Oxidation Mechanism and Toxicity Evolution of Linalool, a Typical Indoor Volatile Chemical Product.

Linalool, a high-reactivity volatile chemical product (VCP) commonly found in cleaning products and disinfectants, is increasingly recognized as an emerging contaminant, especially in indoor air. Understanding the gas-phase oxidation mechanism of linalool is crucial for assessing its impact on atmospheric chemistry and human health. Using quantum chemical calculations and computational toxicology simulations, we investigated the atmospheric transformation and toxicity evolution of linalool under low and high NO/HO2· levels, representing indoor and outdoor environments. Our findings reveal that linalool can undergo the novel mechanisms involving concerted peroxy (RO2·) and alkoxy radical (RO·) modulated autoxidation, particularly emphasizing the importance of cyclization reactions indoors. This expands the widely known RO2·-dominated H-shift-driven autoxidation and proposes a generalized autoxidation mechanism that leads to the formation of low-volatility secondary organic aerosol (SOA) precursors. Toxicological analysis shows that over half of transformation products (TPs) exhibited higher carcinogenicity and respiratory toxicity compared to linalool. We also propose time-dependent toxic effects of TPs to assess their long-term toxicity. Our results indicate that the strong indoor emission coupled with slow consumption rates lead to significant health risks under an indoor environment. The results highlight complex indoor air chemistry and health concerns regarding persistent toxic products during indoor cleaning, which involves the use of linalool or other VCPs.

Understanding secondary particles in a regional site of Yangtze River Delta: Insights from mass spectrometric measurement.

Submicron particulate matter (PM1) poses significant risks to health risks and global climate. In this study, secondary organic aerosols (SOA) and inorganic compositions were examined for their physicochemical characteristics and evolution using high-resolution aerosol instruments in Changzhou over one-month period. The results showed that transport accompanied by regional static conditions leaded to the occurrence of heavy pollution. In addition, regional generation and local emissions also leaded to the occurrence of light and moderate pollution during the observation period in Changzhou. Organic aerosols (OA) and nitrate (NO3-) accounted for 45 % and 23 % of PM1, respectively. The increase in PM1 was dominated by the contribution of NO3- and OA. SOA was dominance in OA (63 % with 40 % MO-OOA), which was higher than primary organic aerosols (POA). Besides, photochemical reactions and the high oxidizing nature of the urban atmosphere promoted the production of OA, especially MO-OOA in Changzhou. Our results highlight that secondary particles contribute significantly to PM pollution in Changzhou, underlining the importance of controlling emissions of gaseous precursors, especially under high oxidation conditions.

Proposal for Observing Yang-Lee Criticality in Rydberg Atomic Arrays.

Yang-Lee edge singularities (YLES) are the edges of the partition function zeros of an interacting spin model in the space of complex control parameters. They play an important role in understanding non-Hermitian phase transitions in many-body physics, as well as characterizing the corresponding nonunitary criticality. Even though such partition function zeroes have been measured in dynamical experiments where time acts as the imaginary control field, experimentally demonstrating such YLES criticality with a physical imaginary field has remained elusive due to the difficulty of physically realizing non-Hermitian many-body models. We provide a protocol for observing the YLES by detecting kinked dynamical magnetization responses due to broken PT symmetry, thus enabling the physical probing of nonunitary phase transitions in nonequilibrium settings. In particular, scaling analyses based on our nonunitary time evolution circuit with matrix product states accurately recover the exponents uniquely associated with the corresponding nonunitary CFT. We provide an explicit proposal for observing YLES criticality in Floquet quenched Rydberg atomic arrays with laser-induced loss, which paves the way towards a universal platform for simulating non-Hermitian many-body dynamical phenomena.

Spatial heterogeneity and infection patterns on epidemic transmission disclosed by a combined contact-dependent dynamics and compartmental model.

