Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling.

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case-control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

Fabrication of Flexible Pyramid Array as SERS Substrate for Direct Sampling and Reproducible Detection.

Rapid extraction and analysis of target molecules from irregular surfaces are in high demand in the field of on-site analysis. Herein, a flexible platform used for surface-enhanced Raman scattering (SERS) based on an ordered polymer pyramid structure with half-imbedded silver nanoparticles (AgNPs) was prepared to address this issue. The fabrication includes the following steps: (1) creating inverted pyramid arrays in silicon substrate, (2) preparing a layer of AgNPs on the surface of the inverted pyramids, and (3) obtaining a substrate with an ordered polymer pyramids array with half-imbedded AgNPs by the molding method. This flexible substrate is capable of rapid extraction via a simple and convenient "paste and peel off" method. In addition, the substrate exhibits great repeatability and good sensitivity thanks to the uniformity and larger surface area of the ordered pyramids. The density of "hot spots" (local electromagnetic field with high intensity) is increased on the structured surface. Semi-imbedding silver particles in the polymer pyramids makes "hot spots" robust on the substrate. In addition, the preprepared silicon template with the inverted pyramids can be reused, which greatly reduces the production cost. With this substrate, we successfully analyzed thiram molecules on the epidermis of apples, cucumbers, and oranges, and the detection limits are 2.4, 3, and 3 ng/cm2, respectively. These results demonstrate the great potential of the substrate for in situ analysis, which can provide reference for the design of ideal SERS substrates.

ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma.

BACKGROUND: Immunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown. METHODS: The relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues. RESULTS: ISG15 promotes the infiltration of CD4+ T lymphocytes. In vivo and in vitro experiments demonstrated that ISG15 induces CD4+ T cell proliferation and invalidity and immune responses against tumors. Mechanistically, we demonstrated that the ubiquitination-like modifying effect of ISG15 on PD-L1 increased the modification of K48-linked ubiquitin chains thus increasing the degradation rate of glycosylated PD-L1 targeting proteasomal pathway. The expression of ISG15 and PD-L1 was negatively correlated in NSCLC tissues. In addition, reduced accumulation of PD-L1 by ISG15 in mice also increased splenic lymphocyte infiltration as well as promoted cytotoxic T cell infiltration in the tumor microenvironment, thereby enhancing anti-tumor immunity. CONCLUSIONS: The ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy.

Exploring the molecular characteristics of the malignant potential of gastric adenocarcinoma with enteroblastic differentiation.

AIMS: Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subset of alpha-fetoprotein (AFP)-producing carcinomas with poor prognosis. However, the molecular features associated with the malignant potential of GEAD remain partially elucidated. METHODS AND RESULTS: In this study, the relationship between clinicopathological parameters and aggressive biological behaviour was analysed in 37 patients with GAED. The results showed that GAED tended to infiltrate the deep layer of the gastric wall and possessed more frequent vascular invasion than conventional gastric adenocarcinoma (CGA) (P < 0.001). All distant metastases were observed in the GAED group, not the CGA group (P < 0.001). High HER2 expression was found in nearly 24.32% of the informative cases, and none showed EBV-encoded RNA positivity or deficient mismatch repair. The most frequently mutated gene in GAED was p53. Programmed cell death-ligand 1 (PD-L1) immunostaining revealed 13 patients with a combined positive score (CPS) ≥ 5 (65%, 13 of 20). Thus, based on these molecular markers (immunostaining, in situ hybridisation and mutation analysis), GAED may be classified as a unique subgroup of the chromosomal instability subtype with HER2+ /EBV- /MSS/TP53+ /PD-L1+ . Next-generation sequencing analyses showed that mutations in the TOPI, ELOA and NOTCH3 genes were found only in GAED, and abnormally expressed genes in GAED were significantly enriched in hepatocellular carcinoma-, gland development-, and gastric cancer-related pathways. CONCLUSION: The HER2+ /EBV- /MSS/TP53+ /PD-L1+ profile and hepatocellular carcinoma-related pathways may be significant in the malignant potential of GAED. In addition to anti-HER2 therapy, immune check-point inhibitors may be an effective treatment option for patients with GAED.

