plasma miRNA in the diagnosis of early CC. In conclusion, we suggested that circulating sEVs enriched fractions have a distinct miRNA profile in CC patients, and sEVs derived miRNA could be used as a promising biomarker to detect CC at an early stage. [ABSTRACT FROM AUTHOR]

Introduction. Circulation microRNAs (miRNAs) perform as potential diagnostic biomarkers of many kinds of cancers. This study is aimed at identifying circulation miRNAs as diagnostic biomarkers in colon cancer. Methods. We conducted a weighted gene coexpression network analysis (WGCNA) in miRNAs to find out the expression pattern among circulation miRNAs by using a "WGCNA" package in R. Correlation analysis was performed to find cancer-related modules. Differentially expressed miRNAs (DEmiRs) in colon cancer were identified by a "limma" package in R. Hub gene analysis was conducted for these DEmiRs in the cancer-related modules by the "closeness" method in cytoscape software. Then, logistic regression was performed to identify the independent risk factors, and a scoring system was constructed based on these independent risk factors. Then, we use data from the GEO database to confirm the reliability of this scoring system. Results. A total of 9 independent coexpression modules were constructed based on the expression levels of 848 miRNAs by WGCNA. After correlation analysis, green (cor=0.77, p=3×10‐25) and yellow (cor=0.65, p=6×10‐16) modules were strongly correlated with cancer development. 20 hub genes were found after hub gene analysis in these DEmiRs by cytoscape. Among all these hub genes, hsa-miR-23a-3p (OR=2.6391, p=6.23×10‐5) and hsa-miR-663a (OR=1.4220, p=0.0069) were identified as an independent risk factor of colon cancer by multivariate regression. Furthermore, a scoring system was built to predict the probability of colon cancer based on both of these miRNAs, the area under the curve (AUC) of which was 0.828. Data from GSE106817 and GSE112264 was used to confirm this scoring system. And the AUC of them was 0.980 and 0.917, respectively. Conclusion. We built a scoring system based on circulation hub miRNAs found by WGCNA to predict the development of colon cancer. [ABSTRACT FROM AUTHOR]

Background: Only a paucity of large-scale perspective and cross-sectional studies on H. pylori infection in China have been published. The purpose of this study was to investigate the prevalence and risk factors for H. pylori infection among residents of Jidong community located in Hebei Province of China.Methods: A perspective, cross-sectional study was conducted in Jidong community. Questionnaires and 13C-urea breath test were performed, and 10-ml blood samples were obtained for laboratory tests.Results: Four thousand seven hundred ninety-six subjects were enrolled in this study, and 2506 (52.25%) were H. pylori positive. There was no difference in prevalence between both sexes (P = 0.5974). Age (P = 0.004) and education level (P = 0.0128) were significantly associated with H. pylori infection, and there were statistical trends in the prevalence across five age subgroups (χ2 test for trend = 23.5; P < 0.001) and education levels (χ2 test for trend = 19.50; P < 0.001). H. pylori infection was also associated with marital status (P = 0.0243), source of drinking water (P = 0.0433), frequency of eating raw garlic (P = 0.0310), alcohol drinking (P = 0.0207), knowledge about H. pylori transmission route (P = 0.0125) and related diseases (P = 0.0257). Age, alcohol drinking and knowledge about transmission route were found to be independent predictors of H. pylori infection.Conclusions: More than half of the population was infected with H. pylori in Jidong community. The socio-demographic profiles, socio-economic factors and lifestyle are worthy taking into consideration to prevent diseases associated with H. pylori infection. Understanding the prevalence and risk patterns for H. pylori infection in China will help in prioritizing public health efforts to better manage the H. pylori infection. [ABSTRACT FROM AUTHOR]

References 1 Zhou H, Wang J, Zhu P. NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2 . 2018; 113: 23. 1:CAS:528:DC%2BC1cXptlylsb4%3D. 10.1007/s00395-018-0682-1. 29744594 2 Zhang X, Li F, Cui Y. Mst1 overexpression combined with yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway. [Extracted from the article]