Epidemics, such as COVID-19, have caused significant harm to human society worldwide. A better understanding of epidemic transmission dynamics can contribute to more efficient prevention and control measures. Compartmental models, which assume homogeneous mixing of the population, have been widely used in the study of epidemic transmission dynamics, while agent-based models rely on a network definition for individuals. In this study, we developed a real-scale contact-dependent dynamic (CDD) model and combined it with the traditional susceptible-exposed-infectious-recovered (SEIR) compartment model. By considering individual random movement and disease spread, our simulations using the CDD-SEIR model reveal that the distribution of agent types in the community exhibits spatial heterogeneity. The estimated basic reproduction number R0 depends on group mobility, increasing logarithmically in strongly heterogeneous cases and saturating in weakly heterogeneous conditions. Notably, R0 is approximately independent of virus virulence when group mobility is low. We also show that transmission through small amounts of long-term contact is possible due to short-term contact patterns. The dependence of R0 on environment and individual movement patterns implies that reduced contact time and vaccination policies can significantly reduce the virus transmission capacity in situations where the virus is highly transmissible (i.e., R0 is relatively large). This work provides new insights into how individual movement patterns affect virus spreading and how to protect people more efficiently.

Secondary organic aerosol formation in China from urban-lifestyle sources: Vehicle exhaust and cooking emission.

An increasing number of people tend to live in cities, where they suffer from serious air pollution from anthropogenic sources. Vehicle exhaust and cooking emission are closely related to daily life of urban residents, and could be defined as "urban-lifestyle sources". The primary emissions of urban-lifestyle sources tend to form abundant secondary organic aerosols (SOA) through complicated atmospheric chemistry processes. The newly formed SOA is a kind of complex mixture and causes considerable health effects with high uncertainty. Most studies focus on formation pathway, mass growth potential and chemical feature of urban-lifestyle SOA under simple laboratory conditions. Few studies have measured the urban-lifestyle SOA in ambient air, let alone verified laboratory findings under complicated atmospheric conditions. In this work, we established a new method that combined laboratory simulation and field observation, which quantified the urban-lifestyle SOA with high time resolution under the real atmospheric condition. The complex SOA was measured and resolved by a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). The multilinear engine model (ME-2) and multilinear correction methods were used to apply laboratory results into ambient SOA apportionment. It was found that the vehicle source dominated the SOA formation during the diurnal photochemical process, and the SOA:POA ratio of vehicle source was about 1.4 times larger than that of cooking source. The vehicle emission may undergo an alcohol/peroxide & carboxylic acid oxidation pathway and form higher oxidized SOA, while the cooking emission may undergo an alcohol/peroxide oxidation pathway and form relatively lower oxidized SOA. The vehicle SOA and cooking SOA contributed 45.6 % and 24.8 % of OA during a local episode in 2021 winter of downtown Beijing. Our findings could not only provide a new way to quantify urban SOA but also demonstrate some laboratory hypotheses, conducing to understand its ambient contributions, chemical features, and environmental effects.

Magnetically Guided Capsule Endoscopy and Magnetic Resonance Enterography in Children With Crohn's Disease: Manifestations and the Value of Assessing Disease Activity.