Risk of lymph node metastasis and feasibility of endoscopic submucosal dissection in undifferentiated-type early gastric cancer.

BACKGROUND: Whether endoscopic submucosal dissection (ESD) applies to undifferentiated-type early gastric cancer (UEGC) remains controversial. We aimed to analyze the risk factors for lymph node metastasis (LNM) in UEGC and evaluate the feasibility of ESD. METHODS: This study included 346 patients with UEGC who underwent curative gastrectomy between January 2014 and December 2021. Univariate and multivariate analyses of the correlation between clinicopathological features and LNM were conducted, and the risk factors for exceeding the expanded ESD indications were evaluated. RESULTS: The overall LNM rate in UEGC was 19.94%. Among the preoperatively assessable factors, submucosal invasion (odds ratio [OR] = 4.77, 95% confidence interval [CI]: 2.14-10.66) and > 2 cm(OR = 2.49, 95% CI: 1.20-5.15) were independent risk factors for LNM, while postoperative independent risk factors were > 2 cm (OR = 3.35, 95% CI: 1.02-5.40) and lymphovascular invasion(OR = 13.21, 95% CI: 5.18-33.70). Patients who met the expanded indications had a low LNM risk (4.1%). Additionally, tumors located in the cardia (P = 0.03), non-elevated type (P < 0.01) were independent risk factors for exceeding the expanded indications in UEGC. CONCLUSIONS: ESD may be applicable for UEGC meeting the expanded indications, and preoperative evaluation should be cautious when the lesion is non-elevated type or located in the cardia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (12/05/2022 ChiCTR2200059841 ).

Comparison of different risk stratifications for gastric cancer and establishing a simplified risk-scoring model based on the Kyoto classification.

BACKGROUND AND AIM: The study aims to assess the value of different risk stratifications in diagnosing early gastric cancer (GC) and explore risk factors based on Kyoto gastritis classification. METHODS: This study was a single-centered cross-sectional study; all epidemiological data and endoscopic findings were obtained prospectively. To evaluate the proportion of GC in each risk stratification and to compare the diagnostic performance of different methods using the receiver operating characteristic curve, univariable and multivariable analyses were used to explore the correlation between endoscopic findings and GC. RESULTS: A total of 240 subjects were enrolled, and the diagnostic efficacy of the Kyoto Classification Score was similar to Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, and the accuracy was higher than that of the Japanese scoring system and OLGA stage. Moderate atrophy (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.52-8.16), severe atrophy (OR = 4.96, 95% CI: 1.75-14.04), map-like redness (OR = 9.89, 95% CI: 1.16-84.15), and xanthelasma (OR = 3.57, 95% CI: 1.15-11.15) were independent risk factors for GC. The simplified Kyoto classification (area under the receiver operating characteristic [AUROC] = 0.76, P = 0.58) based on multivariable analysis demonstrated favorable diagnostic value compared with traditional Kyoto classification score (AUROC = 0.74). CONCLUSIONS: This study confirms the value of the Kyoto classification score and the OLGIM stage in the risk stratification of GC. Simplified Kyoto classification is also promising in risk assessment of GC but still requires validation in the population.

Establishment and validation of a nomogram for predicting new fractures after PKP treatment of for osteoporotic vertebral compression fractures in the elderly individuals.