Background and Aims: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. However, the underlying mechanism of IBS is not fully understood. The aim of this study was to investigate potential mechanism and novel biomarkers of IBS through evaluation of the metabolomic and microbiologic profile. Methods: Fecal samples were collected from 15 irritable bowel syndrome patients and 15 healthy controls. By using gas chromatography coupled to time-of-flight mass spectrometry (GC-TOFMS) and 16S rDNA amplicon sequencing, fecal metabolites and microbiota of healthy controls and the IBS patients were measured. Results: IBS patients had a significantly differential metabolite profile as compared to healthy controls, and 4 clusters with 31 metabolites, including a group of amino acids and fatty acids, were significantly up-regulated as compared to the healthy controls. In addition, 19 microbes were significantly up-regulated, and 12 microbes were down-regulated in the IBS group, when compared with the healthy controls. Some clusters of fecal metabolites or microorganisms were significantly correlated with the severity of IBS symptoms, such as the frequency of abdominal pain/discomfort and the number of bowel movements. Correlation of the metabolite levels with abundances of microbial genera showed some statistically significant metabolite-microbe associations. Four differentially abundant amino acids clustered together were positively correlated with some microbes, including Lachnospira, Clostridium , and so on. Conclusion: The finding of this study puts a global perspective on metabolomics and microbiota profiling in IBS patients and provides a theoretical basis for future research on pathophysiology of IBS. [ABSTRACT FROM AUTHOR]

Background and aims: The aim of this study was to compare and analyze the feasibility and safety of two methods of endoscopic full-thickness resection (EFTR) for the management of challenging epithelial and subepithelial neoplasms that are not amenable to resection techniques. Material and methods: This was a retrospective case series study of patients who underwent one of two methods of EFTR, resection using ESD knives and post-resection closure with OTSC (Group 1), or closure with OTSC and secondary EFTR with snare (Group 2). Results: Of 11 patients, six were in Group 1 and five in Group 2. The mean time of the EFTR procedure was 76.83 ± 34.97 min in Group 1 which is significantly longer than that of Group 2 (p =.0128). The mean time of OSTC closure and length of hospital stay of Group 1 were also longer compared to Group 2, but the difference was not significant. Complete resection (R0) and technical success rates of Group 1 and Group 2 were 83.3% and 100% (p =.338), respectively. VAS scores of Group 1 immediately after the operation and after 24 h are significantly higher than those of Group 2 (p =.047 and p =.009, respectively). In Group 1, one patient had delayed perforation which led to fever and pneumoperitoneum, and one patient developed abdominal pain. No complications associated with the endoscopic procedure were observed in Group 2. Conclusion: EFTR of pre-resection closure are potentially faster compared with the concept of applying closure after EFTR. Larger prospective controlled studies comparing these two techniques are warranted in the future. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common gastrointestinal dysfunctional disease. The pathophysiology of IBS is, however, largely unknown. This study aimed to determine whether evaluation of fecal metabolite and microbiota profiles may offer an opportunity to identify a novel pathophysiological target for IBS, and to reveal possible gut microbe–metabolite associations. By using gas chromatography coupled to time-of-flight mass spectrometry (GC-TOFMS) and 16S rRNA gene sequencing, we measured fecal metabolites and microbiota of the control and water avoidance stress (WAS)-induced IBS rats. We found a significantly differential metabolite profile between the IBS and control groups; a cluster of metabolites was also found to be significantly associated with the amount of defecations. Moreover, the WAS group exhibited a decreased alpha diversity of the microbial population as compared to the control group. However, the characteristics of gut microbiota could not differentiate the IBS group from the control group. Correlation of the metabolite level with the number of microbial genera showed no significant association between the control and IBS groups. This study provides a global perspective on metabolomics and microbiota profiling in WAS-induced IBS model and a theoretical basis for research on the pathophysiology of IBS. [ABSTRACT FROM AUTHOR]

In recent years, microRNA-193b (miR-193b) is regarded as a tumor suppressor in the development and progression of various cancers. Several studies have indicated that KRAS could be regulated by miR-193b in pancreatic cancer cells. However, the function of miR-193b in human esophageal squamous cell carcinoma has not been explored intensively thus far. Herein, the relationship between miR-193b and KRAS was mainly explored in esophageal squamous cell carcinoma cells. In the present study, the expression levels of miR-193b and KRAS were assessed in both human esophageal cancer cells and tissues. The direct regulatory relationship between miR-193b and KRAS was evaluated using dual-luciferase assay. The effect of miR-193b overexpression and inhibitor on cell proliferation, migration/invasion, and apoptosis was further detected herein. Our results indicated that the expression of miR-193b was significantly lower in human esophageal cancer tissues than paracancerous tissues. The expression level of miR-193b/KRAS was stage-dependent in human esophageal cancers. KRAS was indicated as the direct target of miR-193b, and upregulation of miR-193b increased the percentage of cell apoptosis, and suppressed cell proliferation as well as cell migration/invasion via direct regulation of KRAS. Therefore, our study indicated that miR-193b plays an important role in the development and progression of human esophageal squamous cell carcinoma, which may become a novel target in the treatment of human esophageal squamous cell carcinoma in the future. [ABSTRACT FROM AUTHOR]