Objective: To investigate the value of magnetically guided capsule endoscopy (MGCE) and magnetic resonance enterography (MRE) in assessing the activity of pediatric Crohn's disease. Methods: Clinical data from 82 subjects with pediatric Crohn's disease, who underwent MGCE and MRE from October 2018 to March 2021 were analyzed retrospectively. Pairwise comparisons of several indexes, including MaRIA, CECDAI, PCDAI, and SES-CD, were performed by Spearman's rank correlation test and kappa consistency analysis. CECDAI and MaRIA values predicted whether patients were moderately or severely active (PCDAI ≥30) clinically by logistic regression analysis. The area under the receiver operating characteristic curve (AUC) quantified the evaluation value of moderate to severe activity of pediatric CD. Results: In judging the severity of CD in the small intestine, the correlation coefficient between CECDAI and MaRIA was 0.406 (p < 0.05), and the kappa value of the consistency analysis was 0.299 (p < 0.05). MaRIA was weakly correlated with PCDAI (r = 0.254, p < 0.05), and they were weakly consistent in assessing the activity of Crohn's disease (kappa = 0.135, p < 0.05). For predicting clinically moderate to severe activity, the fitted AUC based on CECDAI and MarRIA was 0.917, which was higher than applying a single parameter (CECDAI = 0.725, MarRIA = 0.899, respectively). MaRIA and serum albumin were significantly and negatively correlated (r = -1.064, p < 0.05). The consistency of the detection rate of gastric ulcers by MGCE and gastroscopy was moderate (kappa = 0.586, p < 0.05), and the detection rate of ulcers in the terminal ileum between MGCE and colonoscopy showed high consistency (kappa = 0.609, p < 0.05). Conclusions: MGCE and MRE are valuable, non-invasive methods for evaluating small bowel lesions in children with CD. The combined application of MGCE and MRE can better characterize the disease activity.

Investigation of partition coefficients and fingerprints of atmospheric gas- and particle-phase intermediate volatility and semi-volatile organic compounds using pixel-based approaches.

Ambient gas- and particle-phase intermediate volatility and semi-volatile organic compounds (I/SVOCs) of Beijing were analyzed by a thermal desorption comprehensive two-dimensional gas chromatography quadrupole mass spectrometry (TD-GC × GC-qMS). A pixel-based scheme combing the integration-based approach was applied for partition coefficients estimation and fingerprints identification. Blob-by-blob recognition was firstly utilized to characterize I/SVOCs from the molecular level. 412 blobs in gas-phase and 460 blobs in particle-phase were resolved, covering a total response of 47.5% and 43.5%. A large pool of I/SVOCs was found with a large diversity of chemical classes in both gas- and particle-phase. Acids (8.5%), b-alkanes (5.8%), n-alkanes (C8-C25, 5.3%), and aromatics (4.4%) were dominant in gas-phase while esters (7.0%, including volatile chemical product compounds, VCPs), n-alkanes (C9-C34, 5.7%), acids (4.6%), and siloxanes (3.6%) were abundant in particle-phase. Air pollutants were then evaluated by a two-parameter linear free energy relationship (LFER) model, which could be further implemented in the two-dimensional volatility basis set (2D-VBS) model. Multiway principal component analysis (MPCA) and partial least squares-discriminant analysis (PLS-DA) implied that naphthalenes, phenol, propyl-benzene isomers, and oxygenated volatile organic compounds (OVOCs) were key components in the gas-phase under different pollution levels. This work gives more insight into property estimation and fingerprints identification for complex ambient samples.

The Application of Magnetic-Controlled Capsule Gastroscopy in Patients Refusing C-EGD: A Single-Center 5-Year Observational Study.