BACKGROUND: To investigate the risk factors for new vertebral compression fractures (NVCFs) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and to create a nomogram to predict the occurrence of new postoperative fractures. METHODS: This was a retrospective analysis of the clinical data of 529 OVCF patients who received PKP treatment in our hospital from June 2017 to June 2020. Based on whether there were new fractures within 2 years after surgery, the patients were divided into a new fracture group and a nonnew fracture group. Univariate and multivariate analyses were used to determine the risk factors for the occurrence of NVCFs after surgery. The data were randomly divided into a training set (75%) and a testing set (25%). Nomograms predicting the risk of NVCF occurrence were created based on the results of the multivariate analysis, and performance was evaluated using receiver operating characteristic curves (ROCs), calibration curves, and decision curve analyses (DCAs). A web calculator was created to give clinicians a more convenient interactive experience. RESULTS: A total of 56 patients (10.6%) had NVCFs after surgery. The univariate analysis showed significant differences in sex and the incidences of cerebrovascular disease, a positive fracture history, and bone cement intervertebral leakage between the two groups (P < 0.05). The multivariate analysis showed that sex [OR = 2.621, 95% CI (1.030-6.673), P = 0.043], cerebrovascular disease [OR = 28.522, 95% CI (8.749-92.989), P = 0.000], fracture history [OR = 12.298, 95% CI (6.250-24.199), P = 0.000], and bone cement intervertebral leakage [OR = 2.501, 95% CI (1.029-6.082), P = 0.043] were independent risk factors that were positively associated with the occurrence of NVCFs. The AUCs of the model were 0.795 (95% CI: 0.716-0.874) and 0.861 (95% CI: 0.749-0.974) in the training and testing sets, respectively, and the calibration curves showed high agreement between the predicted and actual states. The areas under the decision curve were 0.021 and 0.036, respectively. CONCLUSION: Female sex, cerebrovascular disease, fracture history and bone cement intervertebral leakage are risk factors for NVCF after PKP. Based on this, a highly accurate nomogram was developed, and a webpage calculator ( https://new-fracture.shinyapps.io/DynNomapp/ ) was created.

Constructing 2D Sandwich-like MOF/MXene Heterostructures for Durable and Fast Aqueous Zinc-Ion Batteries.

Two-dimensional metal-organic frameworks (2D MOFs) can be used as the cathodes for high-performance zinc-ion battery due to their large one-dimensional channels. However, the conventionally poor electrical conductivity and low structural stability hinder their advances. Herein, we report an alternately stacked MOF/MX heterostructure, exhibiting the 2D sandwich-like structure with abundant active sites, improved electrical conductivity and exceptional structural stability. Ex situ characterizations and theoretical calculations reveal a reversible intercalation mechanism of zinc ions and high electrical conductivity in the 2D heterostructure. Electrochemical tests confirm excellent Zn2+ migration kinetics and ideal pseudocapacitive behaviors. As a consequence, Cu-HHTP/MX shows a superior rate performance (260.1 mAh g-1 at 0.1 A g-1 and 173.1 mAh g-1 at 4 A g-1 ) and long-term cycling stability of 92.5 % capacity retention over 1000 cycles at 4 A g-1 .

Enhancing Detection Reproducibility of Surface-Enhanced Raman Scattering by Controlling Analytes under One Laser Spot.

Surface-enhanced Raman scattering (SERS), as a sensitive analytical technique, is expected to be used for quantification of trace analytes. At the current stage, high detection reproducibility should be guaranteed for realizing quantification analysis of trace analytes. The main obstacle to achieving high detection reproducibility is the nonuniform distribution of analyte molecules on substrates, particularly, the "coffee-ring" effect introduced by the flow of solute to the pinning of the contact line. Herein, we report a method to tackle this problem by controlling the location of analytes through tuning the wettability of the SERS substrate. With the combination of silver-assisted chemical etching and photolithography, the ordered Si patterns grafted silver nanoparticles with tunable wettability were integrated into a SERS substrate. With this substrate, high detection reproducibility was achieved by confining all the analyte molecules on the area of active plasmonic hot-spots within one laser, and the quantitative analysis was realized with ultrahigh sensitivity. Furthermore, the substrate is applicable for high-throughput detection.

Rapid and visual detection of Staphylococcus aureus in milk using a recombinase polymerase amplification-lateral flow assay combined with immunomagnetic separation.