Background: Endoscopy is the main approach used for esophageal squamous cell carcinoma (ESCC) screening, especially in high-risk areas. However, little consensus has been achieved in recent ESCC screening programs, and endoscopists have selected patients only by age and family history. Patients and methods: To generate a proper strategy for selecting an eligible population for endoscopic screening based on demographic factors, lifestyle, and eating habits, a total of 7,830 residents in an area with a high risk of ESCC were recruited for this study. All participants underwent endoscopic examinations that were conducted by experienced endoscopists. Risk factors for ESCC and other lesions were selected by univariate and multivariate logistic regressions. A nomogram for the prediction of ESCC and premalignant lesions was constructed, which included information on age, sex, occupation, labor intensity, income, and mining exposure. Receiver operating characteristic (ROC) curve analysis was performed to present the predictive accuracy of the nomograms. Results: The area under the curve (95% CI) was 0.749 (0.711–0.788) for this nomogram. By applying this nomogram, we could exclude 60% (4704/7830) of patients before endoscopy screening and detect all ESCC cases as well as most esophageal lesions in the remaining population. Conclusion: In conclusion, we provided a ready-to-use preclinical tool with the potential to select eligible people with high risk of ESCC for endoscopy screening. [ABSTRACT FROM AUTHOR]

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders. [ABSTRACT FROM AUTHOR]

Background: Biomarkers for esophageal squamous cell carcinoma (ESCC) identification with high sensitivity are not well established. Since abnormal expression of cadherins has been widely reported in cancer, we explored its feasibility as an ESCC biomarker. Methods: Expression of E-cadherin and N-cadherin were detected in 150 esophageal tissues by immunohistochemistry. Staining strength and percentage in different subcellular structures of each specimen were evaluated by 2 independent pathologists. A logistic regression-based classifier derived from E-cadherin and N-cadherin staining was generated. Results: E-cadherin exhibited decreased membrane expression in ESCC, while N-cadherin exhibited decreased expression in the nucleus but elevated expression in the cytoplasm. Both E-cadherin and N-cadherin could distinguish ESCC tissues from non-cancerous tissues (area under the curve (AUC) = 0.748, 0.801, respectively). E-cadherin and N-cadherin staining scores could be merged into a cadherin (CDH) logistic index, which showed better discrimination (AUC = 0.909) than E-cadherin or N-cadherin alone. Further investigation indicated that the CDH logistic index was significantly correlated with tumor size and differentiation in ESCC. Conclusion: Both E-cadherin and N-cadherin had a strong expression shift in ESCC compared with non-cancerous tissues. The CDH logistic index, a parameter integrating the expression data of both cadherins, could be used as a marker with high sensitivity and specificity in the identification of ESCC. [ABSTRACT FROM AUTHOR]

Abstract: The incidence and mortality of colorectal carcinoma are rising in young adults. This population‐based propensity matching study aimed to compare long‐term oncological outcomes of local excision with radical resection for early localized colorectal cancer (CRC) in young patients without preoperative chemoradiotherapy. Patients under 45 years old with T1 colon or rectal adenocarcinoma who underwent local excision or radical resection were included from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2014. Survival curves were plotted using the Kaplan–Meier method. Cancer‐specific survival (CSS) was compared using adjusted hazard ratios (HRs) between local excision and radical resection. After propensity score matching procedure, total of 1719 patients were included in the analysis, among which 573 treated with local excision and 1146 treated with radical resection. The median follow‐up was 80 months (interquartile range(IQR): 37–132), with 1074 patients followed for ≥5 years and 508 patients followed for ≥10 years. Five‐year CSS of local excision versus radical resection was 93.4% versus 96.7% for colon cancer and 96.6% versus 98.4% for rectal cancer. Ten‐year CSS of local excision versus radical resection was 91.4% versus 94.0% for colon cancer and 92.8% versus 96.7% for rectal cancer. On multivariable analysis, compared with radical resection, local excision was not associated with inferior CSS for colon (HR 1.74, 95% CI: 0.92–3.29, P = 0.090) and rectal cancer (HR 2.16, 95% CI: 0.99–4.71, P = 0.052). There is no evidence of differential long‐term oncological outcomes between local excision and radical resection. These findings supported clinical application of local excision for early colon and rectal cancer in young adults. [ABSTRACT FROM AUTHOR]