BACKGROUND AND AIMS: Screening for gastric diseases in symptomatic outpatients with conventional esophagogastroduodenoscopy (C-EGD) is expensive and has poor compliance. We aimed to explore the efficiency and safety of magnetic-controlled capsule gastroscopy (MCCG) in symptomatic outpatients who refused C-EGD. METHODS: We performed a retrospective study of 76794 consecutive symptomatic outpatients from January 2014 to October 2019. A total of 2318 adults (F/M = 1064/1254) in the MCCG group who refused C-EGD were matched with adults in the C-EGD group using propensity-score matching (PSM). The detection rates of abnormalities were analyzed to explore the application of MCCG in symptomatic patients. RESULTS: Our study demonstrated a prevalence of gastric ulcers (GUs) in patients with functional dyspepsia- (FD-) like symptoms of 8.14%. The detection rate of esophagitis and Barrett's esophagus was higher in patients with typical gastroesophageal reflux disease (GERD) symptoms than in patients in the other four groups (P < 0.01). The detection rates of gastric ulcers in the five groups (abdominal pain, bloating, heartburn, follow-up, and bleeding) were significantly different (P = 0.015). The total detection rate of gastric ulcers in symptomatic patients was 9.7%. A total of 7 advanced carcinomas were detected by MCCG and confirmed by endoscopic or surgical biopsy. The advanced gastric cancer detection rate was not significantly different between the MCCG group and the C-EGD matched group in terms of nonhematemesis GI bleeding (2 vs. 2, P = 1.00). In addition, the overall focal lesion detection rate in the MCCG group was superior to that in the C-EGD matched group (224 vs. 184, P = 0.038). MCCG gained a clinically meaningful small bowel diagnostic yield of 54.8% (17/31) out of 31 cases of suspected small bowel bleeding. No patient reported capsule retention at the two-week follow-up. CONCLUSION: MCCG is well tolerated, safe, and technically feasible and has a considerable diagnostic yield. The overall gastric diagnostic yield of gastric focal lesions with MCCG was comparable to that with C-EGD. MCCG offered a supplementary diagnosis in patients who had a previously undiagnostic C-EGD, indicating that MCCG could play an important role in the routine monitoring and follow-up of outpatient. MCCG shows its safety and efficiency in symptomatic outpatient applications.

Secondary aerosol formation from a Chinese gasoline vehicle: Impacts of fuel (E10, gasoline) and driving conditions (idling, cruising).

Chassis dynamometer experiments were conducted to investigate the effect of vehicle speed and usage of ethanol-blended gasoline (E10) on formation and evolution of gasoline vehicular secondary organic aerosol (SOA) using a Gothenburg Potential Aerosol Mass (Go: PAM) reactor. The SOA forms rapidly, and its concentration exceeds that of primary organic aerosol (POA) at an equivalent photochemical age (EPA) of ~1 day. The particle effective densities grow from 0.62 ± 0.02 g cm-3 to 1.43 ± 0.07 g cm-3 with increased hydroxyl radical (OH) exposure. The maximum SOA production under idling conditions (4259-7394 mg kg-fuel-1) is ~20 times greater than under cruising conditions. There was no statistical difference between SOA formation from pure gasoline and its formation from E10. The slopes in Van Krevelen diagram indicate that the formation pathways of bulk SOA includes the addition of both alcohol/peroxide functional groups and carboxylic acid formation from fragmentation. A closure estimation of SOA based on bottom-up and top-down methods shows that only 16%-38% of the measured SOA can be explained by the oxidation of measured volatile organic compounds (VOCs), suggesting the existence of missing precursors, e.g. unmeasured VOCs and probably semivolatile or intermediate volatile organic compounds (S/IVOCs). Our results suggest that applying parameters obtained from unified driving cycles to model SOA concentrations may lead to large discrepancies between modeled and ambient vehicular SOA. No reduction in vehicular `SOA production is realized by replacing normal gasoline with E10.

Magnetically Guided Capsule Endoscopy in Pediatric Patients with Abdominal Pain.

BACKGROUND AND AIMS: Magnetically guided capsule endoscopy (MGCE) offers a noninvasive method of evaluating both the gastric cavity and small intestine; however, few studies have evaluated MGCE in pediatric patients. We investigated the diagnostic efficacy of MGCE in pediatric patients with abdominal pain. PATIENTS AND METHODS: We enrolled 48 patients with abdominal pain aged 6-18 years. All patients underwent MGCE to evaluate the gastric cavity and small intestine. RESULTS: The cleanliness of the gastric cardia, fundus, body, angle, antrum, and pylorus was assessed satisfactorily in 100%, 85.4%, 89.6%, 100%, 97.9%, and 100% of patients, respectively. The subjective percentage visualization of the gastric cardia, fundus, body, angle, antrum, and pylorus was 84.8%, 83.8%, 88.5%, 87.7%, 95.2%, and 99.6%, respectively. Eighteen (37.5%) patients had 19 gastrointestinal tract lesions: one esophageal, three in the gastric cavity, and 15 in the small intestine. No adverse events occurred during follow-up. CONCLUSIONS: MGCE is safe, convenient, and tolerable for evaluating the gastric cavity and small intestine in pediatric patients. MGCE can effectively diagnose pediatric patients with abdominal pain.