AIMS: The aim of this study was to develop a novel approach using lateral flow recombinase polymerase amplification (RPA-LF) combined with immunomagnetic separation (IMS) for the rapid detection of Staphylococcus aureus in milk. METHODS AND RESULTS: Under optimum conditions, the average capture efficiency values for S. aureus strains (104 colony-forming units [CFU] per ml) was above 95.0% in PBST and ~80% in milk within 45 min with 0.7 mg immunomagnetic beads. The RPA-LF assay, which comprised DNA amplification via RPA at 39°C for 10 min and visualization of the amplicons through LF strips for 5 min, detected S. aureus within 15 min. The method only detected S. aureus and did not show cross-reaction with other bacteria, exhibiting a high level of specificity. Sensitivity experiments confirmed a detection limit of RPA-LF assay as low as 600 fg per reaction for the S. aureus genome (corresponding to approximately 36 CFU of S. aureus), which was about 16.7-fold more sensitive than that of the conventional polymerase chain reaction method. When RPA-LF was used in combination with IMS to detect S. aureus inoculated into artificially contaminated milk, it exhibited a detection limit of approximately 40 CFU per reaction. CONCLUSIONS: The newly developed IMS-RPA-LF method enabled detection of S. aureus at levels as low as 40 CFU per reaction in milk samples without culture enrichment for an overall testing time of only 70 min. SIGNIFICANCE AND IMPACT OF THE STUDY: The newly developed IMS-lateral flow RPA-LF assay effectively combines sample preparation, amplification and detection into a single platform. Because of its high sensitivity, specificity and speed, the IMS-RPA-LF assay will have important implications for the rapid detection of S. aureus in contaminated food.

Designed, synthesized and biological evaluation of proteolysis targeting chimeras (PROTACs) as AR degraders for prostate cancer treatment.

As a continuation of our research on developing potent and potentially safe androgen receptor (AR) degrader, a series of novel proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were designed, synthesized and evaluated for their AR degradation activity against LNCaP (AR+) cell line. Most of the synthesized compounds displayed moderate to satisfactory AR binding affinity and might lead to antagonist activity against AR. Among them, compound A16 exhibited the best AR binding affinity (85%) and degradation activity against AR. Due to the strong fluorescence properties of pomalidomide derivatives, B10 was found to be effectively internalized and visualized in LNCaP (AR + ) cells than PC-3 (AR-) cells. Moreover, the molecular docking of A16 with AR and the active site of DDB1-CRBN E3 ubiquitin ligase complex provides guidance to design new PROTAC degrons targeting AR for prostate cancer therapy. These results represent a step toward the development of novel and improved AR PROTACs.

Linked Color Imaging Can Improve Detection Rate of Early Gastric Cancer in a High-Risk Population: A Multi-Center Randomized Controlled Clinical Trial.

BACKGROUND: Early diagnosis of gastric cancer is difficult in China due to the lack of a valid method for endoscopic screening. Early gastric cancer, especially flat gastric cancer, lacks specific endoscopic features. Many cases appear to be similar to ordinary gastritis cases under normal white light endoscopy, which can lead to misdiagnosis. AIMS: In order to find a new method to improve detection rate of early gastric cancer in China, we designed a trial to validate linked color imaging (LCI) for screening of early gastric cancer in a high-risk population, as compared to white light imaging (WLI). METHOD: Subjects were randomly allocated to either the LCI + WLI or WLI group and then subjected to gastroscopy and all endoscopies were made after special preparation. All endoscopists had knowledge of this experiment. The main indicator was the rate of detection of gastric neoplastic lesions. The difference in the detection rate between the two groups is reported. RESULTS: The detection rate was 4.31% in the WLI group and 8.01% in the LCI + WLI group. This is a difference of 3.70% with a P value < 0.001 and an OR (95% CI) of 1.934 (1.362, 2.746). The lower limit of the 95% CI was greater than 0, and the superiority margin was 1%. CONCLUSION: The detection rate of gastric neoplastic lesions was higher in the LCI + WLI group than in the WLI group, LCI might be an effective method for screening early gastric cancer.

ATP6L promotes metastasis of colorectal cancer by inducing epithelial-mesenchymal transition.