Magnetic-Guided Capsule Endoscopy in the Diagnosis of Gastrointestinal Diseases in Minors.

OBJECTIVE: This study aimed at investigating the clinical value of magnetic-guided capsule endoscopy (MGCE) in the diagnosis of gastrointestinal diseases in minors. METHODS: Eighty-four minor patients hospitalized in the pediatric department at Ruijin Hospital between June 2015 and January 2018 were enrolled for this study. Following bowel preparation, all patients underwent MGCE. The feasibility, safety, diagnostic yield, and sensitivity of MGCE were analyzed. Patients were followed up for more than 2 weeks. RESULTS: The main indications for MGCE in minors were Crohn's disease, gastrointestinal bleeding, and abdominal pain. The main causes of gastric disease were gastric inflammatory hyperplasia, exudative gastritis, and polyps. The most common small bowel diseases in minors were Crohn's disease, Henoch-Schonlein purpura, and polyps. The diagnostic yield in the stomach and small intestine was 13.1% and 28.6%, respectively, and the sensitivity was 100% and 96.0%, respectively. No adverse events occurred. CONCLUSION: MGCE is a safe, effective, and well-tolerated procedure with good sensitivity and has a potential clinic value for the diagnosis of gastrointestinal diseases in minors.

Complex clonal mosaicism within microdissected intestinal metaplastic glands without concurrent gastric cancer.

BACKGROUND: The transformation of healthy gastric tissue into intestinal metaplasia (IM) is thought to be a critical premalignant step in the development of intestinal-type gastric adenocarcinoma (GA). How such premalignancies contribute to the development of GA is, however, poorly understood. METHODS: In this study, the extent and clonal complexity in IM tissue from patients without gastric cancer were analysed by measuring variations of multiple microsatellite (MS) markers. RESULTS: Even though these tissues are generally regarded as clinically benign, we found extensive MS length heterogeneity between and within individual IM glands, indicating that complex genome diversity is already pervasive in these tissues. Based on a clonal relationship analysis, we found that there exist multiple clones within individual IM glands and that MS alterations can accumulate in these clones. Moreover, we found spatially distant IM glands with the same MS phenotype, suggesting that these MS alterations were progressed by gland fission. CONCLUSIONS: These results provide evidence that genetic instability is an early event, present within metaplastic tissues of otherwise non-cancer patients, and such frequent genetic alterations can be part of the pathophysiological rationale for the requirement of this phase during gastric carcinogenesis.

Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer.

The importance of Pituitary homeobox 2 (Pitx2) in malignancy remains enigmatic, and Pitx2 has not been previously implicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed gene expression profiling of human PDAC tissues and identified Pitx2 as a promising candidate. Pitx2 expression was decreased from 2.6- to 19-fold in human PDAC tissues from microarray units. Immunochemistry staining showed that Pitx2 expression was moderate to intense in normal pancreatic and pancreatic intraepithelial neoplastic lesions, whereas low in human PDAC tissues. The Pitx2 levels correlated with overall patient survival post-operatively in PDAC. Induction of Pitx2 expression partly inhibited the malignant phenotype of PDAC cells. Interestingly, low Pitx2 expression was correlated with Smad4 mutant inactivation, but not with Pitx2 DNA-methylation. Furthermore, Smad4 protein bound to Pitx2 promoter and stimulated Pitx2 expression in PDAC. In addition, Pitx2 protein bound to the promoter of the protein phosphatase 2A regulatory subunit B55α (PPP2R2A) and upregulated PPP2R2A expression, which may activate dephosphorylation of Akt in PDAC. These findings provide new mechanistic insights into Pitx2 as a tumor suppressor in the downstream of Smad4. And Pitx2 protein promotes PPP2R2A expression which may inhibit Akt pathway. Therefore, we propose that the Smad4-Pitx2-PPP2R2A axis, a new signaling pathway, suppresses the pancreatic carcinogenesis.