ATP6L, the C subunit of the V-ATPase V0 domain, is involved in regulating the acidic tumor micro-environment and may promote tumor progression. However, the expression and functional role of ATP6L in tumors have not yet been well explored. In this study, we found that ATP6L protein overexpression was related to colorectal cancer histological differentiation (P < 0.001), presence of metastasis (P < 0.001) and recurrence (P = 0.02). ATP6L expression in the liver metastatic foci was higher than in the primary foci (P = 0.04). ATP6L expression was notably concomitant with epithelial-mesenchymal transition (EMT) immunohistochemical features, such as reduced expression of the epithelial marker E-cadherin (P = 0.021) and increased expression of the mesenchymal marker vimentin (P = 0.004). Results of in vitro and in vivo experiments showed that ATP6L expression could alter cell morphology, regulate EMT-associated protein expression, and enhance migration and invasion. The effect of ATP6L on metastasis was further demonstrated in a tail vein injection mice model. In addition, the mouse xenograft model showed that ATP6L-overexpressing HCT116 cells grew into larger tumor masses, showed less necrosis and formed more micro-vessels than the control cells. Taken together, our results suggest that ATP6L promotes metastasis of colorectal cancer by inducing EMT and angiogenesis, and is a potential target for tumor therapy.

Assessment of comorbidities and prognosis in patients with COPD diagnosed with the fixed ratio and the lower limit of normal: a systematic review and meta-analysis.

BACKGROUND: Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) is not uniform, COPD guidelines recommend fixed ratio (FR), whereas ATS and ERS define airflow obstruction based on lower limit of normal (LLN). We aim to determine if there is difference between the two diagnostic criteria for morbidity, mortality, exacerbation. METHODS: Four databases and all relevant studies from the references were searched from inception to June 25, 2019, to find studies that described the rate of comorbidity, the exacerbation rates, mortality in COPD patients. Data analysis was performed using STATA/SE 14.0 and followed the standard of Cochrane Collaboration. A sensitivity analysis was performed to find the source of heterogeneity. RESULTS: Thirteen studies and 154,447 participants were finally included in this meta-analysis. The 11 cohort studies and 2 cross-sectional studies were all high-quality. Patients with airflow limitation according to either FR or LLN had higher mortality (HRFR+/LLN- = 1.27, 95% CI = 1.14-1.42; HRFR-/LLN+ = 1.83, 95% CI = 1.17-2.86) than those who met neither criteria. When compared with the FR-/LLN- criteria, those who met the FR criteria were more likely to exacerbate (HR FR+/LLN- = 1.64, 95% CI = 1.09-2.46; HR FR-/LLN+ = 1.58, 95% CI = 0.70-3.55). The meta-analysis for comorbidities showed no significant difference between patients who met neither criteria and those who met LLN or FR criteria. CONCLUSION: The patients with airflow limitations according to FR were more likely to exacerbate than those with LLN only. Patients that met either FR or LLN were more likely to have higher mortality than FR-/LLN-. There was no difference between the FR+/LLN- and FR-/LLN+ groups for the occurrence of comorbidities.

Plasma adiponectin, visfatin, leptin, and resistin levels and the onset of colonic polyps in patients with prediabetes.

BACKGROUND: Prediabetes is associated with a high risk of colon cancer, and abdominal obesity, which can result in the secretion of several obesity-related adipocytokines, is an independent influencing factor for colonic polyps in prediabetes subjects. However, the correlation between adipocytokine levels and colonic polyps in prediabetes subjects is unclear. This research explores the relationship between plasma adiponectin, visfatin, leptin, and resistin levels and the development of colonic polyps in prediabetes subjects. METHODS: A total of 468 prediabetes subjects who underwent electronic colonoscopy examinations were enrolled in this study; there were 248 cases of colonic polyps and 220 cases without colonic mucosal lesions. Then, colonic polyps patients with prediabetes were subdivided into a single-polyp group, multiple-polyps group, low-risk polyps group, or high-risk polyps group. In addition, 108 subjects with normal glucose tolerance who were frequency matched with prediabetes subjects by sex and age were selected as the control group; 46 control subjects had polyps, and 62 control subjects were polyp-free. Plasma adiponectin, visfatin, leptin, and resistin levels were measured in all the subjects, and the related risk factors of colonic polyps in prediabetes subjects were analysed. RESULTS: Plasma adiponectin levels were significantly lower in the polyps group than in the polyp-free group [normal glucose tolerance (9.8 ± 4.8 vs 13.3 ± 3.9) mg/L, P = 0.013; prediabetes (5.6 ± 3.7 vs 9.2 ± 4.4) mg/L, P = 0.007]. In prediabetes subjects, plasma adiponectin levels were decreased significantly in the multiple polyps group [(4.3 ± 2.6 vs 6.7 ± 3.9) mg/L, P = 0.031] and the high-risk polyps group [(3.7 ± 2.9 vs 7.4 ± 3.5) mg/L, P < 0.001] compared to their control groups. Plasma visfatin levels were higher in the polyps group and the multiple-polyps group than those in their control groups (P = 0.041 and 0.042, respectively), and no significant difference in plasma leptin and resistin levels was observed between these three pairs of groups (all P > 0.05). The multivariate logistic regression analysis showed that lower levels of plasma adiponectin was a risk factor for colonic polyps, multiple colonic polyps, and high-risk colonic polyps in prediabetes subjects. CONCLUSIONS: Plasma adiponectin levels are inversely associated with colonic polyps, multiple colonic polyps, and high-risk colonic polyps in prediabetes subjects. And adiponectin may be involved in the development of colon tumours in prediabetes subjects.