Rab11-FIP2 promotes the metastasis of gastric cancer cells.

Rab11-FIP2 can interact with MYO5B and plays an important role in regulating plasma membrane recycling. Our previous study has shown that MYO5B is epigenetically silenced and associated with c-Met signaling in human gastric cancer. However, little is known of the function of Rab11-FIP2 in gastric cancer. In this study, we investigated Rab11-FIP2 expression by immunohistochemistry in 86 patients with gastric cancer. We found that the expression level of Rab11-FIP2 was significantly increased in gastric cancer tissues and high expression of Rab11-FIP2 was closely correlated with nodal metastasis in gastric cancer patients. Rab11-FIP2 overexpression promoted epithelial-mesenchymal transition (EMT) in a manner associated with gastric cancer metastasis in vitro and in vivo. We also found that hypoxia could enhance the expression of Rab11-FIP2 through HIF-1α. Inactivation of Rab11-FIP2 dramatically decreased hypoxia-induced migration of gastric cancer cells. Suppression of the internalization of EGFR, at least in part, plays an important role in EMT induced by overexpression of Rab11-FIP2 in gastric cancer cells. Finally, we demonstrated that Rab11-FIP2 could regulate actin cytoskeleton dynamics. In conclusion, our findings reveal a novel mechanism underlying the role of Rab11-FIP2 in gastric cancer dissemination, suggesting that Rab11-FIP2 may be a promising candidate target for gastric cancer treatment.

Exploring the Wnt pathway-associated LncRNAs and genes involved in pancreatic carcinogenesis driven by Tp53 mutation.

PURPOSE: Study the contribution of long non-coding RNAs (lncRNAs) to progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC). METHODS: We explored lncRNAs profilings in PanIN cell line (SH-PAN) isolated from Pdx-1-Cre; LSL-Kras (G12D/+) mice and PDAC cell line (DT-PCa) isolated from Pdx-1-Cre; LSL- Kras (G12D/+) ; LSL- Tp53 (R172H/+) mice by lncRNAs microarray, and detected expression of lncRNAs and genes in PDAC by Real-time PCR, Western blot, ChIP and immunohistochemistry. RESULTS: Eight lncRNAs and five protein-coding genes, associated with Wnt pathway, were identified with more than five-fold changes between DT-PCa cells and SH-PAN cells. Of them, lincRNA1611 and Ppp3ca were validated significantly high expression in DT-PCa cells and in 22 of 26 fresh resected human PDAC tissues, compared to SH-PAN cells and normal pancreatic tissues, respectively. Moreover, Tp53 mutation status displayed a positive correlation with lincRNA1611 or Ppp3ca level. Immunohistochemical staining for Ppp3ca was weak or lack in 91 of 107 normal pancreatic tissues, 24 of 29 PanIN-I and 13 of 16 PanIN-II tissues, however, was strong in 10 of 27 PanIN-III and 62 of 107 PDAC tissues post operation. CONCLUSIONS: LincRNA1611 and Ppp3ca were high expression in PDAC and may serve as new potential targets for intervention of the disease.

Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b.

TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p=0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3'untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3'UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.

The biological features of PanIN initiated from oncogenic Kras mutation in genetically engineered mouse models.