Epithelial Splicing Regulatory Protein 1 Inhibits the Invasion and Metastasis of Lung Adenocarcinoma.

Despite the development of various treatments, metastasis remains a significant problem with lung adenocarcinoma (ADC). The role and mechanism of epithelial splicing regulatory protein 1 (ESRP1), an epithelial-specific RNA binding protein, on promoting the invasion and metastasis of lung ADC remain to be fully elucidated. Immunohistochemical analysis in 125 human lung ADC tissue samples demonstrated that ESRP1 overexpression was inversely related to the presence of metastases, tumor size, and clinical stage of lung ADC. Impaired ESRP1 expression was also found to stimulate the invasion capacity of lung ADC cells both in vitro and in vivo. Functionally, overexpression of the ZEB1 gene decreased ESRP1 expression, and knockdown of the ZEB1 gene caused increased ESRP1 expression. On the basis of a gene array analysis, the expression of ESRP1 was associated with the regulation of the extracellular matrix. The expression of CD44 and fibroblast growth factor receptor, representatives that interact with the extracellular matrix, was studied. The CD44 subtypes promoted lung ADC cell invasion by regulating matrix metalloproteinase 2 expression. In conclusion, ESRP1 inhibits the invasion and metastasis of lung ADC and plays a role in regulating proteins involved in epithelial-to-mesenchymal transition.

The role of the wzy gene in lipopolysaccharide biosynthesis and pathogenesis of avian pathogenic Escherichia coli.

Avian pathogenic Escherichia coli (APEC) causes severe respiratory and systemic diseases in poultry. The wzy gene encodes the O-antigen polymerase (Wzy), which plays an important role in the synthesis of the lipopolysaccharide (LPS) of bacteria. However, the function of the wzy gene in APEC remains unclear. Hence, in this study, a strain harboring a wzy gene mutant (DE17Δwzy) was constructed and the characteristics of this strain were analyzed. The results showed that mutant of wzy changed the phenotype of the LPS and affected serum agglutination of the O-antigen. Decreased motility and biofilm formation was also observed, but the endotoxin titer of the LPS in APEC was not affected. In addition, the wzy mutation significantly decreased the adherence and invasion to DF-1 cells, especially the survival abilities in duck serum and complement. Furthermore, an LD50 assay revealed that the virulence of mutant strain DE17Δwzy was attenuated 132-fold compared with wild-type strain DE17. Moreover, the bacterial load in the blood, liver, spleen, and kidneys of ducks infected with DE17Δwzy was decreased significantly compared with wild-type strain DE17 (p < 0.0001). These results confirmed that the wzy gene is associated with LPS biosynthesis and bacterial pathogenicity in APEC.

Computer-assisted diagnosis of early esophageal squamous cell carcinoma using narrow-band imaging magnifying endoscopy.