Pancreatic intraepithelial neoplasia (PanIN) is the most common premalignant lesion of the pancreas. Further understanding of the biological behavior and molecular genetic alterations in the stepwise progression of PanINs is necessary toward the development of pancreatic ductal adenocarcinoma (PDAC) interventions. In this study, we analyzed the morphological characteristics, molecular alterations, and biological behavior of pancreatic wild-type and neoplasia tissues, including analysis of PanIN cell line SH-PAN (isolated from Pdx-1-Cre; LSL-KrasG12D/+ mouse) and PDAC cell line DT-PCa (isolated from Pdx1-Cre; LSL-KrasG12D/+; LSL-Tp53R172H/+ mouse. Results show that KrasG12D induces ductal lesion PanINs. Increased expression of EGFR, Her-2/Neu, p-MAPK and ß-Catenin was observed in low-grade PanINs. Tp53 was not expressed in wild-type and low-grade PanINs, however, increased expression was observed in high-grade PanINs. Furthermore, SH-PAN cells did not exhibit any colony formation and showed significantly lower migration and invasion ability compared with DT-PCa cells. Notably, we first found PPP2R2A (protein phosphatase 2, regulatory subunit B, alpha) expression was significantly higher in SH-PAN cells than DT-PCa cells, and was high in 96 of 172 peritumoral normal human pancreatic tissues and 20 of 36 human low- or middle-grade PanIN tissues, whereas, was weak or negligible in 12 of 20 human high-grade PanIN tissues and 124 of 172 human PDAC tissues post-operation. The expression of PPP2R2A appears to be correlated with clinical survival. Taken together, Kras(G12D) - driven PanIN showed the tumorigenic ability, however, did not undergo a malignant transformation, and decreased expression of PPP2R2A in PDACs may provided a new target for pancreatic carcinoma intervention.

MYO5B is epigenetically silenced and associated with MET signaling in human gastric cancer.

BACKGROUND: Our previous study has shown that MYO5B is downregulated in gastric cancer. However, the mechanism by which the expression of MYO5B was inhibited remains unknown. METHODS: Inspection of the human MYO5B locus uncovered a large and dense CpG island within the 5' region of this gene. Methylation-specific PCR (MSP) and bisulfite sequencing (BSP) were used for determination of MYO5B promoter methylation in gastric cancer cell lines and gastric cancer samples. Involvement of histone H3 methylation in those cell lines were examined by ChIP assay. RESULTS: The densely methylated MYO5B promoter region was confirmed by MSP and BSP. Enhanced gene expression was detected when the cells were treated with the DNA-demethylating agent 5-aza-2'-deoxycytidine (DAC) and trichostatin A (TSA), a histone deacetylase inhibitor. Knockdown of MYO5B expression in gastric cancer cells expressing endogenous MYO5B inhibits HGF-stimulated MET degradation, concomitant with sustained c-MET levels and signaling. CONCLUSION: The results of our study showed for the first time that MYO5B is epigenetically silenced in gastric cancer cells by aberrant DNA methylation and histone modification. Inactivation of MYO5B expression in gastric cancer cells expressing endogenous MYO5B inhibits HGF-stimulated MET degradation, concomitant with sustained c-MET levels and signaling.

Double-balloon enteroscopy in the evaluation of small bowel disorders in pediatric patients.

BACKGROUND: The aim of the present study was to investigate the indications, clinical utility, feasibility and safety of double-balloon enteroscopy (DBE) in the diagnosis and management of small intestinal diseases in pediatric patients. METHODS: This is a retrospective analysis of pediatric patients younger than 18 years referred to Shanghai Rui Jin Hospital from May 2003 to June 2008 for investigation of suspected small bowel disorders. Demographic, clinical, procedural and outcome data were collected for analysis. RESULTS: A total of 35 DBE were carried out in 30 children with a mean age of 13 years. Indications for DBE were obscure gastrointestinal (GI) bleeding (n = 22), chronic abdominal pain (n = 4), chronic diarrhea (n = 3), and incomplete small bowel obstruction (n = 1). DBE evidenced pathological findings in 29 patients (96.7%). DBE altered management in 90% of patients with positive findings. Follow up was obtained on all patients with a mean (range) of 40 months (14-75 months). The procedure was successful in all patients and there were no serious complications related to sedation. CONCLUSION: DBE is feasible and safe and has a high diagnostic yield and therapeutic impact on the diagnosis and management of small bowel disorders in selected pediatric patients.

Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer.

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.