BACKGROUND: We developed a computer-assisted diagnosis model to evaluate the feasibility of automated classification of intrapapillary capillary loops (IPCLs) to improve the detection of esophageal squamous cell carcinoma (ESCC). METHODS: We recruited patients who underwent magnifying endoscopy with narrow-band imaging for evaluation of a suspicious esophageal condition. Case images were evaluated to establish a gold standard IPCL classification according to the endoscopic diagnosis and histological findings. A double-labeling fully convolutional network (FCN) was developed for image segmentation. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior > 15 years; mid level 10 - 15 years; junior 5 - 10 years). RESULTS: Of the 1383 lesions in the study, the mean accuracies of IPCL classification were 92.0 %, 82.0 %, and 73.3 %, for the senior, mid level, and junior groups, respectively. The mean diagnostic accuracy of the model was 89.2 % and 93.0 % at the lesion and pixel levels, respectively. The interobserver agreement between the model and the gold standard was substantial (kappa value, 0.719). The accuracy of the model for inflammatory lesions (92.5 %) was superior to that of the mid level (88.1 %) and junior (86.3 %) groups (P < 0.001). For malignant lesions, the accuracy of the model (B1, 87.6 %; B2, 93.9 %) was significantly higher than that of the mid level (B1, 79.1 %; B2, 90.0 %) and junior (B1, 69.2 %; B2, 79.3 %) groups (P < 0.001). CONCLUSIONS: Double-labeling FCN automated IPCL recognition was feasible and could facilitate early detection of ESCC.

Confining analyte droplets on visible Si pillars for improving reproducibility and sensitivity of SALDI-TOF MS.

We present a universal method to efficiently improve reproducibility and sensitivity of surface-assisted laser desorption/ionization time of flight mass spectrometry (SALDI-TOF MS). In this method, the Si pillar array with unique surface wettability is used as substrate for ionizing analyte. The Si pillar is fabricated based on the combination of photolithography and metal-assisted chemical etching, which is of hydrophilic top and hydrophobic bottom and side wall. Based on the surface wettability of the Si pillar, a droplet of an aqueous analyte solution can be confined on the top of the Si pillar. After evaporation of solvent, an analyte deposition spot is formed on the top of Si pillar. The visible size of the Si pillar allows the sample spot to be easily found. Meanwhile, the diameter of the Si pillar is smaller than that of the laser, allowing the observation of all analyte molecules under one laser shot. Therefore, the reproducibility and sensitivity are highly improved with this method, which allows for the quantitative analysis. Furthermore, this method is applicable for different analytes dissolved in water, including amino acids, dye molecules, polypeptides, and polymers. The application of this substrate is demonstrated by analyzing real samples at low concentration. It should be a promising method for sensitive and reproducible detection for SALDI-TOF MS. Graphical abstract ᅟ.

Combination of Scoring Criteria and Whole Exome Sequencing Analysis of Synchronous Endometrial and Ovarian Carcinomas.

OBJECTIVES: The purpose of this study was to distinguish synchronous primary endometrial and ovarian carcinomas from single primary tumor with metastasis by clinical pathologic criteria and whole exome sequencing (WES). MATERIAL AND METHODS: Fifty-two patients with synchronous endometrial and ovarian carcinomas (SEOCs) between 2010 and 2017 were reviewed and subjected to WES. RESULTS: On the basis of the Scully criteria, 11 cases were supposed as synchronous primary endometrial and ovarian carcinomas, 38 cases as single primary tumor with metastasis, and the remaining 3 cases (S50-S52) cannot be defined. Through a quantization scoring analysis, 9 cases that were scored 0-1 point were defined as synchronous primary endometrial and ovarian carcinomas, and 42 cases that were scored 3-8 points were defined as single primary tumor with metastasis. Two of the undefined cases were classified into metastatic disease, and another one that scored 2 points (S52) was subjected to WES. S52 was deemed synchronous primary endometrial and ovarian carcinomas, with few shared somatic mutations and overlapping copy number varieties. The finding of a serous component examined from the uterine endometrium samples further illustrated that the case was synchronous primary endometrial and ovarian carcinomas. CONCLUSION: By scoring criterion, SEOCs were divided into 2 groups: synchronous primary endometrial and ovarian carcinoma group and single primary tumor with metastasis group. The analysis of clonality indicated that the case that scored 2 (S52) can be considered as synchronous primary endometrial and ovarian carcinomas. Scoring criteria of clinical pathology, along with the study of the WES, may further identify the classification of SEOCs.